Objective To investigate the transcriptional regulation mechanism of the Furin gene in adipose tissue under obesity conditions and its effect on the secretion of the adipokine asprosin. Methods Twenty-four C57BL/6J mice were randomly divided into normal control diet （NCD） group and high-fat diet （HFD） group， with 12 mice in each group. The mice were fed for 12 consecutive weeks to establish the diet-induced obesity models. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression levels of Furin， fibrillin 1 （FBN1）， and the candidate transcription factor specificity protein 1 （SP1） mRNA in subcutaneous white adipose tissue（WAT） （sWAT） and epididymal WAT（eWAT） of the mice in two groups. Candidate transcription factors for the Furin gene promoter region were screened based on the JASPAR database. In the 293T cells， the SP1 over-expression plasmid （pcDNA-SP1 group） and its control plasmid containing green fluorescence protein （GFP） （pcDNA-GFP group） were transfected. Simultaneously， a dual-luciferase reporter vector containing the Furin promoter region was co-transfected with the aforementioned plasmids to verify the regulatory interaction between SP1 and the Furin promoter. The stromal vascular fraction （SVF） cells from sWAT were isolated and induced to differentiate into mature adipocytes. SP1 （Ad-SP1 group） or GFP control （Ad-GFP group） was overexpressed via adenoviral transduction. Western blotting method and enzyme-linked immunosorbent assay （ELISA） were used to detect the expression levels of SP1 and Furin proteins in cells in various groups and the levels of asprosin in the cell supernatant in Ad-GFP and Ad-SP1 groups， respectively. Results Compared with NCD group， the body weight， sWAT weight， and eWAT weight of the mice in HFD group were significantly increased （P<0.001）. Compared with NCD group， the expression levels of Furin and SP1 mRNA in sWAT and eWAT of the mice in HFD group were significantly increased （P<0.001）. JASPAR database prediction suggested that SP1 was a core candidate factor regulating Furin transcription. In the dual-luciferase experiment， compared with pcDNA-GFP group， the luciferase activity in 293T cells in pcDNA-SP1 group was significantly increased （P<0.001）. Compared with Ad-GFP group，the expression levels of SP1 and Furin proteins in SVF-derived mature adipocytes in Ad-SP1 group were significantly increased （P<0.001）， and the level of asprosin in the cell supernatant was significantly increased （P<0.001）. Conclusion The expression of SP1 mRNA in WAT and adipocytes of obese mice was up-regulated. SP1 can enhance the transcriptional activity of Furin by directly binding to its promoter region. SP1 overexpression may upregulate the expression level of Furin protein in adipocytes， promoting the secretion of asprosin.

Objective To discuss the protective effect of Qishen Yiqi （QSYQ） dropping pill against sorafenib （SOR）-induced myocardium injury in the rats， and to clarify its possible mechanism. Methods Forty SD rats were randomly divided into control group， SOR group， SOR+QSYQ group， and SOR+ferroptosis inhibitor 1 （Fer-1） group， with 10 rats in each group. The rats in SOR group， SOR+QSYQ group， and SOR+Fer-1 group were intraperitoneally injected with SOR （50 mg·kg^-1） daily for 4 weeks； the rats in SOR+QSYQ group were intragastrically administered with QSYQ dropping pill （300 mg·kg^-1） daily； the rats in SOR+Fer-1 group were intraperitoneally injected with Fer-1 （2 mg·kg^-1） daily starting from 1 d before SOR administration. After the intervention， kits were used to detect the levels of creatine kinase isoenzyme-MB （CK-MB） in serum of the rats in various groups； echocardiography was used to evaluate the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） of the rats in various groups； the heart mass and body mass of the rats were recorded， and the cardiac index was calculated. HE staining was used to observe the morphology of myocardium tissue of the rats in various groups； kits were used to detect the levels of iron ion， glutathione （GSH）， malondialdehyde （MDA）， and reactive oxygen species （ROS） in the myocardium tissue of the rats in various groups； Western blotting method was used to detect the expression levels of acyl-CoA synthetase long-chain family member 4 （ACSL4）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins in the myocardium tissue of the rats in various groups. Additionally， H9c2 cardiomyocytes were divided into control group， SOR group， SOR+QSYQ group， and SOR+Fer-1 group. CCK-8 method was used to detect the survival rates of the cells in various groups； Western blotting method was used to detect the expression levels of ACSL4 and GPX4 proteins in the cells in various groups. Results Compared with control group， the level of CK-MB in serum of the rats in SOR group was significantly increased （P<0.05）， while the LVEF and LVFS were significantly decreased （P<0.05）； compared with SOR group， the levels of CK-MB in the serum of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the LVEFs were significantly increased （P<0.05）. The HE staining results showed that compared with control group， the myocardial fibers of the rats in SOR group were disorderly arranged with enlarged intercellular spaces； compared with SOR group， the degrees of myocardial cell injury in SOR+QSYQ group and SOR+Fer-1 group were alleviated， and the myocardial fibers were arranged more neatly. The kit detection results showed that compared with control group， the levels of iron ion， MDA， and ROS in the myocardium tissue of the rats in SOR group were significantly increased （P<0.05）， while the level of GSH was significantly decreased （P<0.05）； compared with SOR group， the levels of iron ion and ROS in the myocardium tissue of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the levels of GSH were significantly increased （P<0.05）. The Western blotting method results showed that compared with control group， the expression level of ACSL4 protein in the myocardium tissue of the rats in SOR group was significantly increased （P<0.05）， while the expression levels of SLC7A11 and GPX4 proteins were significantly decreased （P<0.05）； compared with SOR group， the expression levels of SLC7A11 and GPX4 proteins in the myocardium tissue of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly increased （P<0.05）， while the expression level of ACSL4 protein was significantly decreased （P<0.05）. The CCK-8 assay results showed that compared with 0 μmol·L^-1 SOR group， the survival rates of H9c2 cells treated with higher doses of SOR were significantly decreased （P<0.05）； compared with SOR group， the survival rates of the cells treated with different concentrations of QSYQ were significantly increased （P<0.05）， and the survival rate of the cells in 1 mg·L^-1 QSYQ intervention group was the highest. The Western blotting method results showed that compared with control group， the expression level of ACSL4 protein in the H9c2 cardiomyocytes in SOR group was significantly increased （P<0.05）， while the expression level of GPX4 protein was significantly decreased （P<0.05）； compared with SOR group， the expression levels of ACSL4 protein in the cells in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the expression levels of GPX4 protein were significantly increased （P<0.05）. Conclusion ?QSYQ dropping pill can alleviate SOR-induced myocardial injury in the rats， and its mechanism may be related to the inhibition of ferroptosis in cardiomyocytes.

Objective To investigate the ameliorative effect of the injectable oxidized dextran（ODex）/carboxymethyl chitosan（CMCS） hydrogel （DCC） loaded with exosomes（Exo） （DCC/Exo） on postoperative peritoneal adhesion （PA） in the mice，and to elucidate its mechanism. Methods The exosomes were extracted from the rats， and DCC/Exo was prepared and its chemical structure was characterized. Immunohistochemical staining method was used to detect the expression of the inflammatory factor Ly-6G in mouse dorsal skin tissue after injection of DCC/Exo to evaluate its biocompatibility. The mouse PA model was established by cecal abrasion. The KM mice were randomly divided into control group， hyaluronic acid （HA） group， DCC group， and DCC/Exo group. The PA condition was observed and scored in the mice in various groups at 5 and 14 d after operation. HE staining was used to observe the pathomorphology of PA tissue of the mice in various groups. At 5 d after operation， immunohistochemical staining method was used to detect the expression levels of myeloperoxidase （MPO） in PA tissue of the mice in various groups. The dihydroethidium （DHE） fluorescence probe assay was used to detect the levels of reactive oxygen species （ROS） in PA tissue of the mice in various groups； immunofluorescence staining was used to detect the expression levels of the oxidative damage marker 8-hydroxy-2'-deoxyguanosine （8-OHdG） and the mesothelial-mesenchymal transition （MMT）- related proteins E-cadherin and Vimentin in PA tissue of the mice in various groups. The Mitotracker fluorescence probe assay was used to detect the degree of mitochondrial damage in PA tissues of the mice in various groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect the apoptotic rates of the cells in PA tissue of the mice in various groups. Results The isolated Exos exhibited a cup-shaped double-membrane structure. After loading with Exos， the characteristic absorption peaks of the DCC hydrogel showed no significant shift. The immunohistochemistry analysis results revealed only minimal neutrophil infiltration in mouse dorsal skin tissues. At 5 and 14 d after operation， compared with control group and DCC group， the mean adhesion score of the mice in DCC/Exo group was significantly decreased （P<0.001）. The HE staining results showed severe PA with massive inflammatory cell infiltration of the mice in control group， mitigated PA in the mice in HA group and DCC group， and no adhesion with only a few inflammatory cells observed in the abdominal cavity of mice in DCC/Exo group. At 5 d after operation， the immunohistochemical staining results showed significant diffuse inflammatory infiltration in PA tissue of the mice in control group. Compared with control group and DCC group， the expression level of MPO in PA tissue of the mice in DCC/Exo group was significantly decreased （P<0.001）. The DHE staining results showed that compared with control group and DCC group， the ROS level in PA tissue of the mice in DCC/Exo group was significantly decreased （P<0.001）.The immunofluorescence staining results showed that compared with control group and DCC group， the expression levels of 8-OHdG and Vimentin in PA tissue of the mice in DCC/Exo group were significantly decreased （P<0.001）， while the expression level of E-cadherin was significantly increased （P<0.001）. Compared with control group and DCC group， the fraction of Mitotracker fluorescence area in PA tissue of the mice in DCC/Exo group was significantly increased （P<0.001）， indicating a decreased degree of mitochondrial damage. Compared with control group and DCC group， the apoptotic rate of the cells in PA tissue of the mice in DCC/Exo group was significantly decreased （P<0.001）. Conclusion Topical application of the DCC/Exo composite hydrogel may effectively attenuate postoperative PA in the mice， and its mechanism may be related to the suppression of local inflammatory infiltration， reduction of tissue oxidative stress， decrease in apoptosis， and inhibition of the MMT process.

