Objective To investigate the causal association between proton pump inhibitor(PPI)use and ischemic stroke(IS),and to evaluate the potential mediating role of gut microbiota in the aforementioned association. Methods Mendelian randomization(MR)method was employed,with single nucleotide polymorphisms(SNPs)associated with commonly used PPI(esomeprazole,lansoprazole,omeprazole,rabeprazole)as instrumental variables,to analyze the causal relationship between PPI use and IS.Furthermore,a two-step Mendelian randomization(two-step MR)method was used to assess the potential mediating effect of gut microbiota in the association between PPI and IS. Results The results of this study showed both esomeprazole and lansoprazole had a significant causal association with the risk of large artery atherosclerotic stroke(LAS).Although specific changes in gut microbiota were observed after the application of the aforementioned PPI,these changes did not mediate the increasing effect on LAS risk,suggesting that the association between PPI and LAS is not mainly mediated by changes in gut microbiota. Conclusion This finding indicates that PPI,as one of the most commonly used prescription drugs in clinical practice,may be a potential risk factor for cardiovascular diseases,providing a new theoretical basis and research direction for the prevention,diagnosis and treatment of IS.

Objective To elucidate the mechanism by which Porphyromonas gingivalis(Pg)promotes the progression of esophageal squamous cell carcinoma(ESCC)through TAGLN2-mediated activation of the YAP/TAZ-ERK axis. Methods Immunohistochemistry was performed to evaluate Pg abundance and TAGLN2 protein expression in 60 ESCC specimens,and the correlation between them was analyzed.ESCC cells were subjected to Pg infection or siTAGLN2 treatment,followed by RNA sequencing to identify Pg- and TAGLN2-related differentially expressed genes and to define a Pg-TAGLN2 gene signature.Transcriptomic and proteomic data from publicly available databases,including GSE53625,TCGA-ESCA,and published proteomic datasets,were integrated for functional enrichment analysis and evaluation of the clinical relevance of the Pg-TAGLN2 gene signature.Western blotting was used to detect the expression of p-ERK/ERK,p-YAP/YAP,p-TAZ/TAZ,RASA1,and F-actin in ESCC cells after Pg infection,TAGLN2 knockdown,or TAGLN2 overexpression.Immunofluorescence assays were performed to examine the subcellular localization of YAP/TAZ in ESCC cells under different treatment conditions.Transwell assays were used to assess cell migration and invasion,and CCK-8 assays were conducted to evaluate cell proliferation. Results Pg abundance was positively correlated with TAGLN2 protein expression in ESCC tissues,and high TAGLN2 expression was associated with poor prognosis in patients with ESCC.A total of 55 Pg-induced differentially expressed genes and 8 Pg-TAGLN2 signature genes were significantly enriched in the MAPK/ERK signaling pathway.In public transcriptomic and proteomic datasets,higher GSVA scores for the Pg-TAGLN2 gene signature were associated with unfavorable prognosis in ESCC patients.Pg infection significantly increased p-ERK levels in ESCC cells.TAGLN2 knockdown reduced p-ERK levels and attenuated Pg-induced ERK activation.Meanwhile,TAGLN2 knockdown increased p-YAP and p-TAZ levels while decreasing YAP and TAZ expression.In contrast,TAGLN2 overexpression produced the opposite changes.Moreover,TAGLN2 knockdown promoted the cytoplasmic retention of YAP/TAZ and reduced their nuclear localization.In TAGLN2-overexpressing ESCC cells,YAP/TAZ knockdown markedly attenuated the promotive effects of TAGLN2 overexpression on cell proliferation,migration,and invasion. Conclusion Pg infection induces upregulation of TAGLN2 in ESCC,thereby activating the YAP/TAZ-ERK signaling axis and promoting ESCC progression.Targeting the RAS-ERK signaling pathway may represent a potential therapeutic strategy for Pg-associated ESCC.

