Objective To discuss the relationship between CXC motif chemokine receptor 6 （CXCR6） expression in tumor tissue and the expression of immune checkpoint molecules as well as the infiltration abundance of CD4? T lymphocytes， and to clarify its impact in the function of regulatory T lymphocytes （Tregs） and underlying mechanism. Methods Bioinformatics analysis was performed using Tumor Immune Estimation Resource （TIMER） database. Transcriptomic and immune infiltration data of 10 solid tumors were collected. Pearson correlation analysis was used to analyze the correlations of CXCR6 with immune checkpoint molecules and the infiltration abundance of CD4? T lymphocytes. In the experiments， the human peripheral blood mononuclear cells （PBMCs） from healthy individuals were used. The CD4? T lymphocytes were isolated and expanded， and then induced into the Treg cells. Recombinant lentiviral vectors of CXCR6 shRNA1-4# were constructed. The experiment was divided into blank group （without Treg）， empty vector Treg group（control group）， and CXCR6 knockdown group. After lentiviral transfection， the Treg cells were co-cultured with CD8? cytotoxic T lymphocytes （CTLs） and T2 tumor target cells. Flow cytometry was used to detect the purity of Treg cells； fluorometric counting method was used to detect the lysis rate of target cells； enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cytokines in the cells； RNA sequencing was used to detect the expression levels of differential genes in the cells； real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the knockdown efficiency of CXCR6 and the expression level of peptidase inhibitor 16（PI16） mRNA. Results The bioinformatics analysis results showed that CXCR6 was highly positively correlated with immune checkpoint molecules and the infiltration abundance of CD4? T lymphocytes in 10 solid tumors （P<0.01）， and was negatively correlated with tumor purity （except for glioblastoma）（P<0.01）. The flow cytometry results showed that high-purity CD4? T lymphocytes （90.13%±3.7%） and CD25?Foxp3? Treg cells （69.6%±3.4%） were successfully obtained. The RT-qPCR results showed that CXCR6-KD3# had the highest knockdown efficiency （P<0.05）. The fluorometric counting method results showed that compared with control group， the lysis rate of target cells in CXCR6 knockdown group was increased （P<0.01）. The ELISA results showed that compared with empty control group， the levels of interferon-γ （IFN-γ） and tumor necrosis factor-α（TNF-α） in CXCR6 knockdown group were increased （P<0.01）. The RT-qPCR results showed that compared with control group， the expression level of PI16 mRNA in Treg cells in CXCR6 knockdown group was increased （P<0.01）. The RNA sequencing results showed that the differential genes were enriched in the extracellular matrix space， regulation of cell migration， and phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） pathway. Conclusion CXCR6 is highly correlated with the expression of immune checkpoint molecules and CD4? T lymphocyte infiltration in 10 solid tumors， and is mainly localized in the tumor immune microenvironment. Knockdown of CXCR6 expression in Treg cells can attenuate their immunosuppressive function and promote the secretion of related cytokines by CTLs， and the mechanism may be related to the upregulation of PI16 mRNA expression level in the Treg cells.

Objective To discuss the therapeutic effect of astilbin （AST） in the mice with myocardial infarction（MI）， and to clarify its mechanism. Methods The MI model was established by ligating the left anterior descending artery（LAD） in the male C57BL/6 mice. A total of 50 mice were randomly divided into model group， low dose of AST group（AST-L group） （12.5 mg·kg^-1）， high dose of AST group （AST-H group） （50 mg·kg^-1）， enalapril group （2 mg·kg^-1）， and sham operation group （only thoracotomy without ligation）， and there were 10 mice in each group. Echocardiography was used to detect the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） of the mice in various groups to evaluate cardiac function； Masson trichrome staining， wheat germ agglutinin （WGA） staining and TUNEL staining were used to detect the MI areas， cardiomyocyte sizes and cardiomyocyte apoptosis in the mice in various groups， respectively. In vitro， cobalt chloride （CoCl₂） was used to induce the H9C2 cells to establish the hypoxia injury model. The cells were divided into control group， CoCl₂ group， CoCl₂+low dose of AST（AST-L） group， CoCl₂+medium dose of AST（AST-M） group， and CoCl₂+high dose of AST（AST-H） group. Cell counting kit-8（CCK-8） method was used to detect the survival rates of the cells in various groups； Western blotting method was used to detect the expression levels of apoptosis-related proteins in the cells in various group； immunofluorescence method was used to detect the levels of reactive oxygen species （ROS） in the cells in various groups. In addition， databases including SwissTargetPrediction and PharmMapper were used to predict the targets related to AST and MI； protein-protein interaction （PPI） network was constructed to screen the core targets； Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway enrichment analysis were performed； and molecular docking validation was conducted using Autodock software. Results In vivo， compared with sham operation group， the LVEF and LVFS of the mice in model group were decreased （P<0.001）， indicating impaired cardiac function； the Masson staining results showed severe myocardial fibrosis in the mice in model group； the cross sectional area of cardiomyocytes was increased （P<0.05）， the number of TUNEL staining positive cells was increased. Compared with model group， the LVEF and LVFS of the mice in AST-L group and AST-H group were increased （P<0.05 or P<0.001）； the myocardial fibrosis areas of the mice were decreased （P<0.05 or P<0.001）， and the cardiomyocyte cross-sectional areas were decreased （P<0.001）. In vitro， compared with control group， the survival rate of the cells in CoCl₂ group was decreased （P<0.01）， the expression level of B cell lymphoma 2 （Bcl-2） was decreased （P<0.01）， while the expression levels of Bcl-2-associated X protein （Bax） and cleaved cysteinyl aspartate-specific proteinase 3（Cleaved-Caspase-3） proteins were increased （P<0.05 or P<0.01）， and the ROS level was increased （P<0.001）. Compared with CoCl₂ group， the expression levels of Bax and Cleaved-Caspase-3 in the cells in CoCl₂+AST-L， CoCl₂+AST-M and CoCl₂+AST-H groups were decreased （P<0.05 or P<0.01）， the expression levels of Bcl-2 were increased （P<0.05 or P<0.01）， and the ROS levels were decreased （P<0.001）. The network pharmacology analysis results showed that AST had 357 potential targets； after intersecting with MI disease targets， core targets were screened by Degree value， among which epidermal growth factor receptor （EGFR） showed good molecular docking score with AST （binding energy <-8.0 kcal·mol^-1）. The KEGG pathway enrichment analysis results showed that the common targets were mainly enriched in phosphatidylinositol 3-kinase （PI3K）-protein kinase B （AKT） signaling pathway and EGFR signaling pathway， etc. The Western blotting results showed that compared with control group， the expression levels of EFGR， phosphorylated PI3K （p-PI3K） and phosphorylated AKT （p-AKT） proteins in the cells in CoCl₂ group were decreased （P<0.05 or P<0.01）； compared with CoCl₂ group， the expression levels of EGFR， p-AKT， and p-PI3K proteins in the cells in CoCl₂+AST-H group were increased （P<0.01）. Conclusion AST can exert anti-oxidative and anti-apoptotic effects through regulating EGFR/PI3K/AKT signaling pathway， improve cardiac function and myocardial pathological injury in MI mice， and its mechanism is related to regulating this signaling pathway.

Objective To discuss the effect of angiopoietin-like protein 6 （ANGPTL6） on improving liver lipid accumulation induced by methionine- and choline-deficient （MCD） diet in the mice， and to clarify its possible mechanism. Methods Forty-two six-week-old C57BL/6 mice were randomly divided into control group， model group and ANGPTL6 overexpression group （ANGPTL6 group）， with 14 mice in each group. After one week of adaptive feeding， the mice in control group were fed normal diet， and the mice in model group and ANGPTL6 group were fed with MCD diet for 8 weeks. One week after starting the MCD diet， adeno-associated virus serotype 8（AAV8）-green fluorescent protein （GFP） empty vector and AAV8-ANGPTL6 overexpression vector were injected into the mice in model group and ANGPTL6 group via the tail vein， respectively. The steatosis model in HepG2 cells was induced by a mixture of oleic acid（OA） and palmitic acid（PA）， and the cells were divided into blank control group （BSA group）， model group （OD group）， ANGPTL6-treated group （OAD group） and mammalian target of rapamycin （mTOR） agonist group （OAM group）. HE staining and oil red O staining were used to evaluate the liver tissue morphology and lipid deposition in the mice in various groups； kits were used to detect the levels of total cholesterol （TC） and triglyceride （TG） in liver tissue of the mice in various groups and in HepG2 cells in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the mRNA expression levels of lipid metabolism-related genes in liver tissue of the mice in various groups and in HepG2 cells in various groups； Western blotting method was used to detect the expression levels of ANGPTL6， mTOR and phosphorylated mTOR （p-mTOR） proteins in liver tissue of the mice in various groups and in the HepG2 cells in various groups. Results Compared with control group， the livers of the mice in model and ANGPTL groups showed severe vacuolar degeneration and abnormal lipid accumulation， and the expression levels of ANGPTL6 protein in the liver tissue were decreased （P<0.05）. Compared with model group， the vacuolar degeneration and lipid accumulation in liver tissue of the mice in ANGPTL6 group were alleviated， the TG level in liver tissue was decreased （P<0.05）； the expression levels of lipid synthesis-related genes sterol regulatory element binding factor 1 （SREBF1） and fatty acid synthase （FASN） mRNA in liver tissue were decreased （P<0.05）， and the expression levels of lipid decomposition-related genes adipose triglyceride lipase （ATGL） and carnitine palmitoyltransferase 1A （CPT1A） mRNA in liver tissue were increased （P<0.05）； the expression levels of mTOR and p-mTOR proteins in liver tissue were decreased （P<0.05）. Compared with BSA group， the TG level， the expression levels of FASN and acetyl-CoA carboxylase alpha （ACACA） mRNA， and the expression levels of mTOR and p-mTOR proteins in the cells in OD group were all increased （P<0.05）； compared with OD group， the TG level， the expression levels of FASN and ACACA mRNA， and the expression levels of mTOR and p-mTOR proteins in the cells in OAD group were all decreased （P<0.05）； compared with OAD group， the TG level， the expression levels of FASN and ACACA mRNA， and the expression levels of mTOR and p-mTOR proteins in the cells in OAM group were all increased （P<0.05）. Conclusion ANGPTL6 can improve MCD diet-induced liver lipid accumulation in the mice， and its mechanism may be related to the inhibition of mTOR signaling pathway activity.