Objective To discuss the improvement effect of fingolimod on liver fibrosis in the mice with type 2 diabetes mellitus （T2DM）， and to clarify its mechanism. Methods Sixty male C57BL/6J mice were randomly divided into control group， control+fingolimod group， model group， and model+fingolimod group， with 15 mice in each group. The T2DM model was induced by high-fat diet combined with low dose of streptozotocin （STZ） intraperitoneal injection. After the model was established， the mice in model+fingolimod group and control+fingolimod group were given daily intraperitoneal injection of fingolimod （1.0 mg·kg^-1） for 8 weeks. The liver coefficients and fasting blood glucose （FBG） levels of the mice in various groups were detected. The kits were used to detect the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） in serum of the mice in various groups； HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups； Masson staining was used to observe the morphology of liver fibrosis of the mice in various groups； Oil red O staining was used to detect the lipid deposition in liver tissue of the mice in various groups； real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression levels of α-smooth muscle actin （α-SMA） and Janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway-related molecules JAK1， JAK2， STAT1， STAT3， interferon-γ （IFN-γ）， and interleukin-6 （IL-6） mRNA in liver tissue of the mice in various groups； Western blotting method was used to detect the expression levels of α-SMA， IFN-γ， IL-6，STAT1， phosphorylated STAT1 （p-STAT1）， STAT3， phosphorylated STAT3（p-STAT3）， JAK1， phosphorylated JAK1（p-JAK1）， JAK2 and phosphorylated JAK2（p-JAK2） proteins in liver tissue of the mice in various groups. Results Compared with control group， the liver coefficient and FBG level of the mice in model group were significantly increased （P<0.001）； the hepatocytes were swollen， the hepatic sinusoids were narrowed， a large number of lipid droplets and obvious collagen accumulation in liver tissue were observed， and the CVF and lipid droplet area proportion of liver tissue were significantly increased （P<0.001）； the activities of ALT and AST and the levels of TC， TG， and LDL-C in serum were significantly increased （P<0.001）， while the level of HDL-C was significantly decreased （P<0.001）； the expression levels of IL-6 and α-SMA mRNA and protein in liver tissue were significantly increased （P<0.001）， the expression levels of IFN-γ mRNA and protein were significantly decreased （P<0.001）， the ratios of p-STAT3/STAT3， p-JAK1/JAK1， and p-JAK2/JAK2 were significantly increased （P<0.001）， and the ratio of p-STAT1/STAT1 was significantly decreased （P<0.001）. Compared with model group， the liver coefficient and FBG level of the mice in model+fingolimod group were significantly decreased （P<0.01）； the hepatocyte steatosis， lipid droplets， and fibrosis degree were alleviated， and the CVF and lipid droplet area proportion of liver tissue were significantly decreased （P<0.001）； the activities of ALT and AST and the levels of TC， TG， and LDL-C in serum were significantly decreased （P<0.001）， while the level of HDL-C was significantly increased （P<0.001）； the expression levels of IL-6 and α-SMA mRNA and protein in liver tissue were significantly decreased （P<0.001）， the expression levels of IFN-γ mRNA and protein were significantly increased （P<0.001）， the ratios of p-STAT3/STAT3， p-JAK1/JAK1， and p-JAK2/JAK2 were significantly decreased （P<0.001）， and the ratio of p-STAT1/STAT1 was significantly increased （P<0.001）. Conclusion Fingolimod can improve glucose and lipid metabolism disorders， liver function injury， and lipid deposition in liver tissue of T2DM mice， and alleviate liver fibrosis. Its mechanism may be related to up-regulating the expressions of IFN-γ and p-STAT1 and down-regulating the expressions of IL-6 and p-STAT3.

Objective To investigate the effect of bisphenol AF （BPAF） on the senescence in the human endometrial stromal cells （hESCs）， and to elucidate the inhibitory effect of rapamycin （Rapa） on the BPAF-induced senescent hESCs. Methods The hESCs were cultured in vitro and treated with 0， 7.5， 15.0， 30.0， 60.0， and 120.0 μmol·L^-1 BPAF. MTT assay was used to detect the cell survival rates of the hESCs after treated with different concentrations of BPAF. The cells were divided into control group （normal medium）， BPAF group （medium containing 30.0 μmol·L^-1 BPAF）， and Rapa group （medium containing both 30.0 μmol·L^-1 BPAF and 100.0 nmol·L^-1 Rapa）. Senescence-associated β-galactosidase （SA-β-gal） staining was used to assess the percentages of SA-β-gal positive cells in various groups； flow cytometry was used to analyze the percentages of cells at different cell cycles in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to assess the expression levels of p16， p21 and p53 mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of senescence-related proteins （p16， p21 and p53）， autophagy-related proteins p62， microtubule-associated protein 1-light chain 3 （LC3）-Ⅱ and LC3-Ⅰ in the cells in various groups. Results The MTT assay results showed that the cell survival rate was 75% when the BPAF concentration was 30.0 μmol·L^-1； therefore， this concentration was selected for subsequent senescence induction experiments. Compared with control group， the percentage of SA-β-gal positive cells in BPAF group was significantly increased（P<0.01）， the percentage of the cells at G₁ phase was significantly increased（P<0.01）， and the expression levels of p16， p21， and p53 mRNA and proteins were significantly increased （P<0.01）. Compared with BPAF group， the percentage of SA-β-gal positive cells in Rapa group was significantly decreased （P<0.01）， the percentage of the cells at G₁ phase was significantly decreased （P<0.01）， the expression levels of p16， p21， and p53 mRNA and proteins in the cells were significantly decreased （P<0.01）， and the expression level of the autophagy-related protein p62 in the cells was significantly decreased （P<0.01） while the LC3-Ⅱ/LC3-Ⅰ ratio was significantly increased （P<0.01）. Conclusion High concentrations of BPAF can inhibit the proliferation of the hESCs and induce cellular senescence. Rapa can suppress BPAF-induced cellular senescence， and its mechanism may be related with the activation of autophagy.

Objective To discuss the effect of microRNA-153-3p （miR-153-3p） on the apoptosis of oral squamous cell carcinoma （OSCC） cells， and to clarify its mechanism. Methods The Cancer tissue and adjacent normal tissue were collected from 84 patients diagnosed with OSCC， and five kinds of OSCC cells and normal human oral mucosa HOK-16A cells were cultured. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of miR-153-3p in the OSCC cancer tissue and adjacent normal tissue， as well as in the five kinds of cells. The Tca8113 cells were randomly divided into blank control group， mimics NC group，mimics group， mimics+vector group， and mimics+peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） group， and were transfected with mimics NC plasmid，miR-153-3p mimic plasmid， PGC-1α overexpression plasmid， or co-transfected with both plasmids. RT-qPCR method was used to detect the expression levels of miR-153-3p in the cells in various groups after transfection； MTT method was used to detect the proliferation activities of the cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups； 2'，7'- dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescence staining was used to detect the levels of reactive oxygen species （ROS） in the cells in various groups； JC-1 probe staining was used to detect the mitochondrial membrane potential of the cells in various groups； Western blotting method was used to detect the expression levels of cytochrome C （Cyt C） protein in the cytoplasm and mitochondria， as well as the expression levels of Cleaved-Caspase-3， PGC-1α， nuclear respiratory factor 1 （NRF-1）， and mitochondrial transcription factor A （TFAM） proteins in the cells in various groups； dual-luciferase reporter assay was used to verify the targeting relationship between miR-153-3p and PGC-1α. Results Compared with adjacent normal tissue and HOK-16A cells， the expression levels of miR-153-3p in OSCC cancer tissue and OSCC cells were significantly decreased （P<0.05）， while the lowest expression level was observed in the Tca8113 cells. After transfection， compared with blank control group and mimics NC group， the expression level of miR-153-3p in the Tca8113 cells in mimics group was significantly increased （P<0.001）； the proliferation activity of the cells at each time point was significantly decreased （P<0.001）； the apoptotic rate and ROS level of the cells were significantly increased （P<0.001）， while the mitochondrial membrane potential of the cells was significantly decreased （P<0.001）； the expression level of Cleaved-Caspase-3 protein in the cells and the expression level of Cyt C protein in the cytoplasm were significantly increased （P<0.001）， while the expression level of Cyt C protein in the mitochondria and the expression levels of PGC-1α/TFAM pathway-related proteins PGC-1α， NRF-1， and TFAM in the cells were significantly decreased （P<0.05）. The dual-luciferase reporter assay results confirmed that miR-153-3p could specifically target and regulate the expression of the PGC-1α gene. After co-transfection， compared with blank control group， the apoptotic rate and ROS level in the cells in mimics group were significantly increased （P<0.001）， while the mitochondrial membrane potential was significantly decreased （P<0.001）； compared with mimics group， there were no significant differences in apoptotic rate， ROS level， and mitochondrial membrane potential in the cells in mimics+vector group （P>0.05）； compared with mimics+vector group， the apoptotic rate and ROS level in the cells in mimics+PGC-1α group were significantly decreased （P<0.01）， while the mitochondrial membrane potential was significantly increased （P<0.001）. Compared with blank control group， the expression levels of PGC-1α， NRF-1， and TFAM proteins in the cells in mimics group were significantly decreased （P<0.001）； compared with mimics+vector group， the expression levels of PGC-1α， NRF-1， and TFAM proteins in the cells in mimics+PGC-1α group were significantly increased （P<0.001）. Conclusion ?Overexpression of miR-153-3p can induce apoptosis in the Tca8113 cells by targeting and down-regulating the expression of PGC-1α， thereby blocking the PGC-1α/TFAM signaling pathway， inducing mitochondrial dysfunction， and activating the mitochondrial apoptotic pathway.

Objective To discuss the correlation between the expression levels of microRNA（miR）-328-3p and miR-671-5p in serum exosomes of the mice with Kawasaki disease and Kawasaki disease as well as their changes after intravenous immunoglobulin （IVIG） treatment， and to provide the potential biomarkers for the early diagnosis and efficacy evaluation of Kawasaki disease. Methods Twelve 4-week-old SPF grade male C57BL/6J mice were randomly divided into control group， model group， and IVIG group， with 4 mice in each group. The mice in model group and IVIG group were intraperitoneally injected with Lactobacillus casei cell wall extract （LCWE） to establish the Kawasaki disease models， while the mice in control group were intraperitoneally injected with equal volume of normal saline； the mice in IVIG group were intraperitoneally injected with IVIG for intervention on the 5th day. Four weeks later， the heart tissue of the mice in various groups was collected， and HE staining was used to observe the pathomorphology of the heart tissue of the mice in various groups； the blood of the mice in various groups was collected and the exosomes were isolated. Particle size detection， transmission electron microscopy， and Western blotting method were used to identify the exosomes. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of miR-328-3p， miR-134-5p， and miR-671-5p in the serum exosomes of the mice in various groups. Results The HE staining results showed that in control group， the myocardial structure of the mice was regular， and there was no inflammatory cell infiltration in the coronary arteries； in model group， diffuse inflammatory cell infiltration was observed in the local coronary arteries of the mice； compared with model group， the inflammatory cell infiltration in the myocardium tissue of the mice in IVIG group was significantly reduced. The exosome identification results showed that spherical or oval vesicles with a diameter of 30-150 nm were observed under transmission electron microscope， the main peak of particle size was within 150 nm， and the exosome markers CD9 and CD63 were positively expressed. The RT-qPCR results showed that compared with control group， the expression level of miR-328-3p in the serum exosomes of the mice in model group was significantly increased （P<0.05）， and the expression level of miR-671-5p was significantly decreased （P<0.05）； compared with model group， the expression level of miR-328-3p in the serum exosomes of the mice in IVIG group was significantly decreased （P<0.05）， and the expression level of miR-671-5p was significantly increased （P<0.01）； there was no statistically significant difference in the expression level of miR-134-5p in the serum exosomes of the mice among the three groups （P>0.05）. Conclusion The up-regulation of miR-328-3p expression and the down-regulation of miR-671-5p expression are both associated with Kawasaki disease， and this abnormal expression can be reversed after IVIG treatment， suggesting that both of them may serve as the potential molecular biomarkers for the diagnosis and efficacy evaluation of Kawasaki disease.

