Objective To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15 （Siglec15） derived from M2 tumor-associated macrophages （M2-TAMs） on promoting the malignant biological behavior of the esophageal squamous cell carcinoma （ESCC） through bioinformatics analysis， and to validate the findings through cell experiment. Methods The Tumor Immune Estimation Resource （TIMER） online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells. Based on the non-contact co-culture of M2-TAMs and ESCC cells， the following groups were set up，such as EC109/KYSE150 group， EC109/KYSE150+si-NC group （transfected with si-NC sequence）， and EC109/KYSE150+si-Siglec15 group （transfected with si-Siglec15#1 and si-Siglec15#2 sequences）. CCK-8 method was used to detect the proliferation activities of the cells in various groups； wound healing assay was used to detect the wound healing rates of the cells in various groups； Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups. Results The bioinformatics analysis results showed that compared with adjacent normal tissue， the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer， colon cancer， and head and neck squamous cell carcinoma tissues were increased （P<0.05 or P<0.01）， and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages （P<0.05）. Compared with the EC109 cells and KYSE150 cells， the expression level of Siglec15 mRNA in M2-TAMs was significantly increased （P<0.01）. There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group， EC109/KYSE150+si-NC group， and EC109/KYSE150+si-Siglec15 group （P>0.05）. Compared with EC109/KYSE150 group， after treated for 24 and 48 h， the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased （P<0.01）， the numbers of migration and invasion cells were increased （P<0.05）， and the apoptotic rate was decreased （P<0.01）. Compared with EC109/KYSE150+si-NC group， the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased （P<0.05）， the numbers of migration and invasion cells were decreased （P<0.05）， and the apoptotic rates of the cells had no significant difference （P>0.05）. Conclusion Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.

Objective To discuss the role of serum and glucocorticoid-induced protein kinase 3 （SGK3） in the resumption of the first meiotic division in the oocytes of the mice， and to preliminarily clarify the regulatory mechanism of SGK3 in the early development of mammalian oocytes. Methods The germinal vesicle （GV） stage mouse oocytes were obtained by superovulation techniques. The SGK3 mRNA， obtained from in vitro transcription of expression plasmids， was injected into the GV stage oocytes by microinjection techniques. The oocytes were divided into control group， Tris-EDTA buffer （TE） group， and SGK3 mRNA group. Western blotting method was used to detect the expression levels of SGK3 protein in the oocytes in various groups； the germinal vesicle breakdown（GVBD） rates of the oocytes in various groups were observed and calculated at 1， 2， 3， and 4 h after microinjection of SGK3 mRNA； the morphological appearance of the oocytes in various groups was observed by SGK3 antibody dilution inhibition experiment； Western blotting method was used to detect the expression levels of phosphorylated SGK3 （pSer48） （SGK3-pSer48） and phosphorylated cell division cycle protein 2 （CDC2） （pTyr15） （CDC2-pTyr15） proteins in the oocytes cultured in vitro at different time points. Results Compared with control group and TE group， the expression level of SGK3 protein in the oocytes in SGK3 mRNA group was increased （P<0.01）， and the GVBD rates at 1 and 2 h after microinjection were increased （P<0.01）. The SGK3 antibody dilution inhibition experiment results showed that as the increasing of concentration of SGK3 antibody， the GVBD rates of the oocytes in various groups were decreased in a concentration-dependent manner. After overexpressing SGK3， compared with control group， the time when CDC2-pTyr15 protein expression could not be detected in the oocytes in SGK3 mRNA group was advanced by at least 1 h. After treated with different concentrations of SGK3 antibody， compared with control group， as the increasing of concentration of SGK3 antibody and the extending of treatment time， the expression level of CDC2-pTyr15 protein in the oocytes was gradually decreased （P<0.01）， and the expression level of SGK3-pSer486 protein was gradually increased （P<0.01）. Conclusion Over-expression of SGK3 can increase the GVBD rate of oocytes of the mice and accelerate the dephosphorylation of CDC2-pTyr15， while the dephosphorylation of CDC2-pTyr15 is later than the phosphorylation of SGK3-Ser486. SGK3 likely serves as an upstream regulator of CDC2 and participates in controlling the resumption of the first meiotic division in the oocytes of the mice.

Objective To discuss the biological function of the spacer domain of ADAM metalloproteinase with thrombospondin type 1 motifs 13 （ADAMTS13） in the cleaving process of von Willebrand factor （vWF），and to clarify the role of ADAMTS13 in the pathogenesis of thrombotic thrombocytopenic purpura （TTP）. Methods The point mutation method was introduced sequentially into the amino acid residues TEDRLPR of the ADAMTS13 spacer domain （mutants M1－M7） by site-directed mutagenesis. The constructed ADAMTS13 and its mutants plasmids were transfected into the human embryonic kidney HEK293 cells， and the recombinant proteins were purified after stable expression. The cleavage capabilities of both wild type and mutant ADAMTS13 were observed under denaturation conditions， shear stress， and after treatment with ADAMTS13 antibodies. Results The fluorescence resonance energy transfer （FRET） assay results showed that compared with wild type ADAMTS13，the cleavage abilities of ADAMTS13 mutant M4 （R635A） and mutant M7 （R638A） on the FRET-vWF73 were decreased （P<0.05）. Under denaturation conditions， the wild-type ADAMTS13 could cleave the vWF multimers； compared with wild-type ADAMTS13， the cleavage activities of ADAMTS13 mutant M4 （R635A） and mutant M7 （R638A） were significantly decreased （P<0.01）. Under in vitro shear stress， compared with wild type ADAMTS13， the abilities of ADAMTS13 mutant M4 （R635A） and mutant M7 （R638A） to cleave vWF multimers were significantly decreased （P<0.01）. Compared with wild type ADAMTS13， the binding affinity between vWF and ADAMTS13 mutant M4 （R635A） and mutant M7 （R638A） had no significant difference （P>0.05）， indicating there were multiple binding sites between C-terminal of ADAMTS13 and vWF. The ADAMTS13 antibodies were able to inhibit the cleavage ability of both wild-type and mutant ADAMTS13 to some extent. Conclusion The activity of ADAMTS13 after spacer domain mutation is decreased. The ADAMTS13 mutant M4 （R635A） and mutant M7 （R638A） may be the important action sites for ADAMTS13 in substrate recognition.

Objective To discuss the effect of urolithin C （UC） on the proliferation， apoptosis， and autophagy of the acute myeloid leukemia （AML） HL-60 cells， and to clarify its mechanism. Methods The HL-60 cells were divided into different concentrations （20， 40， 60， 80， and 100 μmol·L^－1） of urolithin A （UA） groups， urolithin B （UB） groups， and UC groups. CCK-8 assay was used to detect the proliferation activity of the cells in various groups； the morphology of the cells in different concentrations of UC groups was observed under optical microscope. The HL-60 cells were divided into different concentrations （0， 20， 40， and 80 μmol·L^－1） of UC groups and 3-methyladenine （3-MA） combined with different concentrations （0， 20， 40， and 80 μmol·L^－1） of UC groups. CCK-8 assay was used to detect the proliferation activities of the cells in various groups.The HL-60 cells were divided into control group （0 μmol·L^－1） and different concentrations （20， 40， and 80 μmol·L^－1） of UC groups. The live/dead cell staining method was used to detect the dead rates of the cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups；the autophagy of the cells was detected by autophagy staining kit （monodansylcadaverine， MDC）method； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of Beclin 1， autophagy related gene 9 （ATG9）， and autophagy related gene 7 （ATG7） mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of cysteinyl aspartate specific proteinase-3 （Caspase-3）， cleaved cysteinyl aspartate specific proteinase-3 （Cleaved Caspase-3）， microtubule-associated protein 1 light 3 （LC-3）， extracellular regulated protein kinases （ERK）， phosphorylated ERK （p-ERK）， AMP-activated protein kinase （AMPK）， and phosphorylated AMPK （p-AMPK） in the cells in various groups. Results The CCK-8 assay results showed that after cultured for 24， 48， and 72 h， compared with 0 μmol·L^－1 UA， UB， and UC groups， the proliferation activities of the cells in different concentrations of UA， UB， and UC groups were decreased （P<0.01） with a concentration-and time-dependent manner； at 48 h， compared with UA and UB， the half-maximal inhibitory concentration （IC₅₀） of UC was the lowest.The cell morphology observation results showed that compared with control group， the intercellular connection and the number of the cells were decreased with the increasing of UC concentration， and the cell fragment was increased. The CCK-8 assay results showed that compared with 40 and 80 μmol·L^－1 UC groups，the proliferation activities of the cells in 3-MA combined with 40 and 80 μmol·L^－1 UC groups were increased （P<0.05 or P<0.01）. The live/dead cell staining results showed that compared with control group， the dead rates of the cells in 40 and 80 μmol·L^－1 UC groups were increased （P<0.01）. The flow cytometry results showed that compared with control group， the apoptotic rate of the cells in 80 μmol·L^－1 UC group was increased （P<0.01）. The MDC method results showed that with the increasing of UC concentration， the green fluorescence in the cells in different concentrations of UC groups was gradually intensified. The RT-qPCR results showed that compared with control group， the expression levels of Beclin 1， ATG9， and ATG7 mRNA in the cells in 80 μmol·L^－1 UC group were increased （P<0.01）. The Western blotting results showed that compared with control group， the expression levels of Cleaved Caspase-3 protein in the cells in 20， 40， and 80 μmol·L^－1 UC groups were increased （P<0.01）， the ratio of membrane LC3 / cytoplasmic LC3 （LC3-Ⅱ/LC3-Ⅰ） in the cells in 80 μmol·L^－1 UC group was increased （P<0.05）， and the ratios of p-AMPK/AMPK and p-ERK/ERK in the cells in 40 and 80 μmol·L^－1 UC groups were increased （P<0.01）. Conclusion UC can inhibit the proliferation of the AML HL-60 cells，induce the apoptosis and autophagy， and increase the phosphorylation levels of ERK and AMPK proteins in the cells.