Objective To discuss the improvement effect of exogenous brain-derived neurotrophic factor （BDNF） targeted liposomes on the learning and memory abilities of Alzheimer’s disease （AD） model rats， and to clarify its possible mechanism. Methods Thirty-two SD male rats were randomly divided into sham operation group， AD model group， low dose of BDNF group， and high dose of BDNF group. Except for sham operation group， the rats in the other groups were prepared as AD models. The rats in low and high doses of BDNF groups were injected with 1 and 2 μL of exogenous BDNF liposomes via tail vein， respectively. Morris water maze test was used to detect the learning and memory abilities of the rats in various groups； immunohistochemistry staining was used to detect the expression level and distribution of BDNF protein in hippocampus tissue of the rats in various groups； Western blotting method was used to detect the expression levels of phosphorylated Tau （p-Tau） （Thr231） protein in hippocampus tissue of the rats in various groups. Results The Morris water maze test results showed that compared with sham operation group， the escape latency of the rats in AD model group was significantly prolonged （P<0.05）； compared with AD model group， the numbers of crossing platform position and the residence time in target quadrant of the rats in low and high doses of BDNF groups were significantly increased （P<0.05）. The immunohistochemistry staining results showed that compared with AD model group， the expression levels of BDNF protein in cortex and hippocampus tissues of the rats in low and high doses of BDNF groups were significantly increased （P<0.01）. The Western blotting method results showed that compared with AD model group， the expression levels of p-Tau （Thr231） protein in hippocampus tissue of the rats in low and high doses of BDNF groups were significantly decreased （P<0.01）； compared with low dose of BDNF group， the expression level of p-Tau （Thr231） protein in hippocampus tissue of the rats in high dose of BDNF group had no statistically significant difference （P>0.05）. Conclusion Intravenous administration of exogenous BDNF liposomes can improve the learning and memory abilities of AD model rats， and the mechanism may be related to up-regulating the expression level of BDNF protein in cerebral cortex and hippocampus tissue and decreasing the expression level of p-Tau （Thr231） protein in hippocampus tissue.

Objective To evaluate the role of a thermo- and photo-responsive dual-stimuli hydrogel based on Pluronic F127 diacrylate （F127-DA） as an exosomes （Exos） delivery system in articular cartilage repair， and to clarify its mechanism of action. Methods The Exos were isolated from bone marrow mesenchymal stem cells （BMSCs） by ultracentrifugation and characterized. Transmission electron microscope （TEM） was used to observe the morphology of Exos in various groups； nanoparticle tracking analysis （NTA） was used to detect the particle size distribution of Exos in various groups； Western blotting method was used to detect the expression levels of the marker proteins CD9， CD81， and TSG101 in the Exos in various groups； Exos uptake assay was used to detect the distribution of Exos taken up by the BMSCs in various groups； Western blotting method was used to detect the protein expression levels of type Ⅱ collagen （COL Ⅱ） and aggrecan （ACAN） in the BMSCs in two groups； scratch wound healing assay was used to detect the wound healing ability of the BMSCs in two groups； Transwell chamber assay was used to detect the migration ability of the BMSCs in various groups； scanning electron microscope （SEM） was used to observe the pore structure of the hydrogel. Twenty-four 6-week-old rats were randomly divided into control group， F127-DA group， Exos group， and F127-DA+Exos group， with 6 rats in each group. A cartilage defect （2 mm in diameter， 1 mm in depth） was created in trochlear groove of the knee joint； the rats in control group received no treatment， while the rats in the other three groups were treated with F127-DA hydrogel， Exos， or F127-DA hydrogel +Exos filling the cartilage defect site， respectively.At 8 weeks after operation， the rat knee joint tissues were collected for HE staining and safranin O and fast green （SOFG） staining to evaluate cartilage repair at the defect site in trochlear groove of the knee joint of the rats in various groups. Results The TEM and NTA results showed that the Exos were spherical in shape with a particle size concentrated around 80 nm. The Western blotting results showed that the exosomal surface biomarkers CD9， CD81， and Tsg101 were all highly expressed， while Calnexin was not expressed， confirming that the isolated vesicles were Exos. Compared with control group， the expression levels of COL Ⅱ and ACAN proteins in the BMSCs in Exos group were increased （P<0.05）. The Exos uptake assay results showed that the BMSCs efficiently internalized Exos. The scratch wound healing assay and Transwell chamber assay results showed that compared with control group， the migration ability of the BMSCs in Exos group was increased. The SEM results showed that the F127-DA hydrogel exhibited a loose and porous structure. The HE and SOFG staining results showed that in control group， fibrous tissue formed at the defect site in the trochlear groove； in F127-DA group， mild repair was observed at the defect site； in Exos group， neocartilage-like tissue was visible at the defect site； while in F127-DA+Exos group， the defect site was filled with abundant hyaline cartilage-like tissue， with cell arrangement and matrix formation most closely resembling normal cartilage， showing the optimal repair effect. Conclusion The F127-DA hydrogel loaded with Exos can achieve sustained and controlled release of Exos， and significantly promote cartilage regeneration； the results of this study provide an effective strategy for precise delivery of Exos therapy and multi-stage repair of cartilage injury.

Objective To investigate the inhibitory effect of Codonopsis pilosula polysaccharides （CPPs） on colorectal cancer liver metastasis in the mice， and to clarify its regulatory effects on the transforming growth factor-β （TGF-β）/Smad signaling pathway， epithelial-mesenchymal transition （EMT）， and inflammatory cytokine profiles. Methods The mouse liver metastasis model was established by intrasplenic injection of green fluorescent protein （GFP）-labeled mouse colon cancer MC-38 cells. Fifty successul modeling mice were randomly divided into modeling group， 5-fluorouracil （5-FU） group， low dose of CPPs （CPPs-L） group， a medium dose of CPPs （CPPs-M） group， and high dose of CPPs （CPPs-H） group， with 10 mice in each group. Immunofluorescence staining was used to detect the proliferation activities of the tumor cells in the liver tumor tissue， and small-animal in vivo imaging was used to detect the degree of liver metastasis in colorectal cancer of the mice in various groups after treated with CPPs； enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） of the mice in various groups； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of E-cadherin， N-cadherin， and Vimentin mRNA in liver metastatic focus tumor tissue of the mice in various groups； Western blotting method was used to detect the expression levels of TGF-β1， Smad2/3 and their phosphorylated forms， as well as E-cadherin， N-cadherin， and Vimentin proteins in liver metastatic focus tumor tissue of the mice in various groups. Results The HE staining results showed that compared with modeling group， the tumor cells in CPPs groups were arranged more sparsely， with reduced atypia and fewer mitotic figures. The immunofluorescence staining results showed that compared with modeling group， the proliferation activities of the cells in liver tumor tissue of the mice in the other groups was decreased（P<0.05）. In vivo imaging results showed that after 3 weeks of inhibition， compared with model group， the region of interest （ROI） in liver metastatic focus of the mice in CPPs-L， CPPs-M， and CPPs-H groups was gradually decreased in a dose-dependent manner （P<0.05）， and the ROI in liver tumor tissue in CPPs-H group was similar to that in 5-FU group. The ELISA results showed that compared with modeling group， the serum levels of TNF-α， IL-1β， and IL-6 of the mice in 5-FU， CPPs-L， CPPs-M， and CPPs-H groups were decreased （P<0.05）； the serum levels of IL-1β and IL-6 of the mice in CPPs-H group were higher than those in 5-FU group （P<0.05）. The Western blotting results showed that compared with modeling group， the expression level of TGF-β1 protein and the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in liver tumor tissue of the mice in 5-FU and different doses of CPPs groups were decreased； with the increasing of CPPs dose， the expression level of E-cadherin protein was gradually increased， while the expression levels of N-cadherin and Vimentin proteins were gradually decreased. The RT-qPCR results showed that compared with model group， the E-cadherin mRNA expression level in liver tumor tissue of the mice in different doses of CPPs groups were increased（P<0.05）， while the N-cadherin and Vimentin mRNA expression levels were decreased（P<0.05）. Conclusion CPPs can significantly inhibit colorectal cancer liver metastasis in the mice， and its mechanism may be related to blocking EMT by inhibiting the TGF-β/Smad signaling pathway and reducing the expression of inflammatory cytokines to alleviate the inflammatory response.

Objective To investigate the promotion effect of velvet antler polypeptide （VAP） on myocardial injury in the diabetic cardiomyopathy （DCM） mice， and to clarify its mechanism. Methods The DCM model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Fifty successfully modeled C57BL/6J mice were randomly divided into model group， metformin （Met） group （administered 250 mg·kg^-1 Met）， low dose of VAP group （administered 100 mg·kg^-1 VAP）， medium dose of VAP group （administered 200 mg·kg^-1 VAP）， and high dose of VAP group （administered 300 mg·kg^-1 VAP）， with once daily administration for 4 weeks； another 10 C57BL/6J mice were used as control group （fed a standard diet）. The body weights and fasting blood glucose （FBG） levels of the mice in various groups were monitored； cardiac ultrasound was used to detect the cardiac function of the mice； HE staining was used to observe the pathomorphology of myocardium tissue of the mice； Masson staining was used to observe the degree of myocardial fibrosis of the mice； Oil Red O staining was used to observe the lipid distribution in myocardium tissue of the mice； kits were used to detect the activities of superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） and the level of malondialdehyde （MDA） in myocardium tissue of the mice； immunohistochemistry staining was used to observe the expression of Kelch-like ECH-associated protein 1 （Keap1） in myocardium tissue of the mice； immunofluorescence staining was used to observe the expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） in myocardium tissue of the mice； Western blotting method was used to detect the expression levels of Keap1， Nrf2， HO-1， and cysteinyl aspartate-specific proteinase 3 （Caspase-3） proteins in myocardium tissue of the mice. Results Compared with control group， the myocardial injury of the mice in model group was severe， with enlarged myocardial cell gaps， increased collagen fibers， and increased lipid distribution； the body weight， left ventricular posterior wall thickness at end-systole （LVPWs）， and ejection fraction （EF） of the mice were significantly decreased （P<0.05 or P<0.01）； FBG， left ventricular end-diastolic diameter （LVIDd）， and end-systolic diameter （LVIDs） were significantly increased （P<0.05 or P<0.01）； the activities of SOD， CAT， and GSH-Px in myocardium tissue were significantly decreased （P<0.01）， and the MDA level was significantly increased （P<0.01）； the expression levels of Nrf2 and HO-1 proteins in myocardium tissue were significantly decreased （P<0.01）， while the expression levels of Keap1 and Caspase-3 proteins were significantly increased （P<0.01）. Compared with model group， the pathomorphology， myocardial fibrosis， and lipid distribution of myocardium tissue of the mice in Met group， medium dose of VAP group， and high dose of VAP group were improved to varying degrees； the body weight， LVPWs， and EF were significantly increased （P<0.05 or P<0.01）； FBG， LVIDd， and LVIDs were significantly decreased （P<0.05 or P<0.01）； the activities of SOD， CAT， and GSH-Px in myocardium tissue were significantly increased （P<0.05 or P<0.01）， and the MDA level was significantly decreased （P<0.05 or P<0.01）； the expression levels of Nrf2 and HO-1 proteins in myocardium tissue were significantly increased （P<0.01）， and the expression levels of Keap1 and caspase-3 proteins were significantly decreased （P<0.01）. Compared with model group， the body weight of the mice in low dose of VAP group was significantly increased （P<0.05） and FBG was significantly decreased （P<0.05）， but there were no significant differences in LVPWs， EF， LVIDd， LVIDs， activities of SOD， CAT， and GSH-Px， level of MDA， expression level of Keap1， Nrf2， HO-1， and Caspase-3 proteins （P>0.05）. Conclusion VAP can improve myocardial injury and cardiac function in the DCM mice in a dose-dependent manner， and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signaling pathway and reducing oxidative stress and apoptosis.