Objective To discuss the effect of triggering receptor expressed on myeloid cells-1 （TREM-1） inhibitory peptide LR12 on myocardial injury in the septic mice， and to clarify its possible mechanism. Methods The mouse model of sepsis was established by cecal ligation and puncture （CLP）. Forty male mice were randomly divided into sham operation group， model group， CLP+LR12 control peptide （LR12-scr） group， CLP+LR12 group， and CLP+DNase Ⅰ group， and there were 8 mice in each group. Except for sham operation group， the mice in the other groups underwent CLP to establish the sepsis models， and were intraperitoneally injected with LR12-scr， LR12， and DNase Ⅰ at 1 h after operation， respectively. At 24 h after operation， the status and behavior of the mice in various groups were observed. A small animal ultrasound system was used to detect the cardiac function of the mice in various groups； enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of creatine kinase isoenzyme-MB （CK-MB）， cardiac troponin I （cTnI）， and inflammatory indicators interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in serum， as well as the levels of myeloperoxidase （MPO）-DNA and neutrophil elastase （NE）-DNA in myocardium tissue of the mice in various groups； HE staining was used to observe the pathomorphology of myocardium tissue of the mice in various groups； immunofluorescence staining was used to detect the co-expression of lymphocyte antigen 6G （Ly6G） and citrullinated histone H3 （cit-H3） proteins in myocardium tissue of the mice in various groups； Western blotting method was used to detect the expression levels of TREM-1， MPO， NE， and cit-H3 proteins in myocardium tissue of the mice in various groups. Results Compared with sham operation group， the mice in model group were listless， with disordered arrangement of myocardium tissue， and atrophy and deformation of cardiomyocytes； compared with model group， the mental state and myocardium tissue injury of the mice in CLP+LR12 group and CLP+DNase Ⅰ group were significantly improved， while no significant change was observed in CLP+LR12-scr group. The cardiac function detection results showed that compared with sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） of the mice in model group were significantly decreased （P<0.01）； compared with model group， the LVEF and LVFS of the mice in CLP+LR12 group and CLP+DNase Ⅰ group were significantly increased （P<0.01）. The ELISA results showed that compared with sham operation group， the levels of CK-MB， cTnI， IL-1β， IL-6， and TNF-α in serum and the levels of MPO-DNA and NE-DNA in myocardium tissue of the mice in model group were significantly increased （P<0.01）； compared with model group， the levels of CK-MB， cTnI， IL-1β， IL-6， and TNF-α in serum and the levels of MPO-DNA and NE-DNA in myocardium tissue of the mice in CLP+LR12 group and CLP+DNase Ⅰ group were significantly decreased （P<0.01）； no significant changes in the above indicators were observed in CLP+LR12-scr group （P>0.05）. The immunofluorescence staining results showed that compared with sham operation group， the co-expression of Ly6G and cit-H3 proteins in myocardium tissue of the mice in model group was increased； compared with model group， the co-expression of Ly6G and cit-H3 proteins in myocardium tissue of the mice in CLP+LR12 group and CLP+DNase Ⅰ group was decreased. The Western blotting method results showed that compared with sham operation group， the expression levels of TREM-1， MPO， NE， and cit-H3 proteins in myocardium tissue of the mice in model group were significantly increased （P<0.01）； compared with model group， the expression levels of TREM-1， MPO， NE， and cit-H3 proteins in myocardium tissue of the mice in CLP+LR12 group were significantly decreased （P<0.01）， while the expression levels of MPO， NE， and cit-H3 proteins in myocardium tissue of the mice in CLP+DNase Ⅰ group were significantly decreased （P<0.01）， and there was no significant difference in the expression level of TREM-1 protein （P>0.05）. Conclusion TREM-1 inhibitory peptide LR12 can improve the cardiac function and alleviate myocardial inflammation and injury in the septic mice， and its mechanism may be related to inhibiting the formation of neutrophil extracellular traps （NETs）.

Objective To investigate the effect of whole ginseng pectin alcohol-precipitated polysaccharide fraction （WGPA） on the phenotype and function of mouse bone marrow-derived dendritic cells （BMDCs）. Methods Three WGPA fractions were extracted using water extraction， ethanol precipitation， and ion-exchange chromatography： the 30% ethanol-precipitated fraction （WGPA₃₀）， the 50% ethanol-precipitated fraction （WGPA₅₀）， and the 70% ethanol-precipitated fraction （WGPA₇₀）. The primary mouse BMDCs were cultured and categorized into immature BMDCs and mature BMDCs. Cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of mature BMDCs in various groups treated with different concentrations of WGPA to determine the effective WGPA fraction and its appropriate concentration. The effective alcohol-precipitated fraction was analyzed for relative molecular mass， infrared spectrum， and monosaccharide composition. Both immature and mature BMDCs were randomly divided into control group， lipopolysaccharide （LPS） group （treated with LPS）， and WGPA group （treated with effective WGPA）. Flow cytometry was used to detect the expression levels of CD80， CD86， and major histocompatibility complex class Ⅱ （MHC-Ⅱ） on the surface of mature BMDCs in various groups. Fluorescent microsphere phagocytosis assay was used to detect the phagocytic efficiency of immature BMDCs in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-12 （IL-12）， and tumor necrosis factor-α （TNF-α） in the culture supernatants of mature BMDCs in various groups. Results The results of CCK-8 method showed that compared with control group， the proliferation activities of mature BMDCs in 800 and 1 600 mg·L^-1 WGPA₃₀ groups were significantly increased （P<0.01），while the proliferation activities of mature BMDCs after treated with WGPA₅₀ or WGPA₇₀ showed no significant change （P>0.05）. Therefore， 800 mg·L^-1 WGPA₃₀ was selected for subsequent experiments.The structural analysis results revealed that WGPA₃₀ had a relative molecular mass of approximately 24 230， and it was a pyranose connected by α-configuration glycosidic bond whose main monosaccharide composition included glucuronic acid， xylose， glucose， and galactose. The flow cytometry results showed that compared with control group， the expression levels of MHC-Ⅱ， CD86， and CD80 on the surface of mature BMDCs in LPS group and WGPA₃₀ group were significantly increased （P<0.01）. Compared with LPS group， the expression levels of MHC-Ⅱ， CD86， and CD80 on the surface of mature BMDCs in WGPA₃₀ group were significantly decreased（P<0.05）. Compared with control group， the phagocytic activities of immature BMDCs in LPS group and WGPA₃₀ group were significantly decreased（P<0.05）.The ELISA results showed that compared with control group， the levels of IL-6， IL-12， and TNF-α in the supernatants of mature BMDCs in LPS group and WGPA₃₀ group were significantly increased （P<0.01）. Compared with LPS group， the levels of IL-12 and TNF-α in the supernatant of mature BMDCs in WGPA₃₀ group were significantly decreased （P<0.01）， while the level of IL-6 showed no statistically significant difference （P>0.05）. Conclusion WGPA₃₀ is a pyranose with α-configuration glycosidic bonds which contains primary active components such as glucose， galactose， and glucuronic acid， and has a relative molecular mass of approximately 24 230. WGPA₃₀ promotes the maturation and modulates the activity of BMDCs by enhancing their proliferation， stimulating the release of cytokines IL-6， IL-12， and TNF-α， upregulating the expression of surface molecules MHC-Ⅱ， CD86， and CD80， and decreasing their phagocytic efficiency.

Objective To investigate the dynamic regulatory effects of persistent infection with rotavirus （RV） strain SA11 on intestinal inflammation in interleukin-10（IL-10） gene-deficient （IL-10^-/-） mice， and to elucidate its underlying mechanism. Methods The monkey embryonic kidney MA104 cells were routinely cultured. The indirect immunofluorescence assay was used to detect the viral titer of SA11 in MA104 cells. A total of 20 SPF wild-type C57BL/6 （WT-B6） mice were selected as control group， while twenty IL-10 gene knockout C57BL/6 mice （IL-10?/?-B6） were assigned to experimental group. A persistent infection model was established by daily oral gavage with 1×10? FFU·mL?1 SA11 suspension for 42 consecutive days. Both fecal and intestinal tissue samples were collected from the mice in two groups weekly. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the copy numbers of the RV capsid protein VP6 gene in feces and the expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β （TGF-β） mRNA in colorectal tissues of the mice in two groups. HE staining was used to observe the histopathological morphology of duodenal and jejunal tissues of the mice in two groups. Results The indirect immunofluorescence assay determined the titer of the SA11 virus to be 1×10? FFU·mL?1. During the first 21 days of persistent RV infection， the VP6 gene copy numbers in the feces of the mice in both IL-10?/?-B6 and WT-B6 groups remained at low levels， with no statistically significant difference between two groups（P>0.05）. After 28 d of persistent infection， compared with WT-B6 group， the copy number of VP6 gene in the feces of the mice in IL-10?/?-B6 group was significantly increased（P<0.05）. Compared with the status before infection， the expression levels of IL-1β and TGF-α mRNA in the colorectal tissues of the mice in WT-B6 group after RV infection were significantly increased （P<0.001）， the expression levels of IL-1β and TGF-α mRNA in IL-10?/?-B6 group were significantly decreased （P<0.001）， and the expression levels of TGF-β mRNA in both groups were significantly increased（P<0.001）. Conclusion Persistent gastrointestinal infection with RV strain SA11 may alter the intestinal immune microenvironment in the IL-10?/? mice，manifested by downregulated expression of IL-1β and TNF-α and upregulated expression of TGF-β in colorectal tissue， thereby alleviating intestinal inflammation. This regulatory network suggests that RV may influence the progression of intestinal inflammation by reshaping the intestinal immune balance.

