Objective To investigate the protective effect of lovastatin on liver injury in the rats induced by hyperlipidemia， and to elucidate its possible mechanism. Methods Fifteen SD rats were randomly divided into control group， hyperlipidemia model group， and lovastatin group， with 5 rats in each group. The rats in control group were fed with standard diet， while the rats in hyperlipidemia model group and lovastatin group were fed high-fat diet for 12 weeks. Starting from the 8th week， the rats were administered treatments via gavage once a day for 4 weeks： the rats in lovastatin group received 2 mg?kg?1 lovastatin， while the rats in control group and hyperlipidemia model group received an equal volume of normal saline. The body weights of the rats in various groups were measured at weeks 1， 8， 9， 10， 11， and 12 after the experiment began； the histopathology of liver tissue of the rats in various groups was observed using HE staining； the serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， malondialdehyde （MDA）， as well as the activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）， and the levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， interleukin-12 （IL-12）， and tumor necrosis factor-α （TNF-α） of the rats in various groups were detected using commercial kits； the composition of the gut microbiota of the rats in various groups was analyzed by 16S rRNA sequencing. Results Compared with control group， the body weight of the rats in hyperlipidemia model group was significantly increased from the 8th week of high-fat diet feeding （P<0.05 or P<0.01 or P<0.001）. Compared with hyperlipidemia model group， the body weight of the rats in lovastatin group was significantly decreased at weeks 11 and 12 （P<0.05）. Compared with control group， the livers of the rats in hyperlipidemia model group appeared rough， pale， enlarged， with blunt edges， and had a granular and greasy texture. Compared with hyperlipidemia model group， the livers of the rats in lovastatin group were light brownish-red， soft， with slightly blunt edges， reduced volume， and less granularity and greasiness. Compared with control group， the liver cells of the rats in hyperlipidemia model group were swollen and disorganized， with pyknotic nuclei， extensive inflammatory cell infiltration， and numerous vacuolar degenerations. Compared with hyperlipidemia model group， the rats in lovastatin group showed significantly reduced hepatocyte swelling and degeneration， more orderly and intact liver cell arrangement， decreased inflammatory cell infiltration， and reduced vacuolar degeneration. Compared with control group， the serum levels of TC， TG， and LDL-C of the rats in hyperlipidemia model group were significantly increased （P<0.05）， and the serum HDL-C level was decreased （P<0.05）. Compared with hyperlipidemia model group， the serum levels of TC， TG， and LDL-C of the rats in lovastation group were significantly decreased （P<0.05）， and the serum HDL-C level was increased （P<0.05）. Compared with control group， the serum MDA levels and the ALT and AST activities of the rats in hyperlipidemia model group were significantly increased （P<0.05）， and the SOD and GSH-Px activities were significantly decreased （P<0.05）. Compared with hyperlipidemia model group， the serum MDA levels and ALT and AST activities of the rats in lovastatin group were decreased （P<0.05）， and the SOD and GSH-Px activities were increased （P<0.05）. Compared with control group， the serum levels of IL-2， IL-6， IL-12， and TNF-α of the rats in hyperlipidemia model group were significantly increased （P<0.05）. Compared with hyperlipidemia model group， the serum levels of IL-2， IL-6， IL-12， and TNF-α of the rats in lovastatin group were significantly decreased （P<0.05）. Compared with control group， the ACE and Chao1 indexes of the rats in hyperlipidemia model group were significantly decreased （P<0.05）. Compared with hyperlipidemia model group， the ACE and Chao1 indexes of the rats in lovastatin group were significantly increased （P<0.05 or P<0.01）. Compared with control group， the relative abundances of Firmicutes and Proteobacteria of the rats in hyperlipidemia model group were significantly increased （P<0.001）， and the relative abundances of Bacteroidetes and Actinobacteria were decreased （P<0.001）. Compared with hyperlipidemia model group， the relative abundances of Firmicutes and Proteobacteria of the rats in lovastatin group were significantly decreased （P<0.05 or P<0.01）， while the relative abundances of Bacteroidetes and Actinobacteria showed no significant changes. Compared with control group， the relative abundance of Lactobacillus of the rats in hyperlipidemia model group was significantly decreased （P<0.001）， and the relative abundances of Bacteroides， Desulfovibrio， and Clostridium were significantly increased （P<0.01 or P<0.001）. Compared with hyperlipidemia model group， the relative abundance of Lactobacillus of the rats in lovastatin group showed no significant change but the relative abundances of Bacteroides， Desulfovibrio， and Clostridium were significantly decreased （P<0.05 or P<0.01 or P<0.001）. Conclusion Lovastatin ameliorates liver injury induced by hyperlipidemia， and the mechanism may be related to its ability to improve gut microbiota composition and inhibit oxidative stress and inflammatory damage.

Objective To investigate the anti-fatigue effect of Dendrobium and Panax Quinquefolius Granules（DPQG） on the overtrained mice， and to clarify its possible mechanism. Methods A total of 48 mice were randomly divided into control group （equal volume of distilled water）， low dose of DPQG group （400 mg·kg^-1 DPQG）， medium dose of DPQG group （800 mg·kg^-1 DPQG）， and high dose of DPQG group （1 600 mg·kg^-1 DPQG）. The DPQG were administered by gavage for 35 d， and the rotarod test and swimming endurance test were performed 30 min after last administration. Serum， liver tissue， and muscle tissue were collected from the mice in various groups. ELISA method was used to detect the serum lacticacid （LAC） levels and lactate dehydrogenase （LDH） activities， and the malondialdehyde （MDA） levels， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activities， and the liver glycogen and muscle glycogen levels in muscle tissue of the mice in various groups； HE staining was used to observe the pathomorphology of muscle tissue of the mice. Transcriptomics and metabolomics technologies were used to identify the key genes and metabolites in muscle tissue of the mice in control group and high dose of DPQG group and to analyze the correlations between differentially expressed genes（DEGs） and differentially expressed metabolites. Results Compared with control group， the rod turning exhaustion time of the mice in different doses of DPQG groups were significantly increased （P<0.05）， and the swimming exhaution time of the mice in high dose of DPQG group was increased （P<0.05）. Compared with control group， the LDH， SOD， and GSH-Px activities of the mice in medium and high doses of DPQG groups were increased （P<0.01）. Compared with control group， the levels of MDA and liver glycogen of the mice in medium and high doses of DPQG groups were decreased （P<0.05 or P<0.01）. The transcriptomics sequencing results showed that DPQG mainly acted on DEGs such as Trib3 and Olfr495； the Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in olfactory-related processes and signaling pathways； the metabolomics KEGG analysis results showed that the differential metabolites were mainly enriched in the regulation pathway of inflammatory mediators on tryptophan （TRP）； the combined analysis of transcriptomics and metabolomics results showed that the piezo1 gene had high correlations with the differential metabolites β1-solamarine （r=-1， P<0.05） and tilidine （r=1， P<0.05）. Conclusion DPQG can exert an anti-fatigue effect on the overtrained mice by modulating LAC metabolism and glycogen homeostasis， as well as maintaining the oxidative/antioxidant balance in the body； its anti-fatigue mechanism is related to the Olfr495 and piezo1 genes and the regulation pathway of inflammatory mediators on TRP channels.

Objective To investigate the expression of placenta expressed transcript 1（Plet1）in ovarian tissue of the letrozole-induced model rats of polycystic ovary syndrome （PCOS） and its effect on the proliferation of rat ovarian granulosa cells，and to clarify the possible mechanism by which Plet1 may contribute to the pathogenesis of PCOS. Methods The ovarian tissue samples from the rats collected in previous studies were used and divided into control and PCOS groups. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the expression levels of Plet1 mRNA and protein in ovarian tissue of the rat in two groups. Additionally， twenty-four rats underwent vaginal smear cytology were divided into four groups by estrous cycle phase： proestrus，estrus，metestrus and diestrus. RT-qPCR was used to detect the expression level of Plet1 mRNA in ovarian tissue of the rats in various groups，and immunohistochemistry （IHC） method was used to detect the location of Plet1 expression in the rat ovarian tissue in various groups. The rat ovarian granulosa cells were transfected and divided into control group， si-Plet1-rat-266 group， si-Plet1-rat-383 group， and si-Plet1-rat-554 group. Cell counting kit-8（CCK-8）method was used to assess the cell proliferation activities of rat ovarian granulosa cells in various groups， and RT-qPCR method was used to detect the expression levels of cyclin-dependent kinase 6 （CDK6） and P53 mRNA in rat ovarian granulosa cells in various groups. Results The RT-qPCR results revealed that Plet1 mRNA was expressed in the ovaries of normal rats， while no statistically significant difference was observed across estrous cycle phases （P>0.05）. The immunohistochemistry results showed that the expression of Plet1 protein was mainly localized in ovarian granulosa cells and luteal cells in the rat ovarian tissue. Compared with control group，the expression levels of Plet1 mRNA and protein in ovarian tissue of the rats in PCOS group were significantly decreased （P<0.05）. The RT-qPCR results showed that compared with control group， the expression level of Plet1 mRNA in ovarian granulosa cells in si-Plet1-rat-383 group was decreased （P<0.01）， exhibiting the most pronounced reduction. Compared with control group， the proliferation activity of rat ovarian granulosa cells in si-Plet1-rat-383 group was decreased （P<0.05）. Compared with control group， the expression levels of CDK6 and P53 mRNA in rat ovarian granulosa cells in si-Plet1-rat-383 group were significantly decreased （P<0.05 or P<0.01）. Conclusion Plet1 proteinis predominantly expressed and localized in granulosa cells and luteal cells in normal rat ovarian tissue. Its expression is downregulated in the ovarian tissue of PCOS model rats， and interference with Plet1 gene expression may inhibit the proliferation of rat ovarian granulosa cells.

Objective To investigate the effects of microRNA-325-3p （miR-325-3p） over-expression on the invasion and migration of colon cancer cells， and to clarify their mechanisms. Methods The tumor tissue and the corresponding adjacent normal tissue of 25 patients clearly diagnosed with colon cancer were collected. The expression levels of miR-325-3p and relevant evolutionary and lymphoid interest domain containing protein 1（PRELID1） mRNA were detected by real-time fluorescence quantitative PCR （RT-qPCR） method. The expression levels of miR-325-3p and PRELID1 mRNA and the expression levels of PRELID1 protein in human normal colon cells NCM460 and colon cancer cells SW480， HCT116 and HT-29 were detected by RT-qPCR and Western blotting methods. The SW480 cells were divided into control group， NC-mimics group， miR-325-3p mimics group， miR-325-3p mimics+oe-NC group and miR-325-3p mimics+oe-PRELID1 group. The invasion and migration abilities of cells in various groups were detected by Transwell chamber assay and scratch healing assay， respectively. The expression levels of E-Cadherin， N-Cadherin and Vimentin in the epithelial-mesenchymal transition （EMT） of cells in various groups were detected by Western blotting method.The downstream target genes of miR-325-3p were predicted using the Targetscan bioinformatics website， and the targeted regulatory relationship between miR-325-3p and PRELID1 was verified by the dual-luciferase assay. Results Compared with adjacent normal tissue， the expression level of miR-325-3p in cancer tissue was significantly decreased （P<0.05）， while the expression level of PRELID1 mRNA was significantly increased （P<0.05）. The expression levels of miR-325-3p and PRELID1 mRNA was negatively correlated in colon cancer tissue （r<0， R²=0.392， P<0.001）. Compared with NCM460 cells， the expression levels of miR-325-3p in SW480， HCT116 and HT-29 cells were significantly decreased （P<0.05）， and the expression levels of PRELID1 mRNA were significantly increased （P<0.05）. Compared with control group and NC-mimics group， the number of invasive SW480 cells in miR-325-3p mimics group was significantly reduced （P<0.05）， the rate of scratch healing was decreased （P<0.05）， and the expression level of E-Cadherin protein was increased， while the expression levels of N-Cadherin and Vimentin proteins were decreased （P<0.05）. The dual-luciferase assay confirmed that PRELID1 was the direct target of miR-325-3p. Compared with miR-325-3p mimics+oe-NC group， the number of invasive SW480 cells in miR-325-3p mimics+oe-PRELID1 group was significantly increased （P<0.05）， the rate of scratch healing was increased （P<0.05）， the expression level of E-Cadherin protein was decreased， and the expression levels of N-Cadherin and Vimentin proteins were increased （P<0.05）. Conclusion Over-expression of miR-325-3p can inhibit EMT process by down-regulating PRELID1 expression， thereby inhibiting SW480 cell invasion and migration.

