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
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
Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an es...Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an essential reference for comparative analysis.However,their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues.This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.Methods Samples with the pathologic description of molar pregnancy were collected.Routine hematoxylin–eosin(HE)staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines.A novel 26-plex system was explored to classify CHM and diploid pregnancies.The system combined 22 STRs on chromosomes 21/18/13/X,3 sex loci,and 1 quality control marker(TAF9L),enabling molecular diagnosis in the absence of maternal tissue.At last,traditional DNA typing based on villi and decidua(maternal component)of each case was used for result consistency analysis.Results CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features.DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system.CHM(46XX)diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers,excluding chromosomal abnormalities via TAF9L analysis.When the villous tissue analysis revealed single peaks at X-STR/SRY loci,a 1:1 amelogenin ratio,and a 2:1 TAF9L peak ratio,these results overlapped with those of 46XY hydropic abortus or CHM.Notably,p57 immunohistochemical staining resolved the ambiguity.Consistency with traditional DNA genotyping confirmed system accuracy.This multiplex assay enhanced reliability in mole diagnosis,supporting clinical differentiation and genetic counseling.Conclusion This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component.The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.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 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 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 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
Objective The aim of this study was to explore the influence of working length(determined by the screw position)on the stiffness and interfragmentary strain(IFS)of femoral locking compression plate(LCP)external fixato...Objective The aim of this study was to explore the influence of working length(determined by the screw position)on the stiffness and interfragmentary strain(IFS)of femoral locking compression plate(LCP)external fixators for lower tibial fractures under full weight-bearing conditions,with the goal of providing a reference basis for clinical applications.Methods Finite element analysis software was used to construct a model of a lower tibial fracture with external femoral LCP fixation.The models were divided into four groups according to the different working lengths(external femoral locking plate fixation 1[EF1],EF2,EF3,and EF4).Stress distribution clouds,fracture end displacements,stiffness and IFS were tested for each model group at different loads.Results Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 28%,31%,and 37%,respectively,under axial compression loading.Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 19%,33%,and 35%,respectively,under axial torsion loading.Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 32%,33%,and 35%,respectively,under a three-point bending load.The IFS of the four finite element models increased with the working length of the plate,with EF1(76%)<EF2(107%)<EF3(110%)<EF4(122%).Finite element analysis revealed that under full weight-bearing conditions,the structural stiffness of the femoral LCP external fixator decreased with increasing working length,leading to an increase in the IFS,which resulted in an IFS that exceeded the ideal range required for secondary healing.Conclusion For unstable lower tibial fractures,screws in the femoral LCP external fixator should be placed as close to the fracture end as possible to increase stability and promote fracture healing.展开更多
Uterine tumors resembling ovarian sex cord tumors(UTROSCTs)are characterized by an uncertain malignant potential and exhibit prominent sex cord-like differentiation.The purpose of this study was to comprehensively rev...Uterine tumors resembling ovarian sex cord tumors(UTROSCTs)are characterized by an uncertain malignant potential and exhibit prominent sex cord-like differentiation.The purpose of this study was to comprehensively review the clinicopathological characteristics of UTROSCTs and analyze eight cases of UTROSCTs treated at our hospital.We conducted an extensive review of the relevant literature and gathered pertinent data.In addition,we identified eight patients with UTROSCTs and analyzed their clinical