Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective To investigate the clinical significance of serum B cell activating factor(BAFF)and complement lytic factor Bb in patients with idiopathic membranous nephropathy(IMN),as well as their correlation with the urinary albumin-to-creatinine ratio(UACR).Methods A total of 204 IMN patients were enrolled as the study group,and 100 healthy individuals undergoing physical examinations during the same period served as the control group.Serum levels of BAFF,Bb,and UACR were measured and compared between the two groups.Pearson correlation analysis was performed to assess the associations among serum BAFF,Bb,and UACR.The patients in the study group were followed up for 12 months and stratified into a favorable prognosis group and a poor prognosis group(defined as no remission)based on disease remission status.Demographic and clinical characteristics,as well as serum BAFF and Bb levels,were compared between the two outcome groups.Multivariate logistic regression analysis was conducted to identify independent predictors of poor prognosis in IMN patients.Receiver operating char-acteristic(ROC)curve analysis was employed to evaluate the predictive value of these indicators for poor prognosis.Results The levels of BAFF,Bb,and UACR in the research group were significantly higher than those in the con-trol group(P<0.05).Pearson correlation analysis revealed that both BAFF and Bb were positively correlated with UACR(r=0.716 and 0.543,respectively;P<0.05).After one year of follow-up,a total of 200 patients completed the study,among whom 46 experienced poor prognosis.Based on the follow-up outcomes,patients were categorized into a poor prognosis group(n=46)and a good prognosis group(n=154).The poor prognosis group exhibited significantly higher levels of serum creatinine,24-hour urinary protein,BAFF,and Bb,as well as lower eGFR values,compared to the good prognosis group(P<0.05).Multivariate regression analysis identified 24-hour urinary protein,BAFF,and Bb as independent risk factors for poor prognosis in patients with IMN,whereas eGFR was identified as a protective factor(P<0.05).ROC curve analysis demonstrated that the combined assessment of 24-hour urinary protein,eGFR,BAFF,and Bb yielded a higher AUC value for predicting poor prognosis in IMN patients than any single indicator alone(Z=4.145,3.908,4.308,3.864;P<0.05).Conclusions The serum levels of BAFF and Bb in patients with IMN are significantly elevated and positively correlated with the UACR.The combi-nation of 24-hour urinary protein excretion and eGFR demonstrates high predictive value for poor prognosis in these patients.These findings suggest that BAFF and Bb may serve as potential biomarkers for prognostic assessment in IMN,and the integrated measurement of multiple parameters could provide a more comprehensive clinical basis for disease management.

Objective To develop an innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis,and conduct clinical validation.Methods The design concept,technical principles and system composition of the innovative minimally invasive rotary-cutting surgical system for axillary osmidrosis were introduced.A total of 73 patients(146 axillae)with axillary osmidrosis were enrolled as subjects,and underwent surgery using the newly developed surgical system.Clinical validation of the system was performed by evaluating postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Results The study demonstrated favorable clinical outcomes in the following aspects:postoperative scarring,odor elimination rate,postoperative complication incidence,and patient satisfaction.Conclusion The minimally invasive rotary-cutting surgical system for axillary osmidrosis is rationally designed.The rotary-cutting puncture device is safe,effective,minimally invasive,and convenient for axillary osmidrosis surgery,warranting further clinical validation and widespread application.

