Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-i...Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.展开更多
Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly c...Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.展开更多
Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systemat...Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.展开更多
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.展开更多
Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical pract...Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.展开更多
Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NS...Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.展开更多
Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention a...Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.展开更多
Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying...Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.展开更多
Objective Peritoneal carcinomatosis(PC)is a common pattern of recurrence in gastric cancer patients and is associated with a poor prognosis.This study aimed to evaluate the predictive value of the albumin-fibrinogen r...Objective Peritoneal carcinomatosis(PC)is a common pattern of recurrence in gastric cancer patients and is associated with a poor prognosis.This study aimed to evaluate the predictive value of the albumin-fibrinogen ratio(AFR)for PC in patients with gastric cancer and to develop two preoperative prediction models.Methods A total of 745 gastric cancer patients were included in this study.Preoperative AFR,along with other serum markers and clinical tumor characteristics,was assessed.Univariate and multivariate logistic regression analyses were performed to determine the odds ratios(ORs)and 95%confidence intervals(CIs)of the independent variables.Propensity score matching(PSM)was used to control for potential confounders,and one-way ANOVA was conducted to evaluate differences in distribution between groups.Two prediction models incorporating the independent predictive indicators were constructed and validated via receiver operating characteristic(ROC)curves.Results Poorly differentiated type(OR 2.679;P=0.001),nondiffuse morphological type(OR 2.123;P=0.040),BMI<23.550 kg/m^(2)(OR 4.635;P=0.001),AFR<11.275(OR 2.895;P=0.003)and CA199≥73.615 U/mL(OR 2.040;P=0.037)were identified as independent risk factors for PC in patients with gastric cancer.After PSM,the AFR remained the only inflammatory marker that was independently associated with PC(P=0.003).AFR demonstrated consistent robustness in predicting PC across multiple sample sets.Among all the independent risk factors,the AFR had the highest area under the curve(AUC)for ROC analysis(AUC 0.648;95%CI 0.580–0.715).Two combination models incorporating the AFR demonstrated enhanced predictive ability:Combination Model 1(AUC 0.759;95%CI 0.699–0.820)and Combination Model 2(AUC 0.801;95%CI 0.744–0.859).Conclusions The preoperative AFR serves as a useful indicator for predicting PC.Two reliable prediction models based on the AFR have been developed.展开更多
Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation sys...Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.展开更多
Background The molecular mechanisms of early-onset multigenerational diabetes remain unknown.This study aimed to investigate the clinical and genetic characteristics of early-onset diabetes involving at least two cons...Background The molecular mechanisms of early-onset multigenerational diabetes remain unknown.This study aimed to investigate the clinical and genetic characteristics of early-onset diabetes involving at least two consecutive generations.Methods From 1296 inpatients with diabetes,we selected individuals who were≤30 years of age and who were clinically suspected of having familial monogenic diabetes.Clinical data were collected from the probands and their family members.Whole-exome sequencing(WES)was used to identify possible causal variants for diabetes.Candidate pathogenic variants were verified by Sanger sequencing,assessed for cosegregation in family members,and evaluated on the basis of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology(ACMG/AMP)guidelines.Moreover,missense and synonymous variants were subjected to in silico pathogenicity prediction via MutationTaster and PolyPhen-2.RNAfold was used to predict RNA structural alterations for synonymous variants.Results Twenty-five early-onset diabetes patients with a history of familial diabetes were enrolled.Pathogenic/likely pathogenic variants(p.Gly292fs in HNF1A,p.Gly245Argfs*22 in PDX1,p.Asp329His in KCNJ11,p.Leu734Phe and p.Val606Gly in WFS1)were detected in four patients,who were diagnosed accurately and treated with reasonable hypoglycemic agents based on genetic testing results.The variants of uncertain significance(ABCC8 c.3039 G>A(p.Ser1013=Ser),MAPK8IP1 p.Gln144_Gly145insSerGln,and TBC1D4 p.Arg1249Trp)were identified in three probands.Conclusion Patients with early-onset diabetes involving at least two consecutive generations may harbor genetic variants.Genetic testing in this population enables precision diagnosis,informs individualized treatment,and facilitates genetic counseling.展开更多