Objective To discuss the effect of oridonin on the proliferation， migration， epithelial-mesenchymal transition （EMT）， and apoptosis of the human nasopharyngeal carcinoma HONE-1 cells， and to clarify its related antitumor mechanism. Methods The HONE-1 cells were treated with different concentrations （0， 5， 10， 20， 40， 80， and 160 mg·L^-1） of oridonin for 48 h. CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups and the drug concentration for subsequent experiment was confirmed.The HONE-1 cells were divided into control group， 3 mg·L^-1 oridonin group， and 6 mg·L^-1 oridonin group. After 24 and 48 h of culture， CCK-8 method was used to detect the proliferation activities of the cells in various groups； 5-ethynyl-2'-deoxyuridine （EdU） method was used to detect the rates of EdU-positive cells in various groups； colony formation assay was used to detect the numbers of clone formation in the cells in various groups； Transwell chamber experiment and cell wound assay were used to detect the numbers of migration cells and the scratch healing rates of the cells in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of cyclin-dependent kinase 1 （CDK1） and cyclin-dependent kinase 4 （CDK4） mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of E-cadherin， Vimentin， Caspase-3， and poly ADP-ribose polymerase 1 （PARP1） proteins in the cells in various groups. Results The CCK-8 method results showed that the half-maximal inhibitory concentration （IC₅₀） of oridonin at 48 h was 12.18 mg·L^-1，and 1/4 IC₅₀ and 1/2 IC₅₀ values were used as the concentrations for subsequent experiments. Compared with control group， after treated for 24 and 48 h， the proliferation activities of the cells in 3 and 6 mg·L^-1 oridonin groups were decreased （P<0.05 or P<0.01）， the rate of EdU-positive cells were decreased （P<0.05 or P<0.01）， the numbers of clone formation and migraton cells were decreased （P<0.05 or P<0.01）， the scratch healing rates were decreased （P<0.05 or P<0.01）， the expression levels of CDK1 and CDK4 mRNA in the cells were decreased （P<0.05 or P<0.01）， the expression levels of E-cadherin， Caspase-3， and PARP1 proteins were increased （P<0.05 or P<0.01）， and the expression levels of Vimentin protein were decreased （P<0.05）. Conclusion Oridonin can inhibit the proliferation， clone formation， and migration of the human nasopharyngeal carcinoma HONE-1 cells by downregulating the expression of cell cycle-related proteins and EMT， and promote the apoptosis to exert an antitumor effect.

Objective To preliminarily predict the potential pathways and targets of Xiaoban Tongmai Formula in anti-atherosclerosis （AS） by network pharmacology analysis， and to verify its possible mechanism combined with in vitro cell experiment. Method The databases including Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， GeneCards， Swiss Target Prediction， and Uniprot were used to collect the information on active compounds and corresponding targets of Xiaoban Tongmai Formula to construct the “compound-target-disease” network. The potential targets and pathways were predicted by protein-protein interaction （PPI） network， and the intersection targets were subjected to Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis.The human aortic vascular smooth muscle cells （HA-VSMCs） were cultured and identified in vitro， and the abnormal proliferation of HA-VSMCs were induced by oxidized low-density lipoprotein（ox-LDL） and identified； MTT method was used to detect the proliferation activities of the HA-VSMCs in various groups after treated with different concentrations of Xiaoban Tongmai Formula；the safety of Xiaoban Tongmai Fang was confirmed. The HA-VSMCs were divided into blank group， model group （the abnormal proliferation of HA-VSMCs was induced）， rosuvastatin group （treated with 4 μmol·L^-1 rosuvastatin after inducing the abnormal proliferation of HA-VSMCs）， and low， medium， and high doses of Xiaoban Tongmai Formula groups （treated with 0.025， 0.050， and 0.100 mg·L^-1 Xiaoban Tongmai Formula after inducing the abnormal proliferation of HA-VSMCs）；enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of monocyte chemotactic protein-1（MCP-1）， interleukin-6（IL-6）， and interleukin-8（IL-8） in supernatant of the HA-VSMCs in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of nuclear factor kappa-B（NF-κB） p65 mRNA and fibroblast growth factors 2（FGF2） mRNA in the HA-VSMCs in various groups； Western blotting method was used to detect the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in various groups. Results Xiaoban Tongmai Formula contained 103 active ingredients that exert anti-AS effect by acting on 189 target genes. The potential targets included IL-6， IL-8， vascular endothelial growth factor A（VEGFA）， nuclear factor kappa B1（NF-κB1）， and RELA （NF-κB p65）. The GO functional analysis and KEGG pathway enrichment analysis results showed that Xiaoban Tongmai Formula exerted anti-AS effects by regulating lipid metabolism， hypoxia-inducible factor-1（HIF-1）， epidermal growth factor（EGF）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）， and NF-κB signaling pathways.The cell morphology and immunofluorescence staining results confirmed that the cells were HA-VSMCs. The oil red O staining results showed numerous red lipid droplets， indicating successful modeling. The MTT assay results showed that Xiaoban Tongmai Formula had no significant effect on the proliferation rate of HA-VSMCs within a certain dose range， indicating good safety. The ELISA results showed that compared with model group， the levels of MCP-1 and IL-6 in supernatant of the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased （P<0.05 or P<0.01）， and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L^-1 Xiaoban Tongmai Formula groups were decreased （P<0.01）； compared with rosuvastatin group， the levels of MCP-1 in supernatant of the HA-VSMCs in different doses of Xiaoban Tongmai Formula groups were decreased （P<0.01）， and the levels of IL-8 in supernatant of the HA-VSMCs in 0.050 and 0.100 mg·L^-1 Xiaoban Tongmai Formula groups were decreased （P<0.01）. Compared with model group， the expression levels of NF-κB p65 mRNA in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased （P<0.01）， and the expression levels of FGF2 mRNA in the HA-VSMCs in rosuvastatin group and 0.050 and 0.100 mg·L^-1 Xiaoban Tongmai Formula groups were decreased （P<0.01）； compared with rosuvastatin group， the expression levels of NF-κB p65 and FGF2 mRNA in the HA-VSMCs in 0.050 and 0.100 mg·L^-1 Xiaoban Tongmai Formula groups were decreased （P<0.05 or P<0.01）. Compared with model group， the expression levels of NF-κB p65 and FGF2 proteins in the HA-VSMCs in rosuvastatin group and different doses of Xiaoban Tongmai Formula groups were decreased （P<0.01）； compared with rosuvastatin group， the expression levels of NF-κB p65 protein in the HA-VSMCs in 0.050 and 0.100 mg·L^-1 Xiaoban Tongmai Formula groups were decreased （P<0.01）， and the expression level of FGF2 protein in the HA-VSMCs in 0.100 mg·L^-1 Xiaoban Tongmai Formula group was decreased （P<0.01）. Conclusion Xiaoban Tongmai Formula has anti-inflammatory effect， inhibitory effect on the proliferation of HA-VSMCs， and anti-AS effect，and its mechanism may be related to the inactivation of NF-κB/FGF2 pathway.

Objective To discuss the effect of temperature-controlled shrinkage polytrimethylene carbonate （PTMC）/polyvinylpyrrolidone （PVP） nanofiber membrane on the biological behavior of mouse fibroblasts and the repairment effect on full-thickness skin defects in the rats， and to clarify the potential mechanism. Methods The murine L929 fibroblast cells were used in the in vitro experiments and were divided into control group and experimental group （treated with PTMC/PVP nanofiber membranes）. The proliferation activities of the cells in two groups were detected by CCK-8 assay； the numbers of live/dead cells in two groups were observed by live/dead cell staining； the morphology of the cells was observed by cytoskeletal staining. A total of 12 six-week-old male SD rats were selected in the in vivo experiment， and were randomly divided into control group and experimental group， and there were six rats in each group. The full-thickness skin defect model was established， and the rats in experimental group were treated with PTMC/PVP nanofiber membranes. The photographs were taken after operation， and the wound healing rates of the cells in two groups were calculated on the 0， 3rd， 6th， and 12th days. On the 6th and 12th days after operation， the skin samples around the wound of the rats in two groups were taken， and the histopathology of the would skin and adjacent tissue was detected by HE staining； the collagen deposition in wound skin tissue of the rats in two groups was observed by Masson trichrome staining； the numbers of angiogenesis in wound skin tissue of the rats were detected by CD31 immunohistochemical staining. Results The CCK-8 assay results showed that the proliferation activity of the cells in experimental group showed an increasing trend on the 1st, 3st, and 5st days, and there was no significant difference in the proliferation activities of the cells bewteen experimental group and control group (P>0.05). The live/dead cell staining experiment results showed that compared with control group, the cell density and number of the cells in experimental group had no significant changes, and were predominantly live cells. The cytoskeletal staining results showed that the cells in experimental and control groups appeared spindle-shaped and well-spread. In the in vivo experiments, on the 3rd, 6th, and 12th days, compared with control group, the wound healing rates of the cells in experimental group were increased (P<0.01), and the wound healing rate of the cells was 95.45% on the 12th day, indicating nearly complete healing of the wound. The HE staining showed that on the 12th day, the wound skin structure of the cells in experimental group was more similar to the normal skin, and there was abundant granulation tissue, regular epidermal structure, and new blood vessel formation. The Masson trichrome staining results showed that compared with control group, the collagen deposition in wound tissue of the rats in experimental group was increased. The immunohistochemical staining results showed that the expression of CD31 in wound tissue of the rats in experimental group was increased, indicating the increasing of the number of angiogenesis. Conclusion The PTMC/PVP thermoresponsive nanofiber membranes exhibit good biocompatibility and can promote the repairment of full-thickness skin defects in the rats； its mechanism may be related to the enhancement of proliferation activity of the basal cells.

Objective To discuss the effect of downregulating microRNA-208a（miR-208a） on the resistance of the colorectal cancer cells to 5-fluorouracil （5-FU）， and to clarify its related molecular mechanism. Methods Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of miR-208a and secreted frizzled-related protein 1 （SFRP1） mRNA in the 5-FU-resistant colorectal cancer cell line HT-29/5-FU and its parent HT-29 cells. The HT-29/5-FU cells were transfected with miR-208a inhibitor plasmid and its negative control plasmid （inhibitor-NC）， and SFRP1 small interfering RNA （si-SFRP1） and its negative control plasmid （si-NC）， either separately or in combination， followed by treatment with 5-FU. The cells were divided into inhibitor-NC group， miR-208a inhibitor group， miR-208a inhibitor+si-NC group， and miR-208a inhibitor+si-SFRP1 group. MTT assay was used to detect the proliferation activities of the cells and the resistance indexes were calculated； Annexin Ⅴ-FITC/PI double staining and flow cytometry were used to detect the apoptotic rates of the cells after treated with different concentrations of 5-FU； Western blotting method was used to detect the expression levels of SFRP1， β-catenin， P-glycoprotein （P-gp）， and ATP-binding cassette subfamily B member 1 （ABCB1） proteins in the cells in various groups； dual-luciferase reporter gene assay was used to validate the targeting relationship between miR-208a and SFRP1. Results Compared with HT-29 cells， the expression level of miR-208a in the HT-29/5-FU cells was increased （P<0.05）， and the expression level of SFRP1 mRNA was decreased （P<0.05）. Compared with inhibitor-NC group， the proliferation activity of the cells in miR-208a inhibitor group was decreased （P<0.05）， the resistance index was decreased， the apoptotic rate was increased （P<0.05）， and the expression levels of β-catenin， P-gp，and ABCB1 proteins in the cells were decreased （P<0.05）. The dual-luciferase reporter gene assay results showed that SFRP1 was a target gene of miR-208a and miR-208a could negatively regulate the expression of SFRP1. Compared with miR-208a inhibitor+si-NC group， the proliferation activity of the cells in miR-208a inhibitor+si-SFRP1 group was increased （P<0.05）， the resistance index was increased， the apoptotic rate was decreased（P<0.05）， and the expression levels of β-catenin， P-gp， and ABCB1 proteins in the cells were increased （P<0.05）. Conclusion Downregulation of miR-208a can improve the resistance of the HT-29/5-FU cells to 5-FU by targeting and upregulating the SFRP1 expression， thereby inhibiting the transmission of the Wnt signaling pathway.

