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.Advances in posterior scleral reinforcement for pathological myopia
Zhouyi HUANG ; Hongxia LIAO ; Dongcheng LIU ; Qiuying YE ; Jingwen LIU ; Yijie LU ; Tongmiao WANG ; Bo QIN
International Eye Science 2026;26(8):1400-1404
Pathologic myopia(PM)is characterized by progressive axial elongation, posterior staphyloma, and fundus degenerative changes, representing a leading cause of blindness in Asian countries.Posterior scleral reinforcement(PSR)is currently the only surgical intervention to slow axial elongation. Its mechanisms involve mechanical reinforcement, improved blood circulation, and biological stimulation of scleral remodeling. This article reviews recent advances in PSR: surgical techniques have evolved from complex, classic procedures to standardized single-strip methods, incorporating 3D MRI to quantify posterior staphyloma morphology for personalized graft design and facilitating minimally invasive, precision surgery. Among implant materials, biomaterials such as allogeneic dura mater are being continuously optimized, while biomimetic piezoelectric smart materials actively promote scleral collagen synthesis through electrical signals, achieving a paradigm shift from “passive support”to “active reinforcement”. Clinical outcomes indicate advantages in regulating axial length, enhancing visual function and blood circulation, and facilitating early intervention in children. Combined procedures with ICL implantation, cataract surgery or vitrectomy provide comprehensive treatment regimens for individual patients with varied conditions. This article also analyzes long-term issues and core controversies including ectopic posterior staphyloma and reoperation, and prospects future research directions such as artificial intelligence assistance, translation of smart materials and full-cycle prevention and treatment systems, so as to provide references for clinical practice and scientific research.
3.Research progress of systemic inflammatory markers in retinal vein occlusion
Qiyang LIN ; Jingwen LIU ; Yijie LU ; Dongcheng LIU ; Bo QIN
International Eye Science 2026;26(9):1572-1577
Retinal vein occlusion(RVO), the second most common retinal vascular disease, is primarily caused by thrombosis or mechanical compression from adjacent arteries, leading to partial or complete venous obstruction. Emerging evidence suggests that inflammation plays a pivotal role in the pathogenesis of RVO. Various systemic inflammatory markers, such as NLR, SII, and PLR, have gained increasing attention due to their close association with the occurrence and clinical outcomes of RVO and secondary macular edema. Given their accessibility, low cost, and high reproducibility, these markers can serve as valuable adjuncts to ophthalmic imaging in assessing systemic inflammatory status and disease progression. This review systematically summarizes recent advances in systemic inflammatory markers for RVO, highlighting their associations with the occurrence, prognosis, and treatment response of RVO and macular edema. Furthermore, the limitations of current evidence were evaluated and outline future research directions were discussed, aiming to provide hematological adjunctive evidence for early risk identification and treatment monitoring in RVO.