Objective Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease(DKD).However,investigations of immune cell-related ferroptosis genes(ICRFGs)in the context of DKD are insu...Objective Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease(DKD).However,investigations of immune cell-related ferroptosis genes(ICRFGs)in the context of DKD are insufficient.This study aimed to identify ICRFGs relevant to DKD and screen related inhibitors.Methods In this study,two DKD datasets from the GEO database were utilized.We adopted the ESTIMATE algorithm to generate microenvironment scores.The CIBERSORT and WGCNA methods were employed to identify immune-related differentially expressed genes(DEGs).The common ICRFGs were derived through a Venn diagram.We employed random forest,LASSO,K-M survival,receiver operating characteristic(ROC)curve,clinical relevance,and Spearman correlation analyses to select hub ICRFGs further.Immunohistochemical experiments were also performed to validate the expression.Additionally,we utilized the Selleck database to obtain ferroptosis-related compounds and used USCF Chimera 1.14 to minimize energy,combined with molecular dynamics(MD)simulations to explore possible ferroptosis inhibitors.Results Immunohistochemical analysis revealed that arachidonate 5-lipoxygenase(ALOX5)was significantly highly expressed in the db/db group.Clinical correlation and K-M survival analyses confirmed ALOX5 as the most crucial ICRFG in DKD.Furthermore,ALOX5 was significantly enriched in the terms ECM-receptor interaction,regulation of chemokine production,and regulation of the inflammatory response.A positive correlation was observed between ALOX5 and M1 macrophages,γδT cells,and monocytes.Moreover,virtual screening and MD revealed NSC348884,salvianolic acid B,and deltarasin as potential ferroptosis inhibitors in combination with ALOX5.Conclusion We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients.展开更多
Objective The middle turbinate axilla(MTA)is a crucial anatomical landmark for localizing the lacrimal sac(LS)during endonasal dacryocystorhinostomy(En-DCR).Despite being a standard surgical procedure,En-DCR may lead ...Objective The middle turbinate axilla(MTA)is a crucial anatomical landmark for localizing the lacrimal sac(LS)during endonasal dacryocystorhinostomy(En-DCR).Despite being a standard surgical procedure,En-DCR may lead to severe complications,such as cerebrospinal fluid(CSF)leakage,which is closely associated with anatomical variations between the LS and the anterior skull base(ASB).This study aimed to investigate the anatomical location of the LS relative to the MTA and ASB in Chinese patients with nasolacrimal duct obstruction(NLDO)and analyze the influencing factors.Methods This cross-sectional study enrolled 227 Chinese patients who were diagnosed with NLDO and underwent computed tomographic dacryocystography(CT-DCG).Anatomical distances between LS and MTA,as well as LS and ASB,were measured using CT-DCG images.Results The mean distances from the superior and inferior edges of the LS to the MTA were 9.94±4.70 mm and−0.23±4.15 mm,respectively.Male patients showed significantly more superior–anterior displacement of the LS compared to female patients(P<0.001),while patients with chronic dacryocystitis(CD)had an inferior and posterior LS position relative to those with simple NLDO(P=0.005,P=0.001).The mean distance from the intersection(Point P)of the superior and posterior boundaries of the LS to the ASB(MP)was 18.35±4.48 mm,which was shorter in females and those with frontal sinus aplasia(P=0.001;P<0.001).A subgroup(28/227,12.3%)with a critical anatomical feature was identified,where the distance from Point Q(10 mm posterior to P)to the ASB(NQ distance)was≤10 mm.This subgroup had a higher prevalence of complete supra-MTA LS positioning(71.4%vs.41.2%,P=0.003).Conclusion Preoperative CT-DCG provides essential anatomical insights into the spatial relationship between the LS and MTA in Chinese patients with NLDO.The LS position varies significantly by gender and disease type,with males showing more superior–anterior and CD patients more inferior–posterior positioning relative to the MTA.Special attention should be paid to patients with frontal sinus aplasia or LS entirely above the MTA to minimize the risk of CSF leakage during En-DCR.展开更多
Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Alt...Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.展开更多
Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images...Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images in shRNA group in Fig.3 were accidentally used rather than the final,formal experiments.To retain consistency,the entire Fig.3 is replaced here with original images of the experiments.The authors declare that this correction will not affect the conclusion of the study.展开更多
Objective This is a self-controlled multicenter retrospective study based on the clinical efficacy and complications of physiological reconstruction in the treatment of moderate and severe pelvic organ prolapse.Method...Objective This is a self-controlled multicenter retrospective study based on the clinical efficacy and complications of physiological reconstruction in the treatment of moderate and severe pelvic organ prolapse.Methods From December 2014 to August 2021,517 women were included and registered for physiological reconstruction at four Chinese urogynecology institutions.We enrolled 364 women with POP-Q stage≥3.The degree of POP was quantified via a POP-Q system.The surgical purpose of physiological reconstruction is to repair the vagina,levator ani muscle,perineum,and urogenital hiatus and adopt a repair method in accordance with the axial direction of physiology.All 330 evaluable participants were followed for 2 years.The evaluation indices included the PFDI-20,PGI-I,PFIQ-7,PISQ-12,PGI-I,and PGI-S.All complications were coded according to the category-time-site system proposed by the International Urogynecological Association(IUGA)and International Continence Society(ICS).Results Compared with the preoperative POP-Q scores,statistically significant improvements were observed at the 6-month,1-year and 2-year time points(P<0.001).Statistically significant improvements in quality of life were observed across all time points.Conclusions Physiologic reconstructive surgical techniques combined with modified anterior pelvic floor mesh implantation could help restore the physiologic axis and vaginal shape,which may be the most important factors in maintaining the functional position of pelvic floor organs and is the most effective method for repairing the pelvic fascia tendon arch.This surgical method is safe,feasible,and effective in patients with severe prolapse.展开更多
