Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacte...Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].展开更多
The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide associa...The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.展开更多
The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to r...The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.展开更多
Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Meth...Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.展开更多
Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially c...Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially curative treatment,yet only one-fifth of patients are eligible for resection at initial diagnosis[3].Threedimensional(3D)reconstruction technology provides precise preoperative visualization of complex hilar anatomy,significantly enhancing surgical planning and outcomes[4].Recent advances in 3D reconstruction technology have enhanced preoperative planning by providing precise anatomical mapping of tumor-vessel relationships and biliary variations[4,5].Therefore,this report describes a case of left iCCA successfully resected with biliary reconstruction guided by 3D visualization.展开更多
Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Va...Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.展开更多
Background:Upper tract urothelial carcinoma(UTUC)is an aggressive malignancy with high recurrence rates.Lymphovascular invasion(LVI)predicts a poor prognosis,yet its molecular drivers remain unclear.BOC cell adhesion-...Background:Upper tract urothelial carcinoma(UTUC)is an aggressive malignancy with high recurrence rates.Lymphovascular invasion(LVI)predicts a poor prognosis,yet its molecular drivers remain unclear.BOC cell adhesion-associated,oncogene-regulated(BOC,also known as Brother of CDO[Cell adhesion moleculeRelated/Down-regulated by Oncogenes]),a hedgehog-related cell surface receptor,may serve as a biomarker for tumor progression and chemotherapy response.The study aimed to investigate the role of BOC in UTUC and its potential to predict LVI and chemotherapy response.Methods:Sequencing(RNA-seq)of 10 stage III UTUC,treatment-naïve,fresh tissue samples identified BOC as a candidate biomarker,which was subsequently validated in 2 independent cohorts(n=74).Functional assays using urothelial carcinoma cell lines assessed the impact of BOC knockdown on cell migration,proliferation,and drug sensitivity.Methylation-specific PCR(MSP)was used to identify potential regulatory sites influencing BOC expression,and immunohistochemistry(IHC)analysis was conducted to compare BOC levels in high-and low-grade bladder cancer.Results:BOC expression was significantly higher in patients with lymphovascular invasion(LVI+,p<0.01).Knockdown of BOC markedly inhibited cancer cell migration,without affecting proliferation.BOC knockdown enhanced the efficacy of cisplatin and gemcitabine in UTUC cells,although clinical tissue data did not provide direct evidence of its role as a predictor of drug response.Methylation analysis identified key regulatory sites that may control BOC expression,and IHC confirmed increased BOC levels in high-grade bladder cancer,linking it to tumor aggressiveness.Conclusion:BOC may serve as a potential biomarker for predicting LVI and chemotherapy response in UTUC.Its involvement in cancer cell migration and association with high-grade tumors suggests its clinical relevance for prognosis and treatment stratification.Further validation in larger,multi-center studies is warranted.展开更多
Objective:This study aims to develop a drug controlled-release system based on nano-hydrogel technology for stone dissolution and evaluate its dual efficacy in synchronously dissolving calcium oxalate stones and inhib...Objective:This study aims to develop a drug controlled-release system based on nano-hydrogel technology for stone dissolution and evaluate its dual efficacy in synchronously dissolving calcium oxalate stones and inhibiting uropathogenic Escherichia coli.Methods:A pH-responsive chitosan(CS)-sodium alginate(SA)-hydrogel microsphere loaded with potassium sodium hydrogen citrate and fosfomycin(CS/SA@PSHC@CS@F)was constructed using ionic cross-linking.In vitro stone dissolution experiments were conducted to determine drug release kinetics and stone mass reduction rate under different pH environments,and the antibacterial activity against E.coli ATCC 25922 was evaluated using the plate counting method.A rat model of kidney stone combined with infection was established.Stone volume changes were quantified via micro-CT,urinary interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)levels were measured by ELISA,and renal tissue inflammation was scored via histopathological evaluation.Results:The 24-hour cumulative release rate of CS/SA@PSHC@CS@F at pH 5.8 reached 92.3%±4.1%,significantly higher than at pH 7.4(31.2%±3.7%,P<0.01).At 72 h,the mass reduction rate of calcium oxalate stones in CS/SA@PSHC@CS@F was 68.9%±5.2%,significantly higher than that of the PSHC+F mixture(P<0.01).Antibacterial experiments confirmed that the inhibition rate of biofilm colonies by CS/SA@PSHC@CS@F could reach 82.4%±6.7%,compared to 58.2%±5.3%for F,with a statistically significant difference(P<0.01).Animal experiments showed that the stone volume reduction rate in the CS/SA@PSHC@CS@F group was62.3%±8.1%,higher than that in the PSHC+F group,and the decrease in urinary IL-6 level after administration was more significant,while there was no significant difference in TNF-αlevel compared with the other two groups(P>0.05).The renal tissue inflammation score decreased to 2(1,2)points,showing a significant reduction compared with the other two groups(P<0.05).Conclusion:The novel controlled-release system designed in this study achieves targeted drug release in the stone infection microenvironment through the ion exchange mechanism,simultaneously enhancing stone dissolution efficiency and antibacterial effect,thereby providing a new drug delivery strategy for the treatment of urinary stones combined with infection.展开更多