Objective To discuss the effects of kallikrein 5 （KLK5） overexpression on the proliferation， invasion and cisplatin （DDP） sensitivity of cervical cancer cells， and to clarify its mechanism. Methods Western blotting method was used to verify the stable transfection and overexpression of KLK5 in the cervical cancer cell （ME180-OE-KLK5）. The cervical cancer ME180-NC-KLK5 and ME180-OE-KLK5 cells in logarithmic growth phase were subcutaneously inoculated into the nude mice to establish the subcutaneous xenograft models. After successful modeling， the mice were randomly divided into normal saline control group （NC-KLK5+0.9% NaCl group）， DDP treatment group （NC-KLK5+DDP group）， KLK5 overexpression group（OE-KLK5+0.9% NaCl group） and KLK5 overexpression combined with DDP group（OE-KLK5+DDP group）， with 5 mice in each group. The nude mice in NC-KLK5+DDP group and OE-KLK5+DDP group were given intraperitoneal injection of DDP at a dose of 5 mg·kg?1； the nude mice in NC-KLK5+0.9% NaCl group and OE-KLK5+0.9% NaCl group were given intraperitoneal injection of normal saline at a dose of 0.01 mL·g?1. The body weights of nude mice were measured every 2 d， and the long diameter and short diameter of the tumors were recorded to calculate the tumor volume and plot the tumor growth curve. At 24 h after the last administration on day 14， the nude mice were sacrificed， and the tumors were dissected and weighed. HE staining method was used to observe the pathomorphology of tumor tissue in the nude mice in various groups； immunohistochemistry staining method was used to observe the expression levels of KLK5， Ki67 and matrix metalloproteinase-9 （MMP-9） proteins in the tumor tissues of the nude mice in various groups. Results Compared with ME180-NC-KLK5 cells， the expression level of KLK5 protein in ME180-OE-KLK5 cells was increased （P<0.05）. In the first week after subcutaneous xenograft inoculation， the nude mice in various groups showed good feeding and activity status， and their body weights gradually increased. The drug administration phase started from the second week. During the drug treatment period， the feeding and activity status as well as body weight of the nude mice in NC-KLK5+0.9%NaCl group showed no significant changes compared with the first week； compared with NC-KLK5+0.9%NaCl group， the nude mice in NC-KLK5+DDP group began to show loss of appetite， no increase in body weight， and decreased activity. During the drug treatment period in the third week， the feeding and activity status of the nude mice in NC-KLK5+0.9%NaCl group showed no significant changes compared with the second week， while they began to show no increase in body weight； compared with NC-KLK5+0.9%NaCl group， the feeding and activity status of the nude mice in NC-KLK5+DDP group were significantly weakened， and their body weights decreased. Compared with NC-KLK5+0.9%NaCl group， the volume of xenograft tumor in NC-KLK5+DDP group was decreased （P<0.01）； compared with NC-KLK5+DDP group， the volume of xenograft tumor OE-KLK5+DDP group was significantly increased （P<0.001）； compared with NC-KLK5+0.9%NaCl group， the volume of xenograft tumor of the nude mice in OE-KLK5+0.9%NaCl group was increased （P<0.001）； compared with OE-KLK5+0.9%NaCl group， the volume of xenograft tumors in the nude mice in OE-KLK5+DDP group showed no statistically significant difference （P>0.05）. Compared with NC-KLK5+0.9%NaCl group， the weight of xenograft tumor of the nude mice in NC-KLK5+DDP group was decreased （P<0.05）； compared with NC-KLK5+DDP group， the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group was significantly increased （P<0.001）； compared with NC-KLK5+0.9%NaCl group， the weight of xenograft tumor of the nude mice in OE-KLK5+0.9%NaCl group was increased （P<0.001）； compared with OE-KLK5+0.9%NaCl group， the weight of xenograft tumors of the nude mice in OE-KLK5+DDP group showed no statistically significant difference （P>0.05）. Compared with NC-KLK5+0.9%NaCl group， the xenograft tumor cells of the nude mice in OE-KLK5+0.9%NaCl group showed greater nuclear heterogeneity； the xenograft tumor cells of the nude mice in OE-KLK5+DDP group and NC-KLK5+DDP group showed cytomorphological changes， manifested as nuclear pyknosis and fragmentation， reduced cell volume， and the appearance of necrosis and apoptosis. Compared with NC-KLK5+DDP group， the degree of necrosis in xenograft tumor of the nude mice in OE-KLK5+DDP group was more pronounced. Compared with NC-KLK5+0.9%NaCl group， the expression levels of KLK5， Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in NC-KLK5+DDP group were decreased （P<0.05）； compared with NC-KLK5+DDP group， the expression levels of KLK5， Ki67， and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group were increased （P<0.001）； compared with NC-KLK5+0.9%NaCl group， the expression levels of KLK5， Ki67 and MMP-9 proteins in xenograft tumor tissue of the nude mice in OE-KLK5+0.9%NaCl group were increased （P<0.001）； compared with OE-KLK5+0.9%NaCl group， the expression levels of KLK5， Ki67 and MMP-9 in xenograft tumor tissue of the nude mice in OE-KLK5+DDP group showed no statistically significant differences （P>0.05）. Conclusion KLK5 overexpression can promote the growth of subcutaneous xenograft tumors of cervical cancer ME180 cells treated with DDP， up-regulate the expressions of Ki67 and MMP-9 in the xenograft tumor tissue， and reduce the sensitivity of the xenograft tumor to DDP.

Objective To investigate the effect of β-elemene on mitochondrial structure and function of the A549 cells of non-small cell lung cancer （NSCLC）， and to elucidate the mechanism of β-elemene in the treatment of NSCLC. Methods The A549 cells at logarithmic growth stage were divided into blank control group （0 mg·L^-1 β-elemene）， low， medium and high doses of β-elemene groups （10， 25 and 50 mg·L^-1）， and solvent control group （0.5% ethanol in equal volume）. After treatment for 24 h， the cell activities in various groups were detected by MTT assay； the morphology changes of mitochondria in the cells in various groups was observed by transmission electron microscope； the levels of adenosine 5'-triphosphate（ATP） in the cells in various groups were detected by colorimetry； the mitochondrial membrane potential of the A549 cells in various groups were detected by JC-1 flow cytometry； mitochondrial membrane permeability transfer hole assay was used to detect the mitochondrial membrane permeabilities of the cells in various groups. Results The MTT results showed that compared with blank control group， the cell activities in low， medium and high doses of β-elemene groups were decreased gradually （P<0.05）， while the cell activity in solvent control group had no significant change， and the difference was not significant （P>0.05）. The transmission electron microscope results showed that compared with blank control group， the mitochondria of A549 cells in low， medium and high doses of β-elemene groups showed swelling， vacuolation， disordered arrangement and dissolution， while the mitochondrial morphology of the A549 cells in solvent control group had no significant changes. The colorimetric method results showed that compared with blank control group， the ATP levels in the A549 cells in low， medium and high dose β-elemene groups were gradually decreased （P<0.05）， while the ATP level in the A549 cells in solvent control group had no significant change， and the difference was not significant （P>0.05）. The JC-1 flow cytometry method results showed that compared with blank control group， the mitochondrial membrane potential of the A549 cells in low， medium and high doses of β-elemene groups were decreased， and the percentages of the cells in Q2-4 region were increased （P<0.05）； the percentage of the A549 cells in the Q2-4 region in solvent control group had no significant change. The results of mitochondrial membrane permeability transfer hole experiment showed that compared with blank control group， the mitochondrial membrane permeabilities of the A549 cells in low， medium and high doses of β-elemene groups were increased， and the percentages of the cells in M4 region were increased （P<0.05）； the mitochondrial membrane permeability of the A549 cells and the percentage of the M4 cells in solvent control group had no significant changes， and the difference was not significant （P>0.05）. Conclusion β-elemene can inhibit the proliferation of the A549 cells， and the mechanism may be that the mitochondrial structure of A549 cells is damaged by reducing the level of ATP and mitochondrial membrane potential， changing the mitochondrial morphology and increasing the mitochondrial membrane permeability.