Objective Overactive bladder,a storage syndrome characterized by urinary urgency,frequency,and nocturia with or without urgency urinary incontinence,severely affects the quality of life of patients.The aim of this stu...Objective Overactive bladder,a storage syndrome characterized by urinary urgency,frequency,and nocturia with or without urgency urinary incontinence,severely affects the quality of life of patients.The aim of this study was to investigate the role and mechanism of the C/EBP homologous protein in the overactive bladder.Methods An overactive bladder mouse model was established via the intraperitoneal injection of cyclophosphamide in wild-type and Chop-deficient mice.An in vitro model was established using interleukin(IL)-6-induced mouse bladder epithelial cells.Hematoxylin–eosin(HE)staining was used to assess bladder tissue damage,and ELISA was used to measure inflammatory cytokine levels.Western blot analysis was used to examine p-PERK,ATF-6,p-eIF2α,BiP,ATF-4,Bax,Bcl-2,and cleaved caspase-3 protein expression levels.TUNEL staining and flow cytometry were conducted to measure the degree of apoptosis in bladder epithelial cells and macrophages.Results C/EBP homologous protein levels were decreased in overactive bladder tissues;nevertheless,macrophage infiltration was found to be increased.Knockout of Chop exacerbated bladder dysfunction,tissue injury,macrophage infiltration,and bladder epithelial apoptosis and alleviated endoplasmic reticulum stress.Conclusions Chop deficiency exacerbates inflammation,injury,and bladder epithelial apoptosis in overactive bladder model mice by inhibiting endoplasmic reticulum stress.展开更多
Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,po...Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.展开更多
Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating...Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating ANP expression,but its precise role in ANP-mediated cardioprotection remains unclear.This study aimed to investigate whether ANP protects the heart during reperfusion by modulating Zn^(2+)levels and to explore the underlying mechanisms involved.Methods In this study,we utilized an isolated reperfused heart model in rats,as well as wild-type(WT)and ANP knockout(ANP^(-/-))mouse models,for in vivo I/R experiments.For clinical investigations,plasma samples were collected from 216 patients with ischemia-related diseases.Evans blue and TTC staining,radioimmunoassay,ICP-OES,echocardiography,Hydro-Cy3-mediated ROS detection,and Western blotting were employed to evaluate the effect of ANP on Zn^(2+)homeostasis.Results Plasma ANP levels were significantly elevated in patients with ST-elevation myocardial infarction(STEMI),non-ST-elevation myocardial infarction(NSTEMI),and heart failure(HF).ANP secretion increased during reperfusion,rather than infarction,both ex vivo and in vivo,promoting Zn^(2+)accumulation in reperfused tissue.ANP and Zn^(2+)protected mito-chondria and reduced infarct size;these effects were reversed by the Zn^(2+)chelator TPEN.In WT and ANP^(-/-)mice,EF%and FS%decreased after reperfusion,with ANP^(-/-)mice exhibiting significantly worse cardiac function.ANP pretreatment alone improved cardiac function,but combined pretreatment with ANP and TPEN decreased EF%and FS%while increas-ing LVID.Reperfusion increased ROS levels in both WT and ANP^(-/-)hearts,which were reduced by ANP pretreatment.I/R injury elevated Zn^(2+)transporter 8(ZnT8)expression,an effect that was counteracted by ANP,although this effect was reversed by TPEN.Hypoxia-inducible factor 1-alpha(HIF-1α)expression was elevated in I/R rats and ANP^(-/-)mice,and it was inhibited by both Zn^(2+)and ANP pretreatment.However,the HIF-1αinhibitor 2-Me did not reverse the effect of ANP on ZnT8 expression.Additionally,ANP increased PI3K expression in both WT and ANP^(-/-)I/R mice,but this effect was blocked by the PI3K inhibitor LY294002.Conclusions ANP modulates Zn^(2+)homeostasis during reperfusion injury by downregulating ZnT8 through the PI3K signal-ling pathway,thereby reducing myocardial I/R injury.展开更多
Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive...Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82474412 and 82074364)the Innovation Program of Wuhan-Basic Research in 2022(No.2022020801020506)the Natural Science Foundation of Hubei Province(No.2022CFC024).
文摘Objective Safranal is a natural product from saffron(Crocus sativus L.)with anti-inflammatory and nephroprotective potential.This study aimed to explore the role of safranal in a cationic bovine serum albumin(C-BSA)-induced rat model of membranous glomerulonephritis(MGN).Methods After model establishment,Sprague–Dawley rats were administered 100 or 200 mg/kg safranal by gavage.A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters.Hematoxylin–eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG,C3,and Sirt1.Western blotting was performed to measure the protein levels of podocin,nephrin,Sirt1,and factors involved in the NF-κB/p65 pathway.Inflammatory cytokine levels in renal homogenates were determined by ELISA.Results Safranal at 100 or 200 mg/kg reduced kidney weight(2.07±0.15 g and 2.05±0.15 g)and the kidney somatic index(0.83±0.08%and 0.81±0.08%)in MGN rats compared with those in the model group without drug administration(2.62±0.17 g and 1.05±0.1%).C-BSA increased the urine protein level to 117.68±10.52 mg/day(compared with the sham group,5.03±0.45 mg/day),caused dysregulation of renal function indicators,and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples.All the biochemical and histological changes were improved by safranal administration.Safranal at two doses also increased the fluorescence intensities of IgG(0.1±0.009 and 0.088±0.008)and C3(0.065±0.006 and 0.048±0.004)compared with those in the MGN group(0.15±0.013 and 0.086±0.008).Additionally,safranal reversed the downregulation of podocin,nephrin,and Wilms tumor protein-1(WT1)levels and reversed the high inflammatory cytokine levels in MGN rats.Mechanistically,safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats.Conclusions Safranal ameliorates renal damage,inflammation,and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.