Objective To investigate the expression of Panx1 in cisplatin-resistant SKOV3/DDP strains of human ovarian cancer and its mechanism in drug resistance. Methods Western blotting was used to detect the expression of Panx1 in SKOV3 and SKOV3/DDP.Flow cytometry was used to detect the apoptosis of SKOV3/DDP cells,and the expression of Panx1 in SKOV3/DDP cells and its effect on apoptosis were analyzed.SKOV3/DDP overexpression plasmid was constructed,and SKOV3/DDP cells were transfected successfully.Apoptosis was detected by flow cytometry.ATP content in cell supernatant was detected by ELISA to analyze the role and mechanism of Panx1 mediating SKOV3/DDP resistance. Results The expression of Panx1 protein in SKOV3/DDP was significantly lower than that in SKOV3 group(0.17±0.05 vs.0.35±0.03,P<0.01).The cis-diamine dichloroplatinum(DDP)could significantly inhibit SKOV3 cell proliferation in a time-and dose-dependent manner.Subsequent experiments were conducted at 36 h and 32 μmol/L.The apoptosis rate of SKOV3 and SKOV3/DDP groups was significantly increased after DDP treatment(33.96%±0.03% vs.5.01%±0.00%,P<0.01;14.66%±0.02% vs.4.65%±0.01%,P<0.01).The apoptosis rate of SKOV3/DDP overexpression plasmid group was significantly higher than that of untreated group(15.69% vs.4.10%,P<0.01).ATP content in extracellular fluid of SKOV3/DDP overexpression plasmid group was significantly higher than that of control group(33.57±6.00 vs.10.65±0.76 ng/mL,P<0.01). Conclusion Up-regulation of Panx1 can increase apoptosis of SKOV3/DDP cells by increasing ATP release.Cisplatin resistance of ovarian cancer may be related to the decrease of ATP release mediated by low expression of Panx1.

Objective To investigate the effects of cholecystokinin(CCK)-8 on pentylenetetrazole(PTZ)-induced proliferation,apoptosis and activation of glial cells in the mouse hippocampus and its possible mechanisms. Methods First,the cells were randomly divided into control,PTZ-induced,PTZ+CCK-8 low dose,PTZ+CCK-8 middle dose and PTZ+CCK-8 high dose groups.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis and cell cycle.Immunofluorescence was used to detect the expression of activation marker GFAP.ELISA was used to detect the expression levels of GFAP and Cx43.qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of CCK-AR and CCK-BR respectively.Then,with CCK-8 treatment alone as the control,proglumide(a CCK receptor inhibitor)and CCK-8 were used for simultaneous treatment to evaluate the reversing effect of proglumide on the action of CCK-8. Results Compared to the control group,cell proliferation was decreased,apoptosis rate was increased,the proportion of G1 cells was increased,the proportion of G2 cells was decreased,IBA-1 expression was increased,GFAP and Cx43 expression was increased,and mRNA and protein expression of CCK-BR was decreased in the PTZ-induced group.Compared to the PTZ-induced group,cell proliferation was increased,apoptosis rate was decreased,the proportion of G1 cells was decreased,the proportion of G2 cells was decreased,GFAP and Cx43 expression was decreased,and mRNA and protein expression of CCK-BR was increased in the PTZ+CCK-8 group,and all of them were CCK-8 dose-dependent.Compared with the treatment with CCK-8 alone,the combined treatment with proglumide could reverse the effect of CCK-8. Conclusion CCK-8 improves PTZ-induced injury of mouse hippocampal astrocytes through CCK-BR,promotes cell proliferation,reduces apoptosis and inhibits their activation.

