The Type III Secretion System (T3SS) serves as a pivotal virulence apparatus for numerous Gram-negative bacterial pathogens, enabling them to infect both animal and plant hosts. Functioning as a molecular syringe, the T3SS directly translocates bacterial effector proteins from the bacterial cytoplasm into the interior of eukaryotic host cells. These effectors are central weapons that precisely manipulate a wide spectrum of host cellular physiological processes, ranging from cytoskeletal dynamics to immune signaling, to establish a favorable niche for bacterial survival and proliferation. Among the diverse arsenal of T3SS effectors, the YopJ family constitutes a critical group of virulence factors. Members of this family are characterized by a conserved catalytic triad structure—a hallmark of the CE clan of cysteine proteases that has been evolutionarily repurposed to confer acetyltransferase activity. A defining and intriguing feature of these enzymes is their stringent dependence on a host-derived eukaryotic cofactor, inositol hexakisphosphate (IP₆), for allosteric activation. This requirement acts as a sophisticated molecular safeguard, ensuring enzymatic activity only within the appropriate host environment, thereby preventing detrimental effects on the bacterium itself. While seminal studies on individual members such as Yersinia’s YopJ and Salmonella’s AvrA have provided deep mechanistic insights, a systematic and integrative understanding of the structure-function relationships across the entire family remains fragmented. Key questions persist regarding how a conserved catalytic core has diverged to recognize distinct host substrates in different kingdoms of life. To address this gap, this article provides a systematic review of the YopJ family, focusing on three interconnected aspects: their structural features, their catalytic mechanism, and their divergent immunosuppressive strategies in animal versus plant hosts. By conducting a comparative analysis of the sequences and resolved three-dimensional structures of three representative members (e.g., HopZ1a, PopP2, AvrA), we elucidate regions of significant variation embedded within the conserved core catalytic architecture. These variable regions, often involving surface loops and substrate-binding interfaces, are crucial determinants of target specificity and functional specialization. The functional divergence of this effector family is most apparent when comparing their modes of action in different hosts. In animal hosts, YopJ-family effectors primarily sabotage innate immune signaling pathways. They achieve this by acetylating key serine and threonine residues within the activation loops of critical kinases in the MAPK and NF‑κB pathways. This post-translational modification blocks the phosphorylation and subsequent activation of these kinases, leading to potent suppression of inflammatory cytokine production. Conversely, in plant hosts, the strategy broadens to dismantle the two-tiered plant immune system. YopJ homologs target a more diverse set of substrates, including immune-associated receptor-like cytoplasmic kinases (RLCKs), microtubule networks via tubulin acetylation (which disrupts cellular trafficking and signaling), and transcription factors central to defense gene regulation. This multi-target approach effectively suppresses both Pattern-Triggered Immunity (PTI) and Effector-Triggered Immunity (ETI). In conclusion, this synthesis aims to deepen the mechanistic understanding of YopJ family-mediated pathogenesis by integrating structural biology with cellular function across host kingdoms. Elucidating the precise molecular basis for substrate selection—how conserved platforms achieve target diversity—is a major frontier. Furthermore, this knowledge provides a vital theoretical foundation for developing novel anti-virulence strategies. Targeting the conserved IP₆-binding pocket or the catalytic acetyltransferase activity itself represents a promising avenue for designing broad-spectrum inhibitors that could disarm this critical family of bacterial effectors, potentially offering new therapeutic approaches against a range of pathogenic bacteria.

Objective To investigate and compare the epidemiological characteristics of common respiratory viruses among influenza-like illness(ILI)and severe acute respiratory infection(SARI)cases in Huzhou,Zhejiang Province before and after the COVID-19 pandemic,so as to provide a basis for formulating and adjusting the prevention and control strategies for viral respiratory infectious diseases.Methods ILI and SARI cases at two influenza surveillance sentinel hospitals in Huzhou and had throat swab samples collected during Nov 2017 to Feb 2020(pre-COVID-19 pandemic period)and Dec 2022 to Apr 2024(post-COVID-19 mitigation phase)were selected as the participants.Seven common viral respiratory pathogens were tested,including influenza A virus(H1N1 and H3N2 subtypes),influenza B virus(Victoria lineage,FluB),respiratory syncytial virus(RSV),rhinovirus(HRV),adenovirus(ADV),and severe acute respiratory syndrome coronavirus-2(SARS-CoV-2).The positive rates of respiratory pathogens before and after the COVID-19 pandemic were compared across different age groups and different time.Results A total of 7 948 ILI samples and 2 294 SARI samples were included.The overall positive rate of ILI samples increased from 33.6%to 47.1%,primarily due to the increase in influenza and COVID-19 infections;the overall positive rate of SARI samples decreased from 31.4%to 24.8%,mainly due to the reduction in HRV and ADV infections.During the post-COVID-19 mitigation phase,SARS-CoV-2(22.1%),H3N2(12.7%),and FluB(6.0%)were the primary pathogens in ILI samples,while RSV(7.1%),H3N2(5.3%),and HRV(4.5%)dominated in SARI samples.During the post-COVID-19 mitigation phase,the influenza virus circulation period was shortened.Before the COVID-19 pandemic,RSV was mainly detected in autumn and winter,while during the post-COVID-19 mitigation phase,out-of-season RSV epidemics were observed in spring and summer.Co-infection rate in ILI cases increased significantly in the post-COVID-19 mitigation phase,predominantly consisting of co-infections of COVID-19 and influenza A virus,while co-infection rate in SARI cases showed a decline.Conclusion We found important epidemiological changes in respiratory viruses in Huzhou during the post-COVID-19 mitigation phase compared to pre-COVID-19 period,including increased positive rates of influenza and COVID-19,and disruptions to the seasonal patterns of influenza and RSV.The prevention and control strategies should be adjusted in a timely manner based on the monitoring data.