基金supported by the Research Project of Maternal and Child Health Hospital of Hubei Province(No.2023SFYM008)Key Project of Hubei Provincial Natural Science Foundation(No.JCZRLH202500304).
文摘Objective ZW10 interacting kinetochore protein(ZWINT)has been demonstrated to play a pivotal role in the growth,invasion,and migration of cancers.Nevertheless,whether the expression levels of ZWINT are significantly correlated with clinicopathological characteristics and prognostic outcomes of patients with breast cancer remains elusive.This study systematically investigated the clinical significance of ZWINT expression in breast cancer through integrated molecular subtyping and survival analysis.Methods We systematically characterized the spatial expression pattern of ZWINT across various breast cancer subtypes and assessed its prognostic significance using an integrated bioinformatics approach that involved multi-omics analysis.The approach included the Breast Cancer Gene-Expression Miner v5.1(bc-GenExMiner v5.1),TNMplot,MuTarget,PrognoScan database,and Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results Our analysis revealed consistent upregulation of ZWINT mRNA and protein expression across distinct clinicopathological subtypes of breast cancer.ZWINT overexpression demonstrated significant co-occurrence with truncating mutations in cadherin 1(CDH1)and tumor protein p53(TP53),suggesting potential functional crosstalk in tumor progression pathways.The overexpression of ZWINT correlated with adverse clinical outcomes,showing 48%increased mortality risk(overall survival:HR 1.48,95%CI 1.23–1.79),66%higher recurrence probability(relapse-free survival:1.66,95%CI 1.50–1.84),and 63%elevated metastasis risk(distant metastasis-free survival:HR 1.63,95%CI 1.39–1.90).Multivariate Cox regression incorporating TNM staging and molecular subtypes confirmed ZWINT as an independent prognostic determinant(P<0.001,Harrell’s C-index=0.7827),which was validated through bootstrap resampling(1000 iterations).Conclusion ZWINT may serve as a potential biomarker for prognosis and a possible therapeutic target alongside TP53/CDH1 in breast cancer.
文摘Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.
基金supported by the National Natural Science Foundation of China(No.82170326 and No.82470328 to Y.D.,No.82100339 to Q.D.).
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia with a multifactorial pathophysiology involving electrical,structural,and autonomic remodeling of the atria.AF is closely associated with elevated interleukin-6(IL-6)levels,which contribute to atrial remodeling and the progression of AF.This review summarizes the mechanisms by which IL-6 promotes AF through inflammatory pathways,atrial fibrosis,electrical remodeling,and calcium mishandling.Experimental models have demonstrated that IL-6 neutralization reduces the incidence of AF,highlighting its potential as a therapeutic target.Future studies should focus on IL-6 blockade strategies to manage AF,aiming to improve patient outcomes.
文摘Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.
基金supported by the Scientific Research Project of Hubei Cancer Hospital(No.2024HBCHYN08)the Natural Science Foundation of Hubei Province(No.2023AFB988)+1 种基金the Scientific Research Project in the Field of Oncology(No.FB2024025225)the Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC007).
文摘Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.
文摘Objective This study aimed to analyse the trend of the mental disorder spectrum in children and adolescents from 2014 to 2022 in one city in Central China and to provide actionable recommendations for the prevention and management of mental disorders.Methods In this hospital-based retrospective study,we utilized child and adolescent medical records data from the Wuhan Mental Health Center from January 2014 to December 2022 and examined the top 5 mental disorders(schizophrenia,depressive episode,bipolar disorder,pervasive developmental disorder,and unspecified mood disorder)that accounted for the overall proportion of patients admitted.The rank and proportion of these mental disorders,demographic characteristics and disease indicators were analysed.Results There was a significant upwards trend in the number of children and adolescents diagnosed with mental disorders over the past 9 years,with a sharp decline in 2020 due to the COVID-19 pandemic,followed by a rebound in 2021 and a sustained level above prepandemic figures by 2022.The average age of hospitalization decreased significantly from 20.7 to 16.2 years,with a marked increase in the 12-17-year-old age group.The proportion of female hospitalizations increased from 39.2%to 55.2%,with a corresponding decrease in male hospitalizations.There was a notable decrease in the proportion of schizophrenia cases and an ascent of depressive episode to the most prevalent position.Conclusion This study emphasizes the critical need for targeted interventions and resources for severe mental disorders in children and adolescents and the importance of early detection and management of mental disorders to mitigate long-term effects on well-being and development.