Objective To investigate the role of circRNA-007371 in regulating CX3CR1-mediated hepatic stellate cell(HSC)pyroptosis in liver fibrosis(LF)and its possible mechanism. Methods Thirty rats were divided into control group,LF group and low expression circRNA-007371 group,with 10 rats in each group.HSC-T6 cells were cultured and divided into control group,circRNA-007371 overexpression group and NLRP3 inhibition(Antcin A)group.The level of LF was detected by Sirius Red staining.The levels of α-SMA and Collagen1 proteins in liver tissue were detected by immunofluorescence staining.The mRNA levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in liver tissue and HSC-T6 were detected by qRT-PCR.HE staining was used to detect the pathological changes of liver tissue.Masson staining was used to detect collagen deposition in liver tissue.Western blotting was used to detect NLRP3,Caspase-1 and GSDMD protein levels in liver tissue and HSC-T6.The IL-1β and IL-18 levels in serum and HSC-T6 were detected by ELISA. Results Compared with the control group,the liver tissue of LF group showed hyperplasia of collagen fiber,the protein expression levels of α-SMA and Collagen1,the mRNA expression levels of circRNA-007371 and CX3CR1 were increased(P<0.05),the liver tissue showed pathological injury,accompanied by liver steatosis and fat cavity;hepatic lobular structure was abnormal,collagen was increased significantly,the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were increased(P<0.05),and the serum IL-1β and IL-18 levels were increased(P<0.05).Compared with LF group,mRNA expression levels of circRNA-007371 and CX3CR1 in liver tissues of low-expression circRNA-007371 group were decreased(P<0.05),liver tissue pathological injury was alleviated,and collagen protein was reduced;the levels of NLRP3,Caspase-1 and GSDMD proteins in liver tissue were decreased(P<0.05),and the serum IL-1β and IL-18 levels were decreased(P<0.05).Compared with the control group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in HSC in over-expression group were increased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were increased(P<0.05),and the IL-1β and IL-18 levels were increased(P<0.05).Compared with the over-expression circRNA-007371 group,the mRNA expression levels of circRNA-007371,CX3CR1,α-SMA and Collagen1 in the HSC of Antcin A group were decreased(P<0.05),the protein expression levels of NLRP3,Caspase-1 and GSDMD were decreased(P<0.05),and the contents of IL-1β and IL-18 were decreased(P<0.05). Conclusion Low expression of circRNA-007371 can alleviate LF by inhibiting pyroptosis of HSC by regulating CX3CR1.

Objective Based on the expression of COX-2,the effect and mechanism of vitamin A and vitamin E in alleviating intestinal injury in neonatal rats with necrotizing enterocolitis(NEC)were explored. Methods The neonatal rats were randomly divided into control group,model group,positive drug sulfasalazine group,vitamin A group,vitamin E group,vitamin A + vitamin E group(A+E group).The pathological damage of the rat intestinal tissue was evaluated by HE staining.The apoptosis rate of the intestinal tissue was detected by TUNEL staining.The superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)in the intestinal tissue were detected by the kit.The mRNA and protein expression levels of TNF-α,IFN-γ and IL-10 in serum were detected by ELISA,and the mRNA and protein expression levels of TNF-α,IFN-γ,IL-10 and COX-2 in the intestinal tissue were detected by qRT-PCR and Western blot assays,respectively. Results Compared with the control group,necrosis villus structure destruction and transmastic necrosis occurred in intestinal tissue,apoptosis rate of intestinal tissue was significantly increased(P<0.05),the levels of SOD and GSH-Px were significantly down-regulated(P<0.05),and the level of MDA was significantly up-regulated(P<0.05);the levels of TNF-α and IFN-γ in serum were significantly up-regulated(P<0.05),the level of IL-10 was significantly down-regulated(P<0.05);the mRNA and protein levels of TNF-α,IFN-γ,and COX-2 in the intestinal tissue were significantly down-regulated(P<0.05),and the expression of IL-10 was significantly down-regulated(P<0.05)in the model group.Compared with the model group,pathological damage of intestinal tissue was alleviated in positive drug group,vitamin A group,vitamin E group,A+E group,apoptosis rate of intestinal tissue was significantly decreased(P<0.05),the levels of SOD and GSH-Px in intestinal tissue were significantly up-regulated(P<0.05),and the level of MDA was significantly down-regulated(P<0.05);the levels of TNF-α and IFN-γ in serum were significantly down-regulated(P<0.05),and the level of IL-10 was significantly up-regulated(P<0.05),the mRNA and protein levels of TNF-α,IFN-γ,and COX-2 in the intestinal tissue were significantly up-regulated,and the expression of IL-10 was significantly up-regulated(P<0.05),and the effect of the A+E group was significantly better than that of positive drug group(P<0.05). Conclusion The combination of vitamin A and vitamin E alleviates intestinal damage in NEC rats by inhibiting intestinal inflammation and oxidative stress,and the mechanism may be related to the inhibition of COX-2 expression.