Objective:This article reviews the latest updates and outcomes of kidney-sparing surgery(KSS)in patients with upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the Pu...Objective:This article reviews the latest updates and outcomes of kidney-sparing surgery(KSS)in patients with upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed and Embase databases to identify related English-language studies published within the last 10 years.Key search words included“upper urinary tract tumour/cancer/carcinoma”,“kidney-sparing surgery or approach”,“endoscopic treatment for upper tract tumour/cancer/carcinoma”,“topical instillation in the upper urinary tract”,and“urinary marker for urothelial carcinoma”.References within the identified literature were explored and evaluated for relevance.Results:KSS is recommended for both low-risk and selected high-risk UTUC with imperative indications such as solitary kidney.Studies have shown comparable oncological outcomes after KSS including endoscopic ablation,segmental ureterectomy,and topical instillation of novel agents when compared to radical nephroureterectomy in well-selected cases.The development of novel diagnostic tools and risk-stratifying models allows optimal case selection for KSS without compromising oncological outcomes.Conclusion:Kidney-sparing approach for UTUC is an evolving and promising area in urologic oncology,driven by advances in technology,better diagnostic tools,and novel therapeutic agents.Our article provides a comprehensive review of the latest advancements and clinical recommendations.While current evidence is mainly based on retrospective studies,prospective trials are required to address important but unanswered clinical questions in this field.展开更多
In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin famil...In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin family member 14(KIF14),a critical kinesin,is pivotal in the proliferation,migration,and invasion of tumor cells.It has emerged as a focal point in recent studies of malignant tumors in the digestive tract.This article reviews the current research on KIF14 within these tumors and details its significant role in tumor cell behaviors,including proliferation,apo-ptosis,migration,invasion,and angiogenesis,alongside the regulatory mechanisms of the associated intracellular signaling pathways.Additionally,it explores the clinical value of KIF14 as a potential biomarker for early diagnosis,disease monitoring,and prognostic evaluation in malignant tumors of the digestive tract.The article concludes by introducing the potential regulatory role of traditional Chinese medicine,aiming to combine the strengths of both modern and traditional medical approaches to enhance treatment outcomes and prognosis for patients with these tumors.展开更多
Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely p...Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.展开更多
Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial...Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.展开更多
Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyl...Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
BACKGROUND Pelvic fractures are often associated with significant morbidity,including injuries to the urinary tract.Understanding the incidence and risk factors for urinary tract injury in these patients is crucial fo...BACKGROUND Pelvic fractures are often associated with significant morbidity,including injuries to the urinary tract.Understanding the incidence and risk factors for urinary tract injury in these patients is crucial for prompt diagnosis and management.This meta-analysis aims to synthesize existing evidence to determine the overall incidence and identify specific risk factors associated with urinary tract injuries in patients with pelvic fractures.AIM To determine the incidence and risk factors for urinary tract injuries in patients with pelvic fractures.METHODS A systematic search of PubMed,EMBASE,Scopus,and the Cochrane Library was conducted without date restrictions.Studies examining the incidence and risk factors of urinary tract injuries in patients with pelvic fractures were included.Data extracted included demographics,injury mechanism,pelvic fracture type,urinary tract injury incidence,mortality,and discharge disposition.Review Manager 5.4 was used for data analysis.RESULTS Ten studies comprising 22700 patients were included.The pooled incidence of urinary tract injury associated with pelvic fracture was 6.88%(95%CI:6.20%-7.55%).Vehicle,motorcycle,and pedestrian accidents were identified as risk factors for urinary tract injury,with relative risks(RR)of 1.08(95%CI:1.06-1.11),1.89(95%CI:1.78-2.00),and 1.53(95%CI:1.20-1.95),respectively.Pubic fracture and pelvic ring disruption were significantly associated with urinary tract injury[odds ratio(OR)1.94,95%CI:1.09-3.44 and OR 5.53,95%CI:4.67-6.54,respectively)].Patients without urinary tract injury were more likely to be discharged home(RR 0.79,95%CI:0.67-0.92).Mortality was higher in patients with urinary tract injury(OR 1.92,95%CI:1.77-2.09).CONCLUSION Urinary tract injury occurs in nearly 7%of patients with pelvic fractures.Motorcycle accidents,pubic fractures,and pelvic ring disruptions are significant risk factors.Urinary tract injury following pelvic fracture is associated with increased mortality.展开更多