4.A Case of Neuronal Intranuclear Inclusion Disease Presenting Predominantly with Stroke-like Episodes and Literature Review
Tianqing ZHANG ; Kefei YANG ; Yuying YAN ; Luosang DANZENG ; Yuan SHI ; Bo WU ; Qin ZHANG
JOURNAL OF RARE DISEASES 2026;5(3):355-359
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Some NIID patients may present with paroxysmal neurological symptoms, posing challenges for clinical diagnosis. Thisarticle reports a 68-year-old male NIID patient presenting predominantly with stroke-like episodes. The patient was admitted with sudden-onset right-sided limb weakness, and had a prior history of cognitive decline and bradykinesia. Brain magnetic resonance imaging revealed severe subcortical white-matter hyperintensities in bilateral cerebral hemispheres on fluid-attenuated inversion recovery sequences, as well as characteristic "ribbon sign" at the corticomedullary junction on diffusion-weighted imaging. Genetic testing identified an abnormal GGC repeat expansion of 112 times in the
5.Construction of a predictive model for poorly differentiated adenocarcinoma in pulmonary nodules using CT combined with tumor markers
Jie JIANG ; Feng LIU ; Bo WANG ; Qin WANG ; Jian ZHONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):73-79
Objective To establish and internally validate a predictive model for poorly differentiated adenocarcinoma based on CT imaging and tumor marker results. Methods Patients with solid and partially solid lung nodules who underwent lung nodule surgery at the Department of Thoracic Surgery, the Affiliated Brain Hospital of Nanjing Medical University in 2023 were selected and randomly divided into a training set and a validation set at a ratio of 7:3. Patients' CT features, including average density value, maximum diameter, pleural indentation sign, and bronchial inflation sign, as well as patient tumor marker results, were collected. Based on postoperative pathological results, patients were divided into a poorly differentiated adenocarcinoma group and a non-poorly differentiated adenocarcinoma group. Univariate analysis and logistic regression analysis were performed on the training set to establish the predictive model. The receiver operating characteristic (ROC) curve was used to evaluate the model's discriminability, the calibration curve to assess the model's consistency, and the decision curve to evaluate the clinical value of the model, which was then validated in the validation set. Results A total of 299 patients were included, with 103 males and 196 females, with a median age of 57.00 (51.00, 67.25) years. There were 211 patients in the training set and 88 patients in the validation set. Multivariate analysis showed that carcinoembryonic antigen (CEA) value [OR=1.476, 95%CI (1.184, 1.983), P=0.002], cytokeratin 19 fragment antigen (CYFRA21-1) value [OR=1.388, 95%CI (1.084, 1.993), P=0.035], maximum tumor diameter [OR=6.233, 95%CI (1.069, 15.415), P=0.017], and average density [OR=1.083, 95%CI (1.020, 1.194), P=0.040] were independent risk factors for solid and partially solid lung nodules as poorly differentiated adenocarcinoma. Based on this, a predictive model was constructed with an area under the ROC curve of 0.896 [95%CI (0.810, 0.982)], a maximum Youden index corresponding cut-off value of 0.103, sensitivity of 0.750, and specificity of 0.936. Using the Bootstrap method for 1000 samplings, the calibration curve predicted probability was consistent with actual risk. Decision curve analysis indicated positive benefits across all prediction probabilities, demonstrating good clinical value. Conclusion For patients with solid and partially solid lung nodules, preoperative use of CT to measure tumor average density value and maximum diameter, combined with tumor markers CEA and CYFRA21-1 values, can effectively predict whether it is poorly differentiated adenocarcinoma, allowing for early intervention.
6.Nafamostat Mesylate Alleviates Renal Ischemia-Reperfusion Injury in a Rat Model Through HMGB1 Modulation:An Omics Analysis-Based Study of the Protective Effect and the Mechanisms Involved
Yuxuan WU ; Hongqian LI ; Linfeng LIU ; Yu WANG ; Bo CHEN ; Jiang LIU ; Jianhua QIN ; Santao OU ; Weihua WU
Journal of Sichuan University (Medical Sciences) 2025;56(1):175-182
Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P<0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P<0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P<0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.