Objective To investigate whether Shen’an decoction alleviates renal injury in diabetic kidney disease(DKD)rats by improving mitochondrial homeostasis and endoplasmic reticulum stress. Methods The rat model of DKD was established.Venous blood from the tail of the rats and urine were collected at 0,2,4,and 8 weeks respectively.The fasting blood glucose content and the ratio of urinary microalbumin to urinary creatinine(ACR)were detected.The levels of renal function indicators such as serum creatinine(sCr),blood urea(BUN),and serum uric acid(UA),as well as liver function indicators such as albumin(ALB),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were detected by reagent kits.The pathological changes of rat renal tissues were observed by HE staining,PAS staining,Masson staining,and PASM staining.The ATP content,mitochondrial membrane potential(MMP),mitochondrial functional proteins(mitochondrial-related proteins cytochrome C[Cyt C],mitochondrial transcription factor A[TFAM]),and endoplasmic reticulum stress proteins(CHOP,PERK)in renal tissues were detected by using kits,flow cytometry and Western blot,and the oxidative stress levels(MDA,SOD,GSH)were evaluated. Results Compared with the normal group,the fasting blood glucose and urinary ACR of DKD rats in the model group were significantly increased at 0,2,4,and 8 weeks of drug intervention.Renal pathological staining showed that in the model group,narrowing of the glomerular lumen in the renal tissue,edema of the renal tubular epithelial cells,and infiltration of inflammatory cells could be observed,and there were thickening of the glomerular basement membrane,hyperplasia of collagen fibers and glycogen deposition in the tubular epithelium and interstitium of the kidneys,glomerular sclerosis and interstitial fibrosis.After treatment with Shen’an decoction,the above-mentioned pathological changes were significantly improved.Compared with the normal group,the ATP content and MMP expression in the renal tissues of the model group decreased,while the expression levels of Cyt C and TFAM significantly increased.After treatment with the Shen’an decoction,all the above-mentioned changes were reversed,and the pathological damage of the kidneys was significantly improved,suggesting that Shen’an decoction plays an important role in the mitochondrial ecological balance of DKD rats.In addition,the expression levels of reticulum stress-related proteins(CHOP and PERK)and the content of GSH in the renal tissues of rats in the model group were significantly higher,while the contents of MDA and SOD were significantly lower than those in the normal group.After treatment with Shen’an decoction,all the above-mentioned indicators were reversed.It indicates that Shen’an decoction alleviates renal injury by influencing endoplasmic reticulum stress in cells. Conclusion Shen’an decoction inhibits endoplasmic reticulum stress in rats with DKD and promotes mitochondrial homeostasis to alleviate renal tissue damage in rats with DKD.

Objective To investigate the effect of enhancer of Zeste homolog 2(EZH2)on high glucose-induced cardiomyocyte apoptosis and autophagy by regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway. Methods Mouse cardiomyocytes (MCM cells) were divided into control group,high glucose group,high glucose+overexpression control group,high glucose+EZH2 overexpression group,high glucose+silencing control group,high glucose+EZH2 silencing group,and high glucose+EZH2 silencing+PI3K inhibitor(BKM120)group.The qRT-PCR was applied to detect EZH2 mRNA expression in MCM cells.CCK-8 was applied to detect the viability of MCM cells.ELISA was applied to detect the level of lactate dehydrogenase(LDH)in the supernatant of MCM cells.Flow cytometry was applied to detect apoptosis in MCM cells.Transmission electron microscopy was applied to observe the number of autophagosomes inside cells.Western blot was applied to detect EZH2,Bax,LC3-Ⅱ/LC3-Ⅰ,p62,p-PI3K,p-Akt,and p-mTOR proteins in MCM cells. Results The expression of EZH2 mRNA in MCM cells,level of LDH in cell supernatant,apoptosis rate,number of autophagosomes,and EZH2,Bax,LC3-Ⅱ/LC3-Ⅰproteins in high glucose group were higher,the viability of MCM cells and the expression of p62,p-PI3K,p-Akt,and p-mTOR proteins were lower than in the control group(all P<0.05).Compared with the high glucose group and the high glucose+overexpression control group,the expression of EZH2 mRNA in MCM cells,level of LDH in cell supernatant,apoptosis rate,number of autophagosomes,and EZH2,Bax,LC3-Ⅱ/LC3-Ⅰ proteins in high glucose+EZH2 overexpression group were increased,the viability of MCM cells and the expression of p62,p-PI3K,p-Akt,and p-mTOR proteins were decreased(all P<0.05).Compared with the high glucose group and the high glucose+silencing control group,the expression of EZH2 mRNA in MCM cells,level of LDH in cell supernatant,apoptosis rate,number of autophagosomes,and EZH2,Bax,LC3-Ⅱ/LC3-Ⅰ proteins in the high glucose+EZH2 silencing group were decreased,the viability of MCM cells and the expression of p62,p-PI3K,p-Akt,and p-mTOR proteins were increased(all P<0.05).BKM120 reversed the inhibitory effects of silencing EZH2 on high glucose-induced apoptosis and autophagy in MCM cells. Conclusion Silencing EZH2 may inhibit high glucose-induced apoptosis and autophagy in MCM cells by activating the PI3K/Akt/mTOR pathway.