Objective To investigate the effect of Xuebijing injection against blood-brain barrier （BBB） ??damage in the mice with anti-N-methyl-D-aspartate receptor （NMDAR） encephalitis， and to elucidate its regulatory effect on the imbalance of helper T cells 17 （Th17）/regulatory T cells （Treg）. Methods The active immunization models of anti-NMDAR encephalitis in the mice were established using glutamate receptor N1 subunit （GluN1） 356-385 antigen peptide， and the serum anti-NMDAR immunoglobulin G （IgG） antibody levels were detected by enzyme-linked immunosorbent assay（ELISA）. The healthy mice without modeling were served as control group， and the mice with successful modeling were randomly divided into model group， low dose of Xuebijing injection （XBJ-L） group， and high dose of Xuebijing injection （XBJ-H） group， with 10 mice in each group. After modeling， the mice in XBJ-L and XBJ-H groups were intraperitoneally injected with 5 and 10 mL·kg^-1 Xuebijing injection， respectively. The Longa score was used to assess the neurological impairment of the mice in various groups； evans blue （EB） staining was used to determine the BBB permeability； immunofluorescence staining was used to detect the expressions of zonula occludens 1 （ZO-1） and Occludin in cerebral cortex of the mice in various groups； Western blotting method was used to determine the expression levels of ZO-1， Occludin， Claudin-5， and neuron-specific nuclear protein （NeuN） in cerebral cortex of the mice in various groups； ELISA method was used to determine the levels of Th17- and Treg-related cytokines including interleukin （IL）-17， IL-22， and IL-10 in serum of the mice； flow cytometry was used to determine the percentages of Th17 and Treg cells in peripheral blood of the mice in various groups， and the Th17/Treg ratio was calculated. Results The serum of the mice induced with the GluN1 356-385 antigen peptide was positive for NMDAR IgG antibodies， indicating that the models were successfully established. Compared with control group， the neurological impairment score of the mice in model group was significantly increased （P<0.05）， and the EB level in brain tissue was significantly increased （P<0.05）； the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were decreased， and the expression levels of ZO-1， Occludin， Claudin-5， and NeuN proteins in the cerebral cortex were significantly decreased （P<0.05）； the serum levels of IL-17 and IL-22 were significantly increased （P<0.05）， while the IL-10 level was significantly decreased （P<0.05）； the percentage of Th17 cells in peripheral blood was significantly increased （P<0.05）， while the percentage of Treg cells was significantly decreased （P<0.05）， and the Th17/Treg ratio was significantly increased （P<0.05）. Compared with model group， the neurological impairment scores of the mice in XBJ-L and XBJ-H groups were significantly decreased （P<0.05）， the EB levels in brain tissue were significantly decreased （P<0.05）， the fluorescence staining intensities of ZO-1 and Occludin in cerebral cortex were increased， and the expression levels of ZO-1， Occludin， Claudin-5， and NeuN proteins were significantly increased （P<0.05）； the levels of IL-17 and IL-22 in serum were significantly decreased （P<0.05）， and the level of IL-10 was significantly increased （P<0.05）； the percentages of Th17 cells in peripheral blood were significantly decreased （P<0.05）， the percentages of Treg cells were significantly increased （P<0.05）， and the Th17/Treg ratios were significantly decreased （P<0.05）. Compared with XBJ-L group， the neurological function injury score of the mice in XBJ-H group was significantly decreased （P<0.05）， the EB level in brain tissue was significantly decreased （P<0.05）； the fluorescence staining intensities of ZO-1 and Occludin in the cerebral cortex were increased， and the expression levels of ZO-1， Occludin， Claudin-5， and NeuN proteins were significantly increased （P<0.05）； the serum levels of IL-17 and IL-22 were significantly decreased （P<0.05）， and the level of IL-10 was significantly increased （P<0.05）； the percentage of Th17 cells in peripheral blood was significantly decreased （P<0.05）， the percentage of Treg cells was significantly increased （P<0.05）， and the Th17/Treg ratio was significantly decreased （P<0.05）. Conclusion Xuebijing injection can improve BBB injury， regulate Th17/Treg balance， and thereby alleviate the neurological functional damage in anti-NMDAR encephalitis.

Objective To discuss the promotive effect of Shengji Yuhong Ointment extract （SYOE） on skin wound healing of zebrafish， and to clarify its mechanism. ? Methods ?A total of 320 wild-type AB strain zebrafish were used to establish a wound model by making an incision on the lateral abdomen. The zebrafish were randomly divided into control group， low dose of SYOE group （raised in water containing 0.625 mg·L^-1 SYOE）， high dose of SYOE group （raised in water containing 1.250 mg·L^-1 SYOE）， and allantoin group （raised in water containing 1.000 mg·L^-1 allantoin）， and there were 80 zebrafish in each group. The wound areas were recorded by photographs on days 7， 14， and 21 after injury， and the wound healing rates were calculated. The skin tissue samples from the wound sites of the zebrafish in various groups were collected at different time points to prepare histological sections. HE staining was used to observe the widths of skin wound edges of the zebrafish on days 0， 7， 14， and 21 in various groups； Sirius red staining was used to detect the collagen levels in the wound tissues of the zebrafish on days 2， 4， 6， and 8 after injury in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of type Ⅰ collagen （Col Ⅰ） and α-smooth muscle actin （α-SMA） in the wound tissues on day 4 after injury； real-time quantitative PCR （RT-qPCR） was used to analyze the mRNA expression levels of Col Ⅰ-encoding genes （col1a1a， col1a1b， and col1a2） and α-SMA as wall as key factors of the transforming growth factor β （TGF-β）/Smad signaling pathway （tgfb1a， smad2， and smad3a） in the wound tissues of the zebrafish in various groups on day 4 after injury.?? Results The wound healing assessment results showed that compared with control group， the wound healing rates of the zebrafish in low dose of SYOE group， high dose of SYOE group， and allantoin group were significantly increased on days 7， 14， and 21 after injury （P<0.05 or P<0.01）； the wound healing rate in high dose of SYOE group achieved 84% on day 21. The HE staining results showed that compared with control group， the widths of skin wound edges of the zebrafish in low dose of SYOE group， high dose of SYOE group， and allantoin group were significantly decreased on days 14 and 21 after injury （P<0.05 or P<0.01）.The Sirius red staining results showed that compared with control group， the collagen levels in the skin wound tissue of the zebrafish in low dose of SYOE group， high dose of SYOE group， and allantoin group were significantly increased on days 6 and 8 after injury （P<0.01）. The ELISA results showed that on day 4 after injury， compared with control group， the levels of Col Ⅰ and α-SMA in the skin wound tissue of the zebrafish in low dose of SYOE group， high dose of SYOE group， and allantoin group were significantly increased （P<0.05 or P<0.01）. The RT-qPCR results showed that on day 4 after injury， compared with control group， the expression levels of col1a1b， col1a2， α-SMA， tgfb1a， and smad2 mRNA in the skin wound tissue of the zebrafish in low dose of SYOE group were significantly increased （P<0.05 or P<0.01）， while the expression levels of col1a1a， col1a1b， col1a2， α-SMA， tgfb1a， smad2， and smad3a mRNA in the skin wound tissue of the zebrafish in high dose of SYOE group and allantoin group were significantly increased （P<0.01）. Conclusion SYOE can increase the collagen deposition in skin wound of zebrafish， promote wound healing， and upregulate the expression of genes related to the TGF-β/Smad signaling pathway.

Objective To discuss the effect of exosomes （Exos） loaded with microRNA-520a-5p（miR-520a-5p） on the pregnancy outcomes in fetal mice with intrauterine growth restriction （FGR）， and to clarify its mechanism. Methods The mouse placental mesenchymal stem cells （MSCs） were cultured in vitro and transfected with miR-520a-5p adenovirus vector （Ad-miR-520a-5p） to obtain the Exos with high miR-520a-5p load （miR-520a-5p-MSCs-Exos）， which were then identified. The C57BL/6 mice were mated in cages at a female∶male ratio of 2∶1 to achieve successful pregnancy. Forty pregnant mice were divided into control group， FGR group， NC-MSCs-Exos group， and miR-520a-5p-MSCs-Exos group， with 10 mice in each group. Except for control group， the mice in other groups were exposed to excessive dexamethasone （DEX） during pregnancy to induce FGR models in the pregnant mice. The body weights of the fetal mice at birth and at 1， 2， 3， and 4 weeks after birth were detected； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of miR-520a-5p， DNA methyltransferase 3b（DNMT3b）， and vascular endothelial growth factor（VEGF） mRNA in placenta tissue of the mice in various groups； Western blotting method was used to detect the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice in various groups； methylation-specific PCR （MSP） was used to analyze the methylation rates of VEGF promoter in placenta tissue of the mice in various groups； dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-520a-5p and DNMT3b. Results The results of transmission electron microscope（TEM） and nanoparticle tracking analysis（NTA） showed that the Exos were spherical with particle size concentrated near 100 nm； the Western blotting method results showed that the surface biomarkers CD63 and CD81 of Exos were positively expressed. The RT-qPCR results showed that compared with NC-MSCs-Exos and Ad-NC-MSCs-Exos， the expression level of miR-520a-5p in Ad-miR-520a-5p-MSCs-Exos was increased （P<0.001）. The differences in birth body weight and the body weights at 1， 2， and 3 weeks after birth of the fetal mice among four groups were statistically significant （F=36.084， F=19.851， F=77.755， F=103.223； P<0.001）. Compared with control group， the birth body weight and the body weights at 1， 2， and 3 weeks after birth of the fetal mice in FGR group were decreased （P<0.05）； compared with FGR group and NC-MSCs-Exos group， the birth body weight and the body weights at 1， 2， and 3 weeks after birth of the fetal mice in miR-520a-5p-MSCs-Exos group were increased （P<0.05）. The One-way ANOVA results showed that the differences in the expression levels of miR-520a-5p， DNMT3b， and VEGF mRNA in placenta tissue of the mice among four groups were statistically significant （F=103.224， F=856.460， F=214.563； P<0.001）. The pairwise comparison between groups showed that compared with control group， the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in FGR group were decreased （P<0.05）， and the expression level of DNMT3b mRNA was increased （P<0.05）； compared with FGR group and NC-MSCs-Exos group， the expression levels of miR-520a-5p and VEGF mRNA in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group were increased （P<0.05）， and the expression level of DNMT3b mRNA was decreased （P<0.05）. The One-way ANOVA results showed that the differences in the expression levels of DNMT3b and VEGF proteins in placenta tissue of the mice among four groups were statistically significant （F=245.601， F=149.360； P<0.001）. The pairwise comparison between groups showed that compared with control group， the expression level of DNMT3b protein in placenta tissue of the mice in FGR group was increased （P<0.05）， and the expression level of VEGF protein was decreased （P<0.05）； compared with FGR group and NC-MSCs-Exos group， the expression level of DNMT3b protein in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased （P<0.05）， and the expression level of VEGF protein was increased （P<0.05）. The One-way ANOVA results showed that the difference in the methylation rate of VEGF promoter in placenta tissue of the mice among four groups was statistically significant （F=687.096， P<0.001）. The pairwise comparison between groups showed that compared with control group， the methylation rate of VEGF promoter in placenta tissue of the mice in FGR group was increased （P<0.05）； compared with FGR group and NC-MSCs-Exos group， the methylation rate of VEGF promoter in placenta tissue of the mice in miR-520a-5p-MSCs-Exos group was decreased （P<0.05）. Dual-luciferase reporter gene assay results showed that compared with miR-NC group， the luciferase activity in the cells containing DNMT3b-WT reporter vector in miR-520a-5p group was decreased （P<0.05）； compared with miR-NC group， the luciferase activity in the cells containing DNMT3b-MUT reporter vector in miR-520a-5p group had no change， no significant difference was observed （P>0.05）. Conclusion The MSCs-derived Exos highly loaded with miR-520a-5p may improve the pregnancy outcomes of FGR fetal mice by targeting and down-regulating the expression of DNMT3b， inhibiting VEGF methylation， and promoting VEGF expression.

