Abstract:Objective To investigate the effect of tetrandrine on the malignant phenotype of glioma cells and its molecular mechanism.Methods High-expression protein-coding genes potentially bound by tetrandrine in glioma were screened based on TCGA,GEO,MSigDB and CTD databases.The downstream pathways of transforming growth factor-β1(TGF-β1)were screened according to single-gene GSEA pathway analysis.CCK-8 assay was performed to determine cell viability,and crystal violet staining was used to measure colony-forming ability.Flow cytometry was applied to analyze cell cycle distribution and apoptosis rate,and wound-healing assay and Transwell assay were carried out to evaluate cell migration and invasion ability.RT-qPCR and Western blot were used to detect the expression of epithelial-mesenchymal transition(EMT)-related proteins and regulatory factors of the Smad2-Snail pathway.Cell models with high and low expression of TGF-β1 were constructed by transfection.Results TGF-β1 was highly expressed in the tumor tissues of glioma patients and was associated with poor prognosis.Tetrandrine could potentially bind to and inhibit TGF-β1 protein(P＜0.05).Tetrandrine significantly inhibited the proliferation,migration and invasion activities of glioma cells U251 and T98G,induced apoptosis,inhibited the EMT process and blocked the activation of the TGF-β1/Smad2-Snail pathway(P≤0.01).Down-regulation of TGF-β1 expression could inhibit the proliferation of glioma cells and induce apoptosis(P＜0.05,P＜0.01).Conclusion Tetrandrine inhibits the EMT process of glioma by regulating the TGF-β1/Smad2-Snail axis,providing a new theoretical basis for the treatment of glioma.

Abstract:Objective To observe the efficacy and safety of Toripalimab(JS001)combined with Capecitabine(CAPE)and concurrent volumetric modulated arc therapy(VMAT)in the treatment of locally advanced or advanced esophageal squamous cell carcinoma(ESCC).Methods From November 2022 to November 2023,105 patients with locally advanced or advanced ESCC were selected and divided into the observation group(n=54)and the control group(n=51)according to different treatment regimens.The observation group was treated with JS001 combined with CAPE and concurrent VMAT,while the control group was treated with CAPE and concurrent VMAT.CAPE treatment was administered in 21-day courses for a total of 4 cycles;VMAT was administered 5 times per week,for a total of 30 times;JS001 treatment was administered in 2-week courses for a total of 6 cycles.After the completion of all treatments,the efficacy and safety were evaluated at 4 weeks after the end of treatment,and tumor markers[carcinoembryonic antigen(CEA),squamous cell carcinoma antigen(SCC-Ag)],cellular immune function indicators(CD3+,CD8+),and survival status after 1-year follow-up were compared between the two groups.Results After treatment,the objective response rate(ORR)of the observation group was higher than that of the control group(P＜0.05).After treatment,the levels of CES and SCC-Ag in both groups were lower than those before treatment,which were lower in the observation group than in the control group(P＜0.05,P＜0.01).After treatment,the levels of CD3+in both groups were higher than those before treatment,and the levels in the observation group were higher than those in the control group(P＜0.05,P≤0.01).After treatment,the levels of CD8+in both groups were lower than those before treatment,and the levels in the observation group were lower than those in the control group(P＜0.05,P＜0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).The 1-year survival rate of the observation group was 64.81％(35/54),which was higher than that of the control group(49.02％,25/51),and the Kaplan-Meier survival curve showed a significant difference between the two groups(Log-rank x2=4.395,P=0.036).Conclusion The combination of JS001,CAPE and concurrent VMAT for the treatment of locally advanced or advanced ESCC can improve the ORR and 1-year survival rate of patients,regulate tumor markers and cellular immune function,and has good safety.

Abstract:Acute lung injury(ALI)and its critical stage of acute respiratory distress syndrome(ARDS)are common critical illnesses in clinical practice.The pathological process involves complex immune imbalance and tissue repair disorders.Regulatory T cells(Treg)are important regulatory factors in immune regulation that play a crucial protective role in ALI/ARDS through multiple mechanisms such as secreting inhibitory cytokines,blocking the activation of effector T cells,regulating immune cell subsets,and promoting alveolar epithelial repair.Therefore,in-depth exploration of the specific mechanism of Treg in ALI/ARDS will provide important basis for developing targeted immunoregulatory therapeutic strategies.This article reviews the biological characteristics of Treg,its mechanism of action in ALI/ARDS,and related immunotherapy research progress,providing new ideas for targeted immune regulation of ALI/ARDS.