Objective:To investigate the clinical efficacy of trimetazidine,dopamine combined with furosemide in eld-erly patients with rheumatic heart disease(RHD)and chronic heart failure(CHF)and its effect on the levels of me-teorin-like protein(Metrnl),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and syndecan-1.Methods:This randomized controlled study enrolled 106 elderly patients with RHD and CHF who were hospi-talized in the First People's Hospital of Xianyang between March 2022 and December 2023.Patients were divided in-to control group(n=53,routine treatment)and intervention group(n=53,additional trimetazidine,dopamine and furosemide combined treatment),and treated for 1 week.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),6-min walking distance(6MWD),Minnesota living with heart failure questionnaire(MLHFQ)score,serum levels of B-type natriuretic peptide(BNP),Metrnl,sTREM-1 and syndecan-1,and incidence of adverse reactions during treatment were compared between the two groups.Binary Logistic regression was used to analyze the association be-tween influencing factors and therapeutic effect.Results:The total effective rate of intervention group was signifi-cantly higher than that of control group(96.23％vs.83.02％,P=0.026).Compared to patients in the control group after treatment,those in the intervention group had significantly lower LVEDd[(45.27±5.95)mm vs.(50.11±4.47)mm],LVESd[(34.85±4.19)mm vs.(40.93±4.77)mm],MLHFQ score[(34.51±4.47)points vs.(45.62±5.08)points],levels of BNP[(95.29±8.31)pg/ml vs.(145.39±25.71)pg/ml],sTREM-1](43.59±4.21)pg/ml vs.(50.61±5.48)pg/ml]and syndecan-1[(7.01±1.88)μg/L vs.(11.02±2.36)μg/L],and significantly higher LVEF[(58.14±4.02)％vs.(50.61±6.15)％],6MWD[(433.48±45.74)m vs.(386.51±31.25)m]and Metrnl level[(205.08±27.45)ng/L vs.(188.52±22.37)ng/L](P＜0.001 all).Bi-nary Logistic regression analysis showed that the combination of trimetazidine,dopamine and furosemide was an in-dependent protective factor for the efficacy of elderly patients with RHD and CHF(OR=0.096,95％CI:0.011～0.837,P=0.034).There was no significant difference in the total incidence of adverse reactions between interven-tion group and control group(13.20％vs.11.32％,P=0.767).Conclusion:The combination of trimetazidine,do-pamine and furosemide could significantly improve cardiac function and exercise tolerance,reduce serum sTREM-1 and syndecan-1 levels,and increase Metrnl level with good safety in elderly patients with RHD and CHF.

Objective To evaluate the efficacy,safety,and cost-effectiveness of berberine-based quadruple therapy vs.the clarithromycin-based quadruple therapy for Helicobacter pylori(H.pylori)eradication in treatment-na?ve patients.Methods This was a single-center,prospective,open-label randomized controlled trial.A total of 404 treatment-naive patients with H.pylori infection who visited the Outpatient Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital from September 2021 to May 2024 were enrolled.The patients were randomly assigned in a 1:1 ratio to two groups:berberine quadruple therapy group(berberine+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202)and clarithromycin quadruple therapy group(clarithromycin+amoxicillin+esomeprazole+colloidal bismuth pectin;n=202).Both groups received a 14-day treatment course.The H.pylori eradication rate,incidence of adverse reactions,medication compliance,and treatment costs were compared between the two groups.Results By intention-to-treat(ITT)analysis,eradication rate did not differ significantly between the two groups[89.1%(180/202)in berberine quadruple therapy group vs.89.6%(181/202)in clarithromycin quadruple therapy group,P=0.872].The per-protocol(PP)analysis also showed no significant difference in the eradication rate between the two groups[90.4%(179/198)vs.91.3%(178/195),P=0.763].The incidence of adverse reactions in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group[18.2%(36/198)vs.38.5%(75/195),P<0.001].Specifically,the incidence of taste disturbance in berberine quadruple therapy group was significantly lower than that in clarithromycin quadruple therapy group(3.0%vs.15.4%,P<0.001).There was no statistically significant difference in medication compliance between the two groups[98.5%(195/198)in berberine quadruple therapy group vs.97.9%(191/195)in clarithromycin quadruple therapy group,P=0.688].The fixed direct medical cost per patient was significantly lower in berberine quadruple therapy group than that in clarithromycin quadruple therapy group(402.08 yuan vs.693.94 yuan).Conclusions The berberine-based quadruple therapy is as effective as traditional clarithromycin-based quadruple therapy for eradicating H.pylori,with the advantages of a lower incidence of adverse reactions and lower cost.It represents a safe,effective,and economical treatment option worthy of further promotion and application.