Objective To discuss the effect of mangiferin （MGF） on the healing of hip fracture in the rats by regulating the Wnt/β-catenin signaling pathway， and to clarify the mechanism. Methods The hip fracture model in the SD rats was established. After successful modeling， the rats were divided into model group， MGF group， and MGF+XAV-939 （Wnt/β-catenin signaling pathway inhibitor） group， and sham operation group was set up， and there were 15 rats in each group. From the first day after surgery， the rats in each group received MGF or XAV-939 interventions every two days， totally for 14 times. Lane-Sandhu X-ray scoring method was used to detect the fracture healing in the second and fourth weeks after surgery； micro CT was used to detect the microstructural parameters of the bone， such as bone volume （BV）， number of bone trabeculae （Tb.N）， bone volume fraction （BV/TV）， and bone trabecular thickness （Tb.Th）； HE staining was used to observe the morphology of callus tissue of the rats in various groups； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of osteogenic markers bone alkaline phosphatase （BALP） and type Ⅰ procollagen N-terminal propeptide （PINP） and bone resorption markers tartrate resistant acid phosphatase-5b （TRACP-5b） and Carboxy-terminal terminalpeptide of type Ⅰ collagen （CTX） in serum of the rats in various groups；Western blotting method was used to detect the expression levels of β-catenin， Runt-associated transcription factor 2 （Runx2）， and bone morphogenetic protein-2 （BMP-2） in callus tissue of the rats in various groups. Results Compared with sham operation group， the rats in model group showed distinct fracture lines， an abundance of fibrous tissue at the fracture site， and no bony callus at the 2nd and 4th weeks after fracture， the Lane-Sandhu X-ray scores and microstructural parameters BV， Tb.N， BV/TV， and Tb.Th of the rats in model group were decreased （P<0.05），the serum level of BALP was decreased （P<0.05）， while the levels of PINP， TRACP-5b， and CTX were increased （P<0.05），and the expression levels of β-catenin， Runx2， and BMP-2 proteins in callus tissue were decreased （P<0.05）. Compared with model group， the rats in MGF group showed significantly increased new bone callus at 2nd weeks after fracture， almost no visible fracture line at the 4th weeks， faster fracture healing， and replacement of fibrous tissue by bone tissue at the fracture site， the Lane-Sandhu X-ray scores and microstructural parameters BV， Tb.N， BV/TV， and Tb.Th of the rats in MGF group were increased （P<0.05）， the serum level of BALP was increased （P<0.05）， the levels of PINP， TRACP-5b， and CTX were decreased （P<0.05），and the expression levels of β-catenin， Runx2， and BMP-2 proteins in callus tissue were increased （P<0.05）. Compared with MGF group， the rats in MGF+XAV-939 group showed only a small amount of new bone callus at the fracture site at 2nd and 4th weeks after fracture， with no formation of the marrow cavity， and the Lane-Sandhu X-ray scores and microstructural parameters BV， Tb.N， BV/TV， and Tb.Th of the rats in MGF+XAV-939 group were decreased （P<0.05）， the serum level of BALP was decreased （P<0.05）， the levels of PINP， TRACP-5b， and CTX were increased （P<0.05），and the expression levels of β-catenin， Runx2， and BMP-2 proteins in callus tissue were decreased （P<0.05）. Conclusion MGF can promote the healing of hip fracture in the rats， and its mechanism may be related to activation of Wnt/β-catenin signaling pathway.

Objective To discuss the protective effect of velvet antler peptide （VAP） on the postmenopausal osteoporosis （PMOP） model rats，and to clarify its possible mechanism. Methods A total of 60 twelve-week-old female SD rats were randomly divided into sham operation group， model group， alendronate sodium group （1 mg·kg?1·d?1 alendronate sodium administered via gavage）， low dose of VAP group （100 mg·kg?1·d?1 VAP administered via gavage）， medium dose of VAP group （200 mg·kg?1·d?1 VAP administered via gavage）， and high dose of VAP group （300 mg·kg?1·d?1 VAP administered via gavage）， and there were 10 rats in each group. Except for the sham operation group， the rats in the other groups underwent bilateral ovariectomy to establish the PMOP rat models. Dual-energy X-ray absorptiometry was used to detect the femur bone mineral density （BMD） of the rats in various groups；enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of serum calcium （Ca²⁺）， serum phosphorus （P）， bone alkaline phosphatase （BALP）， and procollagen type Ⅰ N-terminal propeptide （PINP） of the rats in various groups； Kits were used to detect the activities of superoxide dismutase （SOD） and the levels of malondialdehyde （MDA） of the rats in various groups； HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups； Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， phosphorylated PI3K （p-PI3K）， protein kinase B （AKT）， and phosphorylated AKT （p-AKT） proteins in bone tissue of the rats in various groups. Results Compared with sham operation group， the BMD in femur of the rats in model group was decreased （P<0.01）； compared with model group， the BMD in femur of the rats in alendronate sodium group， medium dose of VAP group， and high dose of VAP group was increased （P<0.05 or P<0.01）. Compared with sham operation group，the levels of Ca2?， P， BALP， PINP， and SOD activity in serum of the rats in model group were decreased （P<0.05 or P<0.01）， and the MDA level was increased （P<0.01）； compared with model group， the level of P in serum of the rats in medium dose of VAP group was increased （P<0.01）， and the levels of Ca2?， P， BALP， PINP and the activities of SOD in serum of the rats in alendronate sodium group and high dose of VAP group were increased （P<0.05 or P<0.01）， and the level of MDA in serum was decreased （P<0.05）. The HE staining results showed that compared with sham operation group， the bone trabeculae in bone tissue of the rats in model group were thin and fractured， and the medullary cavity was enlarged； compared with model group， the bone trabeculae in bone tissue of the rats in alendronate sodium group， medium dose of VAP group， and high dose of VAP group were thick and tightly arranged， and had more osteocytes. The Western blotting results showed that compared with sham operation group， the ratios of p-PI3K/PI3K and p-AKT/AKT in bone tissue of the rats in model group were decreased （P<0.01）； compared with model group， the ratios of p-PI3K/PI3K in bone tissue of rats in different doses of VAP groups were increased （P<0.05 or P<0.01）， and the ratios of p-AKT/AKT of the rats in alendronate sodium group and high dose of VAP group was increased （P<0.01）. Conclusion VAP can improve PMOP in the rats， and its mechanisms may be related to the regulation of the PI3K/AKT signaling pathway and the reduction of oxidative stress in bone tissue by VAP.

Objective To use pan-genomics and subtractive proteomics techniques to screen the new antibacterial targets from the Staphylococcus aureus genome， and to lay the foundation for the development of anti-Staphylococcus aureus drugs. Methods The genome sequencing data of 50 strains with sequencing level Complete were collected by searching the whole genome sequencing data in the National Center for Biotechnology Information （NCBI） Database with Staphylococcus aureus as the keyword；BPGA tool was used to conduct the pan-genomics analysis on the genomic data to obtain the core genes of Staphylococcus aureus； subtractive proteomics technique was used to screen the potential antibacterial targets from the core genes. These potential antibacterial targets were used as the receptors； LibDock software was used to screen the potential anti-Staphylococcus aureus drugs from the US Food and Drug Administration （FDA）-approved drug library； molecular docking technology was used to analyze the binding abilities of the drugs and targets. Results There were 14 379 gene families in the 50 Staphylococcus aureus genomes， of which 1 620 were the core genes. The subtractive proteomics analysis results showed that tyrosine autokinase 1335 was the potential anti-Staphylococcus aureus target. LibDock software screened out nine compounds， including balofloxacin， tenofovir disoproxil fumarate， and adefovir， that may exert anti-Staphylococcus aureus effects on this target protein. The molecular docking results showed there was good binding abilities between the targets and the compounds. Conclusion Tyrosine autokinase may be the potential target for anti-Staphylococcus aureus.