Abstract:Objective To investigate the correlation between serum interferon-γ(IFN-γ)/interleukin-4(IL-4)and the disease stage of childhood vitiligo,and to evaluate its predictive value for treatment efficacy.Methods In total,125 children with vitiligo admitted from January 2023 to June 2024 were selected as the observation group,including 24 stable-stage patients,53 progressive-stage patients,and 48 rapid-progressive-stage patients.Based on the treatment efficacy at 6 months after treatment,they were divided into an effective subgroup(n=93)and an ineffective subgroup(n=32).Another 125 healthy children during the same period were selected as the control group.The levels of serum IFN-γ,IL-4,and IFN-γ/IL-4 in the observation group and the control group,as well as in children with different disease stages in the observation group,were compared.The correlation between serum IFN-γ,IL-4,and IFN-γ/IL-4 and the disease stage was analyzed.The clinical data and serum IFN-γ,IL-4,and IFN-γ/IL-4 levels of the effective subgroup and the ineffective subgroup were compared to analyze the correlation between serum IFN-γ,IL-4,and IFN-γ/IL-4 and treatment efficacy as well as their value in predicting treatment efficacy.Results The serum IFN-γ and IFN-γ/IL-4 levels in the observation group were higher than those in the control group,while the serum IL-4 level was lower than that in the control group(P＜0.01).The serum IFN-γ and IFN-γ/IL-4 levels showed an increasing trend in stable-stage,progressive-stage,and rapid-progressive-stage patients,while the serum IL-4 level showed a decreasing trend(P≤0.05).Spearman correlation analysis showed that serum IFN-γ and IFN-γ/IL-4 were positively correlated with the disease stage of children with vitiligo,and the serum IL-4 was negatively correlated with the disease stage(P＜0.05).The serum IFN-γ,IFN-γ/IL-4 levels in the ineffective subgroup were higher than those in the effective subgroup,while the serum IL-4 level was lower(P≤0.0l).After adjusting for other factors such as disease duration,lesion area,and disease stage,the restricted cubic spline curve showed a positive non-linear correlation between serum IFN-γ,IFN-γ/IL-4 and treatment efficacy(Ptrend＜0.05,Pnon-linear＜0.05).When serum IFN-γ was ≥66.81 pg/mL and IFN-γ/IL-4 was ≥1.78,the risk of treatment failure gradually increased as the levels of serum IFN-γ and IFN-γ/IL-4 increased;the serum IL-4 showed a negative non-linear correlation with treatment efficacy(Ptrend＜0.05,Pnon-linear＜0.05).When the serum IL-4 was＜40.02 pg/mL,the risk of treatment failure gradually decreased with the increase in serum IL-4 level.Receiver operating characteristic(ROC)curve analysis showed that the area under the ROC curve of serum IFN-γ/IL-4 for predicting the treatment efficacy of children with vitiligo was 0.873,with a sensitivity of 84.37％and a specificity of 77.42％,which was superior to the prediction of IFN-γ and IL-4 alone(Z=2.258,2.165,P=0.024,0.030).Conclusion Serum IFN-γ/IL-4 is significantly correlated with the disease stage of childhood vitiligo and can effectively predict treatment efficacy.

Abstract:Objective To investigate the changes in serum levels of orexin A(OXA),interleukin-33(IL-33),and insulin-like growth factor-1(IGF-1)in adolescent patients with depression,and to analyze their association with sleep disorders.Methods From January to December 2023,146 adolescent patients with depression were selected.According to the Pittsburgh Sleep Quality Index(PSQI),they were divided into the normal sleep group(n=54)and the sleep disorder group(n=92).The sleep disorder group was subdivided into mild subgroup(n=26),moderate subgroup(n=41),and severe subgroup(n=25)according to the severity.And 110 healthy individuals undergoing physical examination during the same period were enrolled as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect and compare the serum levels of OXA,IL-33,and IGF-1 in the control group,normal sleep group,sleep disorder group,and adolescent depressive patients with different severities of sleep disorders.Spearman correlation analysis was used to investigate the relationship between serum levels of OXA,IL-33 and IGF-1 and PSQI scores in adolescent depressive patients with sleep disorders.Multivariate logistic regression analysis was used to investigate the influencing factors of the occurrence of sleep disorders in adolescent depressive patients.Receiver operating characteristic(ROC)curves was drawn to analyze the diagnostic value of serum levels of OXA,IL-33,and IGF-1 in the occurrence of sleep disorders in adolescent depressive patients.Results The serum levels of OXA and IL-33 in the sleep disorder group were higher than those in the normal sleep group and the control group,while the serum level of IGF-1 was lower than that in the normal sleep group and the control group;the serum levels of OXA and IL-33 in the normal sleep group were also higher than those in the control group,while the serum level of IGF-1 was also lower than that in the control group(P＜0.05).The serum levels of OXA and IL-33 increased sequentially in the mild,moderate,and severe subgroups,while the serum level of IGF-1 decreased sequentially(P＜0.05).The serum levels of OXA and IL-33 were positively correlated with PSQI score in adolescent depressive patients with sleep disorders(linear R2=0.328,0.446,P＜0.001),while the serum level of IGF-1 was negatively correlated with PSQI score in adolescent depressive patients with sleep disorders(linear R2=-0.343,P≤0.001).The results of multivariate logistic regression analysis showed that serum levels of OXA and IL-33 were risk factors for the occurrence of sleep disorders in adolescent depressive patients,while the serum IGF-1 level was a protective factor(P＜0.05,P＜0.01).The area under curve(AUC)for the combined diagnosis of sleep disorders by the three indicators in adolescent patients with depression was 0.926,with a sensitivity and a specificity of 93.48％and 75.00％,respectively,which was superior to their individual diagnoses(Zcombined-OXA=2.250,Zcombined-IL-33=2.203,Zcombined-IGF-1=2.375,P=0.024,0.028,0.018).Conclusion The serum levels of OXA and IL-33 in adolescent depressive patients are elevated,while the serum level of IGF-1 is reduced.The serum levels of OXA,IL-33,and IGF-1 are closely related to the occurrence of sleep disorders in adolescent depressive patients.The combined detection of the three is of great significance for the diagnosis and treatment of sleep disorders in adolescent depressive patients.