文摘Objective Vitamin deficiencies,particularly in vitamins A,B12,and D,are prevalent across populations and contribute significantly to a range of health issues.While these deficiencies are well documented,the underlying etiology remains complex.Recent studies suggest a close link between the gut microbiota and the synthesis,absorption,and metabolism of these vitamins.However,the specific causal relationships between the gut microbiota composition and vitamin deficiencies remain poorly understood.Identifying key bacterial species and understanding their role in vitamin metabolism could provide critical insights for targeted interventions.Methods We conducted a two-sample Mendelian randomization(MR)study to assess the causal relationship between the gut microbiota and vitamin deficiencies(A,B12,D).The genome-wide association study data for vitamin deficiencies were sourced from the FinnGen biobank,and the gut microbiota data were from the MiBioGen consortium.MR analyses included inverse variance-weighted(IVW),MR‒Egger,weighted median,and weighted mode approaches.Sensitivity analyses and reverse causality assessments were performed to ensure robustness and validate the findings.Results After FDR adjustment,vitamin B12 deficiency was associated with the class Verrucomicrobiae,order Verrucomicrobiales,family Verrucomicrobiaceae,and genus Akkermansia.Vitamin A deficiency was associated with the phylum Firmicutes and the genera Fusicatenibacter and Ruminiclostridium 6.Additional associations for vitamin B12 deficiency included the Enterobacteriaceae and Rhodospirillaceae and the genera Coprococcus 2,Lactococcus,and Ruminococcaceae UCG002.Vitamin D deficiency was associated with the genera Allisonella,Eubacterium,and Tyzzerella 3.Lachnospiraceae and Lactococcus were common risk factors for both B12 and D deficiency.Sensitivity analyses confirmed the robustness of the findings against heterogeneity and horizontal pleiotropy,and reverse MR tests indicated no evidence of reverse causality.Conclusions Our findings reveal a possible causal relationship between specific gut microbiota characteristics and vitamin A,B12 and D deficiencies,providing a theoretical basis for addressing these nutritional deficiencies through the modulation of the gut microbiota in the future and laying the groundwork for related interventions.
文摘Objective Peritoneal carcinomatosis(PC)is a common pattern of recurrence in gastric cancer patients and is associated with a poor prognosis.This study aimed to evaluate the predictive value of the albumin-fibrinogen ratio(AFR)for PC in patients with gastric cancer and to develop two preoperative prediction models.Methods A total of 745 gastric cancer patients were included in this study.Preoperative AFR,along with other serum markers and clinical tumor characteristics,was assessed.Univariate and multivariate logistic regression analyses were performed to determine the odds ratios(ORs)and 95%confidence intervals(CIs)of the independent variables.Propensity score matching(PSM)was used to control for potential confounders,and one-way ANOVA was conducted to evaluate differences in distribution between groups.Two prediction models incorporating the independent predictive indicators were constructed and validated via receiver operating characteristic(ROC)curves.Results Poorly differentiated type(OR 2.679;P=0.001),nondiffuse morphological type(OR 2.123;P=0.040),BMI<23.550 kg/m^(2)(OR 4.635;P=0.001),AFR<11.275(OR 2.895;P=0.003)and CA199≥73.615 U/mL(OR 2.040;P=0.037)were identified as independent risk factors for PC in patients with gastric cancer.After PSM,the AFR remained the only inflammatory marker that was independently associated with PC(P=0.003).AFR demonstrated consistent robustness in predicting PC across multiple sample sets.Among all the independent risk factors,the AFR had the highest area under the curve(AUC)for ROC analysis(AUC 0.648;95%CI 0.580–0.715).Two combination models incorporating the AFR demonstrated enhanced predictive ability:Combination Model 1(AUC 0.759;95%CI 0.699–0.820)and Combination Model 2(AUC 0.801;95%CI 0.744–0.859).Conclusions The preoperative AFR serves as a useful indicator for predicting PC.Two reliable prediction models based on the AFR have been developed.
基金funded by National Natural Science Foundation of China(No.82272134)Innovative Research Group Project of the National Natural Science Foundation of China(No.82272134,Xiao-lei Chen).
文摘Background and Objective Electromagnetic navigation technology has demonstrated significant potential in enhancing the accuracy and safety of neurosurgical procedures.However,traditional electromagnetic navigation systems face challenges such as high equipment costs,complex operation,bulky size,and insufficient anti-interference performance.To address these limitations,our study developed and validated a novel portable electromagnetic neuronavigation system designed to improve the precision,accessibility,and clinical applicability of electromagnetic navigation technology in cranial surgery.Methods The software and hardware architecture of a portable neural magnetic navigation system was designed.The key technologies of the system were analysed,including electromagnetic positioning algorithms,miniaturized sensor design,optimization of electromagnetic positioning and navigation algorithms,anti-interference signal processing methods,and fast three-dimensional reconstruction algorithms.A prototype was developed,and its accuracy was tested.Finally,a preliminary clinical application evaluation was conducted.Results This study successfully developed a comprehensive portable electromagnetic neuronavigation system capable of achieving preoperative planning,intraoperative real-time positioning and navigation,and postoperative evaluation of navigation outcomes.Through rigorous collaborative testing of the system’s software and hardware,the accuracy of electromagnetic neuronavigation has been validated to meet clinical requirements.Conclusions This study developed a portable neuroelectromagnetic navigation system and validated its effectiveness and safety through rigorous model testing and preliminary clinical applications.The system is characterized by its compact size,high precision,excellent portability,and user-friendly operation,making it highly valuable for promoting navigation technology and advancing the precision and minimally invasive nature of neurosurgical procedures.