A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive...A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.展开更多
Background:Urinary tract infections(UTIs),primarily caused by uropathogenic Escherichia coli(UPEC),are a significant global health concern.The complications arise from antibiotic resistance and biofilm formation,which...Background:Urinary tract infections(UTIs),primarily caused by uropathogenic Escherichia coli(UPEC),are a significant global health concern.The complications arise from antibiotic resistance and biofilm formation,which reduce the effectiveness of conventional treatments.This study aims to evaluate the antibiofilm activity of the homeopathic medicine Terebinthinae oleum in potencies 30C,200C,and 1M against UTI-causing E.coli,and to compare its effectiveness with the standard antibiotic Gentamycin.Methods:An in-vitro biofilm model was employed.E.coli biofilms were cultivated in microtiter plates and treated with Terebinthinae oleum(30C,200C,1M)and Gentamycin.Biofilm biomass was assessed through crystal violet staining,and optical density(OD)was measured using an ELISA microplate reader.Results:Among the tested potencies,Terebinthinae oleum 30C showed the most prominent inhibitory activity on E.coli biofilms.The inhibition percentage was compared with Gentamycin as a control.Terebinthinae oleum 30C demonstrated 41.88%inhibition of biofilm biomass,while Gentamycin exhibited up to 78.98%inhibition.Higher potencies of Terebinthinae oleum(200C and 1M)showed reduced activity(30.15%and 24.81%,respectively).Conclusion:Terebinthinae oleum,especially at 30C potency,exhibits measurable antibiofilm activity against E.coli,although less effective than Gentamycin.These findings support its use as a complementary therapy in managing biofilm-associated UTIs,justifying further clinical and immunological research.展开更多
Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The d...Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.展开更多
Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring ...Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.展开更多
Understanding mixed infections in the female lower genital tract is a critical challenge in modern infection research.The interplay of multiple pathogens complicates disease progression,often resulting in treatment fa...Understanding mixed infections in the female lower genital tract is a critical challenge in modern infection research.The interplay of multiple pathogens complicates disease progression,often resulting in treatment failure,recurrent infections,and significant public health and economic burdens.These infections are further exacerbated by disrupted host immune responses,which hinder the recovery of the vaginal microecosystem.Additionally,microbial biofilms—a fundamental mode of pathogen coexistence—contribute to the persistence and drug resistance of these infections,complicating management strategies.This review examines the pathogenesis,diagnosis,and treatment of mixed infections in the female lower genital tract while exploring potential avenues for future research.These findings emphasize the need for greater focus on these infections and offer insights to enhance further research in this area.展开更多
文摘Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].
基金supported by grants from the National Natural Science Foundation of China(Grant No.32470658)the National Key Research and Development Program of China(Grant Nos.2022YFC2502400 and 2022YFC2502402).
文摘The comorbidity of skin and gastrointestinal tract(GIT)diseases,primarily driven by the gut-skin axis(GSA),is well established.However,the genetic contribution to the GSA remains unclear.Here,using genome-wide association study(GWAS)summary statistics from European populations,we performed a genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases.We observed extensive genetic correlations and overlaps between skin and GIT diseases.A total of 298 pleiotropic loci were identified,75 of which were colocalized,and 61 exhibited pleiotropic effects across multiple trait pairs,including 2p16.1(PUS10),6p21.32(HLA-DRB1),10q21.2(ZNF365),and 19q13.11(SLC7A10).Additionally,five novel loci were identified based on the pleiotropic analysis;among them,the 15q22.2 locus harboring RORA was validated by the latest inflammatory bowel disease GWAS.Gene-based analysis identified 394 unique pleiotropic genes,which were enriched in GSA-associated tissues and the immune system,and protein-protein interaction analysis further revealed that the GPCR-cAMP,chromatin remodeling,JAK-STAT,and HLA-mediated immunity pathways were involved in GSA comorbidity.Notably,the JAK-STAT pathway showed strong potential for drug repurposing,with adalimumab targeting tumor necrosis factor and ustekinumab targeting interleukin-12 subunit beta already being used to treat both skin and GIT diseases.Finally,Mendelian randomization analysis identified five significant causal associations,and subsequent mediation analysis identified three potential microbiota-GIT-skin pathways.Taken together,our study demonstrated that the shared genetic factors between skin and GIT diseases were widely distributed across the genome.These findings will enhance our understanding of the genetic mechanisms underlying GSA comorbidity.