Objective To discuss the ameliorative effect of metformin （Met） on myocardial hypertrophy in the spontaneously hypertensive rats （SHR）， and to clarify its possible mechanism of action. Methods The myocardial hypertrophy models were established with SHR， and the rats were randomly divided into SHR group and SHR+Met group； the age-matched male WKY rats were selected as WKY group. The rats in SHR+Met group were given Met suspension （300 mg·kg^-1·d^-1） by gavage for 6 weeks， and the rats in SHR group and WKY group were given equal volume of distilled water by gavage. After intervention， the body mass and left ventricular mass of the rats in various groups were measured， and the left ventricular mass index （LVMI） was calculated. Western blotting method was used to detect the expression levels of atrial natriuretic peptide （ANP） and brain natriuretic peptide （BNP） proteins in myocardium tissue of the rats in various groups； electron microscope was used to observe the mitochondrial ultrastructure of the cardiomyocytes of the rats in various groups； Western blotting method and real-time fluorescence quantitative PCR （RT-qPCR） method were used to detect the expression levels of mitochondrial fusion indicators optic atrophy 1 （OPA1） and mitofusin 2 （MFN2） proteins and mRNA in myocardium tissue of the rats in various groups. Results Compared with WKY group， the LVMI of the rats in SHR group was significantly increased （P<0.05）， and the expression levels of ANP and BNP proteins in myocardium tissue of the rats were significantly increased （P<0.05）. Compared with SHR group， the LVMI of the rats in SHR+Met group was significantly decreased （P<0.05）， and the expression levels of ANP and BNP proteins in myocardium tissue of the rats were significantly decreased （P<0.05）. The electron microscope results showed that in SHR group， the mitochondria in myocardium tissue of the rats were arranged disorderly， with widened， broken， or disappeared mitochondrial cristae spaces； in SHR+Met group， the mitochondrial morphology of the rats was partially restored， and the cristae remodeling was obvious. Compared with WKY group， the expression levels of OPA1 and MFN2 proteins and mRNA in myocardium tissue of the rats in SHR group were significantly decreased （P<0.05）； compared with SHR group， the levels of OPA1 and MFN2 proteins and mRNA in myocardium tissue of the rats in SHR+Met group were significantly increased （P<0.05）. Conclusion Met can alleviate myocardial hypertrophy in the SHR rats， and its mechanism may be related to improving mitochondrial morphology and up-regulating the expression of mitochondrial fusion proteins OPA1 and MFN2 in the myocardium tissue.

Objective To discuss the inhibitory effect of Chaiqi Yigan （CQ） formula on the malignant biological behaviors of hepatocellular carcinoma HepG2 cells by regulating macrophage polarization through activation of nuclear factor κB （NF-κB） signaling pathway， and to clarify the theoretical basis for the application of CQ in the treatment of hepatocellular carcinoma. Methods CQ-containing serum was prepared and diluted to concentrations of 2.5%， 5.0%， 10.0%， 20.0%， and 30.0%.Cell counting kit-8 （CCK-8） method was used to detect the activities of RAW264.7 cells and HepG2 cells in various groups after treated with CQ-containing serum； enzyme-linked immunosorbent assay （ELISA） kits were used to detect the levels of interleukin （IL）-6 and IL-10 in supernatant of RAW264.7 cells in various groups after treated with CQ-containing serum to screen the optimal concentration of CQ for treatment. A co-culture system of RAW264.7 and HepG2 cells was established， and a nude mouse model bearing HepG2 cell xenograft tumor was constructed. The co-cultured cells and tumor-bearing mice were randomly divided into control group， CQ group， NF-κB inhibitor pyrrolidine dithiocarbamate （PDTC） group， and CQ+PDTC group. CCK-8 method and Transwell chamber assay were used to detect the activities， numbers of migration cells， and numbers of invasion cells of HepG2 cells in various groups， respectively. The volumes and mass of xenograft tumors of the nude mice in various groups were measured. Flow cytometry was used to detect M1 and M2 polarization of RAW264.7 cells in co-culture system and tumor tissue of the nude mice in various groups； ELISA method was used to detect the levels of M1-type cytokines IL-6， tumor necrosis factor α （TNF-α）， and inducible nitric oxide synthase （iNOS）， and M2-type cytokines transforming growth factor β （TGF-β）， arginase 1 （Arg-1）， and IL-10 in supernatant of the RAW264.7 cells in co-culture system and serum of the nude mice in various groups； Western blotting method was used to detect the expression levels of NF-κB pathway-related proteins NF-κB inhibitor protein α （IκB-α）， phosphorylated IκB-α （p-IκB-α）， NF-κB p65， and p-NF-κB p65 in RAW264.7 cells in the co-culture system and serum of the nude mice in various groups. Results Compared with control group， the activity， number of migration cells， and number of invasion cells of HepG2 cells in CQ group were significantly decreased （P<0.05）， while those in PDTC group were significantly increased （P<0.05）； compared with CQ group， the activity， number of migration cells， and number of invasion cells of HepG2 cells in CQ+PDTC group were significantly increased （P<0.05）. Compared with control group， the volume and mass of xenograft tumor of the nude mice in CQ group were significantly decreased （P<0.05）， while those in PDTC group were significantly increased （P<0.05）； compared with CQ group， the volume and mass of xenograft tumor of the nude mice in CQ+PDTC group were significantly increased （P<0.05）. Compared with control group， the percentages of M1-type macrophages in RAW264.7 cells and tumor tissue of the nude mice in CQ group were significantly increased （P<0.05）， while the percentages of M2-type macrophages were significantly decreased （P<0.05）； the percentages of M1-type macrophages in RAW264.7 cells and tumor tissue of the nude mice in PDTC group were significantly decreased （P<0.05）， while the percentages of M2-type macrophages were significantly increased （P<0.05）. Compared with CQ group， the percentages of M1-type macrophages in RAW264.7 cells and tumor tissue of the nude mice in CQ+PDTC group were significantly decreased （P<0.05）， while the percentages of M2-type macrophages were significantly increased （P<0.05）. Compared with control group， the levels of IL-6， TNF-α， and iNOS in supernatant of the RAW264.7 cells and serum of the nude mice in CQ group were significantly increased （P<0.05）， while the levels of TGF-β， Arg-1， and IL-10 were significantly decreased （P<0.05）； the levels of IL-6， TNF-α， and iNOS in supernatant of the RAW264.7 cells and serum of the nude mice in PDTC group were significantly decreased （P<0.05）， while the levels of TGF-β， Arg-1， and IL-10 were significantly increased （P<0.05）. Compared with CQ group， the levels of IL-6， TNF-α， and iNOS in supernatant of the RAW264.7 cells and serum of the nude mice in CQ+PDTC group were significantly decreased （P<0.05）， while the levels of TGF-β， Arg-1， and IL-10 were significantly increased （P<0.05）. Compared with control group， the ratios of p-IκB-α/IκB-α and p-NF-κB p65/NF-κB p65 in RAW264.7 cells and tumor tissue of the nude mice in CQ group were significantly increased （P<0.05）； the ratios of p-IκB-α/IκB-α and p-NF-κB p65/NF-κB p65 in RAW264.7 cells and tumor tissue of the nude mice in PDTC group were significantly decreased （P<0.05）. Compared with CQ group， the ratios of p-IκB-α/IκB-α and p-NF-κB p65/NF-κB p65 in RAW264.7 cells and tumor tissue of the nude mice in CQ+PDTC group were significantly decreased （P<0.05）. Conclusion CQ can promote macrophage polarization from M2 to M1 type by activating NF-κB signaling pathway， thereby inhibiting the proliferation， migration， and invasion of hepatocellular carcinoma HepG2 cells and the growth of subcutaneous xenograft tumor in the nude mice.

Objective To discuss the effect of sodium selenite （SS） on the proliferation， migration， apoptosis， and tumor stemness of breast cancer doxorubicin-resistant MCF-7/ADR cells， and to clarify its mechanism. Methods After the breast cancer doxorubicin-resistant MCF-7/ADR cells were treated with various concentrations （0， 5， 10， 20， 40， and 80 μmol·L^-1） of sodium selenite （SS） for 48 h， cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of the cells in various groups and the drug concentration for the subsequent experiments was determined. The MCF-7/ADR cells were divided into control group （0 μmol·L^-1 SS）， 5 μmol·L^-1 SS group， 10 μmol·L^-1 SS group， and 20 μmol·L^-1 SS group. After cultured for 24， 48， and 72 h， CCK-8 method was used to detect the proliferation activities of the cells in various groups； colony formation assay was used to detect the numbers of colony formation of the cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups； wound healing assay and Transwell chamber assay were used to detect the wound healing rates and the numbers of migration cells in various groups； sphere formation assay was used to detect the numbers of sphere formation in the cells in various groups； Western blotting method was used to detect the expression levels of ATP-binding cassette transporter B subfamily member 1 （ABCB1）， microtubule-associated protein 1 light chain 3-Ⅱ （LC3-Ⅱ）， and p62 proteins in the cells in various groups. Results Compared with 0 μmol·L^-1 SS group， after cultured for 48 and 72 h， the proliferation activities of the MCF-7/ADR cells in 5， 10， 20， and 40 μmol·L^-1 SS groups were significantly decreased （P<0.01）. Compared with 0 μmol·L^-1 SS group， the numbers of clone formation cells in 10 and 20 μmol·L^-1 SS groups were significantly decreased （P<0.01）. Compared with control group， the apoptotic rates of the cells in 5， 10， and 20 μmol·L?1 SS groups showed no significant difference （P>0.05）. Compared with control group， the wound healing rates of the cells in 10 and 20 μmol·L?1 SS groups were significantly decreased （P<0.01）， and the numbers of migration cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.01）. After 14 d of culture， compared with control group， the numbers of spheroid formation in the cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.05 or P<0.01）. Compared with control group， the expression levels of ABCB1 and p62 proteins in the cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.05 or P<0.01）， and the expression levels of LC3-Ⅱ protein in the cells in 10 and 20 μmol·L^-1 SS groups were significantly increased （P<0.01）. Conclusion SS can inhibit the proliferation， migration， and sphere formation ability of the MCF-7/ADR cells， induce cell autophagy， and down-regulate the expression level of ABCB1 protein.