基金supported by Diabetes Talent Research Project of China,International Medical Foundation 2019(No.2018-N-1).
文摘Background The molecular mechanisms of early-onset multigenerational diabetes remain unknown.This study aimed to investigate the clinical and genetic characteristics of early-onset diabetes involving at least two consecutive generations.Methods From 1296 inpatients with diabetes,we selected individuals who were≤30 years of age and who were clinically suspected of having familial monogenic diabetes.Clinical data were collected from the probands and their family members.Whole-exome sequencing(WES)was used to identify possible causal variants for diabetes.Candidate pathogenic variants were verified by Sanger sequencing,assessed for cosegregation in family members,and evaluated on the basis of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology(ACMG/AMP)guidelines.Moreover,missense and synonymous variants were subjected to in silico pathogenicity prediction via MutationTaster and PolyPhen-2.RNAfold was used to predict RNA structural alterations for synonymous variants.Results Twenty-five early-onset diabetes patients with a history of familial diabetes were enrolled.Pathogenic/likely pathogenic variants(p.Gly292fs in HNF1A,p.Gly245Argfs*22 in PDX1,p.Asp329His in KCNJ11,p.Leu734Phe and p.Val606Gly in WFS1)were detected in four patients,who were diagnosed accurately and treated with reasonable hypoglycemic agents based on genetic testing results.The variants of uncertain significance(ABCC8 c.3039 G>A(p.Ser1013=Ser),MAPK8IP1 p.Gln144_Gly145insSerGln,and TBC1D4 p.Arg1249Trp)were identified in three probands.Conclusion Patients with early-onset diabetes involving at least two consecutive generations may harbor genetic variants.Genetic testing in this population enables precision diagnosis,informs individualized treatment,and facilitates genetic counseling.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)(No.Qiankehe Foundation-ZK[2023]General 428)Guizhou Provincial Department of Education 2024 Natural Science Research Project(Youth Science and Technology Talent Growth Project)(No.Qiankejiao[2024]116)the Science and Technology Foundation of Guizhou Provincial Health Commission(No.gzwkj2022-008).
文摘Objective Immune infiltration and ferroptosis play pivotal roles in the progression of diabetic kidney disease(DKD).However,investigations of immune cell-related ferroptosis genes(ICRFGs)in the context of DKD are insufficient.This study aimed to identify ICRFGs relevant to DKD and screen related inhibitors.Methods In this study,two DKD datasets from the GEO database were utilized.We adopted the ESTIMATE algorithm to generate microenvironment scores.The CIBERSORT and WGCNA methods were employed to identify immune-related differentially expressed genes(DEGs).The common ICRFGs were derived through a Venn diagram.We employed random forest,LASSO,K-M survival,receiver operating characteristic(ROC)curve,clinical relevance,and Spearman correlation analyses to select hub ICRFGs further.Immunohistochemical experiments were also performed to validate the expression.Additionally,we utilized the Selleck database to obtain ferroptosis-related compounds and used USCF Chimera 1.14 to minimize energy,combined with molecular dynamics(MD)simulations to explore possible ferroptosis inhibitors.Results Immunohistochemical analysis revealed that arachidonate 5-lipoxygenase(ALOX5)was significantly highly expressed in the db/db group.Clinical correlation and K-M survival analyses confirmed ALOX5 as the most crucial ICRFG in DKD.Furthermore,ALOX5 was significantly enriched in the terms ECM-receptor interaction,regulation of chemokine production,and regulation of the inflammatory response.A positive correlation was observed between ALOX5 and M1 macrophages,γδT cells,and monocytes.Moreover,virtual screening and MD revealed NSC348884,salvianolic acid B,and deltarasin as potential ferroptosis inhibitors in combination with ALOX5.Conclusion We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients.
基金funded by grants from the Natural Science Foundation of Hubei Province(No.2022CFB199)the National Natural Science Foundation of China(No.82271127).