Objective To discuss the effect of exosome （Exo） microRNA-761 （miR-761） on the epithelial-mesenchymal transition （EMT） process of the osteosarcoma （OS） cells by regulating tumor-associated macrophage （TAM） polarization， and to clarify its related mechanism. Methods The miR-761 plasmid and negative control （miR-NC） plasmid were transfected into the HEK293 cells， and the non-transfected cells were regarded as control group. The transfection efficiency was detected using real-time fluorescence quantitative PCR （RT-qPCR） method.The Exo containing miR-761 was isolated， and the morphology of Exo was observed by transmission electron microscope. The concentration and size distribution of Exo samples were detected by nanoparticle analyzer， and the expression of Exo surface marker protein was detected by Western blotting method.The human monocyte leukemia THP-1 cells were stimulated with phorbol 12-myristate 13-acetate （PMA） to become the M0 macrophages， which were then treated with Exo containing miR-761 and co-cultured with the OS MG63 cells to establish the co-culture system. The experiment was divided into M0 group， TAM group， miR-761 NC group， and miR-761 Exo group. The M0 macrophages were collected from various groups， and the positive rates of M1 macrophage marker CD86 and M2 macrophage marker CD206 in various groups were detected by flow cytometry； the protein expression levels of M1 macrophage secreted factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） and M2 macrophage secreted factors interleukin-10 （IL-10） and transforming growth factor-β1 （TGF-β1） in various groups were detected by Western blotting method. The M0 macrophages were treated with Exo containing miR-761 and co-cultured with MG63 cells to establish the co-culture system. The experiment was divided into control group， TAM group， miR-NC Exo+TAM group， and miR-761 Exo+TAM group. The MG63 cells in various groups were collected， and the fluorescence intensities of E-cadherin and Vimentin in the MG63 cells in various groups were observed by immunofluorescence staining； the expression levels of E-cadherin， Vimentin， and EMT regulation-related transcription factors Twist1， Snail， and Slug proteins in the cells in various groups were detected by Western blotting method；the numbers of invasion and migration cells in various groups were detected by Transwell chamber assay. Results The HEK293 cells containing miR-761 were successfully obtained by transfection experiments， and the Exo was isolated. Compared with M0 group， the positive rate of CD86 of the macrophages in TAM group was decreased （P<0.05）， while the positive rate of CD206 was increased （P<0.05）， the expression levels of IL-1β and TNF-α proteins were decreased （P<0.05）， while the expression levels of IL-10 and TGF-β1 proteins were increased （P<0.05）. Compared with TAM group， the positive rate of CD86 of the macrophages in miR-761 Exo group was increased （P<0.05）， while the positive rate of CD206 was decreased （P<0.05）， the expression levels of IL-1β and TNF-α proteins were increased （P<0.05）， while the expression levels of IL-10 and TGF-β1 proteins were decreased （P<0.05）. Compared with control group， the fluorescence intensity of E-cadherin in the MG63 cells in TAM group was decreased， while the fluorescence intensity of Vimentin was increased， the expression level of E-cadherin protein was decreased （P<0.05）， while the expression levels of Vimentin， Twist1， Snail， and Slug proteins were increased （P<0.05）， and the numbers of invasion and migration cells were increased （P<0.05）. Compared with TAM group， the fluorescence intensity of E-cadherin in the MG63 cells in miR-761 Exo+TAM group was increased， while the fluorescence intensity of Vimentin was decreased， the expression level of E-cadherin protein was increased （P<0.05）， while the expression levels of Vimentin， Twist1， Snail， and Slug proteins were decreased （P<0.05）， and the numbers of invasion and migration cells were decreased （P<0.05）. Conclusion The exo-delivered miR-761 can inhibit the EMT process of the OS cells， thereby inhibiting the cell migration and cell invasion； its mechanism may be related to regulating TAM polarization.

Objective To investigate the effect of myogenic differentiation protein 1 （Myod1） on the proliferation inhibition and apoptosis of the SH-SY5Y cells induced by oxygen-glucose deprivation （OGD）， and to elucidate its mechanism. Methods Real-time quantitative fluorescence PCR （RT-qPCR） method was used to detect the mRNA levels of Myod1 and long non-coding RNA （lncRNA） small nucleolar RNA host gene 15 （SNHG15） in peripheral blood of the subjects in normal group and the patients in ischemic cerebral infarction group as well as the normal cultured SH-SY5Y cells（control group） and the cells in OGD model （OGD group）. After transfecting SH-SY5Y cells with si-Myod1， pcDNA3.0-Myod1， si-SNHG15， pcDNA3.0-SNHG15、si-NC， Vector， miR-NC， and miR-24-3p mimics， the cells were treated with OGD， and then the SH-SY5Y cells were divided into control group， OGD group， OGD+Vector group， OGD+Myod1 group， OGD+si-NC group， OGD+si-Myod1 group， OGD+si-SNHG15 group， OGD+si-SNHG15+Vector group， OGD+si-SNHG15+Myod1 group， OGD+miR-NC group， OGD+miR-mimics group， OGD+miR-mimics+Vector group， and OGD+miR-mimics+SNHG15 group. CCK-8 method was used to detect the cell activities in various groups； 5-ethynyl-2'-deoxyuridine （EdU） staining was used to detect the rates of EDU positive cells in various groups； the rates of TdT-mediated dUTP nick end labeling （TUNEL） positive cells in various groups were detected by TUNEL staining； Western blotting method was used to detect the expression levels of cleaved caspase-3， cleaved caspase-9， B-cell lymphoma 2 （Bcl-2） and Bcl-2 associated X protein （Bax） proteins in the cells in various groups； the association between Myod1 and SNHG15 was evaluated by chromatin immunoprecipitate （CHIP）； dual luciferase reporter gene experiment was used to evaluate the targeting relationships between Myod1 and SNHG15 as well as SNHG15 and miR-24-3p. Results Compared with normal control group， the expression levels of Myod1 and SNHG15 mRNA in peripheral blood of the patients in ischemic cerebral infarction group were significantly increased （P<0.05）. Compared with control group， the expression levels of Myod1 and SNHG15 mRNA in the SH-SY5Y cells in OGD group were significantly increased （P<0.05）. Compared with OGD group， the cell activities and rates of EdU positive cells in OGD+Myod1 group at 48 and 72 h were decreased （P<0.01）， and the rates of TUNEL positive cells were increased （P<0.05）； the cell activities and rates of EdU positive cells in OGD+si-Myod1 group were increased （P<0.05）， while the rates of TUNEL positive cells were decreased （P<0.01）. Myod1 binded to the promoter sequence of SNHG15. SNHG15 could absorb miR-24-3p， and there were target relatronships between Myod1 and SNHG15 as well as SNHG15 and miR-24-3p. After SNHG15 knockdown， compared with OGD group， the cell activities and rates of EdU positive cells in OGD+si-SNHG15 group at 48 and 72 h were increased （P<0.01）， and the rates of TUNEL positive cells were decreased （P<0.01）， the expression levels of Bax， cleaved caspase-3 and cleaved caspase-9 proteins were decreased （P<0.01）， and the expression levels of Bcl-2 protein were increased （P<0.01）. Compared with OGD+si-SNHG15 group， the cell activities and rates of EdU positive cells in OGD+si-SNHG15+Myod1 group at 48 and 72 h were decreased （P<0.05）， the rates of TUNEL positive cells were （P<0.05）， the expression levels of Bax， cleaved caspase-3， and cleaved caspase-9 proteins were increased （P<0.05）， and the expression levels of Bcl-2 were decreased （P<0.05）. After over-expression of miR-24-3p and SNHG15， compared with OGD group， the cell activities and rates of EdU positive cells in OGD+miR-mimics group at 48 and 72 h were increased （P<0.01）， the rates of TUNEL positive cells were significantly decreased （P<0.01）， the protein expression levels of Bax， cleaved caspase-3 and cleaved caspase-9 were decreased （P<0.05）， and the expression levels of Bcl-2 were increased （P<0.01）. Compared with OGD+miR-mimics group， the cell activities and rates of EdU positive cells in OGD+miR-mimics+SNHG15 group at 48 and 72 h were decreased （P<0.05）， and the rates of TUNEL positive cells were increased （P<0.05）， the expression levels of Bax， cleaved caspase-3 and cleaved caspase-9 proteins were increased （P<0.05）， and the expression levels of Bcl-2 protein were decreased （P<0.05）. Conclusion Myod1 can promote the proliferation inhibition and apoptosis of OGD-induced SH-SY5Y cells by binding to the SNHG15 promoter region and then absorbing miRNA-24.

Objective To observe the effect of human mesenchymal stem cells （hMSCs） conditioned medium （CM） co-cultured with the human liposarcoma SW872 cells on the proliferation and migration of the tumor cells， and to discuss the effect of hMSCs CM on the liposarcoma cells and the possible mechanism. Methods The hMSCs were cultured in vitro and transfected with either lentiviral vector control shNS （control group） or lentiviral shRNA targeting Yes-associated protein （YAP） （shYAP-hMSCs group） by lentiviral methods. The expression levels of YAP mRNA and protein in the hMSCs in various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods. The CM was then harvested. The SW872 cells were cultured in vitro and divided into control group （normal culture）， hMSCs CM group， and shYAP-hMSCs CM group. The proliferation activities of the cells in various groups were detected by CCK-8 assay； the apoptotic rates of the cells in various groups were detected by flow cytometry； the scratch healing rates of the cells in various groups were detected by cell scratch assay； the expression levels of YAP， matrix metallopeptidase-9 （MMP-9）， and cyclin D1 proteins in the cells in various groups were detected by Western blotting method. Results Compared with control group， the expression levels of YAP mRNA and protein in the cells in shYAP-hMSCs group were decreased （P<0.01）， indicating the successful establishment of a stable transfected cell line. The CCK-8 assay results showed that compared with control group， the proliferation activity of the cells in hMSCs CM group was increased （P<0.05）， and the proliferation activity of the cells in shYAP-hMSCs CM group was decreased （P<0.01）. The flow cytometry results showed that compared with control group， there was no significant change in the apoptotic rate of the cells in hMSCs CM group （P>0.05）， while the apoptotic rate of the cells in shYAP-hMSCs CM group was increased （P<0.01）. The cell scratch assay results showed that compared with control group，the scratch healing rate of the cells in hMSCs CM group was increased （P<0.05）， and the scratch healing rate of the cells in shYAP-hMSCs CM group was decreased （P<0.01）. The Western blotting results showed that compared with control group， there were no significant differences in the expression levels of YAP， MMP-9， and cyclin D1 proteins in the cells in hMSCs CM group （P>0.05）， while the expression levels of YAP， MMP-9， and cyclin D1 proteins in the cells in shYAP-hMSCs group were decreased （P<0.05 or P<0.01）. Conclusion The hMSCs regulate the proliferation and migration of the human liposarcoma SW872 cells， and its mechanism may be related to the expression of YAP.

Objective To discuss the synergistic inhibitory effect of apatinib mesylate （apatinib） combined with radiotherapy （RT） on the hepatocellular carcinoma （HepG2） cells in vitro， and to clarify its related antitumor mechanism. Methods The HepG2 cells were cultured in vitro and treated with different concentrations of apatinib and/or varying doses of X-rays. MTT method was used to detect the survival rates of the cells in various groups； the inhibitory rates of cell proliferation and the 20% inhibitory concentration （IC₂₀） of apatinib were calculated； the X-ray irradiation dose for subsequent experiments was detected. The HepG2 cells were divided into apatinib group， RT group， and apatinib+RT group （combined group）. Flow cytometry was used to detect the apoptotic rates of the cells in various groups； wound healing assay was used to detect the migration rates of the cells in various groups； ELISA method was used to detect the levels of vascular endothelial growth factor （VEGF） in the cell culture supernatant in various groups. Results The MTT results showed that the IC₂₀ of apatinib was 1.32 μmol·L^-1， and this concentration was used for subsequent experiments， and the X-ray irradiation dose for the follow-up experiments was 2 Gy. Compared with control group， the apoptotic rates of the cells in apatinib group and RT group had no significant differences （P>0.05）， while the apoptotic rate of the cells in combined group was increased （P<0.05）. Compared with control group， the migration rates of the cells in apatinib group， RT group， and combined group were decreased （P<0.05）； compared with apatinib group and RT group， the migration rate of the cells in combined group was decreased （P<0.05）. Compared with control group， the levels of VEGF in the cell culture supernatant in apatinib group and combined group were decreased （P<0.05）； compared with apatinib and RT group， the level of VEGF in the cell culture supernatant in combined group was decreased （P<0.05）. Conclusion Apatinib combined with radiotherapy significantly inhibits the proliferation and migration of the HepG2 cells in vitro and induces the apoptosis； its effect may be related to the inhibition of VEGF secretion by cells.

