1.The Structure and Function of The YopJ Family Effectors in The Bacterial Type III Secretion System
Ao-Ning LI ; Wen-Bo LI ; Yu-Ying LU ; Min-Hui ZHU ; Yu-Long QIN ; Yong ZHAO ; Zhao-Huan ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):516-533
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.
2.Application of microecological preparations in patients with chronic kidney disease
Chinese Journal of Clinical Nutrition 2025;33(2):153-160
Uremic toxin accumulation is the main factor that aggravates renal injury and increases complication risks in patients with chronic kidney disease (CKD). While renal replacement therapy such as hemodialysis and peritoneal dialysis are the mainstay of treatment for uremia, they have a limited role in clearing enterogenous uremic toxins, which are produced by gut flora catabolizing food nutrients. Gut flora dysbiosis is one of the common complications in CKD patients. As microecological preparations, probiotics, prebiotics and synbiotics can improve the clinical symptoms and quality of life in such patients through regulating the imbalance of gut flora. This article reviews the recent progress on the roles and mechanisms of these microecological preparations in patients with CKD.
3.Relationship between different types of diabetes and the risk of glaucoma:a bidirectional Mendelian randomization study
Lu YU ; Min DONG ; Kuiliang YANG ; Ning YANG ; Yiqiao XING
Recent Advances in Ophthalmology 2025;45(5):382-386
Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95%CI:1.05~1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95%CI:1.02~1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.
4.Expression of NUDT5 in breast cancer and its correlation with ultrasound signs and clinicopathological charac-teristics
Lu RONG ; Min ZHOU ; Lu-xin YU ; Juan LYU ; Jing WAN ; Qian ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(5):421-424
Objective To explore the expression of Nudix hydrolase 5(NUDT5)protein in breast cancer tissues and its correlation with ultrasound signs and clinicopathological characteristics.Methods A total of 108 patients with breast cancer admitted to our hospital from October 2019 to April 2022 were selected as the research objects.Ultrasound examination was performed before operation to observe the ultrasound signs of patients.Immunohistochemical method was used to detect the expressions of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor 2(HER-2)in breast cancer tissues,and the expression levels of NUDT5 protein in breast cancer tissues and adjacent tissues,and the relationships of NUDT5 protein expression with ultrasound signs and clinicopathological characteristics of patients were analyzed.Results Among 108 patients,there were 62 cases with ER positive,60 cases with PR positive,and 28 cases with HER-2 positive.The positive expression rate of NUDT5 protein in breast cancer tissues was higher than that in adjacent tissues(P<0.05).The positive expression rate of NUDT5 protein was higher in breast cancer tissues with microcalcification,blood flow imaging grade(grade 2 to 3)and lymph node metastasis(P<0.05).The positive expression of NUDT5 protein was correlated with histological grade,ER and HER-2(P<0.05).The expression of NUDT5 protein in breast cancer tissue was positively correlated with ER negative and HER-2 positive(rs=0.463,0.398,P<0.05).Conclusion The positive expression rate of NUDT5 protein in breast cancer tissues is higher than that in adjacent tissues,and its expression has a certain correlation with microcalcification,blood flow imaging grade(grade 2 to 3),lymph node metastasis in ultrasound signs and histological grade,ER,and HER-2 in clinicopathological characteristics.
5.Proficiency testing for 11 clinical biobanks in Beijing City: simulation study and result analysis
Qian ZHANG ; Yun ZHANG ; Lu HAN ; Min LIU ; Yongbo YU ; Yan WANG ; Ying HU ; Hui ZHONG ; Dan GUO ; Shipeng SUN ; Jinxi LIN ; Siyuan XU ; Xiaokun TANG ; Gaoyuan SUN ; Chuanbao ZHANG ; Hexin LI
Chinese Journal of Preventive Medicine 2025;59(9):1590-1596
Objective:To evaluate the sample preparation proficiency and storage proficiency of 11 clinical biobanks in Beijing through simulated experiments, and to establish an assessment method for the quality comparability of biological samples.Methods:An exploratory research design was adopted. In November 2023, artificial composite serum quality control materials containing six recombinant human protein markers—recombinant human alanine aminotransferase (rhALT), recombinant human aspartate aminotransferase (rhAST), recombinant human creatine kinase (rhCK), recombinant human creatine kinase-MB (rhCK-MB), recombinant human B-type natriuretic peptide (rhBNP), and recombinant human troponin I (rhTNI)—were distributed to 11 clinical biobanks in Beijing City. Sample preparation and storage followed the standardized operating procedures. Proficiency differences were assessed through statistical analysis.Results:Three-way repeated measures ANOVA revealed all six protein markers showed a declining trend over storage time in ultra-low-temperature environments ( F values 11.68-4 179.66, all P<0.01). However, neither long-term/temporary refrigerator types ( F values 0.01-1.23, all P>0.05)nor placement locations within refrigerators significantly affected the stability of these six proteins ( F valus 0.03-1.47, all P>0.05). The biases in detection results for rhALT, rhAST, rhTNI, and rhBNP at different storage time points were within the allowable bias limits for each item, supporting their use as markers for protein stability in biobank samples. All 11 institutions passed the storage proficiency assessment. In the preparation proficiency assessment, deviations were observed in post-preparation sample results, with a notably high out-of-control rate for rhCK (36.36%). Conclusion:Sample preparation proficiency can serve as a quality control metric for clinical biobanks. Future external quality assessment systems for biobanks should focus on sample preparation rather than storage processes.