Objective To explore the pregnancy outcomes and prognosis following in vitro fertilization,and tumor prognosis of infertility patients with borderline ovarian tumor(BOT)after fertility-sparing surgery(FSS).Methods A retrospective study was conducted and 35 infertility patients with BOT after FSS from Shanghai Jiai Genetics and IVF Institute,Obstetrics and Gynecology Hospital,Fudan University were enrolled.The pregnancy outcomes and tumor prognosis were analyzed.Results Among the patients,serous BOT accounted for 62.9％.Twenty-five cases were International Federation of Gynecology and Obstetrics(FIGO)stage Ⅰ,2 stage Ⅱ,and 8 stage Ⅲ.Twelve patients experienced borderline tumor recurrence before assisted reproductive therapy,of which 5 patients were stage Ⅲ and 7 stage Ⅰ.After FSS,the 35 patients firstly underwent controlled ovarian stimulation(COS)at an average interval of(47.3±32.6)months.A total of 79 ovulation induction cycles were taken and mild stimulation protocol was adopted first(41.8％),followed by the natural cycle protocol(25.3％).Twenty-seven patients underwent embryo transfer in 37 cycles,resulting in 21 clinical pregnancies in 19 patients.The clinical pregnancy rate was 56.8％,with a cumulative pregnancy rate of 54.3％.The live birth rate was 43.2％,and the cumulative live birth rate was 42.9％.For patients with anti-Müllerian hormone levels<1.0 ng/mL(n=13),the pregnancy rate was 42.9％,and the cumulative clinical pregnancy rate was 23.1％.Among 30 patients,4(13.3％)patient with stage Ⅲ BOT experienced recurrence,and none had malignant transformation at the median follow-up period of 61 months after the first COS.Conclusion Assisted reproductive technology was safe and could improve pregnancy rates in infertile women with BOT.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the clinical efficacy of trimetazidine,dopamine combined with furosemide in eld-erly patients with rheumatic heart disease(RHD)and chronic heart failure(CHF)and its effect on the levels of me-teorin-like protein(Metrnl),soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and syndecan-1.Methods:This randomized controlled study enrolled 106 elderly patients with RHD and CHF who were hospi-talized in the First People's Hospital of Xianyang between March 2022 and December 2023.Patients were divided in-to control group(n=53,routine treatment)and intervention group(n=53,additional trimetazidine,dopamine and furosemide combined treatment),and treated for 1 week.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),6-min walking distance(6MWD),Minnesota living with heart failure questionnaire(MLHFQ)score,serum levels of B-type natriuretic peptide(BNP),Metrnl,sTREM-1 and syndecan-1,and incidence of adverse reactions during treatment were compared between the two groups.Binary Logistic regression was used to analyze the association be-tween influencing factors and therapeutic effect.Results:The total effective rate of intervention group was signifi-cantly higher than that of control group(96.23％vs.83.02％,P=0.026).Compared to patients in the control group after treatment,those in the intervention group had significantly lower LVEDd[(45.27±5.95)mm vs.(50.11±4.47)mm],LVESd[(34.85±4.19)mm vs.(40.93±4.77)mm],MLHFQ score[(34.51±4.47)points vs.(45.62±5.08)points],levels of BNP[(95.29±8.31)pg/ml vs.(145.39±25.71)pg/ml],sTREM-1](43.59±4.21)pg/ml vs.(50.61±5.48)pg/ml]and syndecan-1[(7.01±1.88)μg/L vs.(11.02±2.36)μg/L],and significantly higher LVEF[(58.14±4.02)％vs.(50.61±6.15)％],6MWD[(433.48±45.74)m vs.(386.51±31.25)m]and Metrnl level[(205.08±27.45)ng/L vs.(188.52±22.37)ng/L](P＜0.001 all).Bi-nary Logistic regression analysis showed that the combination of trimetazidine,dopamine and furosemide was an in-dependent protective factor for the efficacy of elderly patients with RHD and CHF(OR=0.096,95％CI:0.011～0.837,P=0.034).There was no significant difference in the total incidence of adverse reactions between interven-tion group and control group(13.20％vs.11.32％,P=0.767).Conclusion:The combination of trimetazidine,do-pamine and furosemide could significantly improve cardiac function and exercise tolerance,reduce serum sTREM-1 and syndecan-1 levels,and increase Metrnl level with good safety in elderly patients with RHD and CHF.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.