Objective To explore the mechanism of myricanone (Myri) in the treatment of osteoarthritis(OA). Methods ATDC5 cells were treated with different concentrations of Myri(0,25,50,100,150,200 μmol/L)for 48 h,and the cell viability was detected by MTT to screen the safe therapeutic concentration.ATDC5 cells stimulated with 100 ng/mL lipopolysaccharides(LPS)were used to induce cell inflammation for 24 h,and then ATDC5 cells were treated with 50 μmol/L Myri,2.0 μg/mL annexin A5(ANXA5) overexpression vector(pcDNA-ANXA5)and 50 nmol/L ANXA5 interference plasmid(si-ANXA5)alone or together.Cell viability and ferroptosis levels were detected by MTT and the corresponding commercial kits.The OA mouse model was constructed by cruciate ligament transection and medial meniscectomy for in vivo experiments. Results When the concentration of Myri was more than 100 μmol/L,the activity of ATDC5 cells was decreased.In addition,Myri improved LPS-induced ATDC5 cells viability reduction and inhibited ferroptosis.ANXA5 was lowly expressed in LPS-treated ATDC5 cells.Overexpression of ANXA5 attenuated LPS-induced decrease in ATDC5 cell viability and increase in ferroptosis by activating the Nrf2/HO-1 pathway.Interfering with ANXA5 offset the inhibitory effect of Myri on the level of ferroptosis in LPS-treated ATDC5 cells.In vivoexperiments further confirmed that Myri inhibited ferroptosis by promoting ANXA5 expression,thereby improving OA. Conclusion Myri inhibits ferroptosis and alleviates OA by activating the ANXA5/Nrf2/HO-1 pathway,which may have potential value for the treatment of OA.

Objective To analyze the trends of Parkinson’s disease(PD)burden in China from 1990 to 2021,compare them with global levels,and predict the epidemic trend of PD in 2035,to provide a scientific basis for formulating PD prevention and control strategies. Methods Data were extracted from the Global Burden of Disease Study 2021(GBD 2021).The age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years rate(ASDR)were selected as core indicators.The Joinpoint regression model was applied to calculate the annual percentage change(APC)and average annual percentage change(AAPC),and the Bayesian age-period-cohort(BAPC)model was used to predict the disease trend in 2035. Results From 1990 to 2021,the ASIR for PD in China increased at a significantly faster rate than the global average,reaching 24.34 per 100000 person-years in 2021,which was 1.56 times the global average;the ASIR in males was approximately 1.5 times that in females.The overall ASMR of PD in China showed a downward trend(AAPC=-0.6186,P<0.01),with a value of 5.03 per 100000 person-years in 2021,slightly higher than the global level of 4.81 per 100000 person-years.The gender difference in mortality shifted from higher in females at the beginning to higher in males at the end of the study period.The disease burden of PD in both China and globally was concentrated in the 70-75 years age group,and the mortality rate of the population aged ≥85 years in China increased significantly(nearly threefold in males and more than double in females).The model prediction showed that by 2035,the number of incident cases,ASMR and ASDR of PD in China and globally would continue to rise,and the ASIR and disease burden of PD in China would still be higher than the global average. Conclusion China bears a heavy PD disease burden with a rapidly increasing incidence.Males and the elderly population are the key populations for PD prevention and control.In the future,considering population aging and the improvement of healthcare capacity,targeted measures including early screening of high-risk groups,risk factor control and chronic disease management for elderly patients should be enhanced to effectively alleviate the public health burden caused by PD.