基金supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-055)the National Natural Science Foundation of China(82471925)。
文摘The objective of this study was to understand the effect of long-term aconitine(AC)oral administration on the digestive tract and serum metabolism.Subjects consumed either 0.9%Na Cl(n=8)or AC(n=17)gavage designed to represent human chronic AC administrations for 13 days.Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry.Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing.Serum samples were collected,and untargeted metabolomics was performed.In this study,AC administration induced proximal intestine,liver,and kidney injury.Microbiome composition remained stable after AC exposure,while several microbes presented dynamic alteration.Moreover,AC affected the abundance of the fatty acid biosynthesis rate-limiting gene acc A at day 7.AC induces 30 serum metabolites to significantly change at day 14,including several short-chain acylcarnitines.WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines.In summary,AC affects the digestive tract and serum metabolism after chronic administration.AC may affect the enrichment of microbial-derived acc A gene.The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.
基金supported and funded by Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)(No.O2208261)supported by the Korea University Guro Hospital(KOREA RESEARCH-DRIVEN HOSPITAL)+1 种基金grant funded by Korea University Medicine(No.K2313971)by Korea University。
文摘Objective:This study aimed to evaluate the associations of baseline income,cumulative income exposure,and income volatility with the incidence of pancreatic and biliary tract cancers in a nationwide Korean cohort.Methods:We analyzed 3,361,091 adults aged 30-65 years who underwent the 2012 National Health Insurance Service(NHIS)health screening.Income level was derived from insurance premium data assessed over the five years preceding baseline(2008-2012)and categorized into baseline income quartiles,cumulative exposure to low or high income,and income volatility based on annual percentage changes.Incident pancreatic and biliary tract cancers were identified using diagnostic codes and the copayment reduction registry.Associations were evaluated using Cox proportional hazards models with adjustment for demographic,lifestyle,and clinical covariates,and cumulative incidence was compared using Kaplan-Meier curves.Results:During a median follow-up of 9.6 years,14,469 pancreatic cancers and 6,647 biliary tract cancers were newly diagnosed.Lower baseline income was associated with a higher risk of pancreatic and biliary tract cancers,whereas sustained high-income exposure was associated with reduced risk.Cumulative low-income exposure showed a positive linear trend with pancreatic cancer incidence.Income volatility was modestly associated with pancreatic cancer and was positively associated with biliary tract cancer in the fully adjusted model.These associations were generally consistent across subgroups,with a stronger inverse association between prolonged high-income exposure and pancreatic cancer among individuals without diabetes.Conclusions:Income level and income stability were significantly associated with the incidence of pancreatic and biliary tract cancers.Lower baseline income was associated with higher risk,whereas sustained high-income exposure was protective.Income volatility was associated with increased cancer risk,particularly for biliary tract cancer.These findings highlight the importance of incorporating income dynamics into cancer prevention strategies and addressing socioeconomic instability among vulnerable populations.
基金supported by grants from the National Natural Science Foundation of China(82170412)Shanghai Municipal Science and Technology Commission Clinical Innovation Research Special Project(23Y11905400).
文摘Perihilar cholangiocarcinoma(pCCA)and intrahepatic cholangiocarcinoma(iCCA)are highly malignant neoplasms with a 5-year overall survival rate of approximately 30%[1,2].Surgical resection remains the only potentially curative treatment,yet only one-fifth of patients are eligible for resection at initial diagnosis[3].Threedimensional(3D)reconstruction technology provides precise preoperative visualization of complex hilar anatomy,significantly enhancing surgical planning and outcomes[4].Recent advances in 3D reconstruction technology have enhanced preoperative planning by providing precise anatomical mapping of tumor-vessel relationships and biliary variations[4,5].Therefore,this report describes a case of left iCCA successfully resected with biliary reconstruction guided by 3D visualization.