Objective To discuss the effect of coagulation factor V （FV） on the immune inflammatory response and the c-Jun N-terminal kinase 1/2 （JNK1/2） and p38 mitogen-activated protein kinase （p38 MAPK） signaling pathways in the septic rats， and to clarify its possible mechanism. Methods A total of 150 rats were divided into sham operation group， model group， sh-NC group， sh-FV group， and anisomycin group， with 30 rats in each group. The sepsis model was established by cecal ligation and puncture （CLP） method. The survival rates of the rats in various groups within 5 d after modeling were observed. Hematoxylin-eosin （HE） staining was used to observe the pathomorphology of lung， kidney， liver， and spleen tissues of the rats in various groups； real-time fluorescence quantitative PCR （RT-qPCR） was used to detect the expression levels of FV mRNA in lung tissue of the rats in various groups； Western blotting method was used to detect the expression levels of FV， JNK1/2， and p38 MAPK signaling pathway-related proteins in lung tissue of the rats in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum of the rats in various groups； flow cytometry was used to detect the apoptotic rates of neutrophils and the percentages of T lymphocyte subsets in blood of the rats in various groups. Results Compared with model group and sh-NC group， the survival rate of the rats in sh-FV group was significantly increased （P<0.05）； compared with sh-FV group， the survival rate of the rats in anisomycin group was significantly decreased （P<0.05）. Compared with sham operation group， the expression levels of FV mRNA in lung tissue of the rats in model group and sh-NC group were significantly increased （P<0.05）； compared with model group and sh-NC group， the expression level of FV mRNA in lung tissue of the rats in sh-FV group was significantly decreased （P<0.05）. The Western blotting results showed that compared with sham operation group， the expression levels of FV protein in lung tissue of the rats in model group and sh-NC group were significantly increased （P<0.05）， and the ratios of p-JNK1/2/JNK1/2 and p-p38 MAPK/p38 MAPK were significantly increased （P>0.05）； compared with model group and sh-NC group， the expression level of FV protein and the ratios of p-JNK1/2/JNK1/2 and p-p38 MAPK/p38 MAPK in lung tissue of the rats in sh-FV group were significantly decreased （P<0.05）； compared with sh-FV group， the ratios of p-JNK1/2/JNK1/2 and p-p38 MAPK/p38 MAPK in lung tissue of the rats in anisomycin group were significantly increased （P<0.05）. The ELISA results showed that compared with sham operation group， the serum levels of IL-1β， IL-6， and TNF-α of the rats in model group and sh-NC group were significantly increased （P<0.05）； compared with model group and sh-NC group， the serum levels of IL-1β， IL-6， and TNF-α of the rats in sh-FV group were significantly decreased （P<0.05）； compared with sh-FV group， the serum levels of IL-1β， IL-6， and TNF-α of the rats in anisomycin group were significantly increased （P<0.05）. The flow cytometry results showed that compared with sham operation group， the apoptotic rates of neutrophils， the percentage of CD4⁺ T lymphocytes， and the ratios of CD4⁺/CD8⁺ T lymphocytes of the rats in model group and sh-NC group were significantly decreased （P<0.05）， while the percentages of CD8⁺ T lymphocytes were significantly increased （P<0.05）； compared with model group and sh-NC group， the apoptotic rate of neutrophils， the percentage of CD4⁺ T lymphocytes， and the ratio of CD4⁺/CD8⁺ T lymphocytes of the rats in sh-FV group were significantly increased （P<0.05）， while the percentage of CD8⁺ T lymphocytes was significantly decreased （P<0.05）； compared with sh-FV group， the apoptotic rate of neutrophils， the percentage of CD4⁺ T lymphocytes， and the ratio of CD4⁺/CD8⁺ T lymphocytes of the rats in anisomycin group were significantly decreased （P<0.05）， while the percentage of CD8⁺ cells was significantly increased （P<0.05）. Conclusion Silencing FV gene can alleviate the damage of lung， liver， spleen， and kidney tissues， induce the apoptosis of blood neutrophils， reduce the serum levels of inflammatory factors， and increase the percentage of CD4⁺ T lymphocytes and the ratio of CD4⁺/CD8⁺ T lymphocytes in blood of the septic rats. Its mechanism may be related to the inhibition of JNK1/2 and p38 MAPK signaling pathways.

Objective To discuss the effect of long non-coding RNA （lncRNA） urothelial carcinoembryonic antigen 1 （UCA1） on the anoikis of human gastrointestinal stromal tumor （GIST） cells， and to clarify its mechanism of action. Methods The human GIST cell line GIST-T1 was cultured under adherent and anoikis conditions， and the GIST-T1 cells resistant to anoikis were induced. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression level of lncRNA UCA1 in the two kinds of cells； Western blotting method was used to detect the expression levels of autophagy markers microtubule-associated protein light chain 3 （LC3）-Ⅰ， LC3-Ⅱ， and p62 proteins in the cells， and the LC3-Ⅱ/LC3-Ⅰ ratio was calculated. The GIST-T1 cells were transfected with lncRNA UCA1 knockdown or negative control lentivirus and treated with the autophagy activator rapamycin （RAPA）. The GIST-T1 cells were divided into control group， sh-NC group， sh-UCA1 group， sh-NC+RAPA group， and sh-UCA1+RAPA group， and the cells were subjected to anoikis induction. Flow cytometry was used to detect the anoikis rates of cells in various groups； Western blotting method was used to detect the expression levels of LC3-Ⅰ， LC3-Ⅱ， and p62 proteins in the cells in various groups； cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of the cells in various groups； cell scratch assay was used to detect the scratch healing rates of the cells in various groups； Transwell chamber assay was used to detect the number of invasive cells in various groups. The GIST-T1 cells from sh-NC group and sh-UCA1 group were collected and injected via the tail vein to establish two groups of nude mouse xenograft models， respectively. After 4 weeks， a fluorescence in vivo imaging system was used to detect the tumor growth and liver metastasis in the nude mice in two groups， and the tumor tissue mass was measured. TUNEL staining was used to observe cell apoptosis in the tumor tissue of the nude mice in two groups； immunohistochemical staining was used to detect the expression levels of LC3B and p62 proteins in the tumor tissue of the nude mice in two groups. Results Compared with adherently cultured GIST-T1 cells， the expression level of lncRNA UCA1 in anoikis-resistant GIST-T1 cells was significantly increased （P<0.05）， the LC3-Ⅱ/LC3-Ⅰ ratio was significantly increased （P<0.05）， and the expression level of p62 protein was significantly decreased （P<0.05）. Compared with sh-NC group， the anoikis rate of GIST-T1 cells in sh-UCA1 group was increased （P<0.05）， the LC3-Ⅱ/LC3-Ⅰ ratio was significantly decreased （P<0.05）， the expression level of p62 protein was significantly increased （P<0.05）， the cell proliferation activity and scratch healing rate were significantly decreased （P<0.05）， and the number of invasive cells was significantly decreased （P<0.05）； compared with sh-UCA1 group， the anoikis rate of GIST-T1 cells in sh-UCA1+RAPA group was significantly decreased （P<0.05）， the LC3-Ⅱ/LC3-Ⅰ ratio was significantly increased （P<0.05）， the expression level of p62 protein was significantly decreased （P<0.05）， the cell proliferation activity and scratch healing rate were significantly increased （P<0.05）， and the number of invasive cells was significantly increased （P<0.05）. In the nude mouse xenograft experiment， compared with sh-NC group， the fluorescence intensity in liver tissue of the nude mice in sh-UCA1 group was weakened， the tumor mass was significantly decreased （P<0.05）， the cell apoptotic rate in tumor tissue was significantly increased （P<0.05）， the expression level of LC3B protein was significantly decreased （P<0.05）， and the expression level of p62 protein was significantly increased （P<0.05）. Conclusion LncRNA UCA1 is highly expressed in anoikis-resistant GIST-T1 cells， and downregulating its expression can promote anoikis of GIST-T1 cells by reducing the autophagy level， thereby inhibiting cell growth， migration， and invasion.

Objective To discuss the role of mitogen-activated protein kinase （MAPK）-myeloid cell leukemia sequence 1 （Mcl-1） signaling axis in the polarization process of macrophages infected with Bacillus Calmette-Guérin （BCG）， and to clarify its possible molecular mechanism. Methods The transcriptome sequencing data of GSE89391 and GSE51029 were downloaded from Gene Expression Omnibus （GEO） database， and the MAPK signaling pathway-related gene sets were downloaded from Molecular Signatures Database （MSigDB）. The gene set variation analysis （GSVA） package was used to perform single-sample gene set enrichment analysis （ssGSEA） on the macrophage data in GEO database， and the activity scores of MAPK signaling pathway were calculated. The infected samples were divided into Mcl-1 high expression group and Mcl-1 low expression group according to the median of Mcl-1 expression level， and gene set enrichment analysis （GSEA） was performed. Spearman correlation analysis was used to assess the correlation between Mcl-1 expression level and MAPK pathway activity in macrophages in GEO database. The extracellular signal-regulated kinase （ERK） pathway blocker PD98059 （50 μmol·L?1）， c-Jun N-terminal kinase （JNK） pathway blocker SP600125 （30 μmol·L?1）， and p38 pathway blocker SB203580 （60 μmol·L?1） were prepared.The Raw264.7 cells were divided into control group， various blocker-treated groups， BCG group， and various blocker-treated groups after BCG infection. BCG bacterial solution was prepared and used to infect the cells in corresponding groups， and the corresponding blockers were added to the cells in various groups. The cell supernatants and cell samples in various groups were collected at 0， 12， and 24 h after treatment. Enzyme-linked immunosorbent assay （ELISA） method was used to detect the levels of Mcl-1， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and transforming growth factor-β （TGF-β） in supernatant of the macrophages in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of M1 marker inducible nitric oxide synthase （iNOS） mRNA and M2 marker found in inflammatory zone 1 （Fizz1） mRNA in the macrophages in various groups. Results Based on GEO databases， compared with uninfected control macrophages， the level of Mcl-1 gene in the macrophages infected with Mycobacterium tuberculosis（MTB） was significantly increased （P<0.05）. The ssGSEA analysis results showed that compared with uninfected control macrophages， the MAPK signaling pathway activity score in MTB-infected macrophages was significantly increased （P<0.05）. The GSEA analysis results revealed that differentially expressed genes in Mcl-1 high expression groups were significantly enriched in the MAPK pathway （P<0.05）. The Spearman correlation analysis results indicated there was a positive correlation between the expression level of Mcl-1 gene and MAPK signaling pathway activity score （P<0.05）. At 12 and 24 h after treatment， compared with BCG group， the levels of Mcl-1 in supernatant of the macrophages in various blocker-treated groups were significantly decreased （P<0.05）. At 12 h after treatment， compared with control group， the levels of IL-6 and TNF-α in supernatant of the macrophages in BCG group were significantly increased （P<0.05）. Compared with BCG group， the levels of IL-6 and TNF-α in supernatants of the macrophages in BCG+SP and BCG+PD+SP groups were significantly decreased （P<0.05）. At 24 h after treatment， compared with control group， the level of TNF-α in supernatant of the macrophages in BCG group was significantly increased （P<0.05）. Compared with BCG group， the levels of IL-6 in supernatants of the macrophages in BCG+PD， BCG+SP， BCG+SB， and BCG+PD+SP groups were significantly decreased （P<0.05）， and the levels of TNF-α in supernatants of the macrophages in all blocker-treated groups were significantly decreased （P<0.05）. At 12 h after treatment， compared with control group， the level of TGF-β in supernatant of the macrophages in BCG group was significantly increased （P<0.05）. Compared with BCG group， the levels of TGF-β in supernatants of the macrophages in BCG+SP， BCG+PD+SP， BCG+PD+SB， BCG+SP+SB， and BCG+PD+SP+SB groups were significantly increased （P<0.05）. At 24 h after treatment， compared with control group， the level of IL-10 in supernatant of the macrophages in BCG group was significantly increased （P<0.05）. Compared with BCG group， the levels of IL-10 and TGF-β in supernatants of the macrophages in BCG+PD， BCG+SP， BCG+PD+SP， BCG+PD+SB， and BCG+SP+SB groups were significantly decreased （P<0.05）. At 0 h after infection， compared with control group， the expression levels of iNOS and Fizz1 mRNA in the macrophages in BCG group were significantly increased （P<0.05）. At 12 h after treatment， compared with control group， the expression level of iNOS mRNA in the macrophages in BCG group was significantly decreased （P<0.01）， while the expression level of Fizz1 mRNA was significantly increased （P<0.01）. Compared with BCG group， the expression levels of iNOS mRNA in the macrophages in all blocker-treated groups were significantly increased （P<0.01）， and the expression levels of Fizz1 mRNA in the macrophages in BCG+PD， BCG+PD+SP， BCG+PD+SB， BCG+SP+SB， and BCG+PD+SP+SB groups were significantly increased （P<0.01）. At 24 h after treatment， compared with control group， the expression levels of iNOS and Fizz1 mRNA in the macrophages in BCG group were significantly increased （P<0.05）. The expression levels of iNOS mRNA in the macrophages between BCG group and all blocker-treated groups showed no statistically significant difference （P>0.05）. Compared with BCG group， the expression level of Fizz1 mRNA in the macrophages in BCG+PD+SP group was significantly decreased （P<0.01）. Conclusion MAPK signaling pathway may mediate the polarization process of macrophages infected with BCG by regulating Mcl-1 activity， in which the JNK pathway plays a core regulatory role， and the p38 and ERK pathways are synergistically involved in the regulation.