Abstract:Objective To investigate the effects of sanguinarine on bone metabolism and inflammatory injury in diabetic osteoporosis rats by regulating the Ras homologous gene family member A(RhoA)/Rho-associated kinase(ROCK)signaling pathway.Methods A total of 60 healthy male 8-week-old SD rats in this study were divided into normal group(without any treatment),model group(intraperitoneal injection of 60 mg/kg 0.2％Streptozotocin+reduced bone mineral density),low-dose sanguinarine group(L-sanguinarine group),high-dose sanguinarine group(H-sanguinarine group),and H-sanguinarine+inhibitor group,with 12 rats per group.In L-sanguinarine group,H-sanguinarine group and H-sanguinarine+inhibitor group,the rats with successful modeling were given 2.50 mg/(kg·d)sanguinarine by gavage+intraperitoneal injection of the same volume of 0.9％sodium chloride injection,6.25 mg/(kg·d)sanguinarine by gavage+intragastric injection of the same volume of 0.9％sodium chloride injection,and 6.25 mg/(kg·d)sanguinarine by gavage+intraperitoneal injection of 40 mg/(kg·d)Rhosin.After the rats in each group were treated for 8 weeks,a dual-energy X-ray absorptiometry scanning system was used to measure bone density,and serum Ca,osteocalcin(OC),osteoprotegerin(OPG),and alkaline phosphatase(ALP)levels were detected.Biomechanical testing was performed to detect the maximum load of the femur of rats in each group,and HE staining was used to detect the histopathological changes of pancreatic tissues and femoral tissue morphology in rats in each group.ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in each group,and Western blot was used to detect the expression of RhoA,ROCK1,and ROCK2 proteins in femoral tissue of rats in each group.Results Compared with the normal group,the model group showed decreased bone density and maximum load on the femur,destruction of pancreatic and femoral tissues,decreased levels of the serum Ca,OC,OPG,reduced expression of RhoA,ROCK1,and ROCK2 proteins,and increased levels of the serum ALP,IL-1β,TNF-α,and IL-6(P＜0.05).Compared with the model group,the L-sanguinarine group and H-sanguinarine group showed increased bone density and maximum load on the femur in rats,reduced pancreatic and femoral tissue damage,increased levels of the serum Ca,OC,OPG,expression of RhoA,ROCK1,and ROCK2 proteins in femoral bone tissue,and decreased levels of the serum ALP,IL-1β,TNF-α,and IL-6,and the changes in the above indicators in the H-sanguinarine group were more significant(P＜0.05).Compared with the H-sanguinarine group,the H-sanguinarine+inhibitor group reversed the effects of sanguinarine on bone metabolism and inflammatory injury in rats(P≤0.05).Conclusion Sanguinarine improves bone metabolism in diabetic osteoporosis rats and reduces its inflammatory injury by activating the RhoA/ROCK signaling pathway.

Abstract:Glaucoma is an irreversible blinding eye disease that affects a large number of people worldwide.In China,the prevalence of glaucoma increases significantly with age,seriously threatening people's visual health and quality of life.Glaucoma is mainly characterized by distinctive optic nerve atrophy and visual field defects.Elevated intraocular pressure(IOP)is one of the main risk factors,but several patients with glaucoma but normal IOP suggest that there are other unidentified pathogenic mechanisms.In recent years,with the continuous deepening of research,the role of the gut microbiota-immune axis in the occurrence and development of various diseases has gradually attracted attention.Glaucoma patients have specific abnormalities in their gut microbiota,such as a decrease in beneficial bacteria like Bifidobacteria and Lactobacilli,and an increase in harmful bacteria like Escherichia coli and Enterococcus.Changes in the level of their metabolites,short-chain fatty acids,may affect the process of optic nerve damage through immune regulation,and are closely related to glaucoma.This suggests that the dysregulation of the gut microbiota-immune axis may play an important role in the pathogenesis of glaucoma,providing a new research direction for investigating potential associations in glaucoma onset.