Objective To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution （CHAaHGS） on the hair growth through in vitro experiments on the human dermal papilla cells （HDPCs）， in vivo experiments in the C57BL/6 mice， and human efficacy tests， and to clarify its potential mechanism. Methods The HDPCs were divided into control group， CHAaHGS group， and minoxidil group. MTT method was used to detect the proliferation activities of HDPCs in various groups； enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of vascular endothelial growth factor （VEGF）， hepatocyte growth factor （HGF）， insulin-like growth factor-1 （IGF-1）， and transforming growth factor β1 （TGF-β1） in the supernatant of HDPCs in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of VEGF， HGF， IGF-1， TGF-β1， and alkaline phosphatase （ALP） mRNA in the HDPCs in various groups； Western blotting method was used to detect the expression levels of β-catenin， dishevelled segment polarity protein 1 （DVL1）， glycogen synthase kinase 3β （GSK-3β）， phosphorylated GSK-3β （p-GSK-3β）， and wingless-type MMTV integration site family member 3a （Wnt3a） proteins in the HDPCs in various groups. A total of 18 mice were randomly divided into control group， CHAaHGS group， and minoxidil group， with 6 mice in each group. The mouse hair loss model was established using hair removal cream， and corresponding drug treatments were administered immediately after hair removal. The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected； HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7； ELISA method was used to detect the levels of VEGF， HGF， IGF-1， and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups. Sixty subjects were randomly divided into control group and CHAaHGS group， with 30 subjects in each group. The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0， 4， 8， and 12. Results The MTT assay results showed that compared with control group， the proliferation activity of the cells in 50 mg·L^-1 CHAaHGS group was significantly increased （P<0.01）. The ELISA assay results showed that compared with control group， the levels of VEGF， HGF， and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased （P<0.05 or P<0.01）， and the TGF-β1 level was significantly decreased （P<0.01）. The RT-qPCR results showed that compared with control group， the expression levels of VEGF， HGF， IGF-1， and ALP mRNA in the cells in CHAaHGS group were significantly increased （P<0.05 or P<0.01）， and the TGF-β1 mRNA expression level was significantly decreased （P<0.01）. The Western blotting results showed that compared with control group， the expression levels of β-catenin， DVL1， p-GSK-3β and Wnt3a proteins in the cells in CHAaHGS group were significantly increased （P<0.05 or P<0.01）， and the GSK-3β protein expression level was significantly decreased （P<0.05）. In animal experiments， on day 21， compared with control group， the length of newly grown hair of the mice in CHAaHGS group was significantly increased （P<0.05）， and the hair weight was significantly increased （P<0.01）. On day 7， the HE staining results showed that compared with control group， the hair follicle spacing of the mice in CHAaHGS group was significantly decreased （P<0.05）， and the number of hair follicles was significantly increased （P<0.01）； the ELISA assay results showed that compared with control group， the levels of VEGF， HGF， and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased （P<0.05 or P<0.01）， and the TGF-β1 level was significantly decreased （P<0.05）. In human efficacy test， compared with control group， the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12 （P<0.01）， and the local hair density was increased （P<0.05）. Conclusion CHAaHGS promotes hair growth， and the mechanism may be related to its ability to increase the proliferation activity of HDPCs， induce the secretion of VEGF， HGF， and IGF-1， and activate the Wnt/β-catenin signaling pathway.

Objective To discuss the effect of erythritol on glucose and lipid metabolism in the body， and to clarify the mechanism of erythritol affecting liver metabolism based on metabonomics. Methods The male ICR mice were randomly divided into normal group， sucrose group （2% sucrose）， low dose of erythritol （1% erythritol） group， medium dose of erythritol （2% erythritol） group， and high dose of erythritol （4% erythritol） group， with 10 mice in each group. The corresponding concentrations of sucrose and erythritol solutions were prepared and placed in water bottles， and the mice were allowed to drink and eat freely for 12 consecutive weeks； the body mass， food intakes， and water intakes of the mice in various groups were measured. Commercial kits were used to detect the serum triglyceride （TG）， total cholesterol （TC）， and blood glucose levels of the mice in various groups； the liver indexes of the mice were calculated. Ultra performance liquid chromatography-orbitrap exactive mass spectrometry （UPLC-OE-MS） non-targeted metabonomics was used to detect the liver metabolites of the mice normal group and high dose of erythritol group； bioinformatics analysis was used to screen the differential liver metabolites between the two groups with variable importance in projection （VIP）>1 and adjusted P<0.05； Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed to investigate the functional roles of the differential liver metabolites. Results ?Compared with normal group， there were no significant differences in the body mass， food intake， liver index， and blood lipid levels of the mice in various groups （P>0.05）； compared with normal group， the blood glucose level of the mice in high dose of erythritol group was significantly increased （P<0.01）. The metabonomics analysis of the liver tissues of the mice in two groups identified 1 144 metabolites， mainly including lipids and lipid-like molecules （17.39%）， organic acids and derivatives （10.87%）， organic heterocyclic compounds （5.80%）， and organic oxygen compounds （5.07%）. Compared with normal group， there were 138 differential liver metabolites in the mice in high dose of erythritol group， among which 112 metabolites were up-regulated and 26 metabolites were down-regulated. The KEGG signal pathway enrichment analysis results showed that the differential metabolites were mainly enriched in metabolism， steroid hormone biosynthesis， cortisol synthesis and metabolism， and Cushing’s syndrome pathways； the further topological analysis of the metabolic pathways results showed that the differential metabolites were mainly involved in sphingolipid metabolism， tricarboxylic acid cycle， riboflavin metabolism， steroid hormone biosynthesis， and purine metabolism signal pathways. Conclusion Long-term intake of high dose of erythritol can increase the blood glucose level in the mice， and the mechanism may be that it affects the tricarboxylic acid cycle by interfering with riboflavin metabolism and interferes with sphingolipid metabolism， leading to impairment of the blood glucose control system.

Objective To prepare the nanodrug paclitaxel dimer（PTX₂）-loaded nanoparticles（NPs） using the block copolymer 1，2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000，（DSPE-PEG₂₀₀₀）， and to explore the killing effect of PTX₂ NPs on the human lung cancer A549 cells and its influence on apoptotis. Methods The PTX₂ NPs were prepared using nanoprecipitation method. Dynamic light scattering （DLS） was employed to determine the particle size distribution， and transmission electron microscope （TEM） was used to observe the ultrastructure of the nanoparticles. After treatment of 0 and 10 mmol·L^-1 dithiothreitol （DTT）， dialysis method was used to evaluate the in vitro drug release profile of PTX₂ NPs. The cell counting kit-8（CCK-8） method was used to assess the survival rates of the A549 cells after treated with PTX₂ and PTX₂ NPs with different concentrations （0.000 1， 0.001 0， 0.010 0， 0.100 0， and 1.000 0 μmol·L^-1）. The A549 cells were divided into control group， PTX₂ group， and PTX₂ NPs group.Live/dead staining method was used to detect the survival of the A549 cells in various groups， and flow cytometry was used to detect the apoptotic rates of the A549 cells in various groups. Results The mean hydrodynamic diameter of PTX₂ NPs was determined to be 144.7 nm by DLS. The TEM imaging confirmed uniform spherical morphology of PTX₂ NPs. In a reductive environment， the PTX₂ NPs exhibited continuous drug release with total paclitaxel（PTX） release of 84% within 72 h. The results of CCK-8 method showed that both PTX₂ and PTX₂ NPs inhibited the proliferation of A549 cells in a dose-dependent manner. When the concentrations of PTX<0.01 μmol·L^-1， compared with PTX₂ group，the survival rates of A549 cells in PTX₂ NPs group were significantly decreased （P<0.01 or P<0.001）. The live/dead staining results showed that compared with PTX₂ group，the number of red fluorescence-labeled dead cells in PTX₂ NPs group was increased. The flow cytometry results demonstrated that compared with control group and PTX₂ group，the apoptotic rates of the A549 cells in PTX₂ NPs group were significantly increased （P<0.05 or P<0.01）. Conclusion The PTX₂-loaded nanoparticles PTX₂ NPs are successfully prepared which exhibits responsive drug release and demonstrates a more significant killing effect on the human lung cancer A549 cells compared to PTX₂.

Objective To elucidate the inhibitory effect of interferon-γ（IFN-γ） on the proliferation of neuroblastoma cells and the protentral gene signature of IFN-γ and the relationship between the expression of gene signature of IFN-γ in the neuroblastoma cells and its adverse prognosis， and to clarify the effect of IFN-γ and its gene signture in the neuroblastoma. Methods The SK-N-BE（2）（proto-oncogene N-MYC amplification type） and SH-SY5Y （proto-oncogene N-MYC non-amplification type） neuroblastoma cells were selected and treated with different concentrations （0， 500， 750， 1 000 and 1 500 μg·L^-1） of IFN-γ for 24 h， followed by cell proliferation assays using cell counting kit-8 （CCK-8）. Transcriptome sequencing was then performed to identify the gene signature of IFN-γ. Additionally， the tissue microarrays from 23 cases of neuroblastoma and 6 cases of normal adrenal gland samples were collected， immunohistochemistry （IHC） analysis was used to to detect the expression of gene signature of IFN-γ. Based on the expression levels of gene signature of IFN-γ， the samples were divided into SULT2B1 low and high expression groups. The correlation between the expression of gene signature of IFN-γ and poor prognosis of the patients was analyzed. Results The CCK-8 assay results showed that as IFN-γ concentration increased，the proliferation of SK-N-BE（2） cells was significantly inhibited （P<0.01）， with inhibitory rates of SK-N-BE（2） cells in four groups were 6.73%， 6.77%，7.67%， and 9.19%， respectively. In contrast， the proliferation rate of SH-SY5Y cells were significantly increased with the increase of IFN-γ concentrations （P<0.01）， and the proliferation rates of SH-SY5Y cells in four groups were 46.80%， 79.19%， 70.30%， and 72.33%， respectively. Transcriptome sequencing identified hydroxysteroid sulfotransferase 2B1 （SULT2B1） as a potential gene signature of IFN-γ. The IHC analysis results showed the expression amount of SULT2B1 protein in neuroblastoma tissues was increased. The clinical data analysis results revealed significant differences in age（Z=-2.618， P=0.018）， lymphnode metastasis （χ²=4.439， P=0.035）， and distant metastasis （χ²=5.856， P=0.016） between low and high SULT2B1 expression groups. Conclusion IFN-γ can inhibit the proliferation of SK-N-BE（2） cells while promoting the proliferation of SH-SY5Y cells. SULT2B1 is a potential gene signature of IFN-γ， and its expression is upregulated in neuroblastoma tissue. SULT2B1 high expression is significantly associated with poor prognosis in the neuroblastoma patients.

Objective To investigate the changes in retinal structure and microcirculation in the patients with high myopia （HM） and the non-HM individuals， and to elucidate the correlations between axial length （AL） and the related parameters. Methods A total of 80 eyes from 40 patients with simple HM （non-pathological myopia） were enrolled as case group， while 80 eyes from 40 age- and sex-matched non-HM subjects were selected as control group. The best-corrected visual acuity （BCVA），AL，spherical equivalent （SE）， and optical coherence tomography angiography （OCTA） examination were performed in all the subjects. OCTA examination was used to measure the vascular density of the superficial retinal capillary plexus （SCP）， deep retinal capillary plexus （DCP）， and radial peripapillary capillary （RPC）， as well as central macular thickness （CMT）， and the area and volume of the foveal avascular zone （FAZ） of the subjects in two groups. The differences in these parameters of the subjects between two groups were analyzed. The AL of the subjects in two groups was measured using a biometer， and its correlations with the parameters mentioned above were evaluated. Results No statistically significant differences were observed in age or sex distribution between two groups （P>0.05）. Compared with control group， both SCP and DCP vessel densities acrossing the whole （excluding the foveal）， parafoveal， and perifoveal regions of the macular retina of the patients in case group were significantly decreased （P<0.05）. Compared with control group， the RPC vessel densities in the optic disc region of the patients in case group were significantly decreased in the whole， peripapillary， peripapillary superior， and peripapillary inferior sectors （P<0.001）， while the RPC vessel density was increased inside the disc （P<0.01）. Compared with control group， the whole FAZ volume of the patients in case group was increased （P<0.01）， while the parafoveal and perifoveal CMT were decreased（P<0.001）. In case group， AL was negatively correlated with SCP vessel density （r=-0.642， P<0.001）， DCP vessel density （r=-0.388， P<0.001）， RPC vessel density （r=-0.639， P<0.001）， and CMT （r=-0.495， P<0.001）， but positively correlated with FAZ volume （r=0.580， P<0.001）； no significant correlation was found between AL and FAZ area （r=-0.062， P=0.587）. Conclusion The patients with HM may exhibit early reductions in SCP， DCP， and RPC vessel densities， thinning of the central retina， and increased FAZ volume. Furthermore， as AL increases， SCP， DCP， and RPC vessel densitiesas as well as CMT decreases， while FAZ volume increases， suggesting significant associations between AL and the parameters mentioned above.