Objective To discuss the potential therapeutic effect of CA3 combined with JSI-124 on lung cancer subcutaneous allografts in the mice and its influence on the lymphocytes， and to clarify its possible mechanism. Methods Four kinds of non-small cell lung cancer （NSCLC） cells （LLC， H460， H292 and LA795） were used. The cell counting kit-8 （CCK-8） method and flow cytometry were used to detect the survival rates and apoptotic rates of the four kinds of NSCLC cells before and after CA3 treatment； the morphology of four kinds of NSCLC cells was detected by trypan blue staining； carboxyfluorescein succinimidyl ester （CFSE） staining was used to detect the expression level of CFSE in splenic lymphocytes； flow cytometry was used to detect the apoptotic rate of splenocytes. The LLC cells at logarithmic growth phase were subcutaneously inoculated into the C57BL/6 mice to establish subcutaneous allograft models. After successful modeling， the mice were were randomly divided into control group， CA3 group， JSI-124 group， and CA3+JSI-124 group， with 4 mice in each group. The mice in control group were intraperitoneally injected with phosphate buffer saline （PBS） containing dimethyl sulfoxide （DMSO）， the mice in CA3 group and JSI-124 group were intraperitoneally injected with CA3 and JSI-124 at a dose of 1 mg·kg^-1， respectively； the mice in CA3+JSI-124 group were intraperitoneally injected with 1 mg·kg^-1 CA3 and 1 mg·kg^-1 JSI-124. At 24 h after the last administration on day 18， the mice were sacrificed by cervical dislocation， and the tumor tissues were removed； the thymus and spleen were taken， and the tumor mass， spleen mass and thymus mass were weighed. Flow cytometry was used to detect the phenotypic changes of lymphocytes in spleen and thymus of the tumor-bearing mice. Results The in vitro experiment results showed that CA3 exhibited time- and dose-dependent inhibitory effects on the four kinds of NSCLC cells and splenic lymphocytes， and the optimal inhibitory effect on proliferation was achieved after treatment with 2 mmol·L^-1 CA3 for 72 h. Compared with control group， the apoptotic rates of four kinds of NSCLC cells in 2 mmol·L^-1 CA3 group were increased at 72 h after treatment （P<0.01）. Compared with control group， the proliferation rate of splenic lymphocytes in 2 mmol·L^-1 CA3 group was decreased （P<0.01）， and the apoptotic rate of splenocytes was increased （P<0.01）.The in vivo experiment results showed that compared with control group， the difference in tumor mass of mice in CA3 group was not statistically significant （P>0.05）， while the tumor mass of the mice in CA3+JSI-124 group was decreased （P<0.01）. Compared with control group， the differences in the percentages of T lymphocytes， B lymphocytes and T lymphocyte subsets in spleen， and T lymphocytes and T lymphocyte subsets in thymus of the mice in CA3+JSI-124 group were not statistically significant （P>0.05）. Conclusion CA3 can inhibit the proliferation of NSCLC cells and induce apoptosis in vitro， but it has inhibitory effect on splenic lymphocytes. The combination of CA3 and JSI-124 can significantly inhibit the growth of lung cancer subcutaneous allografts in the mice， with no significant effects on the mass of thymus and spleen， or the T lymphocytes and B lymphocytes in the thymus and spleen.

Objective To discuss the protective effect of salidroside （SAL） on rat retinal ganglion （RG） cells，and to clarify its possible mechanism. Methods A total of 30 SPF-grade male SD rats were randomly divided into control group， diabetes group and SAL group. Except for control group， the remaining rats were intraperitoneally injected with streptozotocin （STZ） to establish diabetes models. Optical coherence tomography （OCT） was used to detect retinal thickness of rats in various groups； HE staining was used to observe the morphological manifestations of retina in rats in various groups. The high glucose-induced RG cell injury model was established with 300 mmol·L^-1 glucose. Cell counting kit-8 （CCK-8） method was used to evaluate the activity and quantity of RG cells； flow cytometry was used to detect reactive oxygen species （ROS） level in RG cells. Bioinformatics analysis was performed to screen the core targets that may interact with SAL. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the mRNA expression levels of core targets in RG cells. Protein docking was used to predict the core target with the highest correlation with SAL in protecting high glucose-induced RG cell injury； Western blotting method was used to detect the expression levels of glutathione peroxidase 4 （Gpx4） and nuclear factor （erythroid-derived 2）-like 2 （Nfe2l2） proteins in the cells in various groups， so as to verify the mechanism of key proteins on RG cells. Results The OCT results showed that compared with control group， the retinal thickness of the rats in diabetes group was significantly thinned （P<0.05）， which confirmed the successful establishment of diabetic retinopathy model； compared with diabetes group， the retinal thickness of the rats in SAL group was increased （P<0.05）. The HE staining results showed that the boundaries of each retinal layer in diabetes group were unclear， a large number of vacuoles appeared， and RG cells were massively lost； retinal ganglion cells in SAL group were arranged neatly with normal nuclear morphology. The CCK-8 and microscopic observation results showed that compared with control group， the cell activity and cell quantity in high glucose group were decreased （P<0.05）； compared with high glucose group， the cell viability and cell quantity in SAL group were increased （P<0.05）. The flow cytometry results showed that compared with control group， the ROS level in RG cells of high glucose group was significantly increased； compared with high glucose group， the ROS level in cells of SAL group was significantly decreased. A total of 10 Hub genes highly associated with SAL were screened out by bioinformatics analysis， namely mammalian target of rapamycin （MTOR）， cysteine-aspartic protease 3 （CASP3）， hypoxia-inducible factor 1A （HIF1A）， sirtuin 1 （SIRT1）， toll-like receptor 4 （TLR4）， heat shock protein family A member 5 （HSPA5）， nuclear factor （erythroid-derived 2）-like 2 （NFE2L2）， nitric oxide synthase 3 （NOS3）， cysteine-aspartic protease 8 （CASP8） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）. The mRNA expression of the above genes was verified by RT-qPCR method. The protein docking results indicated that NFE2L2 was the core target with the highest correlation with SAL in protecting high glucose-induced RG cell injury. The Western blotting results showed that compared with control group， the expression level of Nfe2l2 protein in the cells （P<0.05） in high glucose group was increased and the expression level of Gpx4 protein was decreased （P<0.05）； compared with high glucose group， the expression level of Nfe2l2 protein in the cells in Nfe2l2 silencing group and SAL group was decreased （P<0.05） and the expression level of Gpx4 protein was increased （P<0.05）. Conclusion SAL treatment increases retinal thickness， alleviates retina tissue damage， enhances RG cell viability and reduces intracellular ROS levels in diabetic rats， and exerts a protective effect on the retina of diabetic rats. Its mechanism may be related to the down-regulation of Nfe2l2 expression by SAL.

Objective To discuss the effect of triptolide （TP） on hippocampal neuron injury in neonatal rats with hypoxic-ischemic encephalopathy （HIE）， and to clarify its related mechanism based on the phosphatase and tensin homolog deleted on chromosome 10 （PTEN）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway. Methods Twelve neonatal rasts were randomly selected as sham operation group； another 58 neonatal rats were usedto establish models.The HIE model was established by right common carotid artery ligation combined with hypoxic exposure. The 48 successful modeling rats were randomly divided into HIE group， low dose of TP group （L-TP group）， high dose of TP group （H-TP group） and high dose of TP+Ad-PTEN group （H-TP+Ad-PTEN group）， with 12 rats in each group. The neurobehavioral function of the rats in various groups was evaluated； triphenyltetrazolium chloride（TTC） staining was used to observe the cerebral infarction status of the rats in various groups； HE staining was used to observe the pathological morphology of the hippocampal CA1 region of the rats in various groups； kits were used to detect the serum levels of interleukin-6 （IL-6）， interleukin-8（IL-8） and tumor necrosis factor-α （TNF-α） of the rats in various groups； kits were used to detect the activities of superoxide dismutase （SOD） and catalase （CAT） and the levels of glutathione （GSH） in brain tissue of the rats in various groups； terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL） method was used to detect the number of positive neurons of the rats in various groups； Western blotting method was used to detect the expression levels of apoptosis-related proteins， PTEN， PI3K and AKT proteins， and phosphorylated PI3K（p-PI3K）/PI3K and phosphorylated AKT（p-AKT）/AKT ratios were caculated in brain tissue of the rats in various groups. Results ompared with sham operation group， the neurological function score， serum levels of IL-6， IL-8 and TNF-α， the number of positive nenrrons in hippocampal tissue， and the expression levels of B cell lymphoma-2（Bcl-2)-associated X protein（Bax）， Cytochrome c（Cyt c）， cysteinyl aspartate-specific proteinase-8（Caspase-8）， cysteinyl aspartate-specific proteinase-3（Caspase-3） and PTEN proteins in brain tissue of the rats in HIE group were increased （P<0.05）； the activities of SOD and CAT， the level of GSH， the expression level of Bcl-2 protein， p-PI3K/PI3K and p-AKT/AKT ratios in brain tissue of the rats in HIE group were decreased （P<0.05）. Compared with HIE group， the activities of SOD and CAT， the levels of GSH， the expression levels of Bcl-2 protein， and the p-PI3K/PI3K and p-AKT/AKT ratios in brain tissue of the rats in L-TP group and H-TP group were increased （P<0.05）， and the expression levels of Bax，Cyt c，Caspase-8，Caspase-3，and PTEN proteins were decreased （P<0.05）. Compared with H-TP group， the activities of SOD and CAT， the level of GSH， the expression level of Bcl-2， and the p-PI3K/PI3K and p-AKT/AKT ratios in H-TP+Ad-PTEN group were decreased （P<0.05）， and the expression levels of Bax，Cyt c，Caspase-8，Caspase-3， and PTEN proteins were increased （P<0.05）. Conclusion TP can inhibit PTEN expression and activate the PI3K/AKT signaling pathway， thereby reducing HIE-mediated hippocampal neuron injury， apoptosis， inflammatory response and oxidative stress in the neonatal rats， and plays a protective role against hippocampal neuron injury induced by HIE.