and pathological features,diagnosis,treatment,and prognosis.Patients presented with symptoms such as abnormal vaginal bleeding or uterine mass detection.Surgical interventions varied,including total abdominal hysterectomy,bilateral salpingo-oophorectomy,and pelvic lymphadenectomy,with adjuvant therapy given to one patient.All eight patients are currently disease-free,with the longest follow-up period being nearly 10 years.Our systematic review of UTROSCTs summarized the clinical and pathological features and revealed several novel markers,including ESR1-NCOA2-3,GREB1-NCOA1-3,GREB1-CTNNB1,and GREB1-NR4A3.UTROSCTs are rare mesenchymal tumors with unclear histogenesis and uncertain malignant potential.Although our understanding of UTROSCTs remains incomplete,the promising findings and increasing availability of clinical data will contribute to the further understanding and development of this rare neoplasm.展开更多
Artificial intelligence(AI)serves as a key technology in global industrial transformation and technological restructuring and as the core driver of the fourth industrial revolution.Currently,deep learning techniques,s...Artificial intelligence(AI)serves as a key technology in global industrial transformation and technological restructuring and as the core driver of the fourth industrial revolution.Currently,deep learning techniques,such as convolutional neural networks,enable intelligent information collection in fields such as tongue and pulse diagnosis owing to their robust feature-processing capabilities.Natural language processing models,including long short-term memory and transformers,have been applied to traditional Chinese medicine(TCM)for diagnosis,syndrome differentiation,and prescription generation.Traditional machine learning algorithms,such as neural networks,support vector machines,and random forests,are also widely used in TCM diagnosis and treatment because of their strong regression and classification performance on small structured datasets.Future research on AI in TCM diagnosis and treatment may emphasize building large-scale,high-quality TCM datasets with unified criteria based on syndrome elements;identifying algorithms suited to TCM theoretical data distributions;and leveraging AI multimodal fusion and ensemble learning techniques for diverse raw features,such as images,text,and manually processed structured data,to increase the clinical efficacy of TCM diagnosis and treatment.展开更多
Adipokines,including C1q/tumor necrosis factor(TNF)-related proteins(CTRPs),adiponectin,TNF-α,and leptin,are crucial bioactive molecules that are secreted by adipose tissue and circulate in the bloodstream.To date,15...Adipokines,including C1q/tumor necrosis factor(TNF)-related proteins(CTRPs),adiponectin,TNF-α,and leptin,are crucial bioactive molecules that are secreted by adipose tissue and circulate in the bloodstream.To date,15 members of the CTRP family,which are collectively classified as part of the C1q/TNF superfamily,have been identified.Among these,CTRP3 stands out as a unique adipokine because of its distinct structural and functional properties.Recent research has highlighted the significant role of CTRP3 in the pathogenesis of various diseases.This review aims to comprehensively summarize the involvement and mechanisms of CTRP3 in the development of numerous disorders,as well as its potential therapeutic implications.展开更多
Objective Placental dysfunction induced by fetal cardiopulmonary bypass(CPB)imposes limitations on the clinical application of this procedure.The potential impact of microRNA-mediated autophagy in placental endothelia...Objective Placental dysfunction induced by fetal cardiopulmonary bypass(CPB)imposes limitations on the clinical application of this procedure.The potential impact of microRNA-mediated autophagy in placental endothelial cells on overall placental function remains elusive,necessitating a comprehensive exploration of the underlying mechanisms involved.Methods We established fetal sheep CPB models and employed immunohistochemistry to assess the placental expression of ATG7.Bioinformatic analysis,coupled with dual-luciferase reporter assays,was used to elucidate the intricate relationship between miR-320a and ATG7.Changes in ATG7 expression were further investigated through Western blotting and quantitative polymerase chain reaction(qPCR).Human umbilical vein endothelial cells(HUVECs)were cultured,and in vitro experiments were conducted to evaluate their regulatory effects on endothelial function.Immunoblotting was used to measure the expression levels of ATG7,endothelin-1(ET-1),SIRT1,and FOXO1,whereas enzyme-linked immunosorbent assay(ELISA)was