Objective To investigate the clinical significance of serum B cell activating factor(BAFF)and complement lytic factor Bb in patients with idiopathic membranous nephropathy(IMN),as well as their correlation with the urinary albumin-to-creatinine ratio(UACR).Methods A total of 204 IMN patients were enrolled as the study group,and 100 healthy individuals undergoing physical examinations during the same period served as the control group.Serum levels of BAFF,Bb,and UACR were measured and compared between the two groups.Pearson correlation analysis was performed to assess the associations among serum BAFF,Bb,and UACR.The patients in the study group were followed up for 12 months and stratified into a favorable prognosis group and a poor prognosis group(defined as no remission)based on disease remission status.Demographic and clinical characteristics,as well as serum BAFF and Bb levels,were compared between the two outcome groups.Multivariate logistic regression analysis was conducted to identify independent predictors of poor prognosis in IMN patients.Receiver operating char-acteristic(ROC)curve analysis was employed to evaluate the predictive value of these indicators for poor prognosis.Results The levels of BAFF,Bb,and UACR in the research group were significantly higher than those in the con-trol group(P<0.05).Pearson correlation analysis revealed that both BAFF and Bb were positively correlated with UACR(r=0.716 and 0.543,respectively;P<0.05).After one year of follow-up,a total of 200 patients completed the study,among whom 46 experienced poor prognosis.Based on the follow-up outcomes,patients were categorized into a poor prognosis group(n=46)and a good prognosis group(n=154).The poor prognosis group exhibited significantly higher levels of serum creatinine,24-hour urinary protein,BAFF,and Bb,as well as lower eGFR values,compared to the good prognosis group(P<0.05).Multivariate regression analysis identified 24-hour urinary protein,BAFF,and Bb as independent risk factors for poor prognosis in patients with IMN,whereas eGFR was identified as a protective factor(P<0.05).ROC curve analysis demonstrated that the combined assessment of 24-hour urinary protein,eGFR,BAFF,and Bb yielded a higher AUC value for predicting poor prognosis in IMN patients than any single indicator alone(Z=4.145,3.908,4.308,3.864;P<0.05).Conclusions The serum levels of BAFF and Bb in patients with IMN are significantly elevated and positively correlated with the UACR.The combi-nation of 24-hour urinary protein excretion and eGFR demonstrates high predictive value for poor prognosis in these patients.These findings suggest that BAFF and Bb may serve as potential biomarkers for prognostic assessment in IMN,and the integrated measurement of multiple parameters could provide a more comprehensive clinical basis for disease management.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective:To discuss the effect of knockdown of receptor-interacting protein kinase 3(RIP3)on autophagy,pyroptosis,and ferroptosis in the human renal tubular epithelial HK2 cells under hypoxia/reoxygenation(H/R)conditions.Methods:The lentiviral interference vector plasmid shRIP3 and negative control lentiviral interference vector plasmid shNC were transfected into the HK2 cells and the HK cells were divided into shRIP3 group and shNC group,and the normal cultured untransfected HK2 cells were regarded as blank group.After 48 h of transfection,real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to verify the lentiviral transfection efficiencies.The HK2 cells were divided into control group,H/R group,shNC+H/R group,and shRIP3+H/R group.CCK-8 method was used to detect the survival rates of the HK2 cells in various groups;immunofluorescence staining was used to detect the fluorescence intensities of light chain 3(LC3B)and NLR family pyrin domain-containing 3(NLRP3)proteins in the cells in various groups;Western blotting method was used to detect the expression levels of LC3Ⅱ,LC3Ⅰ,Beclin1,Caspase-1,Gasdermin D(GSDMD),interleukin(IL)-1β,and IL-18 proteins in the HK2 cells in various groups;Kits were used to detect the ferri ion(Fe2+)levels in the cells in various groups.Results:Compared with blank group and shNC group,the expression levels of RIP3 mRNA and protein in the HK2 cells in shRIP3 group were decreased(P<0.05).The CCK-8 method results showed that compared with control group,the survival rate of the HK2 cells in H/R group was decreased(P<0.05);compared with H/R group,the survival rate of the HK2 cells in shRIP3+H/R group was increased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of LC3B protein in the HK2 cells in H/R group was decreased(P<0.05),and the fluorescence intensity of NLRP3 protein was increased(P<0.05);compared with H/R group,the fluorescence intensity of LC3B protein in the HK2 cells in shRIP3+H/R group was increased(P<0.05),and the fluorescence intensity of NLRP3 protein was decreased(P<0.05).The Western blotting results showed that compared with control group,the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of Beclin1 protein in the HK2 cells in H/R group were decreased(P<0.05);compared with H/R group,the ratio of LC3Ⅱ/LC3Ⅰ and expression level of Beclin1 protein in the HK2 cells in shRIP3+H/R group were increased(P<0.05);compared with control group,the expression levels of Caspase-1,GSDMD,IL-1β,and IL-18 proteins in the HK2 cells in H/R group were increased(P<0.05);compared with H/R group,the expression levels of Caspase-1,GSDMD,IL-1β,and IL-18 proteins in the HK2 cells in shRIP3+H/R group were decreased(P<0.05).Compared with control group,the expression levels of GPX4 and SLC7A11 proteins in the HK2 cells in H/R group were decreased(P<0.05);compared with H/R group,the expression levels of GPX4 and SLC7A11 proteins in the HK2 cells in shRIP3+H/R group were increased(P<0.05).Compared with control group,the Fe2+level in the HK2 cells in H/R group was increased(P<0.05);compared with H/R group,the Fe2+level in the HK2 cells in shRIP3+H/R group was decreased(P<0.05).Conclusion:Targeted knockdown of RIP3 can induce the autophagy,inhibit the pyroptosis,and reduce the ferroptosis of the human renal tubular epithelial HK2 cells induced by H/R.