6.Identification of Medical Surge Risk Influencing Factors and Analysis of Causal Coupling Relationships Based on DEMATEL-ISM
Yiran GAO ; Nan MENG ; Tian YU ; Yanping WANG ; Min WEI ; Wanmeng TENG ; Jialin LU ; Peng WANG ; Kexin WANG ; Ning NING ; Yanhua HAO ; Avdeev SERGEY ; Qunhong WU
Chinese Hospital Management 2025;45(11):6-10
Objective To identify the key factors affecting the risk of medical surges and their coupling relation5 ships,providing strategic support for medical institutions to optimize risk management and emergency governance.Methods 17 influencing factors were determined based on WSR theory,and an expert scoring method was employed to assess the impact strength among the factors.The DEMATEL method was applied to calculate the centrality,cau5 sality,influence,and being influenced degrees of the influencing factors.The ISM method was used to construct a hierarchical structure of the influencing factors related to medical surge risks,thereby revealing the connections and interaction mechanisms among these factors.Results Seven critical influencing factors were identified,including the crisis decision-making capacity and leadership effectiveness of emergency managers,the completeness of the emer5 gency system and dynamic execution capabilities,and the cross-departmental coordination mechanism and com5 mand collaboration efficiency.Deep driving factors and coupling pathways were also revealed.Conclusion The risk of medical surges exhibits multi-factorial coupling cascade effects;attention should be directed towards the construc5 tion of mid-to-deep level mechanisms such as information systems,institutional frameworks,and organizational management,to enhance targeted capabilities and systemic resilience in risk governance.
7.A Dual-Layer Network Dynamics Modeling and Simulation of Medical Surge Risk Diffusion Based on MATLAB and REPAST
Nan MENG ; Yanping WANG ; Yiran GAO ; Tian YU ; Min WEI ; Wanmeng TENG ; Peng WANG ; Fengqian ZHONG ; Lili JIANG ; Jialin LU ; Ning NING ; Avdeev SERGEY ; Qunhong WU
Chinese Hospital Management 2025;45(11):22-27
Objective To explore the coupling mechanism between medical surge response resources and the spread of secondary risks during public health emergencies,as well as the effectiveness of relevant interventions.Methods Based on complex network theory,a dual-layer network model of medical resources and secondary events was constructed.The interactive feedback between medical resource status and secondary event risk,as well as the effects of network structure,were analyzed through MATLAB simulations,REPAST agent-based modeling,and mean-field analysis.Results Simulation and prediction results show that an increase in first-layer resource-deficient nodes significantly raises the activation rate and transmission speed of secondary events,while the clustering and spread of secondary events in the second layer,in turn,intensify resource depletion,creating a negative feedback loop.Mean-field analysis indicates a nonlinear positive correlation between the adequacy of medical resources and the likelihood of secondary events.Network structure analysis reveals that when the average node degree exceeds 8,resource allocation efficiency improves markedly.Conclusion There exists a dynamic coupling and bidirectional feedback relationship between medical resource status and secondary event risks.Enhancing the flexible allocation and responsiveness of medical resources,improving multi-sectoral collaborative monitoring and coordinated regulation,optimizing network connectivity and coordination mechanisms for resource distribution,and establishing dynamic monitoring and tiered early warning systems are key strategies for strengthening the resilience of healthcare systems and effectively containing the spread of secondary events.