文摘Background:Prostate cancer is a common malignancy,with many men on active surveillance for localized,low-risk disease also experiencing lower urinary tract symptoms(LUTS)from benign prostatic hyperplasia(BPH).Water Vapor Thermal Therapy(WVTT)is a minimally invasive BPH treatment,but its safety and efficacy in this setting are unclear.Case Description:We report three men with localized PCa on active surveillance who underwent WVTT for LUTS.Conclusions:WVTT appears safe and potentially effective in treating LUTS,especially in those with lower-risk disease and smaller prostate volumes.Further research is needed to confirm safety,efficacy,and optimal patient selection.
基金funded by the Chang Gung Medical Foundation,Taiwan(CMRPG8M0851,CMRPG8N0681)the Ministry of Science and Technology(NSTC 113-2314-B-182A-105).
文摘Background:Upper tract urothelial carcinoma(UTUC)is an aggressive malignancy with high recurrence rates.Lymphovascular invasion(LVI)predicts a poor prognosis,yet its molecular drivers remain unclear.BOC cell adhesion-associated,oncogene-regulated(BOC,also known as Brother of CDO[Cell adhesion moleculeRelated/Down-regulated by Oncogenes]),a hedgehog-related cell surface receptor,may serve as a biomarker for tumor progression and chemotherapy response.The study aimed to investigate the role of BOC in UTUC and its potential to predict LVI and chemotherapy response.Methods:Sequencing(RNA-seq)of 10 stage III UTUC,treatment-naïve,fresh tissue samples identified BOC as a candidate biomarker,which was subsequently validated in 2 independent cohorts(n=74).Functional assays using urothelial carcinoma cell lines assessed the impact of BOC knockdown on cell migration,proliferation,and drug sensitivity.Methylation-specific PCR(MSP)was used to identify potential regulatory sites influencing BOC expression,and immunohistochemistry(IHC)analysis was conducted to compare BOC levels in high-and low-grade bladder cancer.Results:BOC expression was significantly higher in patients with lymphovascular invasion(LVI+,p<0.01).Knockdown of BOC markedly inhibited cancer cell migration,without affecting proliferation.BOC knockdown enhanced the efficacy of cisplatin and gemcitabine in UTUC cells,although clinical tissue data did not provide direct evidence of its role as a predictor of drug response.Methylation analysis identified key regulatory sites that may control BOC expression,and IHC confirmed increased BOC levels in high-grade bladder cancer,linking it to tumor aggressiveness.Conclusion:BOC may serve as a potential biomarker for predicting LVI and chemotherapy response in UTUC.Its involvement in cancer cell migration and association with high-grade tumors suggests its clinical relevance for prognosis and treatment stratification.Further validation in larger,multi-center studies is warranted.
文摘Objective:This study aims to develop a drug controlled-release system based on nano-hydrogel technology for stone dissolution and evaluate its dual efficacy in synchronously dissolving calcium oxalate stones and inhibiting uropathogenic Escherichia coli.Methods:A pH-responsive chitosan(CS)-sodium alginate(SA)-hydrogel microsphere loaded with potassium sodium hydrogen citrate and fosfomycin(CS/SA@PSHC@CS@F)was constructed using ionic cross-linking.In vitro stone dissolution experiments were conducted to determine drug release kinetics and stone mass reduction rate under different pH environments,and the antibacterial activity against E.coli ATCC 25922 was evaluated using the plate counting method.A rat model of kidney stone combined with infection was established.Stone volume changes were quantified via micro-CT,urinary interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)levels were measured by ELISA,and renal tissue inflammation was scored via histopathological evaluation.Results:The 24-hour cumulative release rate of CS/SA@PSHC@CS@F at pH 5.8 reached 92.3%±4.1%,significantly higher than at pH 7.4(31.2%±3.7%,P<0.01).At 72 h,the mass reduction rate of calcium oxalate stones in CS/SA@PSHC@CS@F was 68.9%±5.2%,significantly higher than that of the PSHC+F mixture(P<0.01).Antibacterial experiments confirmed that the inhibition rate of biofilm colonies by CS/SA@PSHC@CS@F could reach 82.4%±6.7%,compared to 58.2%±5.3%for F,with a statistically significant difference(P<0.01).Animal experiments showed that the stone volume reduction rate in the CS/SA@PSHC@CS@F group was62.3%±8.1%,higher than that in the PSHC+F group,and the decrease in urinary IL-6 level after administration was more significant,while there was no significant difference in TNF-αlevel compared with the other two groups(P>0.05).The renal tissue inflammation score decreased to 2(1,2)points,showing a significant reduction compared with the other two groups(P<0.05).Conclusion:The novel controlled-release system designed in this study achieves targeted drug release in the stone infection microenvironment through the ion exchange mechanism,simultaneously enhancing stone dissolution efficiency and antibacterial effect,thereby providing a new drug delivery strategy for the treatment of urinary stones combined with infection.