Abstract:Objective To investigate the relationship between cytotoxic T lymphocyte-associated antigen-4(CTLA-4)gene polymorphism and breast cancer in female patients with type 2 diabetes mellitus(T2DM).Methods A total of 337 female T2DM patients admitted from July 2022 to March 2025 were selected as the study subjects,and they all underwent CTLA-4 gene polymorphism testing.They were divided into breast cancer group and non-breast cancer group according to the prevalence of breast cancer in female T2DM patients.The clinical data and CTLA-4 gene polymorphism of the two groups were compared,and the relationship between CTLA-4 gene polymorphism and breast cancer in women with T2DM was analyzed.Results Among 337 female T2DM patients,42 patients had breast cancer and the prevalence rate was 12.46％.The glycosylated hemoglobin(HbAlc),homeostasis model assessment of insulin resistance(HOMA-IR),distribution of the AA genotype at the CTLA-4 gene-49 locus and A allele frequencies in breast cancer group at admission were higher than those in non-breast cancer group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that HbAlc,HOMA-IR and the AA genotype and A allele of CTLA-4 gene-49 locus were risk factors for breast cancer in women with T2DM(P＜0.01).Conclusion The AA genotype and A allele of CTLA-4 gene-49 locus are associated with breast cancer in women with T2DM.

Abstract:Objective To investigate the protective effects and potential mechanisms of oxymatrine(OMT)on brain injury in rats with acute carbon monoxide(CO)poisoning.Methods One hundred healthy adult male Sprague-Dawley rats were selected and adapted to standard laboratory conditions with natural light cycles and free access to water and food.On day 8 of feeding,they were randomly divided into four groups:control group(NC group),acute CO poisoning model group(CO group),acute CO poisoning model supplemented with OMT treatment group(OMT group),and acute CO poisoning model combined with OMT and silent information regulator 2 homolog(SIRT1)inhibitor treatment group(OMT+EX527 group),with 25 rats in each group.An acute CO poisoning model was established by CO gas inhalation.The OMT group received OMT at 200 mg/kg via gastric intubation,while the OMT+EX527 group received OMT at 200 mg/kg and SIRT1 inhibitor EX527 at 1 mg/kg via gastric intubation.The learning and memory abilities of rats in each group were evaluated through the Morris water maze test.Brain tissue samples were prepared and stained with HE to examine the morphology of brain tissues in each group.TUNEL staining was performed to detect apoptosis in brain cells of each group,and transmission electron microscopy was used to observe the ultrastructure of neurons in each group.Flow cytometry was employed to measure mitochondrial membrane potential in each group.Reactive oxygen species(ROS)levels in hippocampal tissues were determined using a ROS assay kit.Western blot analysis was conducted to assess the expression of SIRT1,FOXO1,Nrf-2,and Bcl-2 proteins in hippocampal tissues of each group.Results Compared with the CO group,the OMT group exhibited a shortened latency period for escape and a significantly increased number of platform crossings(P＜0.01).Compared with the CO group and OMT+EX527 group,the morphological structure of brain tissue cells in the OMT group was improved,while the rate of TUNEL-positive cells in the OMT group was reduced(P＜0.01).Compared with the CO group and OMT+EX527 group,the average fluorescence intensity of neurons in the hippocampus of the OMT group was increased(P＜0.01),while the ROS level in the hippocampal tissues of the OMT group was decreased(P＜0.01).Compared with the CO group,the expression levels of SIRT1,FOXO1,Nrf-2,and Bcl-2 proteins in hippocampal tissues of the OMT group were elevated(P＜0.05).Conclusion OMT may protect against acute CO-induced brain injury by activating SIRT1/FOXO1 signaling pathway,improving mitochondrial function in neuronal cells and alleviating oxidative stress.