8.Research on Conceptual Connotation and Theoretical Model Construction of Network Dynamic Collaboration Capacity in Medical Surge Response
Yanping WANG ; Nan MENG ; Min WEI ; Yiran GAO ; Tian YU ; Peng WANG ; Jialin LU ; Huan LIU ; Shue ZHANG ; Avdeev SERGEY ; Ning NING ; Yanhua HAO ; Qunhong WU
Chinese Hospital Management 2025;45(11):28-33
Objective To define the conceptual connotation of network dynamic collaboration capacity in medical surge response and construct its theoretical model.Methods A mixed concept analysis method was employed,integrating multidisciplinary literature and collecting empirical evidence through semi-structured expert interviews to extract the concept of network dynamic collaboration capacity in medical surge response.By integrating complex systems,network science,synergetics,and dynamic capability theory,and combining the interview results,the study used the analogy of flood control in hydraulic engineering to develop a"network-dynamic-collaboration"triangular capacity theoretical model.Results It reveals one antecedents(sudden external shocks have led to an abnormal and continuous surge in medical demand),six core attributes(information interconnection accessibility,dynamic resource adaptability,risk perception responsiveness,multi-party collaborative interactivity,service process adaptability elasticity,and learning iterative evolution),and four consequences(mitigation of crowding risk,protection of service continuity,minimization of crisis spillover,and enhancement of system resilience)for the network dynamic collaboration capacity in medical surge response.The theoretical model elucidates the coupling mechanisms among network structural resilience,dynamic regulation processes,and collaborative co-evolution in resisting medical surge.Conclusion The new concept and theoretical model proposed in this study deepen the understanding of medical surge response system mechanisms and offer a theoretical framework and practical guidance for strengthening the full-chain resilience of health emergency systems.
9.Relationship between different types of diabetes and the risk of glaucoma:a bidirectional Mendelian randomization study
Lu YU ; Min DONG ; Kuiliang YANG ; Ning YANG ; Yiqiao XING
Recent Advances in Ophthalmology 2025;45(5):382-386
Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95%CI:1.05~1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95%CI:1.02~1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.
10.Analysis of Factors Influencing Early Postpartum Pelvic Floor Muscle Strength Following Cesarean Delivery
Huanyu LIN ; Min YU ; Xuhong LU
Journal of Practical Obstetrics and Gynecology 2025;41(5):419-424
Objective:To identify the risk factors associated with early postpartum pelvic floor muscle strength following cesarean delivery.Methods:A total of 352 women who underwent cesarean section at the Department of Obstetrics and Gynecology,Affiliated Zhongshan Hospital of Dalian University between September 2022 and Sep-tember 2024 and attended a pelvic floor rehabilitation clinic 6 to 8 weeks postpartum were enrolled in this study,and lectromyographic(EMG)values during anterior and posterior resting phases,as well as fast-twitch and slow-twitch muscle phases,were recorded so as to analyze the factors that might affect the pelvic floor strength in the early postnatal period after cesarean section.Factors with statistically significant differences were further ana-lyzed by multifactorial Logistic analysis.Results:Pre-pregnancy body mass index(BMI)>24 kg/m2,increase in body mass during pregnancy ≥ 11.5 kg,gestational hypertension and term delivery were identified as independent risk factors for abnormal EMG values during the anterior resting phase of the pelvic floor(OR>1,P<0.05).In-crease in body mass during pregnancy≥11.5 kg,preterm rupture of membranes,and term delivery were risk fac-tors for abnormal pelvic floor EMG values in the post-resting stage(OR>1,P<0.05).Pre-pregnancy BMI>24 kg/m2 and pre-eclampsia were risk factors for abnormal pelvic floor EMG values in the fast-muscle stage(OR>1,P<0.05).and a history of uterine fibroids was a risk factor for abnormal pelvic floor EMG values in the slow-muscle stage(OR>1,P<0.05).Conclusions:Early postpartum pelvic floor muscle strength following ce-sarean delivery is influenced by several risk factors,including pre-pregnancy BMI>24 kg/m2,increase in body mass during pregnancy ≥ 11.5 kg,gestational hypertension,full-term labor,premature rupture of membranes,pre-eclampsia,and history of uterine fibroids,pelvic floor muscle strength is more likely to be impaired in the early postpartum period after the prenatal combination of the above risk factors,and Targeted pelvic floor rehabilitation should be initiated as early as possible during the postpartum period.

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