Objective To explore the spatial support capacity and its influence in osteogenic effect of composite biofilm based on poly（propylene carbonate） （PPC） /poly（butylene succinate） （PBS） in rabbit tibial bone defect models， and to clarify its barrier functional reliability and osteogenetic effect in vivo. Methods The composite biofilms of PPC/PBS and PPC/PBS/collegen type Ⅰ （Col-Ⅰ）（PPC/PBS/Co） were prepared.Eighteen Japanese big-ear rabbits were selected and two bone defects were prepared on each side of the tibia of the rabbits. Six rabbits were randomly selected to place PPC/PBS composite biofilm on the bone defects， 2 rabbits were executed at 2， 4， 8 and 12 weeks after operation， and the surface microstructures of PPC/PBS composite biofilm in the rabhit bone defect area were observed by scanning electron microscope （SEM）. The experiment was divided into blank control group， PPC/PBS composite biofilm group， BME-10X collagen membrane group， and PPC/PBS/Co composite biofilm group. The above biofilms were placed on the corresponding bone defects of rabbits by operation， while no biofilm was placed in the rabbits in blank control group. Three rabbits were killed at 2， 4， 8 and 12 weeks after operation respectively， and the gray values of regenerated bone in the bone defect areas of the rabbits in varrous groups were detected by soft X-ray； the fluorescence intensities of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by laser scanning confocal microscope after fluorescence labeling. The pathomorphology of regenerated bone tissue in the bone defect areas of the rabbits in various groups were observed by HE staining and modified Gomori staining， and the expression levels of bone morphogenetic protein 2 （BMP-2） and osteopontin （OPN） in the regenerated bone tissue in bone defect areas of the rabbits in various groups were detected by immunohistochemical staining. Results In general， the PPC/PBS composite biofilm was tightly covered in the bone defect area without displacement and collapse. The SEM results showed that the porous surface of PPC/PBS composite biofilm appeared micropore structure and the number of micropores was increased with the prolongation of time， while the smooth surface of biofilm basically did not form the micropore-like structure. The results of soft X-ray detection showed that the gray values of regenerated bone tissue in bone defect areas of the rabbits in various groups were increased with the prolongation of time， and the gray value of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was significantly higher than those in other groups （P<0.05）. The confocal micrscope results showed that the fluorescence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group was similar to those in blank control group at 4， 8， and 12 weeks； compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group， the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits in PPC/PB/Co composite biofilm group at 4 weeks was increased （P<0.05）， and the fluoresence intensity of regenerated bone tissue in bone defect areas of the rabbits at 8 and 12 weeks were decreased （P<0.05）. The results of HE staining and modified Gomori staining showed that compared with PPC/PBS composite biofilm group and BME-10X collagen membrane group， the new bone formed faster in PPC/PBS/Co composite biofilm group and blank control group at 2 and 4 weeks， and the lamellar bone mineralization was higher at 12 weeks. The immunohistochemical staining results showed that compared with blank control group， PPC/PBS composite biofilm group and BME-10X collagen membrane group， the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in PPC/PBS/Co composite biofilm group at 2 and 4 weeks were increased （P<0.05 or P<0.01）； compared with blank control group and PPC/PBS composite biofilm group， the expression levels of BMP-2 and OPN proteins in the regenerated bone tissue in bone defect areas of the rabbits in BME-10X collage membrane group were decreased （P<0.05 or P<0.01）. Conclusion PPC/PBS composite biofilm has excellent spatial support capacity and reliable physical barrier function. The PPC/PBS/Co composite biofilm has a good effect in guiding bone regeneration in vivo.

Objective To discuss the effect of the small ubiquitin-like modifier-specific protease 1 （SENP-1）/hypoxia-inducible factor 1α （HIF-1α） pathway on chronic intermittent hypoxia （CIH）-induced vascular endothelial injury in the rats， and to clarify the related mechanism. Methods The SD rats were randomly divided into control group and CIH group， and then the rats in each group were further divided into 2， 4， and 6-week subgroups， and there were 8 rats in each subgroup. The rats in CIH group were exposed to CIH in a CIH chamber to induce CIH and create the obstructive sleep apnea hypopnea syndrome （OSAHS） models， while the rats in control group were exposed to normoxic conditions.The serum and thoracic aorta tissue of the rats in various groups were collected at each time point. HE staining was used to observe the thoracic aorta vascular injury of the rats in various groups； ELISA method was used to detect the levels of nitric oxide （NO）， endothelin-1 （ET-1）， von Willebrand factor （vWF）， and thrombomodulin （TM） in serum of the rats in various groups； Western blotting method was used to detect the expression levels of SENP-1， HIF-1α， and vascular endothelial growth factor A （VEGFA） proteins in thoracic aorta tissue of the rats in various groups.In vitro， the aortic endothelial cells （rAECs） of the rats were cultured and infected with SENP-1 shRNA adenovirus （sh-SENP-1） to construct the cell line with low expression of SENP-1. The CIH was used to induce the vascular endothelial cell injury， and the cells were divided into CIH group， CIH+sh-NC group， and CIH+sh-SENP-1 group； control group was set up separately. CCK-8 method was used to detect the proliferation activities of the cells in various groups； ELISA method was used to detect the activities of lactate dehydrogenase （LDH） in the supernatant and the levels of NO， ET-1， malondialdehyde （MDA）， and activities of superoxide dismutase （SOD） in the cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups； Western blotting method was used to detect the expression levels of SENP-1， HIF-1α， and VEGFA proteins in the cells in various groups. Results With the extension of CIH induction time， compared with control group， the thoracic aorta endothelium in CIH group gradually became rough and significantly thickened， the level of serum NO of the rats in CIH group was decreased （P<0.05）， and the levels of serum ET-1， vWF， and TM， and the expression levels of SENP-1， HIF-1α， and VEGFA proteins in thoracic aorta tissue were increased （P<0.05）. Compared with control group， the proliferation activity of the cells in CIH group was decreased （P<0.05）， the LDH activity in the supernatant， the levels of ET-1， MDA， and the apoptotic rate in the cells were increased （P<0.05）， while the levels of NO and activity of SOD in the cells were decreased （P<0.05）， and the expression levels of SENP-1， HIF-1α， and VEGFA proteins in the cells were increased （P<0.05）. Compared with CIH group， the proliferation activity of cells in CIH+sh-SENP-1 group was increased （P<0.05）， the activity of LDH in the supernatant， the levels of ET-1， MDA， and the apoptotic rate of the cells were decreased （P<0.05）， while the level of NO and activity of SOD in the cells were increased （P<0.05）， and the expression levels of SENP-1， HIF-1α， and VEGFA proteins were decreased （P<0.05）. Conclusion The SENP-1/HIF-1α pathway is highly activated in the thoracic aorta injury tissue of the rats induced by CIH. Silencing SENP-1 expression can reduce CIH-induced vascular endothelial cell injury， and its mechanism may be related to downregulating the activation level of SENP-1/HIF-1α pathway.

Objective To discuss the expressions of procollagen-lysine， 2-oxoglutarate 5-dioxygenase 1 （PLOD1） in oral squamous cell carcinoma （OSCC） tissue and OSCC cells and its effect on the biological behavior of the OSCC cells， and to clarify the potential of PLOD1 as a prognostic biomarker for OSCC. Methods The expression level of PLOD1 mRNA in head and neck squamous cell carcinoma （HNSC） tissue and its correlation with the survival of the HNSC patients were analyzed by Tumor Immune Estimation Resource （TIMER）， Gene Expression Profiling Interactive Analysis （GEPIA）， and Kaplan-Meier Plotter databases. Immunohistochemistry method was used to detect the expression level of PLOD1 protein in 110 OSCC tissue and 64 adjacent tissue，and its association with clinicopathological characteristics and prognosis of the OSCC patients were analyzed； the diagnostic value of PLOD1 in OSCC was detected by area under the curve （AUC） of the receiver operating characteristic （ROC）. The expression levels of PLOD1 mRNA and protein in the human normal oral epithelial HOK cells and OSCC SCC15 and CAL27 cells were detected by real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods. The small interfering RNA （siRNA） fragments were transfected into the SCC15 cells by liposome method and the cells were dividing into si-NC group （transfected with negative control si-NC） and si-PLOD1 group （transfected with si-PLOD1）； the proliferation activities， scratch healing rates， and numbers of invasion cells in two groups were detected by CCK-8 method， wound healing assay， and Transwell chamber assay， respectively. Results The public database analysis results showed that the expression level of PLOD1 mRNA in HNSC tissue was higher than that in adjacent tissue（P<0.05）； compared with low expression of PLOD1 group， the survival period of the HNSC patients in high expression of PLOD1 group was shorter （HR=1.41， P=0.018）. The PLOD1 protein was mainly expressed in cytoplasm of the OSCC cells， and the expression intensity of PLOD1 in OSCC tissue was higher than that in adjacent tissue （P<0.01）， and it was related to T stage and TNM stage of the OSCC patients （P=0.021， P=0.004）. The AUC of PLOD1 for diagnosing OSCC was 0.811， and the specificity was 63.64% and the sensitivity was 90.63%. The Kaplan-Meier survival analysis results showed that compared with low expression of PLOD1 group， the survival rate of the OSCC patients in high expression of PLOD1 group was decreased （P<0.01）.The COX regression analysis results showed that high expression of PLOD1 was an independent risk factor for the prognosis of OSCC （P=0.012）. The expression levels of PLOD1 mRNA and protein in the OSCC cells were higher than those in HOK cells （P<0.05）. Compared with si-NC group， the proliferation activity and scratch healing rate of the cells in si-PLOD1 group were decreased （P<0.05）， and the number of invasion cells was decreased（P<0.01）. Conclusion PLOD1 is highly expressed in the OSCC tissue and cells， and silencing of PLOD1 expression can inhibit the proliferation， migration， and invasion of the OSCC cells. PLOD1 may be a new therapeutic target and prognostic biomarker for OSCC.