Objective To identify early Klebsiella pneumoniae(KP)infection after liver transplantation and its impact on prognosis.Methods Clinical data of 171 liver transplant recipients were retrospectively analyzed,and they were divided into the non-infection(n=52)and infection groups(n=119)according to the bacterial culture results at postoperative 2 weeks.In the infection group,KP was not detected in 86 cases(non-KP infection group),and KP was cultured in 33 cases(KP infection group).Preoperative,intraoperative and postoperative data were statistically compared between the non-infection and infection groups,and between the non-KP infection and KP infection groups.The risk factors of early KP infection after liver transplantation and the influencing factors of long-term survival of the recipients were analyzed.Results Compared with the non-infection group,model for end-stage liver disease(MELD)score and total bilirubin level were higher,the operation time was longer,the length of postoperative intensive care unit(ICU)stay and the length of hospital stay were longer,the amount of intraoperative red blood cell transfusion was higher,the hospitalization expense was higher,the incidence of severe complications was higher,white blood cell count,absolute neutrophil cell count and neutrophil-to-lymphocyte ratio at postoperative 14 and 30 d were higher,absolute lymphocyte count at postoperative 14 d was lower and hemoglobin level at postoperative 30 d was lower in the infection group.The differences were statistically significant(all P＜0.05).Compared with the non-KP infection group,MELD score,total bilirubin level and aspartate aminotransferase(AST)level were higher,the operation time and the length of postoperative ICU stay were longer,the hospitalization expense was higher,the 90-d fatality was higher,the albumin level at postoperative 14 d was lower,and total bilirubin level at postoperative 30 d was higher in the KP infection group.The differences were statistically significant(all P＜0.05).Among 33 recipients with KP infection,16 cases were resistant to carbapenem antibiotics,and 7 of them died within postoperative 90 d.Seventeen cases were intermediate or sensitive to carbapenem antibiotics,and 4 of them died within postoperative 90 d.Preoperative MELD score ≥17 and operation time≥415 min were the independent risk factors for KP infection after liver transplantation(both P＜0.05).The length of postoperative ICU stay ≥44 h and KP infection were the independent risk factors for long-term prognosis of liver transplantation(both P＜0.05).Conclusions KP infection is an independent risk factor for death after liver transplantation.High preoperative MELD score and long operation time are the independent risk factors for early KP infection after liver transplantation.

Objective To summarize clinical experience of transabdominal pericardial anastomosis of suprahepatic vena cava of the donor and right atrium of the recipient in liver transplantation for Budd-Chiari syndrome (BCS) complicated with liver cancer. Methods Clinical data of a BCS patient complicated with liver cancer undergoing transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation were retrospectively analyzed. Results The hepatic vein and suprahepatic vena cava were partially occluded in the patient. Liver transplantation was completed by transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium with beating-heart. In addition, due to pathological changes of the recipient's hepatic artery, splenic artery of the recipient was cut off, distal ligation was performed, and the proximal end was reversed and anastomosed with the common hepatic artery of the donor liver, and the reconstruction of hepatic artery was completed. The surgery was successfully performed. At approximately postoperative 1 week, the function of the liver allograft was gradually restored to normal, and no major complications occurred. The patient was discharged at postoperative 25 d. No signs of BCS recurrence was reported after 8-month follow-up. Conclusions It is safe and feasible to treat BCS by liver transplantation with transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium. BCS patients complicated with liver cancer obtain favorable prognosis.