Objective To discuss the protective effect of dexmedetomidine （Dex） on myocardial ischemia/reperfusion injury （MIRI） in the rats， and to clarify its mechanism. Methods Forty-eight SD rats were randomly divided into control group， model group， Dex group， and Dex+Compound C group， with 12 rats in each group. The MIRI model was established by ligation of left anterior descending coronary artery. Echocardiography was used to evaluate the cardiac function of the rats in various groups； HE staining was used to observe the pathomorphology of myocardium tissue of the rats in various groups； kits were used to detect the serum level of cardiac troponin I （cTnI） and the activities of hexokinase （HK）， phosphofructokinase （PFK）， and pyruvate kinase （PKM） of the rats in various groups； high performance liquid chromatography （HPLC） was used to detect the levels of myocardial energy metabolites adenosine triphosphate （ATP）， adenosine diphosphate （ADP）， and adenosine monophosphate （AMP） in myocardium tissue of the rats in various groups， and the energy charge （EC） was calculated； immunohistochemistry and Western blotting method were used to detect the expressions of Toll-like receptor 4 （TLR4）， macrophage migration inhibitory factor （MIF）， AMP-activated protein kinase（AMPK） and phosphorylated AMPK （p-AMPK） proteins in myocardium tissue of the rats in various groups. Results Compared with control group， the left ventricular ejection fraction （EF）， fractional shortening （FS）， cardiac output （CO）， and stroke volume （SV） of the rats in model group were significantly decreased （P<0.05）； the serum level of cTnI was significantly increased （P<0.05）， and the activities of HK， PFK， and PKM were significantly decreased （P<0.05）； the levels of ATP and ADP and EC in myocardium tissue were significantly decreased （P<0.05）， while the level of AMP was significantly increased （P<0.05）； the expression levels of TLR4 and MIF proteins in myocardium tissue were increased （P<0.05）， and the p-AMPK/AMPK ratio was decreased （P<0.05）. Compared with model group， the EF， FS， CO， and SV of the rats in Dex group were significantly increased （P<0.05）； the serum level of cTnI was significantly decreased （P<0.05）， and the activities of HK and PKM were significantly increased （P<0.05）； the levels of ATP and ADP and EC in myocardium tissue were significantly increased （P<0.05）； the expression levels of TLR4 and MIF proteins in myocardium tissue were decreased （P<0.05）， and the p-AMPK/AMPK ratio was increased （P<0.05）. Compared with Dex group， the EF， FS， CO， and SV of the rats in Dex+Compound C group were significantly decreased （P<0.05）， the serum level of cTn I was increased （P<0.05）， and the PKM activity was decreased （P<0.05）； the levels of ATP and ADP and EC in myocardium tissue were significantly decreased （P<0.05）； the expression levels of TLR4 and MIF proteins in myocardium tissue were increased （P<0.05）， and the p-AMPK/AMPK ratio was decreased （P<0.05）. Conclusion Dex improves the imbalance of myocardial energy metabolism and myocardial dysfunction after MIRI by inhibiting TLR4/MIF signaling and activating AMPK phosphorylation. Its therapeutic effect can be antagonized by the AMPK inhibitor Compound C； Dex plays the cardioprotective effect by regulating the TLR4/MIF/AMPK signaling pathway.

Objective To discuss the targeting relationship between microRNA-214-3p （miR-214-3p） and enhancer of zeste homolog 2 （EZH2）， and to clarify its effects on the proliferation， invasion， and apoptosis of ovarian cancer SKOV3 cells. Methods The human ovarian cancer SKOV3 cells were divided into control group， mimics negative control （NC） group， miR-214-3p mimics group， miR-214-3p mimics+overexpression NC （OE-NC） group， and miR-214-3p mimics+overexpression EZH2 （OE-EZH2） group. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of miR-214-3p and EZH2 mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of EZH2 protein in the cells in various groups. Reporter plasmids containing wild-type （WT） or mutant-type （MT） EZH2 were constructed and co-transfected with miR-214-3p mimics or NC into the 293T cells， and the dual-luciferase reporter gene assay was used to detect the luciferase activities of the cells in various groups. Cell counting kit-8 （CCK-8） method was used to detect the activities of the cells in various groups； Transwell chamber assay was used to detect the numbers of invasion cells in various groups； flow cytometry was used to detect the apoptotic rates and cell cycle distribution of the cells in various groups. Results Compared with control group and mimics NC group， the expression level of miR-214-3p in the cells in miR-214-3p mimics group was significantly increased （P<0.05）， and the expression levels of EZH2 mRNA and protein were significantly decreased （P<0.05）. Compared with miR-214-3p mimics group， the expression level of miR-214-3p in the cells in miR-214-3p mimics+OE-EZH2 group was significantly decreased （P<0.05）， and the expression levels of EZH2 mRNA and protein were significantly increased （P<0.05）. Compared with pGL3-EZH2-WT+NC group， the luciferase activity in the cells in pGL3-EZH2-WT+miR-214-3p mimics group was significantly decreased （P<0.05）. Compared with control group and mimics NC group， the activity of the cells in miR-214-3p mimics group was significantly decreased （P<0.05）， the number of invasion cells was significantly decreased （P<0.05）， the apoptotic rate was significantly increased （P<0.05）， and the percentage of the cells at G₁ phase was significantly increased （P<0.05）. Compared with miR-214-3p mimics group， the activity of the cells in miR-214-3p mimics+OE-EZH2 group was significantly increased （P<0.05）， the number of invasion cells was significantly increased （P<0.05）， and the apoptotic rate was significantly decreased （P<0.05）. Conclusion miR-214-3p can down-regulate EZH2 expression by targeting it， thereby inhibiting the proliferation and invasion abilities and promoting the apoptosis of ovarian cancer SKOV3 cells. Overexpression of EZH2 can antagonize the tumor-suppressive effect of miR-214-3p， further confirming the targeting regulatory relationship between them.

Objective To discuss the expression of glutathione S-transferase Omega-1 protein （GSTO1） in epithelial ovarian cancer （EOC） tissue and its relationship with the clinicopathological characteristics and prognosis of the patients， and to investigate the effect of its N-glycosylation modification on the biological behaviors of ovarian cancer A2780 and SKOV3 cells， and to clarify its possible mechanism. Methods GENT2 database was used to analyze the expression levels of GSTO1 mRNA in ovarian cancer tissue and normal ovarian epithelial tissue. The clinical information of 88 EOC patients who visited and underwent surgery in the Department of Gynecology of the First Affiliated Hospital of Shihezi University was collected， the tissue samples were collected， and the prognosis of the patients was followed up regularly. Immunohistochemical method was used to detect the expression of GSTO1 protein in ovarian tissue of EOC patients， and its relationship with the clinicopathological characteristics and prognosis of the patients was analyzed. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors affecting the prognosis of EOC patients. Mass spectrometry was used to compare the difference in N-glycosylation modification of GSTO1 protein between highly metastatic ovarian cancer ES-2 cells and parental SKOV3 cells， and NetNGlyc 1.0 server database was used to identify its modification sites. Tunicamycin was used to inhibit the overall N-glycosylation of cells， and ovarian cancer A2780 and SKOV3 cells were divided into control group， dimethyl sulfoxide （DMSO） group， and tunicamycin group. The ovarian cancer A2780 and SKOV3 cells with different levels of N-glycosylation modification were stably constructed by lentiviral transfection and divided into NC group， WT group， N55Q group， N135Q group， N190Q group， and N3Q group. 5-Ethynyl-2'-deoxyuridine （EdU） assay was used to detect the proliferation rates of the cells in various groups； Transwell chamber assay was used to detect the numbers of migration cells and invasion cells in various groups； Western blotting method was used to detect the expression levels of GSTO1 protein and epithelial-mesenchymal transition （EMT）-related proteins E-cadherin， N-cadherin， and Vimentin in the cells in various groups. Results According to GENT2 database， compared with normal ovarian epithelial tissue， the expression level of GSTO1 mRNA in ovarian cancer tissue was significantly increased （P<0.01）. Immunohistochemical staining results showed that there were 66 cases with high expression of GSTO1 and 22 cases with low expression of GSTO1 in tumor tissues of EOC patients.The high expression of GSTO1 protein in tumor tissue of EOC patients was associated with FIGO stage， lymphovascular space invasion， and tumor diameter （P<0.05）. The univariate and multivariate Cox regression analyses results showed that high FIGO stage， lymph node metastasis， and high GSTO1 expression were independent risk factors affecting the overall survival （OS） and progression-free survival （PFS） of EOC patients. The mass spectrometry results showed that compared with parental SKOV3 cells， the level of N-glycosylation modification of GSTO1 in highly metastatic ovarian cancer ES-2 cells was significantly increased （P<0.05）， and its N-glycosylation modification sites were Asn55， Asn135， and Asn190， respectively. Compared with control group， the expression levels of GSTO1 protein in A2780 and SKOV3 cells in tunicamycin group were significantly decreased （P<0.05）. Compared with WT group， the expression levels of GSTO1 protein in A2780 and SKOV3 cells in N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the proliferation rates of A2780 and SKOV3 cells in N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the numbers of migration cells and invasion cells of A2780 and SKOV3 cells in N55Q， N135Q， N190Q， and N3Q groups were significantly decreased （P<0.05）. Compared with WT group， the expression levels of E-cadherin protein in A2780 and SKOV3 cells in N3Q group were significantly increased （P<0.05）， and the expression levels of N-cadherin protein and Vimentin protein in A2780 and SKOV3 cells in N190Q and N3Q groups were significantly decreased （P<0.05）. Conclusion GSTO1is highly expressed in EOC tissue and cells and is associated with poor prognosis of patients. Mutation of its N-glycosylation sites can inhibit the proliferation， migration， invasion， and EMT process of ovarian cancer cells.