Abstract:Objective To investigate the antitumor mechanism of triptolide(TPL)in liver hepatocellular carcinoma(LIHC).Methods Potential targets of TPL were screened through network pharmacology and transcriptomic analysis based on TCMSP,SuperPred,TCGA-LIHC and AnimalTFDB databases,and molecular docking was used to verify its binding ability to EZH2.RNA sequencing data from TCGA-LIHC and TPL-treated Huh7 cells were integrated for differential expression,correlation,prognostic and GSEA analyses.ChIP-Atlas and ATAC-seq data were used to evaluate the epigenetic regulatory characteristics of CSRNP1.Results EZH2 was identified as a direct binding target of TPL(binding energy=-7.186 8 kcal/mol),and there was a significant negative correlation between EZH2 and CSRNP1 in LIHC patients(r=-0.37,P＜0.001).After treatment of Huh7 cells with 50 nmol/L TPL for 48 h,the expressions of EZH2 were significantly downregulated(P≤0.01),while the expression of CSRNP1 was significantly upregulated(P＜0.01).GSEA showed that EZH2 activated E2F target gene pathway,G2M checkpoint pathway and MYC target gene pathway(all P＜0.01),and high expression of CSRNP1 inhibited MYC signaling(NES=-1.47,P=0.009).Epigenetic analysis confirmed that EZH2 silenced CSRNP1 transcription through H3K27me3 modification:in LIHC cells,the promoter region of CSRNP1 was enriched with H3K27me3 modification signal peaks and lacked ATAC-seq signals,suggesting transcriptional repression.In normal liver tissues,there was no H3K27me3 modification in this region,and the ATAC-seq signal was significant with high chromatin accessibility,which was conducive to normal gene transcription.Conclusion TPL relieves the epigenetic repression of CSRNP1 by inhibiting EZH2,suppresses the MYC pathway and alleviates the immune microenvironment.These findings reveal that the EZH2/CSRNP1/MYC axis is an important mechanism underlying the anti-hepatocarcinoma effect of TPL,providing a potential target for hepatocarcinoma treatment.

Abstract:Objective To systematically evaluate the association between different dietary patterns and the risk of developing urolithiasis,as well as the underlying mechanisms.Methods Data were retrieved from PubMed,Web of Science,Embase,CNKI,and Wanfang databases,covering observational studies published from the database establishment to December 2024 regarding the relationship between dietary patterns and the risk of urolithiasis.Two scholars independently conducted literature screening,data collection,and assessment of the bias of the studies.Meta-analysis was conducted using Stata 17.0 software.Results A total of 17 studies were included,covering 10 cohort studies,5 case-control studies,and 2 cross-sectional studies,with a total sample size of 215,683 participants.The meta-analysis results showed that a plant-based dietary pattern could reduce the risk of urolithiasis(OR=0.83,95％CI:0.72,0.94),while an animal-based food pattern(OR=1.36,95％CI:1.25,1.47)and a high-sugar sweet food pattern(OR=1.24,95％CI:1.06,1.46)would increase the risk of urolithiasis.The impact of different dietary patterns on the risk of urolithiasis might be related to changes in urine pH and the excretion of key lithogenic substances(such as calcium,oxalate,and citrate).Conclusion A plant-based dietary pattern is a protective factor against the development of urolithiasis,while an animal-based food pattern and a high-sugar sweet food pattern are risk factors.It is recommended to promote a diet rich in fruits and vegetables in the primary prevention of urolithiasis,and to moderately limit the intake of animal protein and high-sugar foods.

Abstract:Objective To identify a monoclonal antibody capable of specifically detecting urinary 3-methoxy tyramine(3-MT),so as to underpin the development of a high-performance diagnostic reagent kit.Methods The 3-MT antigen was designed and synthesized.Immune New Zealand white rabbits with 3-MT coupled to bis-succinimidyl suberate sodium salt(BS3)and Keyhole limpet hemocyanin(KLH)to obtain an antibody library.High-affinity phage antibodies were obtained using solid-phase selection strategy based on phage display technology.Antibody performance was verified by coating magnetic particles with biotin-labeled antibodies and combining them with horseradish peroxidase-labeled antigen.Results In total,20 phage antibodies with high affinity for 3-MT were obtained.After enzyme-linked immunosorbent assay(ELISA)for titer determination,recombinant antibody 4354# with the optimal titer and slope was selected.Biotin-conjugated recombinant antibody 4354# was used as the coating antibody,and horseradish peroxidase-labeled acylated 3-MT served as the enzyme-labeled antigen.The magnetic microparticle chemiluminescence method verified that recombinant antibody 4354#could be used for competitive detection of 3-MT in acylated urine.The test results showed a significant positive correlation with the HPLC assay results(R2=0.902 1).Conclusion A recombinant antibody targeting 3-MT was successfully screened using phage display technology.its applicability for detecting 3-MT levels in urine was then validated via a magnetic microparticle chemiluminescence method,thereby laying the foundation for the development of raw materials for 3-MT diagnostic kits.