used to quantify nitric oxide(NO)production.Results Sixty minutes after CPB,a substantial decrease in ATG7 expression in placental tissue was observed.The downregulation of ATG7 expression led to increased ET-1 production in HUVECs,concomitant with decreased NO production.miR-320a was identified as a specific regulator of ATG7 expression,with subsequent experiments demonstrating a significant reduction in placental ATG7 levels upon injection of the miR-320a agomir compared with the miR-320a antagomir during fetal sheep CPB.In HUVECs,miR-320a downregulated ATG7,resulting in increased ET-1 production and diminished NO production.Treatment with the miR-320a mimic/miR-320a inhibitor revealed that miR-320a inhibited the SIRT1/FOXO1 pathway in HUVECs by downregulating ATG7 expression,culminating in increased ET-1 production and reduced NO levels.Conclusion The observed downregulation of placental ATG7 expression subsequent to fetal CPB is intricately associated with endothelial dysfunction.Furthermore,our findings underscore the specific regulatory role of miR-320a in modulating ATG7 expression within the placenta.At the cellular level,increasing the level of miR-320a has emerged as a potential strategy for modulating endothelial function through the inhibition of ATG7 and the SIRT1/FOXO1 pathway.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 Pulmonary arterial hypertension(PAH)poses a growing global health challenge,yet comprehensive epidemiological data remain limited.This study aims to assess the burden of PAH from 1990 to 2021 and project tre...Objective Pulmonary arterial hypertension(PAH)poses a growing global health challenge,yet comprehensive epidemiological data remain limited.This study aims to assess the burden of PAH from 1990 to 2021 and project trends to 2040,addressing critical gaps in incidence,mortality,and disability-adjusted life years(DALYs)across diverse socio-demographic contexts.Methods Using data from the Global Burden of Disease(GBD)2021 study,we analyzed PAH burden across 204 countries and territories,stratified by age,sex,region,and socio-demographic index(SDI).Age-standardized rates(per 100,000 populations)for incidence(ASIR),mortality(ASMR),and DALYs(ASDR)were calculated.Future trends were projected via a Bayesian age-period-cohort(BAPC)model.Results In 2021,there were 43,251(95%uncertainty interval[UI]:34,705,52,441)global incident PAH cases(age standardized incidence rate[ASIR]:0.52).From 1990 to 2021,PAH incidence rose by 85.62%,with the steepest increase in high-middle SDI regions(average annual percentage change[AAPC]:+0.19%).Despite a 48.36%rise in deaths,the age-standardized mortality rate(ASMR)declined annually by 0.84%,reflecting improved management.Central Europe had the highest ASMR(1.06 per 100,000),while low SDI regions showed reduced ASIR(−0.31%AAPC),likely due to underdiagnosis.PAH caused 642,104 DALYs globally in 2021,with infants(<1 year)bearing the highest DALY rate.Projections indicate 75,000 annual cases by 2040,emphasizing an escalating burden.Conclusion PAH burden is increasing disproportionately in aging populations and high-middle SDI regions,while low SDI areas face underdiagnosis and healthcare disparities.Targeted interventions,equitable resource allocation,and enhanced diagnostic capacity are urgently needed to mitigate future PAH-related morbidity and mortality.展开更多
Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefor...Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefore,we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer,elucidate its potential oncogenic functions in this disease,and further explore its feasibility as a therapeutic target.Methods The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test.Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1.Furthermore,functional enrichment analyses were performed to explore the associated signaling pathways and biological functions.The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases.In addition,in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.Results TM4SF1 was overexpressed in nearly all tumors,and its overexpression was associated with poor prognosis in cervical cancer.Moreover,the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy.Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells.Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HeLa and SiHa cells,as well as promoted their apoptosis.Conclusion TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.展开更多
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 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 Key Research and Development Program of Shaanxi(No.S2024-YF-YB-SF-1359).