Objective To investigate the role of ubiquitin-specific peptidase 14(USP14)-mediated deubiquitination of frizzled 8(FZD8)in activating the Wnt/β-catenin pathway and its impact on abdominal aortic aneurysm(AAA)progression in mice. Methods AAA was induced by subcutaneous implantation of AngⅡ osmotic minipumps.Mice were divided into six groups:control,AAA,USP14 negative control(si-NC),USP14 knockdown(si-USP14),empty-vector control(si-USP14+Ad-GFP),and FZD8 overexpression(si-USP14+Ad-FZD8).Aortic morphology was evaluated by hematoxylin and eosin(HE)staining and verhoeff-van gieson(EVG)staining.Vascular smooth muscle cell apoptosis was detected by TUNEL assay.IL-6 and TNF-α levels were measured by ELISA.Protein expression of USP14,FZD8,Wnt3a and β-catenin was assessed by Western blotting.Co-immunoprecipitation and glutathione s-transferase(GST)pull-down assays were used to examine the interaction between USP14 and FZD8.Ubiquitination assays were performed to evaluate FZD8 deubiquitination. Results Compared with controls,AAA mice exhibited markedly elevated USP14 expression,increased aortic diameter and mass ratio,inflammatory infiltration,and severe elastic fiber fragmentation.Knockdown of USP14 significantly alleviated these pathological changes(all P<0.01).Mechanistically,USP14 directly bound to FZD8 and stabilized it via deubiquitination,thereby sustaining Wnt/β-catenin signaling.Knockdown of USP14 increased FZD8 ubiquitination,downregulated Wnt3a and β-catenin protein levels,markedly reduced aortic diameter,and decreased apoptosis as well as IL-6 and TNF-α expression(all P<0.01). Conclusion USP14 promotes AAA development by deubiquitinating FZD8 and activating the Wnt/β-catenin pathway,indicating that USP14-FZD8 axis may serve as a potential therapeutic target for AAA.

Objective To investigate the association between periodontitis and proteinuria in healthy physical examination populations. Methods This cross-sectional study enrolled adult participants who underwent oral examinations and routine urinalysis at the Physical Examination Center in Tongji Hospital between January 2024 and March 2025.General demographic information,past medical history,anthropometric measurements,oral examination results,and urinary laboratory data were collected.Multivariable logistic regression was performed to estimate the association between periodontitis and proteinuria.Subgroup analyses were conducted to evaluate the consistency and robustness of this association across different clinical risk factors. Results A total of 3482 participants were included in the study,comprising 2604 males and 878 females,with a mean age of(57.59±12.11)years.The detection rate of periodontitis was 63.0%.The prevalence of proteinuria was significantly higher in the periodontitis group(24.0%)than the non-periodontitis group(11.0%)(P<0.001).After adjustment for age,gender,body mass index,and past medical history,periodontitis remained positively associated with proteinuria[OR(95%CI):2.40(1.95-2.95),P<0.001].Subgroup analyses with formal interaction tests suggested potential effect modification by sex,hypertension,diabetes,dyslipidemia,smoking status,and alcohol consumption(all P for interaction <0.05),whereas no statistically significant interaction was observed for hyperuricemia(P for interaction=0.120).The direction of association between periodontitis and proteinuria was generally consistent across subgroups. Conclusion Periodontitis is associated with an increased risk of proteinuria in the physical examination population.