文摘Objective:This article reviews the latest updates and outcomes of kidney-sparing surgery(KSS)in patients with upper tract urothelial carcinoma(UTUC).Methods:A comprehensive literature search was performed using the PubMed and Embase databases to identify related English-language studies published within the last 10 years.Key search words included“upper urinary tract tumour/cancer/carcinoma”,“kidney-sparing surgery or approach”,“endoscopic treatment for upper tract tumour/cancer/carcinoma”,“topical instillation in the upper urinary tract”,and“urinary marker for urothelial carcinoma”.References within the identified literature were explored and evaluated for relevance.Results:KSS is recommended for both low-risk and selected high-risk UTUC with imperative indications such as solitary kidney.Studies have shown comparable oncological outcomes after KSS including endoscopic ablation,segmental ureterectomy,and topical instillation of novel agents when compared to radical nephroureterectomy in well-selected cases.The development of novel diagnostic tools and risk-stratifying models allows optimal case selection for KSS without compromising oncological outcomes.Conclusion:Kidney-sparing approach for UTUC is an evolving and promising area in urologic oncology,driven by advances in technology,better diagnostic tools,and novel therapeutic agents.Our article provides a comprehensive review of the latest advancements and clinical recommendations.While current evidence is mainly based on retrospective studies,prospective trials are required to address important but unanswered clinical questions in this field.
基金Supported by the 2023 Government-funded Project of the Outstanding Talents Training Program in Clinical Medicine,No.ZF2023165Key Research and Development Projects of Hebei Province,No.18277731D+1 种基金Natural Science Foundation of Hebei Province,No.H202423105Hebei Provincial Administration of Traditional Chinese Medicine,Scientific Research Project,No.2020014.
文摘In this editorial,we comment on the article by Qin et al,recently published in the World Journal of Gastrointestinal Oncology.Malignant tumors of the digestive tract represent a significant health threat.Kinesin family member 14(KIF14),a critical kinesin,is pivotal in the proliferation,migration,and invasion of tumor cells.It has emerged as a focal point in recent studies of malignant tumors in the digestive tract.This article reviews the current research on KIF14 within these tumors and details its significant role in tumor cell behaviors,including proliferation,apo-ptosis,migration,invasion,and angiogenesis,alongside the regulatory mechanisms of the associated intracellular signaling pathways.Additionally,it explores the clinical value of KIF14 as a potential biomarker for early diagnosis,disease monitoring,and prognostic evaluation in malignant tumors of the digestive tract.The article concludes by introducing the potential regulatory role of traditional Chinese medicine,aiming to combine the strengths of both modern and traditional medical approaches to enhance treatment outcomes and prognosis for patients with these tumors.
文摘Biliary tract cancer(BTC)is a group of heterogeneous sporadic diseases,including intrahepatic,hilar,and distal cholangiocarcinoma,as well as gallbladder cancer.BTC is characterized by high invasiveness and extremely poor prognosis,with a global increased incidence due to intrahepatic cholangiocarcinoma(ICC).The 18Ffludeoxyglucose positron emission tomography(PET)computed tomography(18F-FDG PET/CT)combines glucose metabolic information(reflecting the glycolytic activity of tumor cells)with anatomical structure to assess tumor metabolic heterogeneity,systemic metastasis,and molecular characteristics noninvasively,overcoming the limitations of traditional imaging in the detection of micrometastases and recurrent lesions.18F-FDG PET/CT offers critical insights in clinical staging,therapeutic evaluation,and prognostic prediction of BTC.This article reviews research progress in this field over the past decade,with a particular focus on the advances made in the last 3 years,which have not been adequately summarized and recognized.The research paradigm in this field is shifting from qualitative to quantitative studies,and there have been significant breakthroughs in using 18F-FDG PET/CT metabolic information to predict gene expression in ICC.Radiomics and deep learning techniques have been applied to ICC for prognostic prediction and differential diagnosis.Additionally,PET/magnetic resonance imaging is increasingly demonstrating its value in this field.