文摘Objective Current autosomal short tandem repeat(STR)assays can analyze the zygotic composition by comparing the allelic genes at each locus of complete hydatidiform moles(CHM),with a maternal genotype serving as an essential reference for comparative analysis.However,their application in pathology represents a challenge because of deficiency or contamination of maternal-origin tissues.This study aimed to develop a novel STR genotyping method for identifying CHM genotypes without a maternal component.Methods Samples with the pathologic description of molar pregnancy were collected.Routine hematoxylin–eosin(HE)staining and p57 immunohistochemistry staining were conducted in accordance with standard guidelines.A novel 26-plex system was explored to classify CHM and diploid pregnancies.The system combined 22 STRs on chromosomes 21/18/13/X,3 sex loci,and 1 quality control marker(TAF9L),enabling molecular diagnosis in the absence of maternal tissue.At last,traditional DNA typing based on villi and decidua(maternal component)of each case was used for result consistency analysis.Results CHM and nonmolar abortus could not be distinguished by the basic HE staining with no fetal evidence or other prominent features.DNA typing was successfully processed for all cases according to the novel 26-plex and traditional system.CHM(46XX)diagnosis required single A-STR/X-STR peaks and absent Y-chromosome markers,excluding chromosomal abnormalities via TAF9L analysis.When the villous tissue analysis revealed single peaks at X-STR/SRY loci,a 1:1 amelogenin ratio,and a 2:1 TAF9L peak ratio,these results overlapped with those of 46XY hydropic abortus or CHM.Notably,p57 immunohistochemical staining resolved the ambiguity.Consistency with traditional DNA genotyping confirmed system accuracy.This multiplex assay enhanced reliability in mole diagnosis,supporting clinical differentiation and genetic counseling.Conclusion This study presents a rapid and cost-effective assay for the genotypic identification of CHM without the need for a maternal component.The method combined the characteristics of STR loci distributed across different chromosomes and developed the clinic application of forensic biomarkers.
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.
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 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.
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supported by the Health Commission of Guizhou Province(No.gzwkj2024-400)the“Open Competition Project”of Bijie Science and Technology Bureau(BST Major Project No.1,2022).
文摘Objective The aim of this study was to explore the influence of working length(determined by the screw position)on the stiffness and interfragmentary strain(IFS)of femoral locking compression plate(LCP)external fixators for lower tibial fractures under full weight-bearing conditions,with the goal of providing a reference basis for clinical applications.Methods Finite element analysis software was used to construct a model of a lower tibial fracture with external femoral LCP fixation.The models were divided into four groups according to the different working lengths(external femoral locking plate fixation 1[EF1],EF2,EF3,and EF4).Stress distribution clouds,fracture end displacements,stiffness and IFS were tested for each model group at different loads.Results Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 28%,31%,and 37%,respectively,under axial compression loading.Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 19%,33%,and 35%,respectively,under axial torsion loading.Compared with those in the EF1 group,the stiffnesses in the EF2,EF3,and EF4 groups decreased by 32%,33%,and 35%,respectively,under a three-point bending load.The IFS of the four finite element models increased with the working length of the plate,with EF1(76%)<EF2(107%)<EF3(110%)<EF4(122%).Finite element analysis revealed that under full weight-bearing conditions,the structural stiffness of the femoral LCP external fixator decreased with increasing working length,leading to an increase in the IFS,which resulted in an IFS that exceeded the ideal range required for secondary healing.Conclusion For unstable lower tibial fractures,screws in the femoral LCP external fixator should be placed as close to the fracture end as possible to increase stability and promote fracture healing.
文摘Uterine tumors resembling ovarian sex cord tumors(UTROSCTs)are characterized by an uncertain malignant potential and exhibit prominent sex cord-like differentiation.The purpose of this study was to comprehensively review the clinicopathological characteristics of UTROSCTs and analyze eight cases of UTROSCTs treated at our hospital.We conducted an extensive review of the relevant literature and gathered pertinent data.In addition,we identified eight patients with UTROSCTs and analyzed their clinical and pathological features,diagnosis,treatment,and prognosis.Patients presented with symptoms such as abnormal vaginal bleeding or uterine mass detection.Surgical interventions varied,including total abdominal hysterectomy,bilateral salpingo-oophorectomy,and pelvic lymphadenectomy,with adjuvant therapy given to one patient.All eight patients are currently disease-free,with the longest follow-up period being nearly 10 years.Our systematic review of UTROSCTs summarized the clinical and pathological features and revealed several novel markers,including ESR1-NCOA2-3,GREB1-NCOA1-3,GREB1-CTNNB1,and GREB1-NR4A3.UTROSCTs are rare mesenchymal tumors with unclear histogenesis and uncertain malignant potential.Although our understanding of UTROSCTs remains incomplete,the promising findings and increasing availability of clinical data will contribute to the further understanding and development of this rare neoplasm.