Objective To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases， and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables，and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence. Methods From the UK Biobank Database， 315 896 participants and related variables were included. The feature selection was performed by categorical boosting （CatBoost） algorithm， and the participants were randomly divided into training set and test set in the ratio of 7∶3. A Bayesian network model was constructed based on the max-min hill-climbing （MMHC） algorithm. Results The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8%. The top 10 variables selected by the CatBoost algorithm were age， body mass index （BMI）， low-density lipoprotein cholesterol （LDL-C）， total cholesterol （TC）， the triglyceride-glucose （TyG） index， family history， apolipoprotein A/B ratio， high-density lipoprotein cholesterol （HDL-C）， smoking status， and gender. The area under the receiver operating characteristic （ROC） curve （AUC） for the CatBoost training set model was 0.770， and the model accuracy was 0.764； the AUC of validation set model was 0.759 and the model accuracy was 0.763. The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81. The Bayesian network model analysis results indicated that age， gender， smoking status， family history， BMI， and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors. TyG index， HDL-C， LDL-C， and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio. Conclusion Controlling BMI， apolipoprotein A/B ratio， and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases. The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Objective To compare the changes of the upper airway morphology， hyoid bone position， and craniofacial structure before and after extraction treatment and non-extraction treatment in the adult patients with skeletal class Ⅱ high angle malocclusion，and to analyze the effect of extraction orthodontic treatment on the upper airway structure in these patients，and to provide the theoretical basis for the selection of clinical treatment plans. Methods A retrospective analysis on the clinical data of 60 adult patients with skeletal class Ⅱ high angle malocclusion who required orthodontic treatment was collected from the Orthodontics Department of Stomatology Hospital of Jilin University. The patients were divided into extraction group and non-extraction group according to whether treated with extraction orthodontic treatment， and there were 30 patients in each group.The lateral cephalometric radiographs of the patients before and after orthodontic treatment were obtained， and the upper airway， hyoid bone， and craniofacial tissues were delineated and detected by Dolphin software. SPSS 23.0 statistical software was used to perform the statistical analysis on the related measurement data. Results Compared with before orthodontic treatment， the distance between the uvula tip and midpharyngeal wall （U-MPW）， aryngeal wall （V-LPW）， the inner downward angle between the long axis of the upper central incisor and the anterior cranial base （U1-SN） as well as the inner upward angle between the lower central incisor long axis and mandibular plane （L1-MP）of the patients in extraction group with skeletal class Ⅱ high angle malocclusion after orthodontic treatment were significantly decreased（P<0.05），while the occlusal plane and the anterior cranial base （OP-SN） and the angle between the long axes of the upper and lower central incisors （U1-L1） were significantly increased （P<0.05）.There were no significant differences in the other measurement indicators of the patients between two groups （P>0.05）.Compared with before orthodontic treatment， the angle of posterior nasal spine （ANB） of the patients in non-extraction group with skeletal class Ⅱ high angle malocclusion after orthodontic treatment was significantly decreased （P<0.05）， and the OP-SN and L1-MP significantly were increased （P<0.05）. There were no significant differences in the other measurement indicators of the patients between two groups （P>0.05）. Conclusion The sagittal diameter of upper airway of the adult patients with skeletal class Ⅱ high angle malocclusion tended to be orthodontic treatment after extraction orthodontic treatment，mainly in the oropharynx and laryngopharynx of the upper airway， while the hyoid bone position did not change significantly.

Objective To screen the key genes related to the prognosis， diagnosis， and immune infiltration of the hepatocellular carcinoma （HCC） patients by bioinformatics analysis methods， and to analyze their potential therapeutic drugs. Methods The HCC gene expression profile data and corresponding clinical informations of the HCC patients were downloaded from the Gene Expression Omnibus （GEO） database and The Cancer Genome Atlas （TCGA） database. The R software package limma was used to screen the differentially expressed genes （DEGs） in HCC. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed on the DEGs. The STRING database was used to construct the protein-protein interaction （PPI） network； the Cytoscape software was used to visualize the PPI network and screen the key genes； Kaplan-Meier survival curve and LASSO regression algorithm were used to identify the key genes related to the HCC prognosis；external data sets were used to validate their expressions and analyze the diagnostic efficacy；CIBERSORT algorithm was used to detect the relationship between the expression of prognosis-related key genes and HCC immune cell infiltration. The MiRNet and Network Analyst databases were used to construct the microRNA （miRNA）-key gene mRNA and transcription factors （TFs）-key gene mRNA molecular regulatory networks； CMap database was used to screen the potential small molecule drugs for HCC treatment. Results A total of 146 DEGs were screened， including 30 upregulated genes and 116 downregulated genes. The GO functional enrichment analysis and KEGG pathway enrichment analysis results showed that the DEGs were significantly enriched in biological processes （BP） such as steroid， alkene compound， and hormone metabolism， as well as signaling pathways such as retinol metabolism， drug metabolism-cytochrome P450 （CYP450）， complement and coagulation cascades. The PPI network analysis identified 14 key genes， among which formimidoyltransferase cyclodeaminase （FTCD）， secreted phosphoprotein 2 （SPP2）， thrombin-antithrombin complex （TAT）， complement C6 （C6）， and cytochrome CYP450 family member 2C9 （CYP2C9） were significantly associated with the prognosis， clinical pathological stage， and histological grade of the HCC patients and also had high diagnostic efficacy for HCC and were closely related to immune cell infiltration in HCC. Hsa-mir-182-5p， CUT-like homeobox 1 （CUX1）， early growth response 1 （EGR1）， SMAD family member 4 （SMAD4）， and tumor protein P53 （TP53） were identified as the important regulators targeting the above-mentioned prognosis-related key genes. DL-thiorphan， promethazine， and apigenin may have the therapeutic effects on HCC. Conclusion FTCD， SPP2， TAT， C6， and CYP2C9 may be the potential targets for the diagnosis， prognosis， and treatment of HCC. Three predicted small molecule drugs， DL-thiorphan， promethazine， and apigenin， may provide the references for the development of therapeutic drugs for HCC.

Objective To analyze gene expression data of esophageal adenocarcinoma （EAC） in the Gene Expression Omnibus （GEO） and The Cancer Genome Atlas （TCGA） databases and clarify the relationship between the potential core genes and tumor lymphocyte infiltration in the EAC， and to provide the molecular targets for the diagnosis and treatment of EAC. Methods The high-throughput chip datasets GSE13898， GSE26886， GSE74553， and GSE92396， including EAC and normal esophageal tissues， were downloaded from the GEO database by searching for “esophageal adenocarcinoma”. The limma package of R software was used to screen the differentially expressed genes （DEGs） in EAC tissue and esophageal normal tissue， and the common DEGs were obtained through Venn diagram. After the DEGs were analyzed by STRING database， the results were imported into Cytoscape software to screen the core genes and construct the protein-protein interaction （PPI） network. The Gene Expression Profiling Interactive Analysis （GEPIA） database was used to verify the expression levels of core genes. The UALCAN and Kaplan-Meier Plotter databases were used to analyze the correlations between the core genes and prognosis and clinical data of the EAC patients. The Tumor Immune Estimation Resource （TIMER） database was used to analyze the relationship between core genes and tumor immune infiltration. Gene Ontology （GO） functional and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed to analyze the positively correlated genes of core genes obtained from the LinkedOmics database. Results A total of 340 DEGs were obtained from the intersection of DEGs from the four GEO datasets， including 127 upregulated genes and 213 downregulated genes. After screening with the STRING database and Cytoscape software， the key core genes with the highest scores were secreted phosphoprotein 1 （SPP1） and transforming growth factor beta 1 （TGFB1）. The GEPIA database analysis results showed that compared with esophageal normal tissue， the expression levels of SPP1 and TGFB1 mRNA in cancer tissue were significantly increased （P<0.01）. The 1-year， 3-year， and 5-year overall survival of the EAC patients in SPP1 low expression group was higher than those in SPP1 high expression group （HR=10.1， P<0.05； HR=3.09， P<0.05； HR=2.32， P<0.05）， and the 5-year overall survival of the EAC patients in TGFB1 low expression group was higher than that in TGFB1 high expression group （HR=2.36， P<0.05）. The UALCAN database analysis results showed that compared with esophageal normal tissue， the expression levels of SPP1 and TGFB1 mRNA in cancer tissue of the EAC patients with stage Ⅱ-Ⅲ and N1-N2 lymph node metastasis were significantly increased （P<0.01）.The TIMER analysis results showed that the expression levels of SPP1 and TGFB1 mRNA in cancer tissue of the EAC patients were positively correlated with the infiltration of macrophages （r=0.353，P<0.01； r=0.187，P<0.05） and dendritic cells （r=0.236，P<0.01； r=0.221，P<0.01）. The GO and KEGG pathway enrichment analysis results showed that SPP1， TGFB1， and their top 50 positively correlated genes mainly participated in the biological processes such as cell migration， cell activity， and angiogenesis， and signaling pathways such as tumor proteoglycans， extracellular matrix （ECM）-receptor interaction， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT）. Conclusion SPP1 and TGFB1 are closely associated with clinical staging， lymph node metastasis， and overall survival of the EAC patients. High expressions of SPP1 and TGFB1 may lead to the infiltration of the macrophages and dendritic cells， and change the tumor microenvironment. SPP1 and TGFB1 may become new targets for the diagnosis and treatment of EAC.

Objective To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia （AML） by network pharmacology， and to clarify the active components and their mechanisms in treating AML. Methods The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The targets were predicted by SwissTargetPrediction Database. The AML-related genes and protein targets were retrieved from the SymMap Database， the GeneCards Human Gene Database， the DisGeNET Database， and the Online Mendelian Inheritance in Man （OMIM） Database. The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes， followed by Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis. The drug-active component-target network and protein-protein interaction （PPI） network were constructed by Cytoscape 3.8.0 software， and the core genes were selected by CytoNCA plugin； the molecular docking was conducted by AutoDock software. Results After filtering by databases， 39 active components were identified， and 148 common targets between dandelion-mulberry leaf and AML were collected. The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways， positive regulation of kinase activity， and oxidative stress responses. The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B （PI3K-AKT） signaling pathway， the tumor necrosis factor （TNF） signaling pathway， and the Janus kinase/signal transducer and activator of transcription （JAK-STAT） signaling pathway. The key targets were identified by topological analysis including signal transducer and activator of transcription 3 （STAT3）， epidermal growth factor receptor （EGFR）， protein kinase B1 （AKT1）， recombinant human epidermal growth factor （EGF）， vascular endothelial growth factor A （VEGFA）， oncogene MYC， tumor protein P53 （TP53）， mitogen-activated protein kinase 3 （MAPK3）， cysteiny asparate specific protease-3 （CASP3）， oncogene SRC， heat shock protein 90 alpha family class A member 1 （HSP90AA1）， tenascin XB1 （CTNNB1）， phosphoinositide kinase-3 catalytic subunit alpha （PIK3CA）， interleukin 6 （IL-6）， TNF， mitogen-activated protein kinase 1（MAPK1）， and phosphatidylinositide kinase-3 regulatory subunit 1 （PIK3R1）. The molecular docking results showed the highest affinity pairing to be taraxerol with MYC （-8.74 kcal·mol^-1）， and quercetin， kaempferol， luteolin， and artemetin demonstrated good binding affinities with various targets. Conclusion The main active components of dandelion-mulberry leaf， such as quercetin， taraxerol， kaempferol， luteolin， and artemetin， may exert the anti-AML effect by regulating AKT1， STAT3， HSP90AA1， IL-6， and MAPK1； regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