基金supported by the MISP program at Merck Sharp&Dohme Corp.,USAa grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(Grant Number:HR20C0025).
文摘Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid tumors.However,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still controversial.Materials and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.Results:All patients had microsatellite stable(MSS)type tumors.Three of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab response.Molecular analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor response.Moreover,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated fibroblasts.Conclusions:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.
基金supported by the National Natural Science Foundation of China,Nos.82030071(to JH),82272495(to YC)Science and Technology Major Project of Changsha,No.kh2103008(to JH)Graduate Students’Independent Innovative Projects of Hunan Province,No.CX20230311(to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
文摘BACKGROUND Pelvic fractures are often associated with significant morbidity,including injuries to the urinary tract.Understanding the incidence and risk factors for urinary tract injury in these patients is crucial for prompt diagnosis and management.This meta-analysis aims to synthesize existing evidence to determine the overall incidence and identify specific risk factors associated with urinary tract injuries in patients with pelvic fractures.AIM To determine the incidence and risk factors for urinary tract injuries in patients with pelvic fractures.METHODS A systematic search of PubMed,EMBASE,Scopus,and the Cochrane Library was conducted without date restrictions.Studies examining the incidence and risk factors of urinary tract injuries in patients with pelvic fractures were included.Data extracted included demographics,injury mechanism,pelvic fracture type,urinary tract injury incidence,mortality,and discharge disposition.Review Manager 5.4 was used for data analysis.RESULTS Ten studies comprising 22700 patients were included.The pooled incidence of urinary tract injury associated with pelvic fracture was 6.88%(95%CI:6.20%-7.55%).Vehicle,motorcycle,and pedestrian accidents were identified as risk factors for urinary tract injury,with relative risks(RR)of 1.08(95%CI:1.06-1.11),1.89(95%CI:1.78-2.00),and 1.53(95%CI:1.20-1.95),respectively.Pubic fracture and pelvic ring disruption were significantly associated with urinary tract injury[odds ratio(OR)1.94,95%CI:1.09-3.44 and OR 5.53,95%CI:4.67-6.54,respectively)].Patients without urinary tract injury were more likely to be discharged home(RR 0.79,95%CI:0.67-0.92).Mortality was higher in patients with urinary tract injury(OR 1.92,95%CI:1.77-2.09).CONCLUSION Urinary tract injury occurs in nearly 7%of patients with pelvic fractures.Motorcycle accidents,pubic fractures,and pelvic ring disruptions are significant risk factors.Urinary tract injury following pelvic fracture is associated with increased mortality.
文摘A clinical trial of nab-paclitaxel plus capecitabine as a first-line treatment for advanced biliary tract cancers was conducted.We analyzed the development of systemic therapy recommended by the National Comprehensive Cancer Network guidelines and the development of nab-paclitaxel combination chemotherapy for advanced biliary tract cancers(BTCs)and concluded that nab-paclitaxel plus capecitabine is a promising first-line regimen for advanced BTCs.
文摘Background:Urinary tract infections(UTIs),primarily caused by uropathogenic Escherichia coli(UPEC),are a significant global health concern.The complications arise from antibiotic resistance and biofilm formation,which reduce the effectiveness of conventional treatments.This study aims to evaluate the antibiofilm activity of the homeopathic medicine Terebinthinae oleum in potencies 30C,200C,and 1M against UTI-causing E.coli,and to compare its effectiveness with the standard antibiotic Gentamycin.Methods:An in-vitro biofilm model was employed.E.coli biofilms were cultivated in microtiter plates and treated with Terebinthinae oleum(30C,200C,1M)and Gentamycin.Biofilm biomass was assessed through crystal violet staining,and optical density(OD)was measured using an ELISA microplate reader.Results:Among the tested potencies,Terebinthinae oleum 30C showed the most prominent inhibitory activity on E.coli biofilms.The inhibition percentage was compared with Gentamycin as a control.Terebinthinae oleum 30C demonstrated 41.88%inhibition of biofilm biomass,while Gentamycin exhibited up to 78.98%inhibition.Higher potencies of Terebinthinae oleum(200C and 1M)showed reduced activity(30.15%and 24.81%,respectively).Conclusion:Terebinthinae oleum,especially at 30C potency,exhibits measurable antibiofilm activity against E.coli,although less effective than Gentamycin.These findings support its use as a complementary therapy in managing biofilm-associated UTIs,justifying further clinical and immunological research.