7.Application of Remimazolam in Pediatric Adenoidectomy and Tonsillectomy Anesthesia and Its Effect on Emergence Agitation
Yue CHENG ; Qin SHEN ; Yaolin BO ; Xianwen HU
Journal of Sichuan University (Medical Sciences) 2025;56(4):1098-1103
Objective To evaluate the application of different anesthetic drugs—remimazolam(RM)and propofol(PPF)—in anesthesia for pediatric adenoidectomy and tonsillectomy and its effect on emergence agitation.Methods A total of 120 children undergoing elective adenoidectomy and tonsillectomy under general anesthesia in Xinhua Hospital,Huainan Xinhua Medical Group between December 2022 and August 2024 were enrolled.With a random number table,they were assigned to a PPF group receiving PPF and remifentanil and a RM group receiving RM and remifentanil,with 60 cases in each group.The primary and secondary outcome indicators of the two groups were compared.The primary outcome indicator was the incidence of emergence agitation.Secondary outcome indicators included anesthesia-related parameters,changes in mean arterial pressure(MAP)and heart rate(HR)at different time points during surgery,changes in pediatric anesthesia emergence delirium(PAED)scores at different time points after recovery,changes in Ramsay sedation scores and Face,Legs,Activity,Cry,Consolability(FLACC)pain scores at 2,4,12,and 24 hours after surgery,incidence of negative postoperative behavioral changes(NPOBCs)at 7 and 14 days,and adverse events during anesthesia.Results The incidence rate of emergence agitation was lower in the RM group than that of the PPF group(5.00%vs.18.33%,P<0.05).The RM group also demonstrated significantly shorter anesthesia time,extubation time,wake-up time,and postanesthesia care unit(PACU)than those in the PPF group(P<0.05).HR and MAP in the RM group were higher than those in the PPF group at 3 min after induction,at the time of tracheal intubation,during tonsillectomy,and at the end of surgery,with the difference being statistically significant(P<0.05).The PAED scores at different time points after recovery,Ramsay sedation scores and FLACC scores at 2,4 and 12 hours after surgery,the incidence of NPOBCs at 7 days after surgery,and the incidence of adverse reactions during anesthesia were lower in the RM group than those in the PPF group,with the difference being statistically significant(P<0.05).Conclusion RM improves the anesthesia effect and recovery quality of children undergoing adenoidectomy and tonsillectomy,relieves the severity of emergence agitation,reduces the incidence of agitation,and demonstrates good safety.
8.Research progress of cooling therapy for heat stroke
Jin-Bao ZHAO ; Qian WANG ; Tian-Yu XIN ; Han-Ding MAO ; Ye TAO ; Bo NING ; Zhen-Zhen QIN ; Shu-Yuan LIU ; Qing SONG
Medical Journal of Chinese People's Liberation Army 2025;50(5):612-618
Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.
9.Construction of a postoperative mortality risk model for patients with acute aortic dissection based on XGBoost-SHAP method
Xin ZHANG ; Min FANG ; Yi CAO ; Ting-Ting LI ; Xian-Kong LIU ; Jia-Yi DANG ; Xue-Sen ZHAO ; Hong-Qin REN ; Jia-Ze GENG ; Kai-Wen WANG ; Tie-Sheng HAN ; Yong-Bo ZHAO ; Dong MA
Medical Journal of Chinese People's Liberation Army 2025;50(10):1226-1234
Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.
10.Progress in clinical research of transjugular intrahepatic portosystemic shunt for the treatment of portal cavernous transformation
Jiayang ZHU ; Bing ZHOU ; Xuanyi CHEN ; Junkang WANG ; Bo LI ; Rongqing QIN ; Yubo ZHANG ; Ruochen HU
Journal of Interventional Radiology 2025;34(8):900-904
Clinically,the incidence of portal vein thrombosis(PVT)in patients with cirrhosis can be up to 10%-23%.When PVT is not treated promptly,it may develop to cavernous transformation of the portal vein(CTPV).CTPV can aggravate portal hypertension,accelerate the progression of esophagogastric varices bleeding,refractory ascites,refractory peritonitis,biliary tract diseases,and hepatic insufficiency.At present,noninvasive imaging techniques such as portal vein reconstruction,enhanced CT and ultrasound are mostly used to make the diagnosis and evaluation of CTPV.It is rather difficult to perform portosystemic shunt surgery in patients with CTPV complicated by portal hypertension,which was once regarded as a contraindication for interventional portosystemic shunt procedures.With the improvement of related technologies and surgical instruments,the transjugular intrahepatic portosystemic shunt(TIPS)has become an important treatment for CTPV.This paper aims to make a comprehensive review about the relevant researches concerning the portosystemic shunt surgery in patients with CTPV so as to clarify the importance of TIPS in the treatment of CTPV.

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