文摘Objective The middle turbinate axilla(MTA)is a crucial anatomical landmark for localizing the lacrimal sac(LS)during endonasal dacryocystorhinostomy(En-DCR).Despite being a standard surgical procedure,En-DCR may lead to severe complications,such as cerebrospinal fluid(CSF)leakage,which is closely associated with anatomical variations between the LS and the anterior skull base(ASB).This study aimed to investigate the anatomical location of the LS relative to the MTA and ASB in Chinese patients with nasolacrimal duct obstruction(NLDO)and analyze the influencing factors.Methods This cross-sectional study enrolled 227 Chinese patients who were diagnosed with NLDO and underwent computed tomographic dacryocystography(CT-DCG).Anatomical distances between LS and MTA,as well as LS and ASB,were measured using CT-DCG images.Results The mean distances from the superior and inferior edges of the LS to the MTA were 9.94±4.70 mm and−0.23±4.15 mm,respectively.Male patients showed significantly more superior–anterior displacement of the LS compared to female patients(P<0.001),while patients with chronic dacryocystitis(CD)had an inferior and posterior LS position relative to those with simple NLDO(P=0.005,P=0.001).The mean distance from the intersection(Point P)of the superior and posterior boundaries of the LS to the ASB(MP)was 18.35±4.48 mm,which was shorter in females and those with frontal sinus aplasia(P=0.001;P<0.001).A subgroup(28/227,12.3%)with a critical anatomical feature was identified,where the distance from Point Q(10 mm posterior to P)to the ASB(NQ distance)was≤10 mm.This subgroup had a higher prevalence of complete supra-MTA LS positioning(71.4%vs.41.2%,P=0.003).Conclusion Preoperative CT-DCG provides essential anatomical insights into the spatial relationship between the LS and MTA in Chinese patients with NLDO.The LS position varies significantly by gender and disease type,with males showing more superior–anterior and CD patients more inferior–posterior positioning relative to the MTA.Special attention should be paid to patients with frontal sinus aplasia or LS entirely above the MTA to minimize the risk of CSF leakage during En-DCR.
基金supported by the National Key Research and Development Program of China(No.2023YFC2506504)the National Natural Science Foundation of China(No.82370255,and No.U24A20646)the Shanghai Science and Technology Commission Project(No.23410761200).
文摘Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.
文摘Erratum to:J Huazhong Univ Sci Technol[Med Sci]36(4):548–553,2016 https://doi.org/10.1007/s11596-016-1623-6 In the originally published article(https://doi.org/10.1007/s11596-016-1623-6),the immunofluorescence images in shRNA group in Fig.3 were accidentally used rather than the final,formal experiments.To retain consistency,the entire Fig.3 is replaced here with original images of the experiments.The authors declare that this correction will not affect the conclusion of the study.
基金supported by the National Natural Science Foundation of China(No.82260297)Yunnan Province Clinical Research Center for Chronic Kidney Disease(No.202102AA100060).
文摘Objective This is a self-controlled multicenter retrospective study based on the clinical efficacy and complications of physiological reconstruction in the treatment of moderate and severe pelvic organ prolapse.Methods From December 2014 to August 2021,517 women were included and registered for physiological reconstruction at four Chinese urogynecology institutions.We enrolled 364 women with POP-Q stage≥3.The degree of POP was quantified via a POP-Q system.The surgical purpose of physiological reconstruction is to repair the vagina,levator ani muscle,perineum,and urogenital hiatus and adopt a repair method in accordance with the axial direction of physiology.All 330 evaluable participants were followed for 2 years.The evaluation indices included the PFDI-20,PGI-I,PFIQ-7,PISQ-12,PGI-I,and PGI-S.All complications were coded according to the category-time-site system proposed by the International Urogynecological Association(IUGA)and International Continence Society(ICS).Results Compared with the preoperative POP-Q scores,statistically significant improvements were observed at the 6-month,1-year and 2-year time points(P<0.001).Statistically significant improvements in quality of life were observed across all time points.Conclusions Physiologic reconstructive surgical techniques combined with modified anterior pelvic floor mesh implantation could help restore the physiologic axis and vaginal shape,which may be the most important factors in maintaining the functional position of pelvic floor organs and is the most effective method for repairing the pelvic fascia tendon arch.This surgical method is safe,feasible,and effective in patients with severe prolapse.
基金supported by the National Natural Science Foundation of China(No.81974400 and No.82173068).
文摘Objective Overactive bladder,a storage syndrome characterized by urinary urgency,frequency,and nocturia with or without urgency urinary incontinence,severely affects the quality of life of patients.The aim of this study was to investigate the role and mechanism of the C/EBP homologous protein in the overactive bladder.Methods An overactive bladder mouse model was established via the intraperitoneal injection of cyclophosphamide in wild-type and Chop-deficient mice.An in vitro model was established using interleukin(IL)-6-induced mouse bladder epithelial cells.Hematoxylin–eosin(HE)staining was used to assess bladder tissue damage,and ELISA was used to measure inflammatory cytokine levels.Western blot analysis was used to examine p-PERK,ATF-6,p-eIF2α,BiP,ATF-4,Bax,Bcl-2,and cleaved caspase-3 protein expression levels.TUNEL staining and flow cytometry were conducted to measure the degree of apoptosis in bladder epithelial cells and macrophages.Results C/EBP homologous protein levels were decreased in overactive bladder tissues;nevertheless,macrophage infiltration was found to be increased.Knockout of Chop exacerbated bladder dysfunction,tissue injury,macrophage infiltration,and bladder epithelial apoptosis and alleviated endoplasmic reticulum stress.Conclusions Chop deficiency exacerbates inflammation,injury,and bladder epithelial apoptosis in overactive bladder model mice by inhibiting endoplasmic reticulum stress.