Objective We conducted a meta-analysis to systematically evaluate the clinical efficacy of endocardial radiofrequency ablation of septal hypertrophy(ERASH)for the treatment of hypertrophic obstructive cardiomyopathy(HOCM). Methods Relevant literature was retrieved from PubMed,the Cochrane Library,Embase,CNKI,VIP and Wanfang Data,with the search period spanning from the inception of each database to June 2024.JBI scale was used to evaluate literature quality.Continuous data were described using weighted mean difference(WMD)and 95% confidence interval(CI).Meta-analysis was performed using Stata 18.0 software. Results A total of 11 singlearm clinical studies involving 231 patients with HOCM were included,with a mean age of 51.27 years.The results of the meta-analysis showed that at the final follow-up after ERASH intervention,the resting and provoked left ventricular outflow tract pressure gradient(LVOTPG)was significantly reduced by 61.13 mmHg[95%CI(40.68,82.58),P<0.01]and 91.91 mmHg[95%CI(71.43,112.39),P<0.01],respectively,compared with preoperative levels.The New York Heart Association(NYHA)functional class at the final follow-up decreased by 1.70[95%CI(1.53,1.88),P<0.01]relative to baseline.In addition,the total 6-minute walking distance at the final follow-up was significantly increased by 103.75 m compared with baseline(95%CI:-167.45,-40.05,P=0.01).Plasma brain natriuretic peptide(BNP)levels were markedly decreased by 786.55 pg/mL at the final follow-up(95%CI:724.50,848.60,P<0.01).Nevertheless,the interventricular septum thickness(IVST)at the final follow-up showed no statistically significant difference compared with baseline(P=0.23).Subgroup analysis based on follow-up duration(6 months vs.over 6 months)demonstrated that ERASH intervention significantly reduced resting LVOTPG and improved 6-minute walking distance in both subgroups(all P<0.01). Conclusion ERASH is effective in the treatment of patients with HOCM.However,further large-scale randomized controlled trials are still required to verify these findings.

Objective To investigate the refractive status of preschool children in Hanyang District of Wuhan and to analyze its associated factors,so as to provide scientific evidence for the early prevention and intervention of refractive error in children. Methods A cross-sectional study was conducted among 398 preschool children aged 3-6 years who underwent routine health examinations at the Hanyang District Health Center for Women and Children between September 2023 and February 2024.Binocular refractive status was measured using a SureSight handheld autorefractor.A structured questionnaire was used to collect information on demographic characteristics,visual habits,and dietary and nutritional status.Group differences were compared using the χ² test,and multivariate logistic regression analysis was performed to identify factors associated with refractive error. Results A total of 398 preschool children(796 eyes)were included in the study.The detection rate of refractive error was 13.1%.No statistically significant differences were observed in the prevalence of refractive error across age groups or between sexes(P>0.05).Multivariate logistic regression analysis showed that lower maternal education level(OR=1.621,95%CI:1.038,2.534)and a viewing distance of <50 cm when using computers or other electronic devices(OR=2.301,95%CI:1.200,4.414)were risk factors for refractive error.In contrast,regular vision examinations(OR=0.330,95%CI:0.176,0.618),always taking breaks from the screen during electronic device use(OR=0.252,95%CI:0.068,0.937),not watching television(OR=0.154,95%CI:0.025,0.933),absence of micronutrient deficiency in the past year(OR=0.268,95%CI:0.104,0.693),and absence of vitamin deficiency(OR=0.035,95%CI:0.003,0.384)were protective factors(all P<0.05). Conclusion The prevalence of refractive error among preschool children in Hanyang District of Wuhan remains relatively high.Maternal education level,electronic screen use behaviors,vision examination practices,and nutritional status may influence refractive status in preschool children.Strengthening vision screening programs,regulating electronic device use,and promoting balanced nutrition may help support healthy visual development in early childhood.

Neddylation is a significant post-translational modification that resembles ubiquitination and is a reversible protein modification process that is initiated by the cascade of three essential enzymes:E1,E2,and E3.By altering the stability,shape,subcellular localization,and function of target proteins,neddylation regulate a number of cellular biological processes.According to recent research,neddylation is generally overactivated in tumors,and its hub molecules are intimately associated with a number of malignant characteristics,including immune evasion,invasion and migration,and tumor cell proliferation.This opens up new potential targets for anti-tumor intervention efforts.This study focuses on a systematic analysis of neddylation,classifies its molecular mechanism and functional significance in carcinogenesis and evolution,and thoroughly examines its possible applications in tumor treatment.