Objective To automatically segment four body components at the T4 thoracic veertebra plane on chest CT in the newly diagnosed multiple myeloma （MM） patients by deep learning model， and to discuss the correlation between the four body components and the prognosis of the MM patients. Methods The retrospective analysis was conducted on the clinical data of the MM patients diagnosed in our hospital from January 2017 to December 2021. The clinical informations such as age， gender， weight， height， and body mass index （BMI） of the patients were collected. The laboratory data of the patients were collected， including serum levels of lactate dehydrogenase （LDH）， calcium （Ca）， creatinine （Scr）， albumin （Alb）， hemoglobin （Hb）， β2-microglobulin （β2-MG）， and serum free light chains. The chest CT images of 79 regularly evaluated MM patients detected by deep learning model were divide into four body components： pectoralis major， pectoralis minor， subcutaneous fat， and mediastinal fat. Image J software was used to detect the areas of the four body components at the T4 thoracic vertebra plane， and their correlation with the prognosis of the MM patients was analyzed by Kaplan-Meier survival analysis. Results The univariate analysis results showed that the area of subcutaneous fat， serum Ca levels， Scr levels， and International Staging System （ISS） stage were related to the overall survival （OS） of the MM patients （HR=2.260， 95% CI： 1.116-4.578， P=0.024； HR=2.088， 95% CI： 1.007-4.327， P=0.048； HR=2.209， 95% CI： 1.105-4.414， P=0.025； HR=1.730， 95% CI： 1.040-2.879， P=0.035）. The multivariate analysis results showed that the area of subcutaneous fat among the four body components was an independent risk factor affecting the prognosis of the MM patients （95% CI： 1.228-5.782， P=0.013）. The Log-Rank test results showed that compared with high subcutaneous fat area group， the OS of the patients in low subcutaneous fat area group was decreased（P=0.018）. There was no significant difference in OS of the patients with different genders between high subcutaneous fat area group and low subcutaneous fat area group （P>0.05）. In the patients without hematopoietic stem cell transplantation， compared with high subcutaneous fat area group， the OS of the patients in low subcutaneous fat area group was decreased （P=0.037）. Conclusion Among the four body components at the T4 thoracic vertebra plane， the area of subcutaneous fat is related to the OS of the MM patients and it is an independent risk factor for the prognosis of the MM patients， while the areas of mediastinal fat， pectoralis major， and pectoralis minor have no predictive value for the prognosis of the MM patients.

Objective To study the expression levels of long non-coding RNA （lncRNA） H19 and insulin-like growth factor 2 （IGF2） genes in breast cancer tissue， and to analyze their imprinting status. Methods Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of H19 and IGF2 mRNA in breast cancer tissue and adjacent tissue， and the differences in the expressions of H19 and IGF2 mRNA in breast cancer tissue and adjacent tissue were analyzed； single nucleotide polymorphism （SNP） was used to distinguish the allele expression status （homozygous or heterozygous）. For heterozygous IGF2 （ApaⅠ site） or H19 （AluⅠ site） in genomic DNA， imprinting analysis was used to detect the imprinting status of H19 and IGF2 in breast cancer tissue， that were maintenance of imprinting （MOI） or loss of imprinting （LOI）； the relationship between the expressions of H19 and IGF2 and molecular subtypes in breast cancer tissue were also analyzed. Results The RT-qPCR results showed that the expression levels of H19 and IGF2 mRNA in breast cancer tissue were higher than those in adjacent tissue （P<0.01）. There was a positive correlation between the expression levels of H19 mRNA and IGF2 mRNA （r=0.567， P<0.01）. Compared with adjacent tissue， the expression levels of H19 mRNA in cancer tissue of the breast cancer patients with various molecular subtypes were increased （P<0.05 or P<0.01）. LOI was observed in both H19 and IGF2 in breast cancer tissue， and the incidence of IGF2 LOI was 36.7%， which was higher than that of H19 LOI（4.3%）. The RT-qPCR results showed that the expression level of IGF2 mRNA in breast cancer tissue in IGF2 LOI group was significantly higher than that in IGF2 MOI group （P<0.01）. Conclusion The expression levels of H19 and IGF2 mRNA in breast cancer tissue are significantly higher than those in adjacent tissue. The incidence of IGF2 LOI is higher than that of H19 LOI， and IGF2 LOI may be one of the key factors in the pathogenesis of breast cancer.

Objective To discuss the effect of the force feedback perceptual rehabilitation training on finger motor function of the patients with finger motor dysfunction after stroke， and to provide the basis for the clinical application and promotion of the force feedback perceptual rehabilitation training. Methods A total of 86 patients with hand dysfunction after stroke were randomly divided into experimental group （n=43） and control group （n=43），and 3 cases in each group fell off from the experiment， and 80 cases were ultimately completed. On this basis， the patients in two groups received the conventional rehabilitation training for 40 min. The patients in control group received the conventional hand function training for 20 min， while the patients in experimental group received the force feedback perception rehabilitation training for 20 min， once per day， 5 days per week， for a total of 6 weeks. The hand function recovery of the patients were evaluated before and after treatment by Action Research Arm Test （ARAT），grip strength， modified Ashworth scale （MAS）， total active motion （TAM）， Fugl-Meyer motor function assessment-upper limb （FMA-UL） finger motor part score，and Barthel index （BI）. Results Before treatment， there were no statistically significant differences in ARAT total score， grip strength， MAS grade， TAM， FMA-UL finger motor part score， and BI score of the patients between two groups （P>0.05）. After treated for 6 weeks， the ARAT scores， grip strengths， TAM， FMA-UL finger motor part scores， and BI scores of the patients in two groups were all increased than those before treatment （P<0.05）， while the MAS grades of the patients had no significant differences （P>0.05）. After treated for 6 weeks， compared with control group，the grasp score and grip score in ARAT score， and the difference of total ARAT score of the patients in experimental group were increased （P<0.05）， the TAM after treatment and the differences of grip strength， TAM， and FMA-UL finger motor part score of the patients before and after treatment were increased （P<0.05）， while the pinch scores and gross movement scores in ARAT score， MAS grades， and the differences of BI score before and after treatment had no significant differences（P>0.05）. Conclusion Force feedback perceptual rehabilitation training is helpful in improving the finger motor function of the patients with finger motor dysfunction after stroke.

Objective To observe the application of the controlled respiratory persistence monitor designed based on the principle of rhythmic temperature variations in artificial airways among different populations and in various artificial airways， and to discuss the feasibility and efficacy of monitoring controlled respiration persistence， and to provide a new method for the clinical respiratory monitoring. Methods A total of 60 adult patients scheduled for general anesthesia， and 30 pediatric patients aged from 1 to 3 years old， classified as American Society of Anesthesiologists （ASA） Ⅰ-Ⅱ， were selected. A total of 60 adult patients were randomly divided into adult tracheal intubation （ATI） group and adult laryngeal mask（ALM） group， and there were 30 cases in each group. Additionally， 30 pediatric patients aged from 1 to 3 years old were regarded as pediatric tracheal intubation （CTI） group. After induction of general anesthesia， the patients in CTI and ATI groups were underwent tracheal intubation， while the patients in ALM group were given a laryngeal mask inserted and were connected to the anesthesia machine for mechanical ventilation. Whether or not the device could detect the respiratory rate （RR）of the patients in various groups was observed； the RR detected by the device and the frequency set on the anesthesia machine in various groups were compared. All the patients in three groups were simulated three common clinical scenarios of continuous respiration changes before surgery： disconnection of the breathing circuit， failure to switch from manual to mechanical control on the anesthesia machine， and slow air leakage in the breathing circuit. The ways to report the alert and start time of the atarm by the monitors were compared. Results The controlled respiratory persistence monitor was able to detect the RR of the patients in three groups， and there was no significantly difference between the RR detected by the device and the frequency set on the anesthesia machine （P>0.05）. In the simulated scenarios of common respiratory persistence changes， all the patients in three groups received an artificial voice alarm signaling “Attention， breathing has stopped.”， which was acknowledged. There was no significant difference in the start time of alarm of the controlled respiratory persistence monitor between ATI group and ALM group （P>0.05）. Compared with the start time of alarm of the patients in the same group across different scenarios， compared with slow air leakage in the breathing circuit， the start time to alarm for circuit disconnection and failure to switch from manual to mechanical control was shorter （P<0.05）. Conclusion The clinical application of the controlled respiratory persistence monitor device designed based on the principle of detecting rhythmic temperature variations within artificial airways is feasible and effective in different populations and artificial airways. This device offers a new method for monitoring the respiratory continuity and ensuring the respiratory safety during surgery.

Objective To analyze the intraoperative hemodynamic management by hypotension prediction index （HPI） in one patient underwent robot-assisted laparoscopic cystectomy， and to provide the reference for anesthesia monitoring and hemodynamic management in the similar major surgery. Methods The clinical data， intraoperative hemodynamic data， usage and dosage of vasoactive drugs， and clinical outcomes of one patient underwent robot-assisted laparoscopic cystectomy with HPI-guided intraoperative hemodynamic management were retrospectively analyzed， and the relevant literatures were reviewed. Results The patient， a 72-year-old female， was admitted due to macroscopic hematuria for 5 months accompanied by dysuria for 3 months. The cystoscope results showed a 7 cm×7 cm×5 cm mass on the right side of the bladder trigone and a 4 cm×3 cm×3 cm mass near the bladder neck. The positron emission tomography/computed tomography （PET/CT） results showed thickening of the right posterior bladder wall with high metabolism， and the preliminary diagnosis was bladder malignancy. After preoperative anesthesia evaluation， the robot-assisted laparoscopic cystectomy was planned. After entering the operating room， the routine monitoring was conducted， and the monitor equipped with HPI software was used to guide intraoperative hemodynamic management. After routine anesthesia induction， the tracheal intubation was performed by video laryngoscope. The patient experienced intraoperative hypotension （IOH） for six times， the cumulative time of mean arterial pressure （MAP）<65 mmHg was 13.7 min， accounting for 4.40% of the anesthesia duration， and the time-weighted average of MAP<65 mmHg was 0.28 mmHg. The time range with HPI≥85 roughly overlapped with and included the period of MAP<65 mmHg. At 146 time points with HPI≥85，the MAP remained greater than 65 mmHg at 68.5% （100/146） of the points. At 47 time points with MAP<65 mmHg， HPI≥85 occurred at 97.9% （46/47） of the points. On the first postoperative day， the patient’s hypersensitive cardiac troponin I was <0.01 μg·L^-1， and no perioperative adverse events occurred. The patient was discharged on the eighth day. Conclusion HPI can promptly and accurately predict the occurrence of IOH in the patients undergoing robot-assisted laparoscopic cystectomy. The use of HPI-based hypotension correction strategies during surgery can maintain the time-weighted average of MAP<65 mmHg at a lower level.