Abstract:Objective To analyze the predictive value of atherogenic index of plasma(AIP)and apolipoprotein A1(ApoA1)for the development of diabetic kidney disease(DKD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods Elderly patients with T2DM admitted from January 2018 to January 2020 were selected as the research subjects.After a 5-year follow-up,patients with DKD were included in the DKD group,and those without DKD were included in the T2DM group.The general data at admission and the levels of AIP and serum ApoA1 were compared between the two groups,and the influencing factors of the development of DKD in elderly T2DM patients were analyzed.The dose-response relationship between AIP,serum ApoA1 at admission and the risk of DKD in elderly T2DM patients was analyzed,and the predictive value of AIP and serum ApoA1 at admission for the development of DKD in elderly T2DM patients was analyzed.Based on the conventional influencing factors,a logistic regression(LR)model 1 was constructed,and a LR model 2 was constructed by combining AIP,serum ApoA1 at admission with the conventional influencing factors,to compare the predictive values of the two models.Results The proportion of T2DM duration≥10 years,glycated hemoglobin A1c(HbAlc),and blood urea nitrogen(BUN)levels at admission in the DKD group were higher than those in the T2DM group,showing significant differences(P<0.01).The AIP at admission in the DKD group was higher than that in the T2DM group,while the serum ApoA1 level was lower than that in the T2DM group,showing significant differences(P<0.01).The results of multivariate logistic regression analysis showed that T2DM duration,HbAlc,BUN,AIP,and serum ApoA1 at admission were all independent influencing factors for the development of DKD in elderly T2DM patients(P<0.05,P<0.01).The restricted cubic spline model analysis showed that after correcting for T2DM duration,HbAlc,and BUN at admission,AIP at admission was non-linearly positively correlated with the risk of DKD in elderly T2DM patients,while serum ApoA1 at admission was non-linearly negatively correlated with the risk of DKD in elderly T2DM patients(P<0.05).When AIP was>0.23,the risk of DKD in elderly T2DM patients increased with the increase of AIP,and when serum ApoA1 was<1.26 g/L,the risk of DKD in elderly T2DM patients increased with the decrease of serum ApoA1.The receiver operating characteristic(ROC)curve analysis showed that the area under the ROC curve of LR model 2 for predicting the development of DKD in elderly T2DM patients was significantly larger than that of LR model 1(P<0.05).Conclusion AIP,and serum ApoA1 are related to the occurrence of DKD in elderly T2DM patients.A predictive model combining AIP and ApoA1 with conventional risk factors demonstrates significantly improved predictive value for the development of DKD in elderly T2DM patients,providing a reference for clinical diagnosis and treatment.

Abstract:Autophagy,as a highly conserved degradation process within eukaryotic cells,plays a crucial role in maintaining cellular homeostasis and responding to stress.In recent years,with the continuous in-depth research on autophagy in the field of infectious diseases,an increasing number of scholars have recognized autophagy as a"double-edged sword".Several viruses,after long-term evolution,can evade or even destroy the host cell's autophagy through multiple pathways,thereby creating favorable conditions for their own replication and transmission.Hepatitis E virus(HEV),as an important zoonotic pathogen,can regulate the autophagy process of host cells through multiple molecular pathways to promote virus replication and survival.This article systematically reviews the mechanism of autophagy and its regulatory role in HEV infection,aiming to provide a theoretical basis for in-depth understanding of the pathogenic mechanism of HEV and the development of targeted anti-viral strategies targeting autophagy.

Abstract:Objective To investigate the predictive value of platelet/lymphocyte ratio(PLR),lymphocyte/monocyte ratio(LMR),and neutrophil/lymphocyte ratio(NLR)for the occurrence of liver cirrhosis in patients with hepatitis B.Methods Two hundred patients with hepatitis B who were admitted from January 2022 to December 2023 were selected as the observation group,and 200 healthy individuals who underwent physical examinations during the same period were selected as the control group.The levels of NLR,PLR,and LMR in the two groups were compared;the clinical data,NLR,PLR and LMR levels of hepatitis B patients with cirrhosis and those without cirrhosis were compared,and the influencing factors of cirrhosis in patients with hepatitis B were analyzed.The receiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of NLR,PLR and LMR for the occurrence of cirrhosis in patients with hepatitis B.Results The PLR and LMR levels in the observation group were lower than those in the control group,while the NLR level was higher(P<0.01).The proportions of AST,ALT,TBIL,and HBV-DNA load>105 copies/mL in patients with cirrhosis due to hepatitis B were significantly higher than those in patients without cirrhosis(P<0.01).The PLR and LMR levels in patients with cirrhosis due to hepatitis B were lower than those in patients without cirrhosis,while the NLR level was higher(P<0.01).The results of multivariate logistic regression analysis showed that PLR,NLR,and LMR were all factors influencing the occurrence of cirrhosis in patients with hepatitis B(P<0.01).ROC curve analysis showed that the area under the ROC curve(AUC)of PLR,NLR and LMR in predicting the occurrence of cirrhosis in patients with hepatitis B was 0.817,0.736 and 0.786,respectively.The AUC of the combined prediction of the three was 0.931,which was significantly higher than that of each index alone(P<0.01).The sensitivity and specificity of prediction were 84.00%and 88.00%,respectively.Conclusion The level of NLR in patients with hepatitis B is increased,while the levels of PLR and LMR are decreased,suggesting that the risk of cirrhosis is increased.Regular clinical monitoring of PLR,NLR and LMR levels is helpful to predict the risk of cirrhosis in patients with hepatitis B.