基金supported by National Natural Science Foundation of China(No.82300268)Guangzhou Municipal Science and Technology Project(No.2023B03J1255).
文摘Objective Electronic cigarettes(ECs)differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling.Pulmonary hypertension(PH),characterized by pulmonary artery and right ventricle remodeling,poses a significant risk of mortality in infants,children,and adolescents.However,the impact of maternal EC exposure on PH development in offspring remains unclear.To address this,we established a PH rat model with maternal EC exposure.Methods Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems.Offspring were administered monocrotaline(MCT)at 6 weeks of age(6-wo)to induce PH.Mechanistic experiments were conducted at 10-week-old(10-wo).Protein expression of NADPH oxidases,DNA methyltransferases,and autophagy-related markers was analyzed by Western blot.Morphological changes and the severity of PH were evaluated via hematoxylin and eosin(HE)staining and echocardiography,respectively.Furthermore,the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA,Western blot,HE staining,and echocardiography.Additionally,ATG5 mRNA expression was measured by qRT-PCR.Results Compared with control conditions,maternal EC exposure significantly worsened MCT-induced PH in male offspring.This was associated with increased oxidative stress,DNA hypomethylation,and anomalous autophagy in the offspring.In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC.Furthermore,N-acetylcysteine(NAC),an antioxidant,attenuated maternal EC exposure-induced oxidative stress,DNA hypomethylation,and excessive autophagy,thereby improving PH.DNA hypermethylation also reversed PH development,accompanied by reduced oxidative stress and suppressed autophagy.ATG5,a key regulator of autophagy,was identified as a potential therapeutic target,as its repression mitigated PH in maternal EC-exposed offspring.Conclusion Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring,leading to anomalous autophagy and exacerbation of PH development.Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC.Graphical Abstract Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery,with all offspring undergoing PH induction at 6-wo.Offspring exposed to maternal EC presented increased oxidative stress,which in turn affected DNA methylation patterns.The decreased DNA methylation in male offspring led to the activation of autophagy,exacerbating the development of PH.Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82360065 and No.81760047).
文摘Objective Atrial natriuretic peptide(ANP)and Zn^(2+)have been shown to confer cardioprotection against ischemia/reperfu-sion(I/R)injury.Zn^(2+)alleviates myocardial hypertrophy and pulmonary hypertension by regulating ANP expression,but its precise role in ANP-mediated cardioprotection remains unclear.This study aimed to investigate whether ANP protects the heart during reperfusion by modulating Zn^(2+)levels and to explore the underlying mechanisms involved.Methods In this study,we utilized an isolated reperfused heart model in rats,as well as wild-type(WT)and ANP knockout(ANP^(-/-))mouse models,for in vivo I/R experiments.For clinical investigations,plasma samples were collected from 216 patients with ischemia-related diseases.Evans blue and TTC staining,radioimmunoassay,ICP-OES,echocardiography,Hydro-Cy3-mediated ROS detection,and Western blotting were employed to evaluate the effect of ANP on Zn^(2+)homeostasis.Results Plasma ANP levels were significantly elevated in patients with ST-elevation myocardial infarction(STEMI),non-ST-elevation myocardial infarction(NSTEMI),and heart failure(HF).ANP secretion increased during reperfusion,rather than infarction,both ex vivo and in vivo,promoting Zn^(2+)accumulation in reperfused tissue.ANP and Zn^(2+)protected mito-chondria and reduced infarct size;these effects were reversed by the Zn^(2+)chelator TPEN.In WT and ANP^(-/-)mice,EF%and FS%decreased after reperfusion,with ANP^(-/-)mice exhibiting significantly worse cardiac function.ANP pretreatment alone improved cardiac function,but combined pretreatment with ANP and TPEN decreased EF%and FS%while increas-ing LVID.Reperfusion increased ROS levels in both WT and ANP^(-/-)hearts,which were reduced by ANP pretreatment.I/R injury elevated Zn^(2+)transporter 8(ZnT8)expression,an effect that was counteracted by ANP,although this effect was reversed by TPEN.Hypoxia-inducible factor 1-alpha(HIF-1α)expression was elevated in I/R rats and ANP^(-/-)mice,and it was inhibited by both Zn^(2+)and ANP pretreatment.However,the HIF-1αinhibitor 2-Me did not reverse the effect of ANP on ZnT8 expression.Additionally,ANP increased PI3K expression in both WT and ANP^(-/-)I/R mice,but this effect was blocked by the PI3K inhibitor LY294002.Conclusions ANP modulates Zn^(2+)homeostasis during reperfusion injury by downregulating ZnT8 through the PI3K signal-ling pathway,thereby reducing myocardial I/R injury.
基金funded by the Shandong Provincial Natural Science Foundation(No.ZR2024MH008)Postdoctoral Innovation Program of Shandong Province(No.SDCX-ZG-202400043)Beijing iGandan Foundation(No.iGandanF-1082022-RGG007).
文摘Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.