Objective To discuss the changes of the levels of phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） in serum of the patients with Sj?gren’s syndrome （SS）， and to clarify their relationships with thrombocytopenia （TP） in the SS patients. Methods A total of 198 SS patients admitted to our hospital from January 2022 to December 2024 were selected. According to the platelet （PLT） count levels， they were divided into SS-TP group （n=51） and SS-non-TP （NTP） group （n=147）. The clinical data of the patients in two groups were collected； Pearson correlation analysis was used to analyze the correlations between the serum levels of PI3K and Akt and PLT count in the SS patients； χ2 test and independent sample t test were used to analyze the relationships between the clinical data of the SS patients and TP； multivariate Logistic regression analysis was used to screen the independent predictors for the risk of TP in the SS patients； receiver operating characteristic （ROC） curve was drawn to evaluate the predictive efficacy of the predictors； decision curve was used to assess the clinical utility of the predictors. Results Among the 198 SS patients， 51 patients （25.76%） complicated with TP were included as SS-TP group， and the remaining patients were included as SS-NTP group. Compared with SS-NTP group， the serum levels of PI3K and Akt of the patients in SS-TP group were significantly decreased （P<0.05）. The serum levels of PI3K （r=0.416， P<0.001） and Akt （r=0.425， P<0.001） of the SS patients were positively correlated with PLT count. Compared with SS-NTP group， the percentage of lymphadenectasis of the patients in SS-TP group was significantly increased （P<0.05）， and the lymphocyte count and hemoglobin level were significantly decreased （P<0.05）. The Logistic regression analysis results showed that the concurrent TP in the SS patients was associated with the decrease in the lymphocyte count， hemoglobin level， and serum levels of PI3K and Akt （P<0.05 or P<0.01）. The area under curve （AUC） value of serum PI3K level for predicting concurrent TP in the SS patients was 0.770， the AUC value of serum Akt level for predicting concurrent TP in the SS patients was 0.763， and the AUC value of the combined prediction of the two was 0.853. The efficacy of the combined prediction of serum PI3K level and serum Akt level for concurrent TP in the SS patients was better than that of either alone （combined prediction-serum PI3K level： Z=2.779， P=0.006； combined prediction-serum Akt level： Z=2.907， P=0.004）. Within the threshold range of 0.10-0.82， the net benefit rate of the combined prediction of serum PI3K and Akt levels for the risk of concurrent TP in the SS patients was higher than that of the separate assessment of serum PI3K or Akt levels. Conclusion The decrease of serum PI3K and Akt levels are associated with the risk of concurrent TP in SS patients， and the combined assessment of the two has a high predictive value for the occurrence of TP.

Objective To analyze the differences in carotid plaque composition in the patients who underwent carotid endarterectomy （CEA）， and to explore the influencing factors for symptomatic carotid artery stenosis （CAS） in combination with high-density lipoprotein cholesterol （HDL-C） levels. Methods A total of 130 CEA patients in our hospital were selected as the subjects. The patients were divided into symptomatic CAS group and asymptomatic CAS group based on whether they experienced ischemic stroke （IS） or transient ischemic attack （TIA） within 6 months before CEA. The gender， age， and medical history of the patients in two groups were collected. The levels of homocysteine， glycated hemoglobin， high-sensitivity C-reactive protein （hs-CRP）， vitamin B₁₂， uric acid， fasting blood glucose， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and HDL-C in peripheral blood of the patients were measured. HE staining was used to evaluate the indexes of carotid artery plaque in the CAS patients； Sirius red staining was used to evaluate the collagen Ⅲ/collagen Ⅰ ratio in carotid artery plaques of the CAS patients. The differences in baseline data between two groups were compared； multivariate Logistic regression model was used to analyze the influencing factors for symptomatic CAS； receiver operating characteristic （ROC） curves were plotted， and the area under the ROC curve （AUC） was calculated to evaluate the predictive efficacy of the influencing factors. Results A total of 130 patients were included in the study， with 60 cases in symptomatic CAS group and 70 cases in asymptomatic CAS group. There were statistically significant differences between two groups in smoking history， fibrous cap integrity， white blood cell count， neovascularization count， collagen Ⅲ/collagen Ⅰ ratio， HDL-C level， and fasting blood glucose level （P<0.05）. The multivariate Logistic regression analysis results showed that incomplete fibrous cap of carotid plaque， high white blood cell count， and high collagen Ⅲ/collagen Ⅰ ratio were the independent risk factors for symptomatic CAS， while high HDL-C level was an independent protective factor for symptomatic CAS. These four factors showed certain predictive value for symptomatic CAS （AUC>0.6）. Conclusion Incomplete fibrous cap of carotid plaque， high white blood cell count， and high collagen Ⅲ/collagen Ⅰ ratio are the risk factors for symptomatic CAS， while high HDL-C level is a protective factor. These four factors can serve as the independent predictors for symptomatic CAS.

Objective To discuss the levels of cytokines and the immune status in the serum of patients with acute ischemic stroke （AIS）， and to clarify the effects of factors such as homocysteine （Hcy） level， post-stroke infection， and smoking on the immune response in AIS patients. Methods A total of 53 AIS patients were selected. Basic information of the patients was collected， and serum samples were collected within 72 h of onset. The levels of various cytokines in the serum of the patients were measured， including Hcy， interleukin （IL）-2， IL-4， IL-6， IL-10， IL-17A， interferon-γ （IFN-γ）， and tumor necrosis factor-α （TNF-α）. The patients were grouped according to the tertiles of Hcy level， the occurrence of post-stroke infection， and smoking status， respectively. The differences in baseline data and the levels of the above cytokines were compared among the patients in various groups； multiple linear regression models were used to analyze the correlations between the levels of various cytokines and Hcy level， smoking status， and other baseline indicators in AIS patients. Results Compared with low Hcy level group， the serum levels of IL-6 and IFN-γ in the patients in high Hcy level group were significantly increased （P<0.05）. Multiple linear regression analysis showed an association between Hcy level and IFN-γ level （β=0.363， P<0.05）. Compared with non-infection group， the serum level of IL-4 in the patients in infection group was significantly increased （P<0.01）， while the IFN-γ/IL-4 ratio in serum of the patients showed a decreasing trend， but the difference was not statistically significant （P>0.05）. Compared with non-smoking group， the serum levels of IL-2， IL-6， IL-10， and IFN-γ in the patients in smoking group were significantly increased （P<0.05）. Conclusion In AIS patients， high Hcy level and smoking are associated with increased levels of multiple pro-inflammatory cytokines in the serum of the patients， and the occurrence of post-stroke infection is associated with increased levels of anti-inflammatory cytokines in the serum of the patients.

Objective To retrospectively analyze the etiological characteristics and risk factors for postoperative infection in the patients who underwent oral and maxillofacial surgery， and to provide the reference for clinical infection prevention and control and formulation of antibacterial treatment strategies. Methods A total of 462 inpatients were selected who underwent oral and maxillofacial surgical treatment at our hospital from May 2021 to September 2024. Based on the occurrence of postoperative infection， they were divided into infection group （130 cases） and non-infection group （332 cases）. The distribution and the antibacterial drug susceptibility of the pathogenic bacteria in clinical specimens from the patients in infection group were analyzed. Univariable analysis was performed for the surgical data of the patients in two groups， and variables showing significant differences were further included in the multivariable Logistic regression model to screen for independent risk factors for postoperative infection in oral and maxillofacial surgery patients. Results In clinical specimens from the patients in infection group， Gram-negative bacteria were the main pathogens （57.4%）， with the susceptibility rates of common strains to cefepime， meropenem， and levofloxacin and so on exceeding 90%. The susceptibility rates of Gram-positive bacteria such as Staphylococcus and Streptococcus to vancomycin and chloramphenicol were greater than 70%. The univariate analysis results showed that there were statistically significant differences between the patients in two groups in age， surgical risk assessment level， surgical complexity， intraoperative blood loss， duration of surgery， placement of post-operative drainage device， implantation of medical device and performance of temporary tracheotomy （P<0.05）. The results of multivariate Logistic regression analysis showed that high surgical complexity （P=0.022）， increased intraoperative blood loss （P=0.005）， and high surgical risk assessment level （P=0.001） were the independent risk factors for postoperative infection in the patients underwent oral and maxillofacial surgery. Conclusion Postoperative infections in oral and maxillofacial surgery are mainly caused by Gram-negative bacteria， and antibacterial therapy should be guided by drug susceptibility results. Perioperative management should be intensified for high-risk patients to reduce the incidence of infection.

Objective To investigate the relationship between the glucose coefficient of variation （GCV） and the risk of hyperuricemia （HUA） in the patients with early-onset type 2 diabetes mellitus （T2DM）. Methods A total of 224 hospitalized patients with T2DM between September 2023 and November 2024 were enrolled. The general clinical data， laboratory biochemical indicators， and continuous glucose monitoring （CGM）-derived metrics were collected.The early-onset T2DM patients were stratified into HUA and non-HUA groups based on their serum uric acid （SUA） levels. Fasting venous blood was collected to detect SUA， glycated hemoglobin （HbA1c）， blood lipids， liver and kidney function indexes， and other indicators. Glucose variability parameters， including GCV， time in range （TIR）， and mean amplitude of glycemic excursions （MAGE）， were obtained using the CGM system. The t-test and Mann-Whitney U test were used to compare the differences in the indicators of the patients between various groups； Spearman correlation analysis was used to analyze the correlation between GCV and SUA level in the patients； modified Poisson regression models were used to evaluate the association between GCV and HUA in early-onset T2DM patients； receiver operating characteristic （ROC） curve analysis along with the area under the curve （AUC） were used to determine the predictive values of GCV and HbA1c level for HUA in early-onset T2DM patients. Results The prevalence of HUA in early-onset T2DM group was significantly higher than that in late-onset T2DM group （P<0.001）. Significant differences were observed between the patients in two groups in age， disease duration， gender， family history of diabetes， body mass index （BMI） as well as serum levels of SUA， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） （P<0.05）. Among early-onset T2DM patients， compared with non-HUA group， the serum levels of creatinine （Scr） and triglyceride（TG）， atherogenic index （AI）， fasting C-peptide （FC-P）， 2-hour postprandial C-peptide （2hC-P）， GCV， and MAGE in the patients in HUA group were significantly increased （P<0.05）， while the level of high-density lipoprotein cholesterol （HDL-C） was significantly decreased （P<0.05）. The Spearman correlation analysis results showed a positive correlation between SUA level and GCV in early-onset T2DM patients （r=0.403， P<0.001）. After adjusting for confounding factors， compared with the patients in the lowest GCV quartile， the risk of HUA among those in the highest GCV quartile was significantly increased （RR=2.12，P <0.05）. The AUC of GCV for predicting HUA in early-onset T2DM patients was 0.859 （95% CI： 0.783-0.935）， with an optimal cutoff value of 58.5%， a sensitivity of 79.7%， and a specificity of 76.7%. Conclusion The proportion of HUA in early-onset T2DM patients is higher than that in late-onset T2DM patients. Increased GCV level is significantly associated with an increased risk of HUA in the patients with early-onset T2DM.