Objective To discuss the effect of exosome-induced macrophage polarization to M2 type on the biological behavior of human esophageal squamous cell carcinoma （ESCC） cells， and to clarify its molecular mechanism. Methods The data of esophageal cancer and normal esophageal tissue from The Cancer Genome Atlas （TCGA） database were analyzed； Gene Expression Profiling Interactive Analysis （GEPIA） was used to identify the enrichment of different subtypes of tumor-associated macrophages （TAMs） in esophageal cancer and normal tissues and the correlation between hypoxia-inducible factor 1α （HIF-1α） and related molecule expression in esophageal cancer； Tumor Immune Estimation Resource （TIMER） software was used to analyze the impact of TAMs on the survival indicators of esophageal cancer patients； single-sample gene set enrichment analysis （ssGSEA） was used to screen genes related to M2-type TAMs polarization. The Gene Expression Omnibus （GEO） database was searched with the keywords “ESCC” and “exosome” to obtain the GSE104926 dataset， which included plasma exosome gene expression profile data from ESCC patients and non-ESCC patients. GEO2R was used to analyze differential genes， exosome isolation kit was used to extract and purify exosomes produced by human ESCC cell line EC109. Transmission electron microscope （TEM） and nanoparticle tracking analysis （NTA） were used to detect the morphology and particle size of exosomes； Western blotting method was used to detect the expression of exosome-related proteins cluster of differentation（CD）9 and CD63 in the purified exosomes and the purified EC109 supernatant. Human peripheral blood mononuclear cell line THP-1 was induced into M0 macrophages using phorbol ester； immunofluorescence staining was used to observe the internalization process of exosomes by macrophages； flow cytometry was used to detect the expression of phenotypic markers CD80 and CD206 in macrophages after treated with EC109 exosomes and untreated M0 macrophages. Under hypoxic conditions， real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the expression levels of HIF-1α mRNA and protein in macrophages before and after EC109 exosome treatment. The macrophages before and after exosome induction were co-cultured with EC109 cells； cell counting kit 8（CCK-8） method was used to detect the proliferation activity of the EC109 cells； flow cytometry was used to detect the apoptotic rate of the EC109 cells； Transwell chamber assay was used to detect the rate of invasion EC109 cells； scratch wound healing assay was used to detect the migration ability of the EC109 cells and the wound closure rate was calculated. Results The TCGA and GEO data analysis results showed that compared with normal esophageal tissue， the infiltration numbers of various subtypes of TAMs in esophageal cancer were significantly increased （P<0.05）； the infiltration number of M2-type TAMs was closely related to the disease-free interval（DFI） of esophageal cancer patients （P<0.05）. Biglycan （BGN） was a gene with increased expression in plasma exosomes of ESCC patients and significantly associated with M2-type TAMs polarization （P<0.05）. In esophageal cancer tissue， there were significant positive correlations between the expression levels of M2-type TAMs markers macrophage scavenger receptor 1 （MSR1）， biglycan（BGN） and HIF-1α （r>0， P<0.05）. The isolated EC109-derived exosomes exhibited a cup-shaped morphology with a size of （127.17±0.90） nm. Compared with extracted EC109 supernatant， the expression levels of CD9 and CD63 in the extracted EC109 exosomes were significantly increased （P<0.05）. The EC109 exosomes could be taken up and internalized by macrophages. Compared with untreated M₀ macrophages， the number of CD80^- and CD206⁺ cells in macrophages treated with EC109 exosomes was significantly increased （P<0.05）， and the expression levels of HIF-1α mRNA and protein in the cells were significantly increased （P<0.05）. Compared with M0 macrophage treatment group， after co-culture of exosome-induced macrophages with EC109 cells， the proliferation activity of the EC109 cells was increased （P<0.05）， the apoptotic rate was increased （P<0.05）， the rate of invasion cells was increased （P<0.05）， and the migration area was increased （P<0.05）. Conclusion The ESCC cell-derived exosomes may regulate macrophage polarization by activating HIF-1α through BGN， thereby promoting ESCC proliferation and invasion， and inhibiting apoptosis； its mechanism is related to the role of exosomes in signal transmission in the interaction between ESCC and TAMs.

Objective To discuss the regulatory role of ETS translocation variant 4 （ETV4） in the biological behavior of esophageal cancer cells， and to clarify its possible molecular mechanism. Methods The expression levels of ETV4 mRNA in esophageal cancer tissue and normal esophageal tissue were analyzed using the Gene Expression Profiling Interactive Analysis 2 （GEPIA2） database. The esophageal cancer transcriptome dataset GSE199967 was obtained from the Gene Expression Omnibus （GEO） database， and the ETV4 mRNA expression level was analyzed using R software. Based on the TCGA-ESCA dataset， the expression distribution characteristics of ETV4 were systematically evaluated according to clinical stage， pathological grade， and histological subtype using the UALCAN online platform. The human esophageal cancer KYSE-150 cells were divided into control group and ETV4 interference group （shETV4 group）； the cells were transfected with control lentivirus or ETV4-targeted short hairpin RNA （shRNA） lentivirus， and after puromycin selection， the control cells and cells with stable ETV4 interference were established. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the ETV4 mRNA expression level in the cells in two groups； Western blotting method was used to detect the ETV4 protein expression levels in the cells in two groups； cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of the cells in the two groups； Transwell chamber assay was used to count the numbers of migration cells in two groups； wound healing assay was used to detect the wound healing rates of the cells in two groups. The target genes of ETV4 were predicted using the TF-Target Finder platform； potential binding sites of ETV4 in the promoter region of MDM2 binding protein （MTBP） were screened using the JASPAR database； dual-luciferase reporter assay was used to verify the regulatory effect of ETV4 on the MTBP promoter. The KYSE-150-shMTBP cells with stable MTBP interference was established； RT-qPCR method was used to detect the expression levels of MTBP， cyclin-dependent kinase inhibitor 1A （CDKN1A）， and cyclin-dependent kinase inhibitor 1B （CDKN1B） mRNA in the cells in two groups； flow cytometry was used to detect the percentages of the cells at different cell cycles. Results The bioinformatics analysis results showed that compared with normal esophageal tissue， the expression level of ETV4 mRNA in esophageal cancer tissues was increased （P<0.05）. In the TCGA-ESCA cohort， the expression levels of ETV4 mRNA in esophageal cancer tissues at clinical stages Ⅰ-Ⅳ， in tumor tissues with pathological grades G₁-G₃， and in adenocarcinoma and squamous cell carcinoma subtypes were all higher than those in normal tissue （P<0.001）； however， there was no statistically significant difference in ETV4 mRNA expression levels among the subgroups stratified by clinical stage， pathological grade， and histological subtype （P>0.05）. The KYSE-150-shETV4 cells with stable ETV4 interference was successfully constructed. Compared with control group， the ETV4 mRNA and protein expression levels in the cells in shETV4 group were decreased （P<0.001）. The CCK-8 assay results showed that compared with control group， the proliferation activity of the cells in shETV4 group was decreased （P<0.001）. The Transwell chamber assay results showed that compared with control group， the number of migration cells in shETV4 group was decreased （P<0.01）. The wound healing assay results showed that compared with control group， the wound healing rate of the cells in shETV4 group was decreased （P<0.001）. The KYSE-150-shMTBP cells with stable MTBP interference was successfully constructed. Compared with control group， the MTBP mRNA expression level in the cells in shMTBP group was decreased （P<0.001）. The bioinformatics analysis and dual-luciferase reporter assay results confirmed that MTBP was a downstream target gene of ETV4， and TFBS2 in its promoter region was the key binding site for ETV4. The RT-qPCR results showed that compared with control group， the expression levels of CDKN1A and CDKN1B mRNA in the cells in shMTBP group were increased （P<0.001）. The flow cytometry results showed that compared with control group， the percentage of cells in shMTBP group at G₀/G₁ phase was increased （P<0.001）， and the percentage of the cells at S phase was decreased （P<0.001）. Conclusion The transcription factor ETV4 activates the expression of MTBP by binding to its promoter， regulates the cell cycle， and promotes the proliferation and migration of esophageal cancer cells； its mechanism is related to the ETV4/MTBP axis.

Objective To investigate the effect of targeting protein for targeting protein for xenopus kinesin-like protein 2 （TPX2） on immune escape in the non-small cell lung cancer A549 cells， and to clarify its mechanism. Methods The TPX2 small interfering RNA plasmid （si-TPX2） and its negative control plasmid （si-NC） were transfected into the A549 cells using the liposome transfection method； the cells were divided into blank control group， si-TPX2 group， and si-NC group. The conditioned medium （CM） from A549 cells was collected and used to treat the CD8⁺ T lymphocytes； the cells were divided into CD8⁺ T group， CD8⁺ T+CM/blank group， CD8⁺ T+CM/si-NC group， and CD8⁺ T+CM/si-TPX2 group. The transfected A549 cells were pretreated with the wingless-type MMTV integration site family（Wnt）/β-catenin signaling pathway activator CHIR-99021； the cells were divided into si-NC group， si-TPX2 group， si-NC+CHIR-99021 group， and si-TPX2+CHIR-99021 group. A co-culture system of A549 cells and CD8⁺ T lymphocytes was established using Transwell chambers； the cells were divided into A549 group， A549si-NC group， A549si-TPX2 group， A549/T group， A549si-NC/T group， A549si-TPX2/T group， A549si-NC+CHIR-99021/T group， and A549si-TPX2+CHIR-99021/T group. Cell counting kit-8（CCK-8） method was used to detect the survival rates of the cells in various groups； flow cytometry was used to detect the levels of human leukocyte antigen DR （HLA-DR）， and programmed death-ligand 1 （PD-L1） and apoptotic rate in the cells in various groups； enzyme-linked immunosorbent assay（ELISA） method was used to detect the levels of interferon-γ （IFN-γ）， tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， transforming growth factor-β （TGF-β）， and IL-10 in supernatant of the cells in various groups； lactate dehydrogenase （LDH） release assay was used to detect the killing effect of CD8⁺ T lymphocytes on A549 cells； real-time fluorescence quantitative PCR（PT-qPCR） method was used to detect the expression levels of TPX2 mRNA in the cells in various groups； Western blotting method was used to detect the expression level of β-catenin protein in the cells in various groups. Results Compared with CD8⁺ T+CM/blank group， the survival rate of CD8⁺ T cells， the level of HLA-DR on cell surface， and the levels of IFN-γ， TNF-α， and IL-2 in the supernatant in CD8⁺ T+CM/si-TPX2 group were significantly increased （P<0.05）. Compared with A549si-TPX2 group， the survival rate of A549 cells in A549si-TPX2/T group was significantly decreased （P<0.05）. Compared with A549/T group， the survival rate of A549 cells in A549si-TPX2/T group was further decreased （P<0.05）， while the apoptotic rate and mortality rate of A549 cells were significantly increased （P<0.05）. Compared with blank group， the expression levels of total and nuclear β-catenin protein， the level of PD-L1 on cell surface， and the levels of TGF-β and IL-10 in the supernatant of A549 cells in si-TPX2 group were significantly decreased （P<0.05）. Compared with si-TPX2 group， the level of PD-L1 on A549 cell surface and the levels of TGF-β and IL-10 in the supernatant in si-TPX2+CHIR-99021 group were significantly increased （P<0.05）. Compared with A549si-TPX2/T group， the survival rate of A549 cells in A549si-TPX2+CHIR-99021/T group was significantly increased （P<0.05）， while the apoptotic rate and mortality rate of A549 cells on A549 cells were significantly decreased （P<0.05）. Conclusion TPX2 gene silencing inhibits immune escape in non-small cell lung cancer A549 cells， and its mechanism is related to blocking the activation of the Wnt/β-catenin signaling pathway.