Objective To evaluate the expression characteristics of the FBJ murine osteosarcoma viral oncogene homolog B（FOSB） gene in immunoglobulin A nephropathy （IgAN） and common chronic kidney diseases （CKDs）， and to determine its value as a potential key candidate gene or biomarker. Methods The RNA sequencing datasets for IgAN，diabetic kidney disease （DKD）， membranous nephropathy（MN）， and minimal change disease（MCD） glomerular samples were downloaded from the Gene Expression Omnibus（GEO） database. The feature genes for CKD were identified using machine learning methods including least absolute shrinkage and selection operator（LASSO） regression， random forest（RF）， and support vector machine（SVM）. Gene Ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） signaling pathway enrichment analyses were performed on the identified IgAN feature genes. The “pROC” package was used to plot the receiver operating characteristic（ROC） curves to evaluate the diagnostic efficacy of IgAN feature genes.The gene with the highest diagnostic value was selected for Gene Set Enrichment Analysis（GSEA） and correlation analysis with core immune cells in IgAN. Clinical correlation analysis between the FOSB expression level in kidney tissue and renal function was performed using the Nephroseq v5 platform. Kidney tissue samples were collected from 5 cases of IgAN patients，DKD patients， MCD patients， and MN patients，respectively，along with 5 samples of adjacent normal kidney tissues （control group）. Immunohistochemistry staining method was used to detect the expression levels of FOSB protein in tissue samples in various groups. Results A total of 110 differentially expressed genes（DEGs） were identified in IgAN glomeruli， among which FOSB， NR4A2， and DUSP1 were identified as the feature genes. Compared with control group， the expression level of FOSB mRNA in IgAN group was significantly decreased（P<0.05）. The GO fuctional enrichment analysis results revealed that these IgAN feature genes were primarily enriched in biological processes related to dopamine biosynthesis，midbrain dopaminergic neuron differentiation， peptidyl-serine/threonine dephosphorylation， and response to corticosterone. The KEGG signaling pathway enrichment analysis results showed that the DEGs were significantly enriched in cocaine addiction，amphetamine addiction， interleukin 17 （IL-17） signaling pathway，aldosterone synthesis and secretion， and serotonergic synapse. The ROC curve analysis results demonstrated that FOSB showed high diagnostic accuracy for IgAN. GSEA analysis revealed that arginine and proline metabolism，butyrate metabolism， erythroblastic leukemia viral oncogene homolog（ERBB） signaling pathway，mitogen-activated protein kinase （MAPK） signaling pathway， and fructose and mannose metabolism pathways were enriched in FOSB high-expression group， while allograft rejection， extracellular matrix receptor interaction，and type 1 diabetes pathways were significantly enriched in FOSB low-expression group. The immune cell infiltration analysis results identified natural killer cells， neutrophils，and M1 macrophages as core immune cells in IgAN， and the expression of FOSB gene was positively correlated with neutrophil infiltration （r=0.42， P<0.05）. The immunohistochemistry analysis results demonstrated that compared with control group，the expression level of FOSB protein in glomeruli of the patients in IgAN， DKD， MN， and MCD groups were significantly decreased（P<0.05）. Conclusion The expressions of FOSB gene in the glomeruli tissue of IgAN，DKD，MN，and MCD patients ware decreased， suggesting FOSB may represent a potential biomarker for IgAN.

Objective To discuss the relationship between three proinflammatory factors and muscle mass （MM） in the elderly patients with sarcopenic obesity and diabetes， and to provide theoretical basis for the development of clinical treatment protocols in the elderly patients with sarcopenic obesity and diabetes. Methods The elderly patients with diabetes who visited our hospital from January 2021 to May 2023 were selected， including 41 patients with obesity and diabetes （OD group） and 46 patients with sarcopenic obesity and diabetes （SOD group）； 80 healthy subjects（control group） and 62 subjects with simple obesity （SO group） who underwent physical examination in our hospital during the same period were included. The clinical data of the subjects in four groups were compared， and the correlations between proinflammatory factors and MM and fat mass （FM） were analyzed. All the subjects were divided into sarcopenia group and normal group based on the presence of sarcopenia. Logistic regression model was used to analyze the independent influencing factors of sarcopenia； receiver operating characteristic （ROC） curve was drawn to determine the predictive value of the above factors for sarcopenia. Results Compared with control group， the body mass index （BMI）， FM and body fat percentage （BFP） of the subjects in SOD， OD and SO groups were significantly increased （P<0.05）； compared with control group， OD group and SO group， the appendicular skeletal muscle mass （ASM）， appendicular skeletal muscle mass index （ASMI） and grip strength （GS） of the subjects in SOD group were significantly decreased （P<0.05）， and the levels of serum interleukin-6（IL-6）， C-reactive protein（CRP） and tumor necrosis factor-α（TNF-α） were significantly increased （P<0.05）. In all the subjects， the IL-6， CRP and TNF-α were negatively correlated with ASMI （r=-0.589，r=-0.621，r=-0.620； P<0.05）， and positively correlated with BFP （r=0.252，r=0.221，r=0.147； P<0.05）. Compared with normal group， the ASM， ASMI and GS of the subjects in sarcopenia group were significantly decreased （P<0.05）， and the levels of serum proinflammatory factors IL-6， CRP and TNF-α were significantly increased （P<0.05）. The univariate Logistic regression analysis results showed that IL-6， CRP and TNF-α were the influencing factors of sarcopenia （P<0.05）. The multivariate Logistic regression analysis results showed that the increased levels of IL-6 and TNF-α were the independent risk factors for sarcopenia （OR>1， P<0.05）. The ROC curve results showed that the area under the curve （AUC） values of IL-6， CRP and TNF-α were all >0.700， indicating that the above indicators had good predictive value for sarcopenia. Conclusion The increased levels of proinflammatory factors IL-6， CRP and TNF-α are associated with the decrease of MM in the elderly patients with sarcopenic obesity and diabetes， and IL-6 and TNF-α are the independent risk factors for the sarcopenia.

Objective To compare the analgesic effects of sufentanil patient-controlled intravenous analgesia （PCIA） and liposomal bupivacaine incision local infiltration anesthesia （LIA） in the elderly patients undergoing single- or double-segment posterior lumbar surgery， and to provide the basis for selecting postoperative analgesia methods in the elderly patients undergoing lumbar surgery. Methods A total of 124 elderly patients in our hospital scheduled for elective single-or double-segment posterior lumbar surgery under general anesthesia were selected and divided into sufentanil PCIA group （PCIA group） and liposomal bupivacaine incision LIA group （LIA group） in a 1∶1 ratio， with 62 patients in each group. After excluding those who withdrew from the trial midway， 58 patients were finally included in PCIA group and 60 in LIA group. Thirty minutes before the end of surgery， the patients in PCIA group were treated with a analgesia pump regimen of sufentanil 1.5 μg·kg^-1 combined with dexmedetomidine 1.5 μg·kg^-1. At the end of surgery， the patients in LIA group received multi-point bilateral injections along the surgical incision by a spine surgeon using liposomal bupivacaine 266 mg （diluted in 40 mL of saline）. The resting visual analog scale （VAS） pain scores （non-inferiority margin δ=10 mm） at 30 min， 6 h， 24 h， 48 h， and 72 h postoperatively， the incidences of postoperative adverse reactions （such as nausea and vomiting， respiratory depression， pruritus， constipation， dizziness and drowsiness）， the number of postoperative rescue analgesia interventions， anesthesia satisfaction scores at 48 and 72 h postoperatively， postoperative hospital stay， and wound healing status at discharge were recorded. Results From 30 min to 48 h postoperatively， the resting VAS pain scores of the patients in LIA group were higher than those in PCIA group （P<0.001）， while the resting VAS pain scores at 72 h postoperatively in LIA group were lower than those in PCIA group （P<0.001）. At 30 min， 24 h， and 48 h postoperatively， non-inferiority was established， indicating that the analgesic effect of liposomal bupivacaine incision LIA was not inferior to that of sufentanil PCIA. At 6 h postoperatively， non-inferiority was not established. At 72 h postoperatively， the analgesic effect of liposomal bupivacaine incision LIA was superior to that of sufentanil PCIA （P<0.001）. Compared with PCIA group， the incidence of postoperative nausea and vomiting of the patients in LIA group was decreased （P<0.05）. There were no significant differences in the incidences of postoperative dizziness and drowsiness， constipation， respiratory depression， and pruritus between two groups （P>0.05）. Compared with PCIA group， the postoperative hospital stay of the patients in LIA group was shortened（P<0.001）. There were no significant differences in the number of postoperative rescue analgesia interventions or wound healing grade between two groups （P>0.05）. The anesthesia satisfaction scores of the patients in LIA group at 48 and 72 h postoperatively were higher than those in PCIA group （P<0.05）. Conclusion In the elderly patients undergoing single-or double-segment lumbar surgery， the analgesic effect of liposomal bupivacaine incision LIA is not inferior to that of sufentanil PCIA， with a lower incidence of postoperative adverse reactions and higher postoperative analgesia satisfaction scores.

Objective To discuss the infection status and clinical outcomes in the patients with bullous pemphigoid （BP）， and to analyze the risk factors for infection in hospitalized BP patients， as well as to construct and evaluate the risk prediction model. Methods A total of 126 patients first diagnosed with BP were selected. According to the occurrence of infection， the patients were divided into infection group （52 cases） and non-infection group （74 cases）. The infection status and outcomes of the patients in two groups were recorded； statistical analysis was performed on the general data， laboratory examination results， FRAIL scale scores for frailty screening， NRS2002 scores， and skin lesion severity of the patients in two groups； multivariate Logistic regression model was used to identify the risk factors for infection in the patients； the goodness-of-fit test was used to evaluate the model； receiver operating characteristic （ROC） curve was used to evaluate the predictive value of the model for infection. Results Among the 126 hospitalized BP patients， 52 cases had infection， with an infection rate of 41.27%. The mortality rate of the patients in infection group was higher than that in non-infection group （P<0.05）， and the remission rate of the patients in non-infection group was higher than that in infection group （P<0.05）. The FRAIL scale score for frailty screening， NRS2002 score， serum albumin level， prealbumin level， number of hospitalization， skin lesion severity， and time of hospital stay of the patients in infection group were significantly higher than those in non-infection group （P<0.05）. The multivariate Logistic regression analysis results derived the regression equation： Logistic（P）=-7.63+0.922×skin lesion severity+2.565×FRAIL scale score for frailty screening+1.214×NRS2002 score. The area under the curve of the Logistic regression model was 0.916. Conclusion The FRAIL scale score for frailty screening， NRS2002 score， and skin lesion severity are the risk factors for infection in the hospitalized BP patients. The constructed infection risk prediction model based on these factors has good predictive value and may provide new ideas for the prevention and control of infection in the hospitalized BP patients.?