基金supported by grants from the National Natural Science Foundation of China(Key Program)(No.82230124)Traditional Chinese Medicine Inheritance and Innovation“Ten million”talent project-Qihuang Project Chief Scientist Project(No.0201000401)+1 种基金State Administration of Traditional Chinese Medicine 2nd National Traditional Chinese Medicine Inheritance Studio Construction Project(Official Letter of the State Office of Traditional Chinese Medicine[2022]No.245)National Natural Science Foundation of China(General Program)(No.81974556).
文摘Artificial intelligence(AI)serves as a key technology in global industrial transformation and technological restructuring and as the core driver of the fourth industrial revolution.Currently,deep learning techniques,such as convolutional neural networks,enable intelligent information collection in fields such as tongue and pulse diagnosis owing to their robust feature-processing capabilities.Natural language processing models,including long short-term memory and transformers,have been applied to traditional Chinese medicine(TCM)for diagnosis,syndrome differentiation,and prescription generation.Traditional machine learning algorithms,such as neural networks,support vector machines,and random forests,are also widely used in TCM diagnosis and treatment because of their strong regression and classification performance on small structured datasets.Future research on AI in TCM diagnosis and treatment may emphasize building large-scale,high-quality TCM datasets with unified criteria based on syndrome elements;identifying algorithms suited to TCM theoretical data distributions;and leveraging AI multimodal fusion and ensemble learning techniques for diverse raw features,such as images,text,and manually processed structured data,to increase the clinical efficacy of TCM diagnosis and treatment.
基金funded by the National Natural Science Foundation of China(No.81873489).
文摘Adipokines,including C1q/tumor necrosis factor(TNF)-related proteins(CTRPs),adiponectin,TNF-α,and leptin,are crucial bioactive molecules that are secreted by adipose tissue and circulate in the bloodstream.To date,15 members of the CTRP family,which are collectively classified as part of the C1q/TNF superfamily,have been identified.Among these,CTRP3 stands out as a unique adipokine because of its distinct structural and functional properties.Recent research has highlighted the significant role of CTRP3 in the pathogenesis of various diseases.This review aims to comprehensively summarize the involvement and mechanisms of CTRP3 in the development of numerous disorders,as well as its potential therapeutic implications.
基金supported by the National Key Research and Development Program of China(No.2022YFC2407406)Guangzhou Science and Technology Planning Project(No.2023B03J0596)2023 Stability Support for Innovative Capacity Building of Guangdong Provincial Scientific Research Institutions(No.KD022023019).
文摘Objective Placental dysfunction induced by fetal cardiopulmonary bypass(CPB)imposes limitations on the clinical application of this procedure.The potential impact of microRNA-mediated autophagy in placental endothelial cells on overall placental function remains elusive,necessitating a comprehensive exploration of the underlying mechanisms involved.Methods We established fetal sheep CPB models and employed immunohistochemistry to assess the placental expression of ATG7.Bioinformatic analysis,coupled with dual-luciferase reporter assays,was used to elucidate the intricate relationship between miR-320a and ATG7.Changes in ATG7 expression were further investigated through Western blotting and quantitative polymerase chain reaction(qPCR).Human umbilical vein endothelial cells(HUVECs)were cultured,and in vitro experiments were conducted to evaluate their regulatory effects on endothelial function.Immunoblotting was used to measure the expression levels of ATG7,endothelin-1(ET-1),SIRT1,and FOXO1,whereas enzyme-linked immunosorbent assay(ELISA)was used to quantify nitric oxide(NO)production.Results Sixty minutes after CPB,a substantial decrease in ATG7 expression in placental tissue was observed.The downregulation of ATG7 expression led to increased ET-1 production in HUVECs,concomitant with decreased NO production.miR-320a was identified as a specific regulator of ATG7 expression,with subsequent experiments demonstrating a significant reduction in placental ATG7 levels upon injection of the miR-320a agomir compared with the miR-320a antagomir during fetal sheep CPB.In HUVECs,miR-320a downregulated ATG7,resulting in increased ET-1 production and diminished NO production.Treatment with the miR-320a mimic/miR-320a inhibitor revealed that miR-320a inhibited the SIRT1/FOXO1 pathway in HUVECs by downregulating ATG7 expression,culminating in increased ET-1 production and reduced NO levels.Conclusion The observed downregulation of placental ATG7 expression subsequent to fetal CPB is intricately associated with endothelial dysfunction.Furthermore,our findings underscore the specific regulatory role of miR-320a in modulating ATG7 expression within the placenta.At the cellular level,increasing the level of miR-320a has emerged as a potential strategy for modulating endothelial function through the inhibition of ATG7 and the SIRT1/FOXO1 pathway.