Objective To investigate the effect of stromal cell-derived factor 1 （SDF-1） on ferroptosis of Schwann cells （SCs） after peripheral nerve injury （PNI）， and to elucidate its possible mechanism. Methods Animal experiment， 45 male 8-week-old SD rats were randomly divided into sham operation group， PNI group and SDF-1 treatment group （PNI+SDF-1 group）， with 15 rats in each group. The rats in sham operation group were subjected to sciatic nerve exposure without injury； the rats in PNI group and SDF-1 treatment group were subjected to sciatic nerve clamping method to establish the models. After modeling， the rats in PNI group were intramuscularly injected with 0.2 mL·d^-1 normal saline， and the rats in SDF-1 treatment group were intramuscularly injected with 4 μg·kg^-1·d^-1 SDF-1 for 5 consecutive days. On the 5th day after operation， 10 rats from each group were randomly selected and sacrificed to harvest the sciatic nerves. Western blotting method was used to detect the expression levels of long-chain acyl-CoA synthetase 4 （ACSL4）， glutathione peroxidase 4 （GPX4）， and ferroptosis suppressor protein 1 （FSP1） proteins in sciatic nerve of the rats in various groups； transmission electron microscope was used to observe the morphology of mitochondria in SCs in the sciatic nerve； Western blotting method was used to detect the expression levels of extracellular signal-regulated kinase （ERK）， phosphorylated extracellular signal-regulated kinase （p-ERK）， and nuclear factor erythroid 2-related factor 2 （Nrf2） proteins in the sciatic nerve. On the 14th day after operation， the remaining 5 rats from each group were sacrificed to harvest the sciatic nerves. HE staining was used to observe the morphology of sciatic nerve fibers； immunofluorescence staining was used to detect the expression levels of neurofilament 200 （NF200） and myelin basic protein （MBP） in sciatic nerve of the rats in various groups. Cell experiment， the SCs were divided into control group， lipopolysaccharide （LPS）- induced injury group （LPS group） and SDF-1 treatment group （LPS+SDF-1 group）. 2'，7'- Dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescence probe method was used to detect the reactive oxygen species （ROS） levels in the SCs in various groups； FeRhoNox-1 fluorescence probe method was used to detect the ferrous ion （Fe²⁺）） levels in the SCs in various groups； immunofluorescence staining was used to detect the expression of ACSL4 and GPX4 proteins in the SCs in various groups； Western blotting method was used to detect the protein expression levels of ACSL4， GPX4， FSP1， ERK， p-ERK， and Nrf2 in the SCs in various groups. Rescue experiment， the SCs were divided into LPS group， LPS+SDF-1 group， LPS+SDF-1+SCH772984 group and LPS+SCH772984 group； Western blotting method was used to detect the expression levels of Nrf2， ACSL4， GPX4， and FSP1 proteins in the SCs in various groups. Results In animal experiment， on the 5th day after operation， compared with sham operation group， the expression level of ACSL4 protein in sciatic nerve of the rats in PNI group was increased （P<0.01）， while the protein expression levels of GPX4 and FSP1 proteins were decreased （P<0.05）； the mitochondria in SCs were shrunken and the cristae structure was blurred； the p-ERK/ERK ratio and the protein expression level of Nrf2 were decreased （P<0.01）. Compared with PNI group， the expression level of ACSL4 protein in sciatic nerve of the rats in PNI+SDF-1 group was decreased （P<0.05）， while the expression levels of GPX4 and FSP1 proteins were increased （P<0.05）； the mitochondria in SCs showed increased volume and cristae structure tended to be normal； the p-ERK/ERK ratio and the protein expression level of Nrf2 were increased （P<0.01）. The HE staining results showed that on the 14th day after operation， compared with sham operation group， the sciatic nerve fibers in PNI group were arranged in disorder， and the fluorescence intensities of NF200 and MBP proteins in the sciatic nerve were decreased （P<0.01）； compared with PNI group， the sciatic nerve fiber arrangement in PNI+SDF-1 group tended to be normal， and the expression levels of NF200 and MBP proteins in the sciatic nerve were increased （P<0.05）. In cell experiment， compared with control group， the levels of ROS and Fe²⁺ in the SCs in LPS group were increased （P<0.01）， the expression level of ACSL4 protein was increased （P<0.01）， the expression level of GPX4 protein was decreased （P<0.05 or P<0.01）， the expression level of FSP1 protein was decreased （P<0.01）， and the p-ERK/ERK ratio and Nrf2 protein expression level were decreased （P<0.01）. Compared with LPS group， the levels of ROS and Fe²⁺ in the SCs in LPS+SDF-1 group were decreased （P<0.05）， the expression level of ACSL4 protein was decreased （P<0.05）， the expression level of GPX4 protein was increased （P<0.05）， the expression level of FSP1 protein was increased （P<0.05）， and the p-ERK/ERK ratio and Nrf2 protein expression level were increased （P<0.01）. In rescue experiment， compared with LPS group， the expression level of Nrf2 protein in the SCs in LPS+SDF-1 group was increased （P<0.01）， the expression level of ACSL4 protein was decreased （P<0.05）， and the expression levels of GPX4 and FSP1 proteins were increased （P<0.01）； the expression level of Nrf2 protein in the SCs in LPS+SCH772984 group was decreased （P<0.05）， the expression level of ACSL4 protein was increased （P<0.05）， and the expression levels of GPX4 and FSP1 proteins were decreased （P<0.05）. Compared with LPS+SDF-1 group， the expression level of Nrf2 protein in the SCs in LPS+SDF-1+SCH772984 group was decreased （P<0.01）， the expression level of ACSL4 protein was increased（P<0.05）， and the expression levels of GPX4 and FSP1 proteins were decreased（P<0.05）. Conclusion SDF-1 can inhibit ferroptosis of the SCs after PNI and promote the repair of the injured sciatic nerve， and its mechanism is related to the activation of ERK/Nrf2 signaling pathway.

Objective To discuss the regulatory effect of keratin 23 （KRT23） on the stem cell activity in hepatocellular carcinoma （HCC）， and to clarify its mechanism. Methods The Gene Expression Profiling Interactive Analysis （GEPIA） database was used to analyze the expression of KRT23 in hepatocellular carcinoma tissues and normal liver tissues； Kaplan-Meier Plotter survival analysis was performed to compare the survival of hepatocellular carcinoma patients with high and low expression of KRT23， and to evaluate the impact of KRT23 on the prognosis of hepatocellular carcinoma patients. Second-generation sequencing analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were conducted to identify the signaling pathways potentially regulated by KRT23， and the Wnt/β-catenin signaling pathway was finally selected for mechanistic study. Real-time fluorescence quantitative PCR （RT-qPCR）， Western blotting， and immunohistochemistry methods were used to verify the expression of KRT23 in HCC cells and HCC tissue， respectively， and immunofluorescence was used to clarify its subcellular localization. A lentiviral vector for KRT23 knockdown was constructed using a small interfering RNA （siRNA） with verified knockdown efficiency. After knocking down the expression level of KRT23， the stem cell sphere formation assay was performed to verify the regulatory effect of KRT23 on hepatocellular carcinoma stem cell activity， and RT-qPCR and Western blotting methods were used to detect the changes of related stem cell markers. Immunofluorescence and nuclear-cytoplasmic protein extraction were further used to verify the regulation effect of KRT23 on stem cells related indicators in the Wnt/β-catenin signaling pathway. Results The expression level of KRT23 in hepatocellular carcinoma tissues was higher than that in normal liver tissue. Compared with immortalized hepatocyte LO2， the expression levels of KRT23 in hepatocellular carcinoma cells were increased （P<0.05）； compared with the hepatocellular carcinoma patients with low expression of KR23， the hepatocellular carcinoma patients with high expression of KRT23 had a poorer prognosis （P=0.038）. The second-generation sequencing and KEGG signaling pathway analysis results showed that KRT23 might regulate stem cell activity and participate in the Wnt/β-catenin signaling pathway. The immunofluorescence localization results showed that KRT23 was mainly located in the cytoplasm. After verification of the knockdown efficiency of siRNA targeting KRT23， a lentiviral vector for KRT23 knockdown was constructed， and the transfection efficiency was re-verified. After KRT23 expression was reduced， compared with sh-NC group， the stem cell sphere formation rate in sh-KRT23 group was significantly decreased （P<0.01）， and the expression levels of stem cell-related markers cluster of differentiation 133 （CD133）， cluster-of-differentiation 44（CD44）， pctamer-blinding transcription factor 4（OCT4）， and SRY-box transcription-factor 2（SOX2） were also decreased （P<0.05 or P<0.01）. Conclusion KRT23 enhances the stem cell activity in hepatocellular carcinoma by regulating the Wnt/β-catenin signaling pathway， and the mechanism is related to the activation of the Wnt/β-catenin signaling pathway.

Objective To discuss the regulatory effect of silent information regulator 1 （SIRT1） on ovarian granulosa cells of advanced-age women， and to preliminarily clarify the mechanism by which SIRT1 activator resveratrol （RESV） improves the function of ovarian granulosa cells of advanced-age women. Methods Sixty patients underwent in vitro fertilization-embryo transfer （IVF-ET） were enrolled， including 30 advanced-age patients （advanced age group， age ≥40 years） and 30 non-advanced-age patients （non-advanced age group， age <35 years）. Density gradient centrifugation was used to collect the granulosa cell samples from follicular fluid of female patients in advanced age group（n=30） and non-advanced age group （n=30）. The granulosa cells from each advanced-age female patient were divided into control group， RESV group， and EX527 （SIRT1 inhibitor） group. The granulosa cells in control group were treated without any drug； the granulosa cells in RESV group were cultured in medium containing 100 μmol·L^-1 RESV for 48 h； the granulosa cells in EX527 group were cultured in medium containing EX527 for 48 h. After trypsin digestion， the granulosa cells were collected. Real-time fluorescence quantitative PCR（RT-qPCR） method was used to detect the expression levels of SIRT1， steroidogenic acute regulatory protein （StAR）， cytochrome P450 family 19 （CYP19）， and cytochrome P450 family 17 （CYP17） mRNA in the cells in various groups； Western blotting method was used to detect the expression levels of cysteine-containing aspartate protease 3 （Caspase-3） and B-cell lymphoma 2 （Bcl-2） proteins in the cells in various groups； chemiluminescence method was used to detect the estradiol level in the cell culture medium of the cells in various groups on the day of human chorionic gonadotropin （HCG） injection； terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL） method was used to detect the apoptotic rate of the cells in various groups. Results The RT-qPCR results showed that compared with non-advanced age group， the expression levels of SIRT1 mRNA and protein in the granulosa cells of the patients in advanced age group were decreased （P<0.05）. Compared with control group， the expression levels of SIRT1 mRNA and protein in granulosa cells of the patients in RESV group were increased （P<0.05）， while those in EX527 group were decreased （P<0.05）. Compared with control group， the expression levels of StAR， CYP19， and CYP17 mRNA and protein in granulosa cells of the patients in RESV group were increased （P<0.05）， while those in EX527 group were decreased （P<0.05）. The chemiluminescence method results showed that compared with control group， the estradiol level in granulosa cell culture medium of the patients in RESV group was increased （P<0.05）， while that in EX527 group was decreased （P<0.05）. The TUNEL method and Western blotting method results showed that compared with control group， the apoptotic rate of the granulosa cells of the patients in RESV group was decreased （P<0.05）， the expression level of Bcl-2 protein in the granulosa cells was increased （P<0.05）， and the expression level of Caspase-3 protein was decreased （P<0.05）； compared with control group， the apoptotic rate of granulosa cells of the patients in EX527 group was increased （P<0.05）， the expression level of Bcl-2 protein in the granulosa cells was decreased （P<0.05）， and the expression level of Caspase-3 protein was increased （P<0.05）. Conclusion The expression of SIRT1 in ovarian granulosa cells of advanced-age women is decreased. RESV inhibits granulosa cell apoptosis， increases the expression of steroidogenic enzymes in granulosa cells， and promotes estradiol synthesis in granulosa cells by promoting the expression of SIRT1 in granulosa cells of advanced-age women.