Ion channels are responsible for the flow of ions across cell membranes and play vital roles in human physiology,including the regulation of ion homeostasis,electrical excitability,and cell signaling.However,when ion channel function or expression is altered,these channels can interact with carcinogens,increasing susceptibility to HPV infection and inducing cancer.Therefore,this study focuses on potassium,sodium,and chloride ion channels,identifies HPV-related carcinogenic factors,elucidates relevant mechanisms and the potential for targeting ion channels for treatment,and provides a new approach to the clinical determination of HPV-related cancer early diagnosis,prognosis,and treatment.

Neurogenic bladder(NB)is the most common complication after spinal cord injury,often causing bladder storage and urination dysfunction,seriously affecting patients’daily life.Although current treatments for NB such as antimuscarinic drugs,botox injections,and surgery relieve NB symptoms,they are not effective in reducing cystic fibrosis progression.Cystic fibrosis is the key to cause irreversible changes in the structure of the bladder in the pathological process,so finding ways to alleviate cystic fibrosis is crucial for the treatment of NB.The inability of the bladder to accept neurotrophic factors,inflammatory response mediated by inflammatory factors and cell pyrodeath,and the activation of mechanically sensitive ion channels caused by mechanical stress of the bladder may be related to NB fibrosis after spinal cord injury.Understanding the molecular mechanism and potential activation pathway of NB fibrosis after spinal cord injury is expected to provide a new direction for the treatment of NB fibrosis.In this paper,the potential mechanism of NB fibrosis after spinal cord injury and the possible signaling pathway were reviewed in order to provide new ideas for clinical treatment and drug development.

Osteoporosis is an age-related degenerative disease characterized by reduced bone mineral density and deterioration of bone microarchitecture,which markedly increases the risk of fractures.With the rising field of osteoimmunology,increasing attention has been given to the role of the immune system—particularly macrophages—in maintaining bone metabolic homeostasis and in the pathogenesis of osteoporosis.As aging progresses,macrophages exhibit a pro-inflammatory tendency,characterized by elevated expression of inflammatory cytokines,alterations in metabolic and signaling pathways,and a phenotypic shift toward the M1 subtype.Concurrently,changes in the extracellular environment further reinforce these senescent features.Such macrophage senescence not only impairs their intrinsic functions but also exerts profound effects on systemic immune responses and tissue repair capacity.In bone metabolism,macrophages exert dual roles:they can promote bone loss through the secretion of pro-inflammatory cytokines and chemokines,while also supporting bone regeneration by enhancing osteoblast activity and regulating the clearance of apoptotic cells.Macrophages are essential for maintaining the hematopoietic stem cell niche,and their senescence can disrupt this microenvironment.Moreover,macrophage senescence influences the bone microenvironment and osteogenesis through multiple mechanisms,including altered secretion profiles,metabolic signaling,inflammatory pathways,mitochondrial homeostasis,and extracellular vesicles.This review systematically summarizes recent advances in understanding the role of macrophages in skeletal aging,aiming to provide a more comprehensive immunological perspective for the precise intervention of osteoporosis.

The pathogenesis of Parkinson’s disease is rather complex,and no complete cure is currently available.Recent in-depth studies on the microbiota-gut-brain axis have revealed that bidirectional communication between gut microbiota and the brain is mediated by the vagus nerve.The microbiota-gut-brain axis is closely associated with Parkinson’s disease and represents a promising direction for its diagnosis and treatment.This paper aims to construct a framework centered on“gut microbiota dysbiosis-vagus nerve mediation-α-synuclein-Parkinson’s disease”,organizing intervention strategies targeting the vagus nerve.By analyzing its multiple mechanisms,such as regulating gut microbiota and providing neuroprotection,the study further elucidates its unique advantages in improving both motor and non-motor symptoms of Parkinson’s disease,thereby exploring the potential of vagus nerve stimulation as a treatment for the condition.

Vascular cognitive impairment is a cerebrovascular-related disorder with high prevalence and disability,imposing a substantial burden on patients,families,and society.The Sonic Hedgehog signaling pathway is involved in multiple pathophysiological processes relevant to vascular cognitive impairment and has emerged as a highly promising therapeutic target.This review summarizes recent advances in elucidating the mechanisms by which the Sonic Hedgehog signaling pathway modulates vascular cognitive impairment,aiming to clarify its critical role and provide new insights to guide future basic research and clinical translation in this field.