Abstract:Objective To investigate the effects of Ezetimibe combined with Atorvastatin on serum oxidized low-density lipoprotein(ox-LDL),small dense low-density lipoprotein cholesterol(sdLDL-C),and prognosis in elderly patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI).Methods A total of 86 elderly patients with AMI who received PCI from January to December 2022 were selected as study subjects.They were divided into the combination group and the control group according to random number table method,with 43 patients in each group.Both groups were given conventional PCI.The control group was supplemented with oral Atorvastatin Calcium(20 mg)once a day,and the combination group was supplemented with oral Ezetimibe(10 mg)once a day on the basis of the control group.All patients were treated for 1 month.Serum levels of ox-LDL,sdLDL-C,and inflammatory factors[monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6)],and tumor necrosis factor-α(TNF-α)]in both groups were observed before and after treatment.Changes in left ventricular ejection fraction(LVEF)and left ventricular end-diastolic dimension(LVEDD)before and after treatment were compared between the two groups.Major adverse cardiovascular events(MACE)that occurred within 6 months after treatment and adverse reactions during treatment were recorded.Results After treatment,the serum levels of ox-LDL,sdLDL-C,MCP-1,IL-6,and TNF-α in both groups decreased,and the levels were lower in the combination group than in the control group(P<0.05,P<0.01).After treatment,serum levels of MCP-1,IL-6,and TNF-α decreased in both groups compared with those before treatment,which were lower in the combination group than in the control group(P<0.05,P<0.01).After treatment,LVEF increased,while LVEDD decreased in both groups.Moreover,the combination group had higher LVEF and lower LVEDD than the control group(P<0.05,P<0.01).The incidence of MACE in the combination group[4.65%(2/43)]was lower than that in the control group[20.93%(9/43)],showing significant difference(P<0.05),and the incidence of adverse reactions during treatment was comparable between the two groups(P>0.05).Conclusion Ezetimibe combined with Atorvastatin Calcium can more effectively reduce serum ox-LDL and sdLDL-C levels,alleviate inflammation,improve cardiac function,and lower the risk of short-term MACE in elderly patients with AMI after PCI,with controllable adverse reactions.

Abstract:Iron metabolism plays a crucial role in cellular physiological processes.In recent years,the regulatory effect of iron metabolism on immune cells has become a research hotspot.Increasing studies have shown that iron metabolism is closely associated with the function of the immune system.Iron is not only necessary for the proliferation and differentiation of immune cells,but also participates in the immune response of the body by regulating the activation and function of immune cells.Iron overload and ferroptosis are two important manifestations of abnormal iron metabolism.This article systematically reviews the latest research progress on the regulation of iron metabolism on the activation and function of different types of immune cells,providing relevant theoretical basis for in-depth understanding of the interaction between iron metabolism and the immune system.

Abstract:Objective To elucidate the differentiation and functional heterogeneity of neutrophil subsets in the lung tissue of mice infected with Klebsiella pneumoniae(Kpn).Methods C57BL/6J mice were selected.An acute pulmonary infection mouse model was established by using the clinical isolated Klebsiella pneumoniae through a pulmonary nebulization delivery device.Twenty-eight mice were randomly divided into the control group and the Kpn infusion group.The pulmonary neutrophils of the mice were detected and analyzed by flow cytometry and single-cell transcriptome sequencing technology.Results Kpn infection induced significant lung damage and led to release of inflammatory cytokines,while recruiting a large number of neutrophils to the lungs.Based on scRNA-seq results,we identified two distinct subsets of lung tissue-recruited neutrophils(G0 and G1)by marker genes.Integrative analysis of differential gene expression and functional gene scoring revealed that G0 exhibited a granule regulation-associated signature,whereas G1 exhibited a phagocytosis-related signature.Both G0 and G1 were determined as mature through the expression of genes including Spi1,Cebpd,and Runx1.Furthermore,CXCR2 as a surface marker associated with neutrophil maturation,was not highly expressed on neutrophils in the lungs during mouse pulmonary infection,which differed from its role in the bone marrow and peripheral blood.Conclusion During pulmonary infection caused by Kpn,neutrophils in lung tissues exhibit significant heterogeneity.The expression of myeloid development-related transcription factors and granule-associated genes present a more accurate maturation status of neutrophils in the lung tissues.This finding is crucial for elucidating the mechanisms underlying neutrophil-mediated immune responses.