Objective To discuss the effect of interleukin-24 （IL24） on the biological behaviors of cervical cancer HeLa cells through regulation of V-Rel reticuloendotheliosis viral oncogene homolog B （RelB）， and to clarify the mechanism. Methods The HeLa cells were divided into control group ［pcDNA3.1（+） group， transfected with pcDNA3.1（+） plasmid］ and IL-24 overexpression group ［pcDNA3.1（+）-IL-24 group，transfected with pcDNA3.1（+）-IL-24 plasmid］. Real-time fluorescence quantitative PCR （RT-qPCR） and Western blotting methods were used to detect the transfection efficiencies of the cells in two groups； cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of the cells in two groups； flow cytometry was used to detect the apoptotic rates of the cells in two groups； Transwell chamber assay was used to detect the migration rates and invasion rates of the cells in two groups； transcriptome sequencing （RNA-seq） method and bioinformatics were used to explore the differentially expressed genes in two groups of IL-24； RT-qPCR and immunofluorescence staining methods were used to detect the expression level of RelB mRNA and protein in HeLa cells after IL-24 overexpression. In validation experiment， the HeLa cells were divided into pcDNA3.1（+） group， pcDNA3.1（+）-IL-24 group， HPV18 E6 overexpression group ［pcDNA3.1（+）- IL-24+E6 group， co-transfected with pcDNA3.1（+）-IL-24 plasmid and pcDNA3.1（+）-HPV18 E6 plasmid］， HPV18 E7 overexpression group ［pcDNA3.1（+）-IL-24+E7 group， co-transfected with pcDNA3.1（+）-IL-24 plasmid and pcDNA3.1（+）-HPV18 E7 plasmid］， and HPV18 E6/E7 overexpression group ［pcDNA3.1（+）-IL-24+E6+E7 group， co-transfected with pcDNA3.1（+）-IL-24 plasmid， pcDNA3.1（+）- HPV18 E6 plasmid， and pcDNA3.1（+）-HPV18 E7 plasmid］.RT-qPCR method was used to detect the expression levels of human papillomavirus（HPV18） E6 and HPV18 E7 mRNA and the expression level of RelB mRNA in the HeLa cells after transfection； Western blotting method was used to detect the expression level of RelB protein in the HeLa cells. Results Compared with pcDNA3.1（+） group， the expression levels of IL-24 mRNA and protein in the HeLa cells in pcDNA3.1（+）-IL-24 group were significantly increased （P<0.01）， the proliferation activity of the HeLa cells was decreased （P<0.001）， the migration rate of cells was decreased （P<0.05）， the invasion rate of cells was decreased （P<0.01）， and the apoptotic rate was increased （P<0.01）. The RNA-seq results showed that a total of 952 differentially expressed genes were identified， which were involved in multiple signaling pathways related to tumor occurrence and development， including nuclear factor-kappa B （NF-κB）， cyclic adenosine monophosphate （cAMP）， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）. The protein-protein interaction （PPI） network analysis results showed that RelB was located in core regulatory region of the network. Compared with pcDNA3.1（+） group， the expression levels of HPV18 E6， HPV18 E7 and RelB mRNA in the HeLa cells in pcDNA3.1（+）-IL-24 group were significantly decreased（P<0.01）. Furthermore， after overexpression of HPV18 E6 and E7 in the HeLa cells in pcDNA3.1（+）-IL-24 group， the expression level of RelB mRNA and protein was significantly increased （P<0.05）. Conclusion Overexpression of IL-24 can inhibit the proliferation， migration and invasion of the HeLa cells and promote the cell apoptosis. The mechanism may be related to the inhibition of HPV18 E6 and E7 expressions and the down-regulation of RelB protein expression level.

Objective To analyze the clinical characteristics of the patients with poor prognosis after ventilator associated pneumonia （VAP） following endovascular treatment for acute cerebral infarction， and to construct a prognostic nomogram and validate its clinical application. Methods The clinical data of 105 patients diagnosed with acute large vessel occlusion cerebral infarction （AIS-LVO） who developed postoperative VAP after undergoing endovascular treatment under general anesthesia with endotracheal intubation were retrospectively analyzed. According to the 90 d modified Rankin Scale （mRS） score， the patients were divided into good prognosis group （43 cases） and poor prognosis group （62 cases）. LASSO regression analysis was used to screen the predictive factors， and multivariate Logistic regression analysis was performed to construct the prognostic prediction model and generate a nomogram. The discrimination， calibration， and clinical utility of the model were evaluated using receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis （DCA）. Results A total of 105 patients with VAP after ventilator-associated pneumonia were included. According to the 90 d mRS score， all postoperative VAP patients were divided into good prognosis group and poor prognosis group， with good prognosis rate of 40.95%（43/105）， poor prognosis rate of 59.05%（62/105）， and mortality rate of 11.43%（12/105）. The LASSO regression analysis screened out 9 variables， including male， age， history of coronary heart disease， mechanical thrombectomy， balloon angioplasty， systemic inflammatory response index （SIRI）， swallowing dysfunction， admission mRS score， and intensive care unit （ICU） length of stay. The predictive factors screened by LASSO regression were incorporated into multivariate Logistic regression analysis， and male ［odds ratio（OR）=0.287， 95% confidence interval （CI）： 0.089-0.838， P=0.028］， ICU length of stay （OR=1.238， 95%CI： 1.064-1.498， P=0.014）， swallowing dysfunction （OR=3.347， 95%CI： 1.336-8.918， P=0.012）， and SIRI （OR=1.168， 95%CI： 1.022-1.399， P=0.044） were identified as independent risk factors for poor prognosis in the VAP patients after endovascular treatment for cerebral infarction. A prognostic prediction model was constructed based on these 4 indicators， with the formula： Logit （P）=-0.613-1.250×sex （male）+1.208×swallowing dysfunction+0.155×SIRI+0.214×ICU length of stay. The area under the ROC curve （AUC） of the prediction model was 0.806 （95%CI： 0.804-0.910， P<0.05）. The internal validation was performed using 1 000 bootstrap resampling， and the calibration curve was close to the ideal line， indicating good model accuracy. DCA demonstrated favorable clinical net benefit of the nomogram. Conclusion The prognostic prediction model constructed based on male， ICU length of stay， swallowing dysfunction， and SIRI has good predictive value for poor prognosis in the VAP patients after endovascular treatment for acute cerebral infarction， which can assist the clinicians in early identification and intervention.

Objective To discuss the construction method of phenotypic age （PA） models based on different combinations of multiple clinical biomarkers， and to clarify the influencing factors of PA acceleration. Methods Using the National Health and Nutrition Examination Survey （NHANES） database， the chronological age（CA） and the measurement results of nine clinical biomarkers including albumin（ALB）， alkaline phosphatase（ALP）， creatinine（Cr）， serum glucose（Glu）， C-reactive protein（CRP）， white blood cell count（WBC）， lymphocyte percent（LYM%）， mean cell volume（MCV）， and red cell distribution width（RDW） were collected from NHANES Ⅲ （1988-1994） and NHANES Ⅳ （1999-2018）. In the NHANES Ⅲ dataset， different subset combinations of the nine clinical biomarkers were constructed， and PA models were built and trained for each combination. The trained models were applied in the NHANES Ⅳ dataset to calculate PA and PA acceleration. Pearson correlation analysis and intraclass correlation coefficient（ICC） were used to assess the correlation and consistency between PA of each combination and PA of the full-indicator combination model. A weighted linear regression model was used to analyze the influencing factors of PA acceleration. An interactive website for dynamic PA assessment was established using HBuilder software based on hyper text markup language（HTML）， cascading style sheets（CSS）， and JavaScript technologies. Results A total of 502 combinations of the nine biomarkers were generated， and 324 high-quality combinations were identified. Among them， 142 high-quality combinations had correlation coefficients and ICC greater than 0.990 0. The weighted linear regression model results showed that female and higher education level were protective factors for PA acceleration （β=-0.85， 95%CI： -0.97--0.73； β=-1.14， 95%CI：-1.37--0.90）， while higher body mass index（BMI） and smoking were the risk factors for PA acceleration （β=2.45， 95%CI： 2.26-2.64； β=1.09， 95%CI： 0.94-1.24）. Other Hispanic individuals had significantly higher PA acceleration levels compared with Mexican Americans （β=0.84， 95%CI： 0.55-1.12）. Conclusion PA models based on different combinations of multiple clinical biomarkers have been successfully constructed， and an interactive website for dynamic PA assessment has been established， providing an effective tool for individual aging assessment. Higher BMI and smoking are the risk factors that accelerate biological aging of the body.

Objective To systematically evaluate the effect of oral supplementation of docosahexaenoic acid （DHA） and arachidonic acid （ARA） on the incidence of necrotizing enterocolitis （NEC） in the preterm infants， and to clarify the correlation. Methods Seven Chinese and English databases including PubMed， CNKI， and Wanfang were searched for studies on the association between oral DHA and ARA supplementation and NEC in the preterm infants from inception to October 2025. Two researchers independently completed literature screening and data extraction. The publication bias was assessed using funnel plots and Egger’s test. Relative risk （RR） and 95% confidence interval （CI） were used as effect indicators， and Meta analysis was performed. Results A total of 10 studies were included， including 6 studies with low risk of bias and 4 studies with unclear risk. The Meta-analysis results showed that oral DHA and ARA supplementation had no significant effect on the incidence of NEC （RR=1.01， 95%CI： 0.72-1.43， P=0.94）. The subgroup and sensitivity analyses results indicated that the form of supplementation （DHA combined with ARA or DHA alone）， the dose level （high or low dose）， and different gestational ages of the preterm infants didn’t significantly affect the incidence of NEC； no significant effect was observed on the NEC incidence of preterm infants with Bell stage≥Ⅱ grade. Conclusion Oral supplementation of DHA and ARA in the preterm infants has not been shown to have a significant protective effect on the incidence of NEC， and its clinical value in the prevention and treatment of NEC still needs to be further verified by research.

Objective To construct a machine learning（ML）-based prediction model for esophageal cancer （EC） using routine clinical laboratory data， and to clarify the relative contribution of key laboratory indicators to model prediction. Methods A retrospective case-control study was conducted. The clinical laboratory data were collected from 2 763 patients with EC and 3 297 age-and sex-matched healthy controls（HC） treated at the First Affiliated Hospital of Air Force Medical University between January 2019 and December 2024. After missing value imputation， outlier removal， and data normalization， recursive feature elimination （RFE） combined with least absolute shrinkage and selection operator （LASSO） regression was used to screen predictive features. Based on the selected features， extreme gradient boosting （XGBoost）， logistic regression （LR）， light gradient boosting machine （LightGBM）， random forest （RF）， adaptive boosting （AdaBoost）， and decision tree （DT） models were constructed. Model performance was comprehensively evaluated using the area under the receiver operating characteristic（ROC） curve （AUC）， decision curve analysis （DCA）， calibration curves， and precision-recall （PR） curves. SHapley Additive exPlanations （SHAP） were applied to interpret the optimal model. Results From 67 routine laboratory indicators， 10 EC-related predictive features were identified， including carcinoembryonic antigen （CEA）， urinary cast quantity （UCQ）， red cell distribution width-standard deviation （RDW-SD）， platelet （PLT） count， platelet distribution width （PDW）， alkaline phosphatase （ALP）， uric acid （UA）， creatinine （Cr）， alanine aminotransferase （ALT）， and total protein （TP）. Among the compared models， the LightGBM model achieved the best performance in the test cohort， with an AUC of 0.953 ［95% confidence interval（95%CI）： 0.942-0.964］， and demonstrated good calibration and higher clinical net benefit in calibration and DCA. Conclusion The ML-based prediction models for EC was developed using routine clinical laboratory data and systematically validated in an internal dataset. Among the compared models， the LightGBM model showed the best performance， with high discriminative ability and good validation performance.