Objective To analyze the role of interleukin-33 （IL-33） in the occurrence and development of glioma and its related mechanism by bioinformatics technology， and to validate it through histopathological experiments， and to discuss the possibility of IL-33 as an auxiliary marker for the diagnosis and treatment of brain glioma. Methods The glioblastoma multiforme/lower grade glioma（GBMLGG） case data were downloaded from the UCSC XENA database， including data of 689 glioma samples， 5 paracancerous samples， and 1 152 normal brain tissue samples； Mann-Whitney U test was used to analyze the difference in the expression of IL-33 mRNA between the GBMLGG samples and the normal brain tissues； according to the expression level of IL-33 in GBMLGG tissue， the tumor samples were divided into IL-33 low expression group and IL-33 high expression group； the Human Protein Atlas （HPA） was used to validate the difference in the protein expression of IL-33 in the GBMLGG samples； the R language DESeq2 （v.1.36.0） package was used to screen the differentially expressed genes （DEGs） in the GBMLGG tumor case samples； Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were used to perform pathway analysis on the DEGs； Gene Set Enrichment Analysis （GSEA） was used to discuss the pathways significantly enriched by IL-33 in the GBMLGG tissues； GSVA package was used to analyze the immune infiltration in the GBMLGG samples； survival package and survminer package were used to analyze the effect of IL-33 expression level on the survival of the patients in different clinical subgroups of GBMLGG； univariate and multivariate Cox proportional hazards regression models were used to analyze the relationship between IL-33 expression and the clinicopathological characteristics of the GBMLGG patients； the GBMLGG and control tissue samples were collected； immunohistochemical staining was used to detect the expression levels of IL-33 and its receptor suppression of tumorigenicity 2 （ST2） in the GBMLGG and normal brain tissue samples. Results The expression levels of IL-33 mRNA and protein in the GBMLGG tissues were significantly increased compared with those in normal brain tissues； there were 634 DEGs in total between the IL-33 low and high expression groups， including 283 up-regulated DEGs and 351 down-regulated DEGs； the GO functional enrichment analysis and KEGG signaling pathway enrichment analysis results showed that the DEGs were associated with biological behaviors such as activation of the classical pathway of complement， immunoglobulin complex formation， and mediated immunoglobulin receptor binding； in the course of GBMLGG development， high expression of IL-33 could degrade valine， leucine， and isoleucine， induce limonene and pinene degradation， promote propanoate metabolism， and simultaneously activate the Leishmania infection pathway， NOD-like receptor signaling pathway， and allograft rejection pathway； the infiltration levels of dendritic cell （DC） and mast cell in the IL-33 high expression group were higher than those in IL-33 low expression group； the infiltration levels of eosinophil， helper T cell， and central memory T cell （Tcm） were lower than those in IL-33 low expression group； the expression level of IL-33 was positively correlated with the infiltration of γδT cell （Tgd）， helper T cell， macrophage， eosinophil， Tcm， and effector memory T cell （Tem） （P<0.05）； it was negatively correlated with the infiltration levels of DC， natural killer cell （NK）， CD8+T cell， and CD56bright NK cell （P<0.05）. There were no significant differences in the overall survival （OS）， disease-specific survival （DSS）， and disease-free interval （DFI） of the GBMLGG patients between IL-33 high expression group and IL-33 low expression group （P>0.05）； the clinical subgroup analysis results showed that the expression level of IL-33 in oligodendrocytoma tissues was lower than those in astrocytoma and oligoastrocytoma tissues， and the expression level of IL-33 in glioblastoma tissues was higher than that in oligodendroglioma tissues. World Health Organization （WHO） stage and age were risk factors affecting the prognosis of the GBMLGG patients， and IDH mutation and primary treatment effect were protective factors affecting the prognosis； The immunohistochemical staining results showed that compared with normal brain tissues， the expression levels of IL-33 and its receptor ST2 proteins in the malignant glioma tissues were significantly increased （P<0.05）， and their expression levels were positively correlated in both normal brain tissues and malignant glioma tissues （P<0.05）. Conclusion The expression level of IL-33 in the glioma tissue is significantly increased， and high expression of IL-33 may be a potential factor for poor prognosis in the glioma patients.

Objective To detect the biological markers related to Alzheimer’s disease（AD） in the peripheral blood of AD patients， and to explore the activities and levels of the antioxidant function indexes and the expressions of related genes and proteins in the blood of AD patients and the changes after intervention of selenium-rich food. Methods The Mini-Mental State Examination （MMSE） combined with electroencephalogram or brain CT and clinician diagnosis were used for screening AD. Fifty-six elderly patients with AD aged 75-90 years old were selected. Among them，28 cases were selected as normal diet group for AD （AD group）， and 28 cases were selected as dietary selenium intervention group （Se-AD group）. The patients in Se-AD group were given daily dietary selenium supplementation （increaseing dietary selenium by 15-20 μg per day） for 3 months.Meanwhile， 30 people with the same age were selected as healthy control group. The activities of serum superoxide dismutase（SOD）， cholinesterase（CHE）， and glutathione peroxidase （GSH-Px） and the levels of serum malondialdehyde （MDA）， homocysteine （Hcy）， and nitric oxide （NO） as well as reagent kit the levels of serum β-amyloid protein （Aβ）， and microtubule-associated protein （Tau） and phosphorylated microtubule-associated protein（p-Tau） of the subjects in various groups were detected by and enzyme-linked immunosorbent assay（ELISA） method； the expression levels of apolipoprotein E4 （ApoE4）， presenilin 1 （PS1）， presenilin 2 （PS2）， cysteinyl aspartate specific proteinase 3 （Caspase3）， sorting associated protein receptor 1 （SORL1）， β-site amyloid precursor protein cleaving enzyme 1 （BACE1）， hypoxia-inducible factor 1 （HIF1）， nuclear factor-kappa B （NF-κB）， β-amyloid precursor protein （APP）， protein kinase C （PKC）， and Aβ mRNA in peripheral blood of the subjects various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） method. Results Compared with healthy control group， the serum SOD activities of the patients in Se-AD group and AD group were significantly decreased （P<0.05）， while serum CHE activity and the levels of MDA and Hcy were significantly increased （P<0.05）；the serum GSH-Px activity of the patients in AD group was significantly decreased （P< 0.05）， and the level of NO was significantly increased （P<0.05）. Compared with Se-AD group， serum CHE activity and the level of Hcy of the patients in AD group were significantly increased （P<0.05）. The expression levels of ApoE4， PS1， Caspase3， BACE1， NF-κB and APP mRNA of the patients in Se-AD group and AD group were significantly increased （P<0.05）， and the expression levels of PKC mRNA were significantly decreased （P<0.05）； the expression level of PS2 mRNA of the patients in AD group was significantly increased （P<0.05）， and the expression levels of Aβ mRNA of the patients in Se-AD group and AD group were significantly increased （P<0.05）. Conclusion The activities of serum SOD， GSH-Px and CHE and the levels of MDA， Hcy and NO， the levels of Aβ， Tau and p-Tau proteins，and the expression levels of ApoE4， PS1， Caspase3， BACE1， NF-κB， PKC， PS2， Aβ and APP mRNA in peripheral blood of the AD patients may vary and can be used for clinical diagnosis of the AD patients．Selenium-rich food can improve AD to some extent， and its mechanism is related to reducing the oxidative damage of brain tissue and decreasing the expression of AD related genes PS2 and Aβ．

Objective To discuss the improvement effect of short-chain fatty acids (SCFAs) on the injury of ovarian granulosa cells in polycystic ovary syndrome (PCOS), and to clarify its possible mechanism. Methods The ovarian granulosa cells were extracted from the follicular fluid of PCOS patients and non-PCOS patients， respectively. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the expression levels of tumor necrosis factor-α （TNF-α）， interferon γ （IFN-γ）， interleukin （IL）-6， and IL-18 mRNA and proteins in the two kinds of cells； Western blotting method was used to detect the microtube-associated protein 1 light chain 3 （LC3）-Ⅱ/LC3-Ⅰ ratios and ubiquitin-binding protein p62 expression levels in two types of cells. The human ovarian granulosa cells KGN were treated with three kinds of SCFAs sodium acetate （NaA）， sodium propionate （NaP）， and sodium butyrate （NaB） at different concentrations （0， 6， 12， 24， and 48 mmol·L^-1）， respectively. Cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of normal KGN cells after treated with three kinds of SCFAs. The human ovarian granulosa cells KGN were taken and divided into control group， lipopolysaccharide （LPS） group （1 mg·L^-1 LPS）， NaA+LPS group （48 mmol·L^-1 NaA+1 mg·L^-1 LPS）， NaP+LPS group （48 mmol·L^-1 NaP+1 mg·L^-1 LPS）， and NaB+LPS group （48 mmol·L^-1 NaB+1 mg·L^-1 LPS）. CCK-8 method was used to detect the proliferation activities of the cells in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of estradiol （E2） and progesterone （P） in supernatant of the cells in various groups； RT-qPCR method was used to detect the expression levels of TNF-α， IFN-γ， IL-6， and IL-18 mRNA in the cells in various groups； Western blotting method was used to detect the the expression levels of TNF-α， IFN-γ， IL-6， and IL-18 proteins and LC3-Ⅱ/LC3-Ⅰ ratios and p62 protein expression levels in the cells in various groups. Results Compared with non-PCOS patients， the mRNA and protein expression levels of TNF-α， IFN-γ， IL-6， and IL-18 in the ovarian granulosa cells of PCOS patients were significantly increased （P<0.05）， the LC3-Ⅱ/LC3-Ⅰ ratio was increased （P<0.05）， and the p62 protein expression level was decreased （P<0.05）. Compared with control group， there were no significant differences in the proliferation activities of the KGN cells in various groups after treated with different concentrations （6， 12， 24， and 48 mmol·L^-1） of NaA， NaP， and NaB （P>0.05）. Compared with LPS group， the proliferation activities of the cells in NaA+LPS group， NaP+LPS group， and NaB+LPS group were increased （P<0.05）， the levels of E2 and P in the cell supernatant were increased （P<0.05）， the expression levels of TNF-α， IFN-γ， IL-6， and IL-18 mRNA in the cells were decreased （P<0.05）， the LC3-Ⅱ/LC3-Ⅰ ratio was decreased （P<0.05）， and the p62 protein expression level was increased （P<0.05）. Conclusion The levels of inflammatory factors are increased in the ovarian granulosa cells of PCOS patients and induce cell autophagy. SCFAs can improve the inflammatory-induced autophagic injury of ovarian granulosa cells and increase the cell proliferation activity.