Abstract:Objective To investigate the effects of Qishen Huanwu capsules as adjuvant therapy on the regulatory T cells(Treg)/helper T cell 17(Th17)immune balance and vascular endothelial function in patients with coronary heart disease(CHD)and hypertension presenting with qi deficiency and blood stasis syndrome.Methods From February 2023 to October 2024,91 patients developing CHD and hypertension presenting with qi deficiency and blood stasis syndrome were selected and randomly divided into the combination group(n=45)and the Western medicine group(n=46)using a random number table.The Western medicine group received conventional Western medicine treatment,while the combination group was supplemented with Qishen Huanwu capsules.After 8 weeks of continuous medication,both groups were compared in terms of qi deficiency and blood stasis syndrome score,blood pressure,cardiac function indicators[left ventricular ejection fraction(LVEF),the ratio of early to late diastolic mitral inflow peak velocities(E/A)],Treg/Th1 immune balance status,and vascular endothelial function indicators[endothelin-1(ET-1),nitric oxide(NO)]before and after treatment.Results At 8 weeks after treatment,the qi deficiency and blood stasis syndrome score,systolic blood pressure,and diastolic blood pressure in both groups were lower than those before treatment,and lower in the combination group than in the Western medicine group(P<0.05,P<0.01).At 8 weeks after treatment,the LVEF and E/A in both groups were higher than those before treatment,and higher in the combination group than in the Western medicine group(P<0.05,P<0.01).At 8 weeks after treatment,Treg and Treg/Th17 in both groups were higher than those before treatment,and Th17 was lower than that before treatment(P<0.05);and at 8 weeks after treatment,Treg and Treg/Th17 in the combination group were higher than those in the Western medicine group,and Th17 was lower than that in the Western medicine group(P<0.05,P<0.01).At 8 weeks after treatment,ET-1 in both groups was lower than that before treatment,while NO was higher than that before treatment(P<0.05).At 8 weeks after treatment,ET-1 in the combination group was lower than that in the Western medicine group,while NO was higher than that in the Western medicine group(P<0.01).Conclusion For hypertensive CHD patients with qi deficiency and blood stasis syndrome,Qishen Huanwu capsules as adjuvant therapy can effectively regulate the Treg/Th17 immune balance,significantly improve vascular endothelial function,blood pressure and cardiac function,and significantly alleviate related symptoms.

Abstract:Objective To investigate the structural and functional characteristics of the endometrial microbiome in patients with recurrent implantation failure(RIF)and to investigate their potential mechanism influencing the local immune microenvironment of the uterine cavity.Method Endometrial fluid samples were collected from a total of 299 women undergoing in vitro fertilization between January 2024 and January 2025,including 203 from the non-RIF group and 96 from the RIF group.The V3-V4 region of the 16S rRNA gene was amplified and sequenced on the Illumina NovaSeq 6000 platform.Bioinformatic analyses were performed using QIIME2,including ASV clustering,taxonomic annotation,and α-and β-diversity analyses.Differentially abundant genera between groups were identified by LEfSe.Functional profiles were predicted with PICRUSt2 and combined with the KEGG/COG databases for immune-related pathways.Results Sequencing revealed a significant difference in community structure between the RIF and non-RIF groups.At the phylum level,both sets of samples were dominated by Firmicutes,Actinobacteriota and Proteobacteria.At the genus level,the relative abundance of Streptococcus was markedly higher in the RIF group than in the non-RIF group[(3.92±1.56)%vs(2.34±0.87)%,P<0.05],whereas Gardnerella showed the opposite pattern[(4.97±12.9)%vs(2.26±8.20)%,P<0.05].α-diversity analysis further indicated that the Shannon index was lower in the RIF group than in the non-RIF group,showing no significant difference(P>0.05).β-diversity analysis demonstrated that the microbial community structure of the RIF group was more heterogeneous.Functional prediction indicated significant up-regulation of"glycolysis/gluconeogenesis"and"starch and sucrose metabolism"pathways in the RIF group,together with enrichment of pathways related to Staphylococcus aureus infection,while the activity of multiple amino acid metabolic pathways in the microbiota of the RIF group was reduced relative to that of the non-RIF group.Conclusion The endometrial microbiota of the RIF group exhibited reduced diversity,enhanced carbohydrate metabolism,a higher detection rate of opportunistic pathogens,and reduced amino acid metabolic activity-features potentially linked to endometrial microenvironmental inflammation and diminished immune tolerance in RIF patients.