Objective To discuss the clinical efficacy of sacubitril/valsartan （SV） combined with dapagliflozin （DAPA） in the treatment of heart failure with preserved ejection fraction （HFpEF）， and to clarify the effectiveness and safety of the combination therapy， so as to provide evidence-based basis for clinical treatment decisions. Methods The randomized controlled trials on SV combined with DAPA for HFpEF were retrieved from Chinese and English databases including CNKI， Wanfang， VIP， SinoMed， PubMed， the Cochrane Library， Embase， Web of Science， China Medical Journal Network， ClinicalTrials.gov， and the International Traditional Medicine Clinical Trial Registry Platform， with the search period from the establishment of the databases to July 2025. Two researchers independently completed literature screening and data extraction， and evaluated the risk of bias of the included literature. The Cochrane risk assessment tool was used for quality evaluation； the heterogeneity test was conducted using I 2 to assess the degree of heterogeneity among the study results； when I 2<50%， a fixed effect model was used； when I 2≥50%， a random effect model was used. Sensitivity analysis was performed for studies with high heterogeneity to verify the stability of the results. RevMan 5.4 and Stata 18.0 software were used for Meta-analysis. Results A total of 10 randomized controlled trials involving 1 015 patients were included. The Meta-analysis results showed that compared with SV alone， the combination of SV and DAPA had more advantages in improving the total clinical effective rate ［odds ratio（OR）=5.52， 95% confidence interval（CI）：2.87—10.62， P<0.000 01］， improving the quality of life of patients （OR=5.54， 95%CI：3.59—7.50， P<0.000 01）， improving the left ventricular ejection fraction（LVEF） （OR=3.66， 95%CI：1.69—5.63， P=0.000 3） and the 6-minute walking distance （6MWD）［mean difference（MD）=48.70， 95%CI：1.40—96.00， P=0.04］， reducing the N-terminal pro-B-type natriuretic peptide （NT-proBNP） level ［standardized mean difference（SMD）=-1.84， 95%CI：-2.99—-0.69）， P=0.002］， reducing the incidence of major adverse cardiovascular events（MACE） （OR=0.38， 95%CI：0.22—0.67， P=0.000 8）， and reducing 2 h postprandial glucose（2hPG） （MD=-1.19， 95%CI：-2.08—-0.30）， P=0.009）， and the differences were statistically significant. There were no statistically significant differences between experimental group and control group in the incidence of adverse reactions， fasting blood glucose（FBG） level， and glycated hemoglobin（HbA1c） level （P>0.05）. Conclusion The combination of SV and DAPA in the treatment of HFpEF can effectively improve clinical efficacy. It has certain advantages in improving the patient’s cardiac function， enhancing the quality of life， and reducing 2hPG， and does not increase the risk of adverse reactions or MACE， showing good safety.

Objective To discuss the expression changes of poly（rC）-binding protein 1 （PCBP1）， ferritin heavy chain 1 （FTH1）， and glutathione peroxidase 4 （GPX4） proteins in placental tissue from the postpartum women with preeclampsia （PE） and the human trophoblast cells HTR-8/SVneo after treated with hypoxia or erastin， and to clarify their mechanisms. Methods The placental tissues were collected from 12 postpartum women with PE （PE group） and 12 women with normal pregnancy （normal group）. Transmission electron microscope was used to observe the ultrastructures of placental trophoblasts； immunohistochemistry and Western blotting methods were used to detect the expression levels of PCBP1 and GPX4 proteins in placental tissue of the women in two groups. The HTR-8/SVneo cells were treated with different concentrations （0， 5， 10， 20， 40和80 μmol·L^-1） of erastin， and cell counting kit-8 （CCK-8） method was used to measure the cell viabilities to screen the erastin concentration. The HTR-8/SVneo cells were exposed to normal enulorment（normoxia group）， hypoxia （<1% O?， 24 h， hypoxia group） or erastin （0， 20， 40 μmol·L^-1）， and Western blotting method was used to detect the expression levels of PCBP1， FTH1 and GPX4 proteins in the cells under different treatments； Pearson correlation analysis was used to analyze the correlations between the expression level of PCBP1 protein in placental tissue of the postparum with PE and systolic and diastolic blood pressures. Results Compared with normal group， the placental trophoblasts in PE group showed obvious mitochondrial ultrastructural damage； the expression level of PCBP1 protein in placental tissue of the postpartum women PE group was increased （P<0.01）， while the expression level of GPX4 protein was decreased （P<0.01）. Compared with normoxia group， the expression levels of PCBP1 and FTH1 proteins in the HTR-8/SVneo cells in hypoxia group were increased （P<0.05 or P<0.01）， and the expression level of GPX4 protein was decreased （P<0.05）. Compared with 0 μmol·L^-1 erastin group， the cell viabilities in 20 and 40 μmol·L^-1 erastin groups were decreased （P<0.05）， the expression level of PCBP1， protein in the cells in 40 μmol·L^-1 erastin group and the expression levels of FTH1 proteins in the cells were increased （P<0.05）， and the expression levels of GPX4 protein in the cells in 20 and 40 μmol·L^-1 erastin groups were decreased （P<0.01）， but the difference in GPX4 protein expression level between 20 μmol·L^-1 erastin group and 40 μmol·L^-1 erastin group was not statistically significant （P>0.05）. The Pearson correlation analysis results showed that the expression level of PCBP1 protein in placental tissue of the postparum women was positively correlated with both systolic and diastolic blood pressure （r=0.761 4， P<0.01； P=0.623 9， P<0.01）. Conclusion The PCBP1 protein expression is increased and the GPX4 protein expression is decreased in placental tissue of the postpartum woment with PE； hypoxia and erastin treatment can increase the expressions of PCBP1 and FTH1 protein and decrease the expression of GPX4 protein in the HTR-8/SVneo cells， and their mechanisms may be related to iron homeostasis imbalance and impaired antioxidant defense.

Objective To investigate the independent risk factors for venous thromboembolism （VTE） in lung cancer patients， clarify the respective advantages of four risk assessment models（RAM） in predicting and assessing the risk of VTE occurrence in lung cancer patients， explore the most suitable RAM for predicting VTE occurrence in lung cancer patients， and to evaluate the predictive value of each model in different pathological types of lung cancer. Methods A total of 390 lung cancer patients admitled to hospital from Mar.2013 to Mar.2013 were included in this study， with 130 cases allocated to VTE group and 260 cases to non-VTE group based on their medical records. The general and clinical data characteristics of all lung cancer patients were collected， and 35 related risk factors were included. The independent risk factors of lung cancer patients with VTE were screened by Logistic regression analysis. Khorana RAM， Caprini RAM， COMPASS-CAT RAM and Padua RAM were used to score the lung cancer patients. The receiver operating characteristic （ROC） curves of the four RAM were plotted and the area under curve （AUC） was caculated； MedCalc software was used to analyze and compare the predictive value of the four RAM for VTE risk in the lung cancer patients， and to compare the prediction probability of the same RAM in the different lung cancer patients. Results The results from stepwise regression analysis showed that varicose veins ［odds ratio （OR）=2.23， P<0.05）］， COMPASS-CAT RAM≥7 points （OR=9.332， P<0.05）， acute disease hospitalization （OR=2.732， P<0.05）， ZPS score （OR=2.178， P<0.05）， and D-dimer （OR=3.034， P<0.05） were independent risk factors for VTE in the lung cancer patients. The ROC curves were plotted for the four models， showing that COMPASS-CAT RAM’s predictive performance for VTE occurrence in the lung cancer patients （AUC=0.742） was significantly superior to Caprini RAM （AUC=0.613）， Khorana RAM （AUC=0.558）， and Padua RAM （AUC=0.642）. The analysis using MedCalc software revealed that there were no significant differences in the prediction of four kinds of RAM for VTE occurreuce in the lung cancer patients with different types （P>0.05）. Conclusion Varicose veins， COMPASS CATRAM≥7 points， acute disease hospitalization， D-dimer score and ZPS score are the independent risk factors for VTE. COMPASS-CAT RAM has higher predictive value for VTE risk in the lung cancer patients than Khorana RAM， Padua RAM and Caprini RAM. It is more suitable for the risk prediction of VTE occurrence in the lung cancer patients. There is no significant difference between four kinds of RAM in predicting VTE occurence in lung adenocarcinoma， squamous cell carcinoma and small cell lung cancer.

Objective To discuss the clinical application effect of anesthesia induction with remimazolam combined with propofol in modified electroconvulsive therapy （MECT） for the patients with mental disorders， and to clarify its mechanism. Methods A total of 62 patients with mental disorders who were scheduled for MECT were enrolled and randomly divided into combined medication group （receieved remimazolam combined with propofol， n=31） and single medication group （receieved propofol alone， n=31）. Before MECT， anesthesia induction was administered to the patients. The patients in combined medication group were intravenously injected with 0.1 mg·kg^-1 remimazolam and 1 mg·kg^-1 propofol， while the patients in single medication group were intravenously injected with 2 mg·kg^-1 propofol. MECT was performed after the patients lost consciousness. The anesthesia outcomes were recorded， including the time to loss of consciousness， time to recovery of spontaneous breathing， and time to awakening. The hemodynamic changes of the patients were recorded， including mean arterial pressure （MAP） and heart rate （HR） before induction （T0）， after induction （T1）， during seizure （T2）， and at awakening （T3）. Electroencephalogram monitoring was used to record the stimulation duration， stimulation charge， and seizure duration of MECT. The occurrence of adverse reactions after MECT was recorded. Results Compared with single medication group， the time to loss of consciousness in the patients in combined medication group was prolonged （P<0.001）， while the time to awakening and the time to recovery of spontaneous breathing were shortened （P<0.001）. There was no statistically significant difference in baseline （T0） hemodynamic indices of between patients two groups （P>0.05）. However， the time-group interaction effects for HR and MAP of the patients in combined medication group were significant （P<0.01 or P<0.001）， indicating that the hemodynamic change pattern was superior to that in single medication group. The seizure duration of MECT in the combined medication group was longer than that in single medication group （P=0.008）， and the incidences of injection pain， hypotension， and agitation were lower than those in single medication group （all P<0.05）. There was no statistically significant difference in the incidence of headache of the between patients two groups （P>0.05）. Conclusion For the patients with mental disorders undergoing MECT， anesthesia induction with remimazolam combined with propofol maintains circulatory stability， shortens awakening time， prolongs seizure duration， and reduces the occurrence of adverse reactions， achieving good clinical application effects. The mechanism may be related to the r-aminobutyric acid receptor α （GABA_a） receptor modulation of remimazolam and the reduction of propofol injection pain.