Objective To analyze the efficacies of unilateral biportal endoscopy （UBE） and percutaneous endoscopic transforaminal discectomy （PETD） in treatment of lumbar disc herniation （LDH）， and to explore the optimal selection of minimally invasive surgical approaches for the The LDH patients. Methods A retrospective analysis was performed on the clinical data of 64 LDH patients who underwent surgery at Liwan Central Hospital of Guangzhou City in Guangdong Province， between January 2020 and June 2024. The surgical approaches were determined through physician-patient communication， and the patients were divided into UBE group （n=30） and PETD group （n=34）. The materials of patients were recorded including gender， age， body mass index （BMI）， percentages of affected segments，course of disease， duration of hospitalization， operation duration， intraoperative blood loss， numbers of intraoperative fluoroscopy， total incision length， and time to full weight-bearing （WB）. The therapeutic outcomes were evaluated using Oswestry disability index （ODI）， Visual Analog Scale （VAS） scores for low back pain and leg pain， MacNab criteria， and spinal canal areas at the affected segment. the postoperative complications of the patients in two groups were analyzed. Results There were no statistically significant differences in age， gender composition ratio， BMI， course of disease， and percentages of affected segments of the patients between UBE group and PETD group （P>0.05）. Compared with PETD group， the intraoperative blood loss， total incision length， and time to full WB of the patients in UBE group were significantly increase （P<0.01）， while the number of intraoperative fluoroscopy time was decreased （P<0.01）. Compared with pre-operation， the ODI scores and VAS scores for low back and leg pain of the patients at final follow-up in both groups were decreased （P<0.01）， and the spinal canal areas at the affected segments of the patients were increased （P<0.01）. At final follow-up， compared with PETD group， the ODI score and VAS scores for low back and leg pain of patients in UBE group were decreased （P<0.01）， while the spinal canal areas at the affected segments of the patients was increased （P<0.01）. According to MacNab criteria， the percentages of excellent and good had no significant difference between two groups （P>0.05）. The incidence of complication showed no statistical difference between two groups （P>0.05）. Conclusion Both UBE and PETD yield satisfactory outcomes in the treatment of single-segment LDH. PETD is less invasive and permits earlier time to full WB， whereas UBE provides more extensive decompression and superior long-term efficacy. The surgical approach selection should be individualized based on specific factors in the clinic.

The clinical data of a patient with differentiated thyroid carcinoma （DTC） who developed physiological thymic uptake after postoperative iodine-131 （¹³¹I） therapy were analyzed， and the 3-year follow-up changes in the patient’s condition were reviewed. Combined with the literatures and the diagnosis and treatment process， the causes of possible false positives in whole-body scans after iodine therapy for DTC and the mechanism， clinical features， and identification methods of benign thymic ¹³¹I uptake were discussed to improve clinicians’ understanding and diagnostic ability regarding such conditions and avoid unnecessary multiple iodine treatments. The patient， a 28-year-old female， showed mediastinal imaging after the first ¹³¹I treatment， with more pronounced mediastinal iodine uptake during the second treatment. SPECT/CT localized the uptake to enlarged thymus tissue. The stimulated thyroglobulin （Tg） levels before two ¹³¹I treatments were high but gradually decreased. Apart from thymic uptake， no other examination evidence suggested DTC metastases. Subsequent follow-up for 3 years showed no pathological changes in the thymus， confirming physiological thymic uptake. Thymic ¹³¹I uptake is a common cause of false-positive whole-body scans in post-thyroidectomy patients. When post-¹³¹I therapy whole-body imaging shows only mediastinal uptake， especially in the young patients undergoing multiple ¹³¹I treatments where thymic ¹³¹I uptake intensity increases with successive treatments， even with elevated Tg levels， comprehensive use of imaging results such as SPECT/CT is essential to determine if it is normal thymus， thereby avoiding unnecessary repeated therapies.

Angle class Ⅱ malocclusion is often characterized by mandibular retraction and lip incompetence， which affects the patient’s lateral appearance and may even lead to upper airway stenosis. It can be classified into dental and skeletal types. For skeletal class Ⅱ malocclusion patients with mandibular retraction during the peak growth period， mandibular anterior guidance with a functional orthodontic appliance is generally considered as the optimal clinical treatment approach. At present， there remains a paucity of clinical reports on the clinical application of bracket-free clear aligners in mandibular anterior guidance， both domestically and internationally. This article presented a case of an adolescent patient with skeletal class Ⅱ malocclusion accompanied with deep overbite treated with bracket-free clear aligner for mandibular anterior guidance in combination with intermaxillary class Ⅱ traction. During the treatment， vertical correction involved anterior intrusion of the anterior teeth to improve the deep overbite， while horizontal correction included maxillary and mandibular expansion to coordinate the width of the dental arches，and asymmetric anterior guidance was used to correct the midline deviation. After 35 months of treatment，the patient’s convex facial profile and mandibular retrusion were significantly improved. The subspinale-nasion-supramentale angle （ANB） was decreased from 6.8° to 3.9°， the overbite and overjet were normalized， and the bilateral canine and molar reached a neutral relationship. The mentolabial sulcus depth （Si-LiPg'） and the soft tissue thickness of pogonion to pogonion （Pm-Pm'） were decreased，resulting in a shallower mentolabial sulcus and a more harmonized lateral facial soft tissue profile. The mandibular incisor to mandibular plane angle （IMPA）was decreased from 116.6° to 110.7°， indicating retraction of the lower incisors during mandibular anterior guidance. In conclusion， the orthodontic strategy of mandibular advancement with clear aligners in skeletal class Ⅱ malocclusion patients can avoid excessive overcompensation of the upper and lower anterior teeth and shorten the orthodontic treatment cycle.

Transalveolar technique for sinus floor elevation（TSFE） offers the advantages of minimal invasiveness， reduced postoperative reaction， and shorter operative time for vertical bone augmentation in the maxillary posterior region. The clinical data of one patient with severe deficiency of residual bone height （RBH） in the maxillary posterior region， a blood vessel visible in the lateral wall of the maxillary sinus and a visible septum at the floor of the maxillary sinus were reported， and two-stage flexible TSFE was used to improve the vertical bone height of the operated area while reducing trauma， the risk of Schneiderian membrane rupture and maxillary sinus infection， etc.， and the relevant literatures were reviewed. The patient， male， 26 years old， complained of missing left maxillary posterior teeth for more than 1 year and requested restoration. The patient had 27 missing teeth， normal keratinized gingiva， full alveolar ridge， no elongation of the opposing teeth， fair width of the proximal and normal occlusal distance. The results of cone beam CT （CBCT） showed that the distance between the sinus crests at the site of the 27 teeth was about 3 mm， the width of the alveolar bone was about 12.8 mm， the bone density was normal， and there were no residual roots or other abnormalities； no cyst-like lesions were seen in the walls of the maxillary sinuses bilaterally， and separation was seen at the floor of the maxillary sinus on the left side and a blood vessel was seen in the lateral wall of the maxillary sinus. A diagnosis of Kennedy class Ⅱ maxillary tooth defects was made. After two stages of TSFE， the Schneiderian membrane was intact and the bone height of the implant area was elevated to 9.6 mm from 3 mm preoperatively after the completion of the restoration， with stable bone augmentation， good osseointegration，and restoration of normal occlusal function. For the patients with severe bone height deficiency in the maxillary posterior region， flexible two-stage TSFE should be considered， which can help to reduce the risk of maxillary sinus infection and Schneiderian membrane rupture while minimizing the damage and obtaining the ideal bone augmentation results.

Lower extremity arteriosclerosis obliterans （LEASO） is a disease characterized by the formation of atherosclerotic plaques in the lower extremity arteries， leading to arterial stenosis， occlusion， and consequent chronic limb ischemia. This article analyzes the clinical data of a patient with LEASO complicated by an iodine contrast agent allergy， along with the treatment involving intravascular ultrasound （IVUS）-guided endovascular intervention performed without contrast agent， and reviews relevant literature. The patient， a 53-year-old female， presented with coldness and numbness in the left lower extremity and pain after walking for 2 years， symptoms which had worsened over the past 2 months， with a maximum claudication distance of less than 50 meters. The lower extremity arterial CT angiography （CTA） results indicated “left iliac artery occlusion and left superficial femoral artery stenosis.” After examination， the patient exhibited allergic symptoms. Upon admission， other diseases were ruled out. Given that the lower extremity symptoms severely impacted the patient’s daily life and considering the potential for contrast agent allergy， the use of contrast agent was abandoned. IVUS guidance alone was employed to assess the intravascular condition for the interventional procedure. The surgical interventions chosen were drug-coated balloon angioplasty of the left superficial femoral artery and stent implantation in the left iliac artery. Postoperatively， the patient was able to walk normally， the discomfort resolved， and the treatment outcome was satisfactory. For LEASO patients with contrast agent allergy or other contraindications to contrast use， the sole use of IVUS guidance combined with invasive blood pressure monitoring to intraoperatively assess efficacy can effectively avoid contrast agent administration， providing a valuable reference for clinicians managing such cases.

Atypical lipomatous tumor （ALT） is a rare soft tissue sarcoma originating from adipocytic tissue. The clinical manifestations， imaging findings， and pathological examinations of one patient with ALT in the lower extremity were reported to provide reference for the clinical diagnosis and treatment of this disease. The patient was a 64-year-old male who was admitted due to a mass in the left thigh with swelling and pain for 5 years. The physical examination results showed a subcutaneous mass was palpable on the medial side of the left thigh， soft in texture， demonstrating good mobility and positive tenderness.The magnetic resonance imaging （MRI） non-contrast scan showed a well-defined lesion with an intact capsule. The lesion presented high signal intensity on T1-weighted image（T1WI）， similar to subcutaneous fat signal； on T2-weighted image （T2WI）-Ideal in-phase images， the lesion showed high signal， while water images showed low signal， with multiple high-signal foci inside. On T2WI fat-suppression sequence， a low-signal mass was observed with multiple patchy high signals inside.Three days after admission， the patient underwent lesion resection. Intraoperatively， the tumor was located within the fascia， between the medial quadriceps muscles， presenting as lipomatous tissue with an intact capsule， mildly adherent to surrounding tissue， and with partial muscle invasion. The mass and invaded muscle were completely excised. The postoperative pathological examination results revealed a gray-yellow nodule measuring 16.0 cm×10.0 cm×4.0 cm， with a smooth surface and intact capsule. The cut surface was gray-yellow， fatty-like， and soft in texture. Additional gray-yellow tissue fragments were found， with a total volume of 5.0 cm×4.0 cm×1.2 cm， exhibiting a gray-brown cut surface with moderate texture. Under microscope， the lesion consisted mainly of relatively mature adipose tissue. Enlarged and hyperchromatic nuclei were observed， with scattered mononuclear or multinuclear atypical stromal cells. Fibrous septa contained variable numbers of univacuolated or multivacuolated lipoblasts. The immunohistochemistry results showed positivity for cyclin-dependent kinase 4 （CDK4） and murine double minute 2（MDM2）. The fluorescence in situ hybridization （FISH） results demonstrated MDM2 gene amplification in tumor cells. The pathological diagnosis was ALT of the left lower extremity. At 6-month follow-up after operation， no tumor recurrence was observed. The preoperative MRI detection may provide effective evidence for the diagnosis of ALT， while postoperative pathological examination can confirm the diagnosis and help evaluate the prognosis of the patients.