Objective To analyze the clinical data of the patients with leucine-rich glioma inactivated 1 （LGI-1） antibody-positive autoimmune encephalitis （AE） （LGI-1 AE） complicated with sleep structure abnormality and cognitive impairment， and to discuss the possible pathogenic mechanism. Methods A 68-year-old male patient was admitted to our hospital due to memory decline for 2 months and seizures for 1 month.After diagnosed with LGI-1 AE， the patient was treated with intravenous immunoglobulin combined with methylprednisolone sodium succinate， resulting in the improved symptoms. Excluding any pharmaceutical influences， the neuropsychological assessments， including sleep evaluations with polysomnography （PSG）， were performed during both the acute phase and the recovery phase. Results During the acute phase assessment， the patient exhibited severe cognitive impairments， scoring 22 on the Mini-Mental State Examination （MMSE） and 19 on the Montreal Cognitive Assessment （MoCA）.The PSG results showed that the total sleep time （265 min） was shortened， the sleep fragmentation throughout could be seen， the sleep efficiency was reduced， and N3 and rapid eye movement （REM） sleep stages were complete absent. In the recovery phase， the patient’s cognitive functions improved （MMSE score was 30， MoCA score was 26）， the total sleep time returned to normal with PSG， the sleep onset latency was 13.5 min， the sleep fragmentation notably improved， the sleep efficiency was increased to 84.3%，the N3 sleep lasted 26 min （5.1%）， and the REM sleep lasted 69 min （13.6%）. Conclusion The abnormality in sleep structure and cognitive impairment in the patients with LGI-1 AE are synchronous in onset and outcome， and may be one of the etiologies of cognitive dysfunction in these patients. The pathological origin of the sleep disorder may lie in the hypothalamus. Hypothalamic secretions and the Lhx6 pathway might become new targets for correcting the sleep structure while treating the cognitive impairment.

Objective To discuss the clinical presentations， diagnosis， and treatment methods of the patients with Fournier’s gangrene， and to enhance the clinicians’ awareness of this condition. Methods The clinical data including symptoms， signs， radiological findings， and surgical outcomes of one patient with Fournier’s gangrene were collected.The relevant literatures were reviewed to summarize the clinical characteristics， diagnosis， and treatment methods for this condition. Results The patient， a 42-year-old male， was admitted because of a history of infection around the perineum， scrotum， and perianal area for 13 d. His medical history included acute myeloid leukemia for 10 months， during which the patient underwent eight chemotherapy sessions in the local hospital. The abdominal CT scan results showed thickened， dense， and turbid soft tissue in the left inguinal area. The complete blood count reuslts showed the white blood cell count was 23.99×10⁹ L^-1. The cultures of wound secretions grew the Escherichiacoli and Proteus mirabilis. The examination results showed there was necrosis of the scrotal skin and skin near the anus on the left buttock； the skin was blackened， hard， and demarcated from the surrounding normal skin with slight purulent exudation and no foul smell. The surrounding skin was significantly swollen and red； the rectal examination results showed no bleeding or fistulas. The patient underwent emergency debridement surgery on the admission day， followed by dressing changes， multiple applications of simplified negative pressure， perineal flap reconstruction， and skin grafting. The patient recovered well with normal function and had no complications. Conclusion Fournier gangrene has acute onset and rapid progression， and the clinical manifestations are non-specific. The range of infection is not consistent with the progression of the disease. The diagnosis mainly depends on intraoperative exploration. Repeated radical surgery is the main treatment. The prognosis of this disease is good， and the recurrence rate is low， although long-term follow-up is still necessary after surgery.

Objective To analyze the imaging manifestations of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography （¹⁸F-FDG PET/CT） in the patients with pleural and peritoneal mesothelioma， and to enhance the diagnostic accuracy for this disease. Methods A retrospective analysis was conducted on the ¹⁸F-FDG PET/CT imaging and immunohistochemical results of 22 patients confirmed pleural and peritoneal mesothelioma （21 malignant and 1 benign） by pathology. The imaging features and glucose metabolism characteristics were summarized. Results The majority of the patients with malignant pleural mesothelioma presented with unilateral pleural diffuse thickening accompanied by increased radiotracer uptake， and the thicknesses were ranged from 1.0 to 10.6 cm and the average semi-quantitative maximum standard uptake value （SUV_max） was 10.1. Over half of these patients also had a small amount of pleural effusion. The patients with malignant peritoneal mesothelioma mostly showed diffuse thickening of the peritoneum， omentum， and mesentery with increased radiotracer uptake， and the thicknesses were from 1.2 to 6.6 cm and the average SUVmax was 8.4， and over half of these patients had a significant amount of abdominal ascites. Besides the primary sites， nodular， striated， and mass-like abnormal radiotracer uptakes were observed in other metastatic sites in 17 cases of malignant mesothelioma， suggesting metastasis， and the average SUV_max was 7.4， predominantly surrounding lymph node metastasis. Bone and muscle metastases were visible in the patients with malignant pleural mesothelioma， while no such metastasis were seen in those with malignant peritoneal mesothelioma. One patient with benign pleural mesothelioma presented with bilateral pleural diffuse thickening approximately 3.5 cm thick， without significant abnormal radiotracer uptake and with a minor pleural effusion. Conclusion The ¹⁸F-FDG PET/CT imaging manifestations of pleural and peritoneal mesothelioma exhibit the distinctive characteristics. The mode and thickness of pleural and peritoneal thickening， the presence and degree of ¹⁸F-fluorodeoxyglucose uptake， can preliminarily differentiate between benign and malignant mesothelioma， thus providing valuable references for the early clinical diagnosis of mesothelioma. PET/CT based on whole-body imaging can determine whether there are other sites of metastasis， which is helpful for clinical staging.

Gag-Pol protein is one of the important structural proteins of human immunodeficiency virus （HIV）， comprising the basic scaffold proteins and functional enzymes required during the lifecycle of HIV. Currently，the inhibitors targeting different functional domains on Gag-Pol include capsid（CA） inhibitors，protease inhibitors， reverse transcriptase inhibitors， and integrase inhibitors. The CA inhibitors inhibit the maturation of CA or disrupt the assembly of CA，so as to affect the replication of HIV. The primary mechanism of protease inhibitors is to inhibit the protease from cleaving at the cleavage site CA-spacer peptide 1（SP1）. The reverse transcriptase inhibitors block the reverse transcription process of HIV by mimicking the reverse transcription substrates. The integrase inhibitors impact the activity of integrase by targeting the zinc-finger structure at the active center of integrase. This article summarizes the inhibitors targeting HIV Gag-Pol protein and their mechanisms， and reviews the approved dosages and usages of approved patent drugs，so as to provide the references for the future clinical combination therapies and the development of new inhibitors targeting HIV Gag-Pol protein.

Chitooligosaccharides （COS）， as the degradation products of the natural polysaccharide chitosan （CS）， retain the good biocompatibility， non-toxicity， and biodegradability of CS. Additionally， due to the shortened sugar chains and reduced molecular weight， their water solubility and bioactivity are improved， making them more easily absorbed and utilized by organisms. In recent years， COS has received increasing attention. While there are numerous studies on the biological functions of CS and its applications in the biomedical field， the research on the functions and applications of COS is relatively limited. This study summarizes and analyzes the main biological functions of COS （anti-inflammatory， anti-tumor， antibacterial， and tissue regeneration promotion） and their possible mechanisms. It also discusses the research progress in the applications of COS in the biomedical field， in order to provide the theoretical basis and reference for the further research and broader application of COS in biomedicine.

The inflammatory response runs through the entire process of the onset and progression of coronary atherosclerotic heart disease （CHD）； various inflammatory cells and inflammatory factors are involved， and to a certain extent， determine the stability of coronary atherosclerotic plaques and the progression of the disease. Lipoprotein（a） ［Lp（a）］， C-reactive protein （CRP）， neutrophils， platelets， and monocytes participate in the inflammatory response through various mechanisms such as inducing inflammatory factors， stimulating inflammatory cells， and secreting active substances， thus promoting the atherosclerosis. In contrast， the lymphocytes， as important immune cells， serve as the indicators of anti-inflammation. High-density lipoprotein cholesterol （HDL-C） exerts its anti-atherosclerotic effects by reversing cholesterol transport and inhibiting the aggregation of the inflammatory cells. In recent years， novel inflammatory markers composed of the aforementioned inflammation-related indicators have been closely related to the onset and progression of CHD and have significant guiding value in the diagnosis， treatment， and prognosis of CHD. Reducing inflammation remains a hotspot in current CHD research. The study analyzes the mechanism of promoting the CHD development by new inflammatory markers and reviews the therapeutic advancements targeting these relevant inflammatory markers， and provides the basis for the diagnosis and treatment of CHD.

The incidence of breast cancer is increasing year by year， and its pathogenesis is highly complex. The dysregulation of gut microbiota function is closely related to the occurrence and development of breast cancer. The estrogen levels through enterohepatic circulation is regulated by β-glucuronidase produced by the gut microbiota， thereby influencing the occurrence and development of hormone receptor-positive breast cancer and leading to tamoxifen resistance. The metabolites from the gut microbiota， such as short-chain fatty acids （SCFAs） and lithocholic acid （LCA）， can participate in regulating the tumor cell cycles and cell proliferation. The colonization of gut microbiota maintains the integrity of the intestinal barrier and regulates the anti-tumor immunity mediated by T lymphocytes. Maintaining gut microbiota homeostasis can enhance the efficacy of tumor chemotherapy and immunotherapy and reduce the adverse reactions in anti-tumor treatments. The targeted action of engineered probiotics in immunotherapy can improve the precision of drug treatment. The effect of gut microbiota on radiotherapy is not yet clear， but regulating gut microbiota can aid in the treatment of radiation enteritis. This review discusses the correlation and effect of gut microbiota on breast cancer and analyzes its role in the treatment of breast cancer.