Objective To discuss the clinical efficacy and feasibility of one-stage fracture reduction and internal fixation in the patients with maxillofacial skin and soft tissue contusions and lacerations complicated with fractures caused by trauma， and to clarify the basis for optimizing the treatment plan for open maxillofacial fractures. Methods A total of 47 patients with open maxillofacial fractures were selected as subjects. All the patients underwent pre-operative multi-departmental joint assessment or treatment to exclude life-threatening emergencies such as craniocerebral， injury limb fracture， and spinal injury. After admission， all the patients underwent surgery under general anesthesia with endotracheal intubation or tracheostomy. Thorough debridement of the traumatic wound was performed， followed by fracture reduction and fixation using metal internal fixators. The patients were followed up for 6 months to observe the healing situation and the occurrence of complications. Results Among the 47 patients， 45 patients healed well， with a healing rate of 95.7% （45/47）； only 2 patients developed complications， including 1 patient with mandibular fracture who developed postoperative wound infection and achieved delayed healing after secondary debridement； 1 patient presented with a non-healing intraoral wound and exposure of the titanium plate for fracture of anterion wall of maxillary sinus， and the wound was repaired after the removal of the fixator. The reason was that both patients had intraoral mucosal wounds， possibly due to poor postoperative oral hygiene care leading to infection. Conclusion For the patients with maxillofacial trauma as the main injury， stable vital signs， fully exposed fractures， without need for additional auxiliary incisions， one-stage reduction and internal fixation can achieve satisfactory reduction results in those with clean wounds or after strict debridement. The one-stage surgery simultaneously treats facial trauma and facial bone fractures， can effectively reduce the physical and economic burden caused by secondary surgery， and promote good recovery of facial appearance and function.

Objective To observe the safety and aesthetic outcomes of immediate breast reconstruction using silicone gel prosthesis combined with titanium mesh patch via prepectoral breast reconstruction（PBR） and subpectoral breast reconstruction（SBR）， and to clarify its clinical application value. Methods From April 2021 to October 2023， 171 patients who met the inclusion criteria and underwent immediate breast reconstruction with silicone gel prosthesis combined with titanium mesh patch after nipple-sparing mastectomy（NSM） or skin-sparing mastectomy（SSM） were enrolled. According to the reconstruction method， they were divided into PBR group （n=64） and subpectoral SBR group （n=107）. The clinical data of the patients in two groups were collected to analyze the intraoperative blood loss， postoperative complications， aesthetic outcomes of the reconstructed breast， and short-term follow-up results. Results The total postoperative drainage volume of the patients in PBR group was lower than that in SBR group （P=0.022）. The overall complication rate of all the patients was 39.18%， and the incidence of capsular contracture in SBR group was higher than that in PBR group （P<0.001）. There was no statistically significant difference in the excellent/good rates of the Harris scale for breast reconstruction between PBR group （93.7%） and SBR group （94.4%） （P=0.888）. At one year after operation， the scores of the BREAST-Q 2.0 scale in PBR group were significantly better than those in SBR group in terms of physical well-being（P=0.003）， psychosocial well-being（P=0.038）， and satisfaction with the reconstructed breast （P=0.034）. The regarding oncological safety， tumor recurrence and metastasis rates of the patients in PBR group and SBR group were 1.6% and 4.7%， and the difference between two groups was not statistically significant （P=0.257）. Conclusion Compared with SBR， PBR can significantly reduce the risks of breast animation deformity， capsular contracture， and rippling， and achieves better aesthetic outcomes， and improves patients’ postoperative psychological well-being. There is no significant difference in short-term oncological safety between the two surgical approaches.

Objective To discuss the imaging risk factors for invasiveness of mixed ground-glass nodule （mGGN）-like pulmonary adenocarcinoma， to construct a machine learning model combining clinical imaging features and radiomics， and to clarify its diagnostic efficacy. Methods A total of 261 patients with postoperative pathologically confirmed mGGN-like pulmonary adenocarcinoma were retrospectively collected， and 278 mGGNs met the inclusion criteria. According to the pathological results， they were divided into indolent group （n=73） and invasive group （n=205）. The clinical data and imaging data of the patients in two groups were collected. All the patients underwent thin-slicecomputed tomography（CT） scanning； radiomic features were extracted. Feature dimensionality reduction was performed on the data via Z-score standardization combined with LASSO regression， and a 10-fold cross-validation was adopted to complete the screening process. The optimal omics features were identified， and a radiomics model based on the machine learning algorithm of Logistic Regression （LR） was constructed. Univariate and multivariate logistic regression analyses were used to identify the imaging features with significance for invasiveness of mGGN-like pulmonary adenocarcinoma； nomogram was drawn by combining the optimal radiomic features； the area under the receiver operating characteristic （ROC） curve （AUC）， calibration curve， and decision curve analysis （DCA） were used to evaluate the predictive performance of the model. Bootstrap method was used for model validation. Results Among the 278 included mGGNs， a total of 205 patients were pathologically confirmed as invasive mGGN-like pulmonary adenocarcinoma. Compared with indolent group， the optimal radiomic features extracted from the patients in invasive group included maximum three dimension（3D） diameter， the 90th percentile， inverse difference moment normalized， and surface area to volume ratio. The univariate Logistic analysis results showed that the incidences of spiculation， lobulation， air bronchogram sign， pleural indentation sign， spinous process， long diameter， short diameter， and mean CT value in the patients in invasive group were higher than those in indolent group （P<0.05）. The multivariate Logistic regression analysis results showed that lobulation was significantly associated with the risk of group classification ［odds ratio（OR）=3.724， 95% confidence interval（CI）： 1.373-10.100， P=0.010］； for every 1 mm increase in long diameter， the risk of group classification was increased by 31.8% （OR=1.318， 95%CI： 1.152-1.509， P<0.001）； for every 1 HU increase in mean CT value， the risk of invasive carcinoma was increased by 0.6% （OR=1.006， 95%CI： 1.003-1.009， P<0.001）. The AUC of the fusion nomogram constructed by combining lobulation， nodule long diameter， mean CT value and radiomics score was 0.858 （95%CI： 0.813-0.914）， and the bootstrap concordance index （C-index） of model was 0.835. The DCA curve results showed that the model had good clinical applicability. The Hosmer-Lemeshow test results showed that the nomogram had a good fit. Conclusion Lobulation， nodule long diameter and mean CT value are the risk factors for invasiveness of mGGN-like pulmonary adenocarcinoma. The fusion nomogram has good diagnostic efficacy for invasiveness of mGGN-like pulmonary adenocarcinoma， and may provide a new method for non-invasive diagnosis and individualized treatment in clinical practice.

Creutzfeldt-Jakob disease （CJD） is a fatal neurodegenerative disorder caused by prions， characterized by a rapidly progressing clinical course. Diagnosis often occurs in the mid-to-late stages， and the fast disease progression and high lethality pose significant challenges for clinical treatment. Although understanding of prions has deepened in terms of molecular mechanisms， effective interventions and drugs remain lacking in clinical diagnosis and management. Based on the latest domestic and international research advances in the treatment of CJD， this article summarized and reviewd the main research directions and recent achievements in CJD treatment. It coverd four aspects： historical drug therapies， immunotherapy， gene therapy， and emerging treatment strategies. The mechanisms， preclinical studies， and clinical trial outcomes of various approaches were summarized and evaluated. The breakthroughs and limitations of current treatment strategies were discussed to provide the foundation for exploring future research directions and developing novel therapies.

Pituitary adenoma （PA） is a common primary brain tumor， and its tumor microenvironment （TME） plays a critical role in the occurence and development and treatment response of tumor. The TME consists of various cellular components， including regulatory T lymphocytes （Tregs）， cytotoxic T lymphocytes （CTLs）， B lymphocytes， macrophages， and stromal cells. Tregs promote immune escape and tumor progression by secreting inhibitory cytokines， while CTLs exhibit dual roles， either killing tumor cells or， under certain conditions， facilitating tumor growth. B lymphocytes show limited infiltration in PA， but their presence is associated with tumor progression and prognosis. The macrophages predominantly exhibit the M2 phenotype， promoting immune evasion and metastasis through the secretion of inhibitory cytokines， pro-angiogenic factors， and matrix metalloproteinase. Stromal components， including the extracellular matrix （ECM） and cancer-associated fibroblasts （CAFs）， remodel the TME and influence tumor growth and invasion. In recent years， immunomodulatory therapies and anti-angiogenic therapies targeting the TME have achieved some progress.The immune checkpoint inhibitors have demonstrated certain efficacy in aggressive pituitary tumors， while anti-angiogenic drugs restrict tumor growth by inhibiting vascular endothelial growth factor （VEGF）. However， current therapeutic strategies still require further optimization to improve efficacy and life quality of the patients. This review summarized the cellular components of TME in PA and their mechanisms， highlighted the advances in immunotherapy and anti-angiogenic therapy， and explored future optimization strategies， aiming to provide the insights for precision treatment of PA.

Acetylation modification is an important type of post-translational acylation modification for protein. Under the dynamic regulation of histone acetyltransferase （HAT） and histone deacetylase （HDAC）， it affects the biological functions of proteins， and thereby alters the activation state of tumor-related signaling pathways. Consequently， acetylation modification plays a dual role in tumorigenesis and tumor progression， exhibiting both oncogenic and tumor-suppressive effects in various types of cancer. Drawing on recent literatures， this review systematically elucidated the potential molecular mechanisms involved in the regulation of tumor occurrence and development by acetylation modification， focusing on its regulatory effects on key signaling pathways， as well as its impact on crucial biological processes such as tumor cell proliferation， differentiation， metabolism， and apoptosis. Additionally， it further summarized the progress in the application of HDAC inhibitor （HDACi） in tumor therapy， elucidated therapeutic strategies targeting histone or non-histone deacetylation sites， and discussed the significance and potential clinical value. Acetylation modification influences the biological behavior of tumor by regulating the key signaling pathways. HDACi interferes with tumor progression by increasing the acetylation levels of target proteins， and its mechanism is related to the regulation of acetylation modifications in key signaling pathways.

Metabolic-associated fatty liver disease （MAFLD） is a common liver disorder， and its incidence continues to rise along with the increasing prevalence of metabolic diseases such as obesity and diabetes. chronic periodontitis（CP）， a prevalent oral disease， has also been confirmed to be closely associated with overall health. A certain correlation exists between CP and MAFLD. CP may affect hepatic fat metabolism through multiple pathways， thereby increasing the risk of MAFLD. Periodontal pathogens and their metabolites may directly act on the liver， inhibiting the insulin signaling pathway， reducing hepatic glycogen synthesis， and leading to hyperglycemia. The chronic inflammatory response induced by CP elevates the levels of pro-inflammatory cytokines in the blood， such as tumor necrosis factor α（TNF-α） and interleukin-6 （IL-6）. These factors can disrupt the adipocytes and affect the balance of adipokines， thus leading to hepatic insulin resistance. CP also increases the level of reactive oxygen species （ROS） in the blood， triggering systemic oxidative stress， damaging liver cells， and exacerbating the condition of MAFLD. Furthermore， CP may influence hepatic fat metabolism and inflammatory response by activating signaling pathways such as nuclear factor κB （NF-κB）， c-Jun N-terminal kinase （JNK）， and high mobility group box 1-Toll-like receptors （HMGB1-TLR）， thereby promoting the occurrence and development of MAFLD. Future studies are needed to explore the association mechanism between CP and MAFLD， and to conduct cohort studies and prospective studies to evaluate the impact of CP treatment on the patients with MAFLD. Additionally， combined treatment strategies， such as dietary adjustments， exercise， and anti-inflammatory drug therapy， should be explored to improve therapeutic outcomes. This review summarized the correlation between CP and MAFLD， providing new insights for clinical practice， and reminding clinicians to pay attention to the periodontal health status of patients and take appropriate preventive and therapeutic measures when treating MAFLD.