Objective To prepare the polyclonal antibody against pilus assembly protein（SpaD）， a biofilm formation related protein of Corynebacterium striatum（C.striatum）， and to evaluate its inhibitory effect on biofilm formation by strong biofilm-producing strains of C.striatum along with its potential application value. Methods A total of 117 strains of C.striatum isolated from clinical specimens of hospitalized patients at Affiliated Hospital of Inner Mongolia Medical University from 2011 to 2021 were selected as the study subjects. The biofilm formation ability of each strain was detected by crystal violet staining assay. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to examine the distribution of SpaD proteinencoding gene spaD in strong biofilm-producing strains of C.striatum. The strong biofilm-producing strains of C.striatum were divided into control group， and proteinase K group， and cystol violet staning method was used to detect the inhibitory effect of proteinaskon the biofilm formation abilitys of the strong biofilm-producing strains of C.striatum.The recombinant SpaD protein was constructed using protein recombination technology and the was divided into control group and 5 and 10 mg·L^-1 SpaD recombinant proterin groups， and cystol violet staning method was used to detect the inhibitory effect of SpaD recombinant protein. The rabbit anti-SpaD polyclonal antibodies were subsequently obtained through animal immunization， the experiment was divided into control group and 1∶400， 1∶200， and 1∶100 SpaD polyclonal antibody groups， the inhibitory effect of SpaD polyclonal antibodies on biofilm and crystal violet staining method was used to detect abilities of strong biofilm-producing strains of C.striatum. Results The Crystal violet staining results revealed that strong， moderate， and weak biofilm-producing strains accounted for 47.9% （56/117）， 29.0% （34/117）， and 23.1% （27/117）， respectively. The RT-qPCR results showed that all the strong biofilm-producing strains carried the spaD gene. Compared with control group， the biofilm formation abilities of 13 strong biofilm-producing C.striatum strains in both 5 and 10 mg·L^-1 SpaD recombinant protein groups were significantly decreased （P<0.05）. Compared with control group， the biofilm formation abilities in 61.5% （8/13） and 7.7% （1/13） of strong biofilm-producing C.striatum strains in 1∶100 and 1∶200 SpaD polyclonal antibody groups were decreased， respectively （P<0.05）. Conclusions The spaD gene is highly expressed in strong biofilm-producing clinical strains of C.striatum. Anti-SpaD polyclonal antibodies significantly inhibits biofilm formation in these clinical isolates， demonstrating a inhibitory effect as a manner of concentration-dependent. SpaD can be a promising novel target for therapeutic intervention against biofilm-producing C.striatum infections.

Objective To establish a rapid detection method for pathogenic microorganisms by combining loop-mediated isothermal amplification （LAMP） and clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR-associated protein 12a（Cas12a） （CRISPR-Cas12a） system， and to evaluate its efficacy for detecting the thermolabile hemolysin （tlh） gene of Vibrio parahaemolyticus（Vp）. Methods Using the tlh gene of Vp as the target gene， LAMP primers and CRISPR RNA（crRNA） were designed to construct and optimize the optimal concentration ratio of each component in the LAMP-CRISPR detection system. Bacillus cereus， Staphylococcus aureus， and Escherichia coli were used as control groups， and the specificity， sensitivity， reproducibility and positive conformity rate were verified to establish a rapid LAMP-CRISPR/Cas12a method for detecting the tlh gene of Vp. Results The method specifically detected Vp， while Bacillus cereus， Staphylococcus aureus， and Escherichia coli yielded negative results. The DNA extraction concentration of Vp was 190.67 mg·L^-1 with an A（260）/（A280） ratio of 1.84. Under the reaction conditions of 37 ℃ with 80 cycles for 40 min using quantitative PCR （qPCR） method， when the concentrations of Cas12a protein and crRNA in the LAMP-CRISPR/Cas12a system were 50 nmol·L^-1， the visual brightness and relative fluorescence intensity peaks were high. The sensitivity of LAMP CRISPR/Cas12a for detecting Vp DNA concentration could reach 10^-6 mg·L^-1. The reproducibility test results showed that different experimenters had consistent results in different experimental environments and times. Conclusion The established LAMP-CRISPR/Cas12a method can rapidly detect the tlh gene of Vp with high sensitivity and specificity， and can achieve short-term visual detection in the field.

Objective To prepare the bacterial outer membrane vesicles （OMV） that can express programmed death ligand 1（PD-L1） nanobody on surface， and to discuss its structural characteristics， cell compatibility， intracellular distribution， and its blocking effect on the programmed cell death protein-1（PD-1）/PD-L1 signaling axis. Methods The pET28a-ClyA-PD-L1nb prokaryotic expression vector was constructed and transformed into Escherichia coli BL21 （DE3） competent cells； the OMV was isolated from the BL21 （DE3） monoclonal colonies transformed with the PD-L1nb expression vector by ultracentrifugation； the protein purification was performed using the histidine （His） tag； transmission electron microscope and nanoparticle size analyzer were used to analyze and identify the OMV； the OMV isolated from the BL21 （DE3） monoclonal colonies transformed with the PD-L1nb expression vector was used as experimental group； the OMV isolated from the untransformed BL21 （DE3） monoclonal colonies was used as control group； Western blotting method was used to detect the expression levels of ClyA-PD-L1nb fusion protein in the OMV in two groups； cell counting kit-8 （CCK-8） assay was used to detect the activities of mouse macrophage RAW 264.7 cells， mouse triple-negative breast cancer 4T1 cells， and human embryonic kidney HEK293T cells after treated with OMV； fluorescence imaging technology was used to observe the tumor cell endocytosis of OMV； flow cytometry was used to detect the binding effect of OMV to the PD-L1 on surface of the tumor cells in PBS group， OMV-PD-L1nb group， and aPD-L1+OMV-PD-L1nb group. Results The sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS-PAGE） results showed that after induction of Escherichia coli， significantly thickened protein bands appeared near the predicted relative molecular mass （about 49 000）， and after purification， no obvious impurity proteins existed in the lanes； the OMV-PD-L1nb with a size of about 120 nm was isolated by ultracentrifugation， and it presented a uniform spherical structure under transmission electron microscope； the Western blotting results showed that the specific band of ClyA-PD-L1nb was detected in the OMV in experimental group； the CCK-8 assay results showed that after treated with different concentrations of OMV， the viabilities of the RAW 264.7 cells， 4T1 cells， and HEK293T cells were all close to 100%； the fluorescence imaging results showed that OMV-PD-L1nb was endocytosed by 4T1 cells and dispersed in the cytoplasm； compared with OMV-PD-L1nb group， the average fluorescence intensity in the cells in aPD-L1+OMV-PD-L1nb group was significantly decreased （P<0.001）. Conclusion The OMV surface-displaying PD-L1nb， OMV-PD-L1nb， is successfully prepared and isolated； OMV-PD-L1nb shows good compatibility on mouse macrophage cells， tumor cells， and human embryonic kidney cells， can be endocytosed by tumor cells， and successfully blocks the PD-1/PD-L1 signaling pathway.

Diabetic nephropathy （DN） is a significant causative factor of end-stage renal disease globally， and its pathogenesis involves dysregulation of multiple cellular and hormonal pathways. Podocytes play crucial roles in the process of DN， with the extent of podocyte injury closely associated with key pathological manifestations of renal damage， such as proteinuria， glomerular filtration rate， and glomerulosclerosis. However， due to the complexity and interplay of mechanisms contributing to podocyte injury， such as oxidative stress， abnormal lipid metabolism， and mitochondrial damage， the precise mechanisms underlying podocyte injury remain incompletely understood. This review integrated the latest research findings from both domestic and international studies on the core mechanisms of podocyte injury in DN. Furthermore， this article summarized the implications of these mechanisms for DN treatment， particularly focusing on potential therapeutic targets and the development of related pharmacological interventions derived from targeting podocyte injury pathways， so as to provide a theoretical foundation for the development of clinical therapeutic strategies for DN.

Hypoxic-ischemic brain damage （HIBD） is a leading cause of neonatal mortality and neurological dysfunction in the infants， and it remains a focal point of research in neonatology. MicroRNA （miRNA） is involved in neural development， and its alterations is closely associated with the pathological progression of HIBD. However， there is a lack of effective integration of studies on the specific roles and mechanisms of miRNAs at different pathological stages of the disease. This review summarized the recent researches on miRNA in various stages of HIBD. During the hypoxic-ischemic phase， abnormal expression of certain hypoxia-related miRNA can serve as novel biological diagnostic markers. In the cerebral edema phase， miRNA may maintain the integrity of the blood-brain barrier， alleviating neuronal swelling and structural changes. In the cerebral infarction phase， miRNA can inhibit the expression of apoptotic proteins， enhance the neuronal survival rates， reduce the infarct size， and improve neurological behavior. Further research into the mechanisms of miRNA in HIBD will provide new insights for the development of diagnostic and therapeutic strategies for HIBD.

The cutaneous resident memory T cells （T_RM） are important immune surveillance cells in skin tissue and are highly heterogeneous. The T_RM achieve residency in skin by expressing residency markers such as CD69 and CD103， and their development and survival are regulated by several molecules such as interleukin-15 （IL-15）. In addition to their roles in infection and tumors， the T_RM， especially CD8+T_RM， play an important role in the development and recurrence of autoimmune skin diseases such as vitiligo. Under the continuous stimulation of melanocyte antigens， melanocyte-specific CD49a+T_RM1 can directly kill the melanocytes by expressing the interferon-γ（IFN-γ）， granzyme B and perforin and they also recruit circulating memory CD8+T cells through the IFN-γ-Janus kinase（JAK）-signal transducer and activator of transcription（STAT） （IFN-γ-JAK-STAT） signaling pathway to collectively kill the melanocytes， which promotes vitiligo development and recurrence. Combined with the research progress at home and abroad， this article now summarizes the source， function and biological properties of cutaneous T_RM， provides an overview of the research on T_RM in vitiligo development and recurrence， and elaborates on the strategy of intervening in the recurrence of vitiligo by targeting T_RM， aiming to provide the new ideas for the pathogenesis research and precise treatment of vitiligo.

Macrophage polarization is involved in the entire process of the occurrence and development of knee osteoarthritis（KOA）. By polarizing into distinct functional phenotypes， macrophages play key regulatory roles in the initiation of inflammation， matrix degradation，suppression of cartilage formation，and progression of the disease. The M1-type macrophages secrete numerous pro-inflammatory cytokines to exacerbate the inflammatory responses and promote the destruction of articular cartilage. Conversely， the M2-type macrophages help maintain the extracellular matrix homeostasis and facilitate cartilage formation by releasing anti-inflammatory factors while suppressing the secretion of inflammatory factors，thereby exerting anti-inflammatory effects and promoting tissue repair. Recent studies have shown that an imbalanced ratio of M1/M2 macrophages（M1/M2 ratio） is closely linked with both the pathogenesis and progression of KOA. Restoration of the dynamic balance between these two subtypes could be an essential strategy for treating and preventing KOA. This article reviewed the current literatures retrieved from PubMed and CNKI databases using the keywords “knee osteoarthritis” and “macrophages” over the past decade. The review introduced the process of macrophage polarization and the mechanisms of different macrophage phenotypes in KOA， and further discussed the recent advances in modulating the M1/M2 ratio for KOA management through chemical drugs， bioactive molecules， and traditional Chinese medicine and so on， aiming to provide the theoretical insights for future research and clinical interventions.