基金financially supported by the Natural Science Foundation of China(No.82003766)Taishan Scholars Program(NO.tsqn202211219)+1 种基金the Key Research and Development Project of Shandong Province(No.2021ZDSYS27)Shandong Province nature fund surface project(Grant No.ZR2024MH088)。
文摘Background:Studies have shown that individuals who receive early treatment for rheumatoid arthritis(RA)are more likely to approach life positively,avoiding joint damage and the need for joint replacement surgery.The diagnosis of early rheumatoid arthritis(ERA)is crucial for effective treatment and prognosis of patients.Urine,as a diagnostic medium,offers the advantages of non-invasive diagnosis.Urinary metabolites can serve as biomarkers for diagnosis,prognosis,and risk prediction,improving specificity and accuracy.Methods:We recruited 37 ERA patients with a history of less than 3 months and a score of 6,26 osteoarthritis(OA)patients,and 30 healthy controls(HC).Urine samples were collected for 16S rRNA sequencing,and untargeted liquid chromatography-mass spectrometry(LC-MS)was used to detect metabolites.Bioinformatics approaches were employed to identify pathogenic metabolites as specific risk factors for ERA precisely.Results:2-methylnaphthalene was identified as a biomarker for ERA in urine.Prevotella,a major part of the urinary microbiome in ERA patients,exhibited a positive correlation with 2-methylnaphthalene.Notably,there were significant variations in urine metabolites among patients with ERA,OA,and HC.2-Methylnaphthalene was found to be significantly enriched in ERA.Besides,inflammatory factors were elevated in ERA patients.The research further demonstrated a positive correlation between rheumatoid factor(RF),erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and the metabolite 2-methylnaphthalene.Conclusion:The urine metabolite 2-methylnaphthalene can be a risk factor for early urinary tract infections and may contribute to accurately screening early-risk metabolites in ERA.
基金supported by the Capital’s Funds for Health Improvement and Research(CFH,shoufa-2022-1G-1131 and shoufa 2022-4G-1133)the High Level Technical Talent Construction Project of Beijing Municipal Health Commission(Discipline Leader-02-20)+1 种基金Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-10)the Pathogen Spectrum and Host Marker Analysis in Children with Respiratory Tract Infections of Children(Grant 2024-0040).
文摘Objective Recombination events are common and serve as the primary driving force of diverse human adenovirus(HAdV),particularly in children with acute respiratory tract infections(ARIs).Therefore,continual monitoring of these events is essential for effective viral surveillance and control.Methods Respiratory specimens were collected from children with ARIs between January 2022 and December 2023.The penton base,hexon,and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type.In cases with inconsistent typing results,genes were cloned into the pGEM-T vector to detect recombination events.Metagenomic next-generation sequencing(mNGS)was performed to characterize the recombinant HAdV genomes.Results Among 6,771 specimens,277(4.09%,277/6,771)were positvie for HAdV,of which 157(56.68%,157/277)were successfully typed,with HAdV-B3 being the dominant type(91.08%,143/157),and 14(5.05%,14/277)exhibited inconsistent typing results,six of which belonged to species B.The penton base genes of these six specimens were classified as HAdV-B7,whereas their hexon and fiber genes were classified as HAdV-B3,resulting in a recombinant genotype designated P7H3F3,which closely resembled HAdV-B114.Additionally,a partial gene encoding L152/55 kD was identified,which originated from HAdV-B16.Conclusion A novel recombinant,P7H3F3,was identified,containing sequences derived from HAdV-B3 and HAdV-B7,which is similar to HAdV-B114,along with additional sequences from HAdV-B16.
基金supported by a grant from the National Natural Science Foundation of China(No.81874483).
文摘Understanding mixed infections in the female lower genital tract is a critical challenge in modern infection research.The interplay of multiple pathogens complicates disease progression,often resulting in treatment failure,recurrent infections,and significant public health and economic burdens.These infections are further exacerbated by disrupted host immune responses,which hinder the recovery of the vaginal microecosystem.Additionally,microbial biofilms—a fundamental mode of pathogen coexistence—contribute to the persistence and drug resistance of these infections,complicating management strategies.This review examines the pathogenesis,diagnosis,and treatment of mixed infections in the female lower genital tract while exploring potential avenues for future research.These findings emphasize the need for greater focus on these infections and offer insights to enhance further research in this area.