Switch/sucrose non-fermentable （SWI/SNF）-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 （SMARCB1）/integrase interactor 1 （INI1） （SMARCB1/INI1）-deficient undifferentiated pancreatic carcinoma （UPC） is an extremely rare special type of pancreatic cancer. This article reported the clinical manifestations， auxiliary examinations， diagnosis， and treatment of a patient with SMARCB1/INI1-deficient UPC， and reviewed the relevant literature. The patient， a 65-year-old female， was admitted due to intermittent upper abdominal pain for more than one month， aggravated with nausea and vomiting for 9 d. The abdominal CT scan performed at another hospital suggested a pancreatic space-occupying lesion. The physical examination results on admission revealed upper abdominal tenderness， without rebound tenderness or muscle guarding. The laboratory tests results showed a carbohydrate antigen 199 （CA199） level of 50.58 U·mL^-1 and a fasting blood glucose level of 9.98 mmol·L^-1. The abdominal MRI results revealed a mixed cystic and solid abnormal signal in the pancreatic body and tail， showing irregular extraluminal protrusion； it appeared as a slightly hypointense signal on T1-weighted imaging （T1WI）， with the hemorrhagic part of the tumor appearing hyperintense； it appeared as a hyperintense signal on T2-weighted imaging （T2WI） with unclear boundaries， measuring 2.0-5.6 cm， causing compression and invasion of the gastric wall； enhanced scanning showed obvious rim enhancement of the tumor capsule， invasion of the splenic artery and vein， and portal vein thrombus formation. The gastroscope results revealed a 4.0 cm×5.0 cm mucosal elevation on the greater curvature of the gastric body， considered to be caused by compression from the pancreatic mass. The clinical diagnosis was a pancreatic space-occupying lesion， highly suspected to be malignant， with surgical resection being the preferred treatment option. The postoperative pathological diagnosis was SMARCB1/INI1-deficient UPC with a small component of moderately differentiated squamous cell carcinoma. The patient received chemotherapy after surgery and has been followed up for 5 months， with an improved quality of life compared to before surgery， no significant discomfort， and remains under close follow-up. SMARCB1/INI1-deficient UPC is relatively rare， with non?specific clinical manifestations， usually progressing rapidly and associated with a poor prognosis； therefore， early diagnosis and treatment should be pursued in clinical practice.

Pancreatic-derived pleural effusion is commonly caused by pancreatic pseudocysts， pancreaticopleural fistula （PPF）， and pancreatitis. Its clinical presentation is primarily characterized by thoracic symptoms， with abdominal symptoms being less common and lacking specificity， leading to frequent diagnostic and therapeutic delays. Bilateral pleural effusions presenting as yellowish-brown turbid fluid with rapid alternating progression are rare， and no related cases were reported domestically or internationally. This article reported a case of patient with pancreatic-derived pleural effusion， summarized its clinical presentation， pleural pathological features， and management strategy， and the relevant literatures were reviewed. The patient， a 40-year-old male， presented with “cough， sputum production， chest pain accompanied by paroxysmal dyspnea”. His pleural effusion exhibited rapid progression with a yellowish-brown turbid appearance. After ruling out common causes， a definitive diagnosis remained elusive. During treatment， the patient developed sudden abdominal pain. Given his history of chronic alcohol consumption and prior gastrostomy for pancreatic pseudocyst， amylase testing of the pleural effusion was performed. This confirmed a diagnosis of pancreatic-derived pleural effusion secondary to pancreatic pseudocyst. The patient subsequently underwent endoscopic retrograde cholangiopancreatography （ERCP） and related interventional procedures. Regular follow-up revealed no recurrence of pleural effusion. For the patients with pleural effusion and a history of pancreatic disease， pancreatic origin should be considered regardless of abdominal symptoms， while vigilance is warranted for severe complications including hemothorax， empyema， mediastinitis， and respiratory failure. When medical management proves inadequate， meticulous evaluation of pancreatic drainage pathways and anatomical anomalies is essential to guide precise and individualized treatment and improve the patient’s prognosis.

Objective To construct a lentiviral vector targeting the transgelin-2 （TAGLN2） gene in the mouse brain microvascular endothelial cell line bEnd.3 cells， and to identify its silencing effect. Methods Short hairpin RNA （shRNA） interference target sites were designed based on the coding region of the TAGLN2 gene. The amplified products were ligated into the GV493 lentiviral vector linearized by double digestion with EcoR Ⅰ and Age Ⅰ to construct the GV493-TAGLN2-shRNA recombinant lentiviral vector. The positive clones were screened by PCR and identified by sequencing. The GV493 control lentiviral vector and the GV493-TAGLN2-shRNA recombinant lentiviral vector were respectively transfected into the HEK293T cells， and the supernatants were collected and purified， and the viral titers were determined. The bEnd.3 cells were infected with a multiplicity of infection （MOI） of 100. After 48 h of infection， the complete medium containing 10 mg·L^-1 puromycin was replaced for screening and culture for 14 d. An inverted fluorescence microscope was used to observe the expression of green fluorescence protein （GFP） in the cells in two groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of TAGLN2 mRNA in cells in two groups； Western blotting method was used to detect the expression levels of TAGLN2 protein in the cells in two groups. Results The fluorescence microscope observation results showed that there was a strong GFP fluorescence signal in the transfected HEK293T cells， indicating that the lentiviral packaging system was successfully constructed. The titer of the GV493 control lentivirus was 5×1011 TU·L^-1， and the titer of the TAGLN2 interference lentivirus was 6×1011 TU·L^-1. After transfection， the bEnd.3 cells in two groups showed obvious GFP fluorescence signals， indicating that the stable transfected cell lines were successfully constructed. The RT-qPCR results showed that compared with GV493 control group， the expression level of TAGLN2 mRNA in the cells in GV493-TAGLN2-shRNA group was significantly decreased （P<0.01）. The Western blotting results showed that compared with GV493 control group， the expression level of TAGLN2 protein in the cells in GV493-TAGLN2-shRNA group was significantly decreased （P<0.01）. Conclusion A lentiviral vector targeting the TAGLN2 gene in bEnd.3 cells is successfully constructed， which can efficiently silence TAGLN2 expression.

Exosomes are a class of membranous vesicles containing lipids， nucleic acids， and proteins， which are capable of transporting various bioactive molecules and play key regulatory roles in physiological and pathological processes. With in-depth research into the mechanisms of action， exosomes have been demonstrated to possess the potential diagnostic and therapeutic value in oral diseases. Liquid biopsy techniques based on the extraction of exosomes from body fluids such as saliva， serum， and plasma have revealed the broad potential for exosomes in the early diagnosis and disease progression monitoring of oral conditions. In diseases such as oral squamous cell carcinoma， periodontitis， oral lichen planus， and primary Sj?gren’s syndrome， components carried by exosomes， including microRNA （miRNA） and proteins， exhibit characteristic differences in their expressions， thereby holding potential as diagnostic biomarkers. Furthermore， the diverse functions of exosomes in promoting tissue regeneration， modulating immunity， and delivering drugs have opened new avenues for the treatment of oral diseases such as pulpitis， periodontitis， and tissue injuries. This article provided an in-depth discussion of the advances in the application of exosomes in the diagnosis and treatment of oral diseases， aiming to offer a theoretical foundation for the prevention， diagnosis， and management of these conditions.

B-cell chronic lymphocytic leukemia/lymphoma 6 member B （BCL6B） gene is a homolog of B-cell/lymphoma 6 （BCL6） and belongs to the zinc finger and BTB domain-containing protein （ZBTB） family， playing an important role in regulating gene expression and cell proliferation. The function of BCL6B in various cellular processes and its potential clinical applications have attracted widespread attention. The BCL6B protein participates in the formation of transcriptional repression complexes and regulates multiple key signaling pathways including Notch and p53. In various solid tumors including hepatocellular carcinoma， gastric cancer， colorectal cancer， and breast cancer， BCL6B expression is frequently downregulated due to promoter hypermethylation， functioning as a tumor suppressor gene involved in inhibiting cell proliferation， migration， and invasion， and inducing apoptosis and cell cycle arrest； its high expression in a few tumors such as differentiated thyroid carcinoma also suggests the complexity of its function. Given the close association between BCL6B expression and tumor progression as well as patient prognosis， BCL6B is considered a promising prognostic biomarker and epigenetic therapeutic target. This article systematically reviewed the gene and protein structures and biological functions of BCL6B， with a focus on its role in the occurrence and development of various tumors and the latest research progress on the related molecular mechanisms， aiming to provide new insights for the precision diagnosis and treatment of tumors.

Burn injury-induced chronic pain is a common and refractory complication， of which the pathogenesis involves multifaceted mechanisms including neuropathic damage， central sensitization， and neuroinflammation. The underlying pathophysiology primarily consists of abnormal peripheral nerve regeneration， epigenetic reprogramming in the dorsal root ganglion， activation of spinal glial cells， and neuronal hyperexcitability mediated by pro-inflammatory signaling pathways. As an N-methyl-D-aspartate （NMDA） receptor antagonist， esketamine exerts analgesic effects through various pathways such as inhibiting glutamatergic signaling， modulating synaptic plasticity， and attenuating neuroinflammation. Esketamine may effectively alleviate acute and chronic pain in burn patients， reduce opioid consumption， and improve their mood and cognitive functions. This review summarizes the mechanism， clinical efficacy， and medication strategies of esketamine for burn injury-induced chronic pain. It also proposes stratified analgesia strategies based on burn severity， location， and patient age. The short-term and long-term safety profiles， as well as adverse effects associated with esketamine， are discussed， aiming to provide theoretical foundation and clinical reference for the precise application of esketamine in the management of burn injury-induced chronic pain.

White spot lesions （WSLs） represent a change in the optical properties of tooth enamel due to mineral loss， manifesting as a chalky appearance and serving as an early indicator of caries. Remineralization therapy， a non-invasive approach for managing early caries， aims to restore tooth structure and microhardness by inducing mineral deposition through the application of remineralizing agents to remineralize the partially demineralized tooth tissues. Fluoride contributes by forming a protective “fluoride reservoir” and promoting the deposition of fluorapatite； when fluoride is combined with biomaterials or antimicrobial agents， they demonstrate potential to synergistically enhance mineralized restorations while reducing toxicity risks. Biomineralizing substances also show promising applications in inducing enamel repair and maintaining biocompatibility. Additionally， natural ingredients， plant and animal extracts， can effectively synchronize dental hard tissue remineralization with oral microbial control. This review examines various remineralization therapeutic agents， including fluoride， biomineralizing substances， and plant and animal extracts， and elucidates their remineralization mechanisms， application characteristics， interactions， and therapeutic effects. The findings aim to provide a foundation for the remineralization treatment of WSLs.