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supported by the Hubei Provincial Natural Science Foundation of China(Grant No.2025AFB068)Jin-zhu Zhao was supported by the Wuhan Natural Science Foundation Exploration Program(Chen Guang Program,Grant No.2024040801020344).
文摘Objective Pulmonary arterial hypertension(PAH)poses a growing global health challenge,yet comprehensive epidemiological data remain limited.This study aims to assess the burden of PAH from 1990 to 2021 and project trends to 2040,addressing critical gaps in incidence,mortality,and disability-adjusted life years(DALYs)across diverse socio-demographic contexts.Methods Using data from the Global Burden of Disease(GBD)2021 study,we analyzed PAH burden across 204 countries and territories,stratified by age,sex,region,and socio-demographic index(SDI).Age-standardized rates(per 100,000 populations)for incidence(ASIR),mortality(ASMR),and DALYs(ASDR)were calculated.Future trends were projected via a Bayesian age-period-cohort(BAPC)model.Results In 2021,there were 43,251(95%uncertainty interval[UI]:34,705,52,441)global incident PAH cases(age standardized incidence rate[ASIR]:0.52).From 1990 to 2021,PAH incidence rose by 85.62%,with the steepest increase in high-middle SDI regions(average annual percentage change[AAPC]:+0.19%).Despite a 48.36%rise in deaths,the age-standardized mortality rate(ASMR)declined annually by 0.84%,reflecting improved management.Central Europe had the highest ASMR(1.06 per 100,000),while low SDI regions showed reduced ASIR(−0.31%AAPC),likely due to underdiagnosis.PAH caused 642,104 DALYs globally in 2021,with infants(<1 year)bearing the highest DALY rate.Projections indicate 75,000 annual cases by 2040,emphasizing an escalating burden.Conclusion PAH burden is increasing disproportionately in aging populations and high-middle SDI regions,while low SDI areas face underdiagnosis and healthcare disparities.Targeted interventions,equitable resource allocation,and enhanced diagnostic capacity are urgently needed to mitigate future PAH-related morbidity and mortality.
基金the Natural Science Fund of Hubei Province(No.2022CFC019 and No.2021CFB430).
文摘Objective Accumulating evidence suggests that transmembrane 4 L6 family member 1(TM4SF1)is associated with the development of various cancers;yet comprehensive studies on TM4SF1 in cervical cancer are lacking.Therefore,we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer,elucidate its potential oncogenic functions in this disease,and further explore its feasibility as a therapeutic target.Methods The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test.Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1.Furthermore,functional enrichment analyses were performed to explore the associated signaling pathways and biological functions.The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases.In addition,in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.Results TM4SF1 was overexpressed in nearly all tumors,and its overexpression was associated with poor prognosis in cervical cancer.Moreover,the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy.Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells.Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HeLa and SiHa cells,as well as promoted their apoptosis.Conclusion TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.
