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.Establishment of a high-risk medication list and preventive and therapeutic measures for drug-induced hypofi-brinogenemia based on the Delphi method
Xiao WEN ; Le CAI ; Ning LIU ; Ao GAO ; Man ZHU
China Pharmacy 2026;37(7):848-853
OBJECTIVE To establish a high-risk medication list and preventive and therapeutic measures for drug-induced hypofibrinogenemia, and to provide a reference for the prevention and treatment of this condition. METHODS By integrating domestic and international case reports, retrospective case-control studies, and spontaneous adverse drug reaction reporting databases, 19 domestically marketed high-risk drugs for drug-induced hypofibrinogenemia were identified. Based on the clinical characteristics and mechanisms of these drugs, relevant risk factors were systematically reviewed, and existing treatment options were summarized, leading to the preliminary development of recommended preventive and therapeutic measures. A two-round Delphi consultation was conducted to evaluate, revise, and ultimately reach consensus on the preliminary findings, using a mean importance score of ≥3.5 points for indicators and a coefficient of variation <0.3 as screening criteria. RESULTS The coefficient of expert authority for both rounds of expert consultation was 0.904. In the first round, the Kendall coordination coefficients (Kendall’s W ) for the high-risk medication list and the proposed preventive and therapeutic measures were 0.390 and 0.223 ( P <0.05), respectively. In the second round, the Kendall’s W were 0.227 and 0.200 ( P <0.05), respectively. After two rounds of expert consultation and discussion, 11 high-risk drugs for drug-induced hypofibrinogenemia, represented by hemocoagulase and certain anti-infective agents, were ultimately identified, along with 5 preventive and therapeutic measures spanning the entire process of “pre-medication assessment, intra-medication monitoring, and bleeding event management”. CONCLUSIONS This study has established a scientific and reliable high-risk medication list, and corresponding preventive and therapeutic measures for drug-induced hypofibrinogenemia, providing a theoretical basis and practical support for the early identification, stratified management, and precise intervention of this condition.
3.Research on classification management model based on Karajek matrix for ECG monitoring equipment in emergency ICU
Xi TANG ; Ting ZENG ; Wangsheng DENG ; Yanhua DU ; Ao LIU ; Yuquan DENG ; Jinfeng MENG ; Xiaogui QI ; Lili WU ; Wanrong ZHU
China Medical Equipment 2025;22(2):132-137
Objective:To construct a classification management model on the basis of Kraljic matrix for electrocardiogram(ECG)monitoring equipment in emergency intensive care unit(ICU),so as to explore its application value in the management for ECG monitoring equipment in emergency ICU.Methods:The classification management model on the basis of index for ECG monitoring equipment in emergency ICU was constructed.According to two classification dimensions included the market supply risk and the self-value,an indicator system of classification management,which aimed at strategic materials with high value and high risk,leverage materials with high value and low risk,bottleneck materials with low value and high risk,and conventional materials with low value and low risk,was constructed.A total of fifty-one ECG monitoring equipment in the emergency ICU of The People's Hospital of Longhua of Shenzhen from January to December 2023 were selected,and they were managed respectively by conventional management mode(25 sets)and classification management mode(26 sets)according to different management modes.The standardization level of operation management for equipment,the occurrence of safety risk and the level of management for equipment of the two management modes were compared,and the satisfaction of 30 relative personnel,who used and managed these equipment,for classification management of equipment also were compared.Results:The average values of the percentage of standardization level of normality of equipment operation,disinfection and sterilization,maintenance and fault repair of using classification management mode were respectively(91.58±4.33)%,(92.1±3.28)%,(91.49±3.54)%and(92.58±3.32)%,all of which were higher than those of conventional management mode,and the differences were statistically significant(t=12.537,15.706,14.196,18.946,P<0.05),repsectively.The average incidences of the risk of pressure injury,electrical injury and body fluid extravasation of adopting classification management mode were respectively(2.54±0.87)%,(3.02±0.82)%and(1.29±0.65)%,all of which were lower than those of adopting conventional management mode,and the differences were statistically significant(t=22.825,17.453,24.424,P<0.05),respectively.The satisfaction scores of 30 relative management personnel,who used equipment on the process rationality,system standardization and quality effectiveness,of adopting classification management mode were respectively(94.26±3.54),(92.57±4.36)and(91.87±3.69),all of which were higher than those of conventional management mode,and the differences were statistically significant(t=14.052,13.991,13.551,P<0.05),respectively.The reasonable placement rate,recording rate of standardization,and intact rate of equipment in the 26 equipment by adopting classification management mode were respectively 92.31%,92.31%and 88.46%,all of which were significantly higher than those by adopting conventional management mode,and the differences were statistical significant(x2=12.052,10.398,11.338,P<0.05).Conclusion:The classification management model of ECG monitoring equipment in emergency ICU can increase the management efficiency for the equipment in operating room of hospital,and improve the operation quality of equipment,and enhance the safety of equipment in clinical use,and the standardization of operation management for equipment.
4.Proteomic analysis of Trichosporon asahii's response to fluconazole stress
Xin YANG ; Zhikuan XIA ; Junhong AO ; He ZHU ; Jijin LI ; Jiamin WU ; Lingzhi XU ; Rongya YANG
Chinese Journal of Nosocomiology 2025;35(6):801-806
OBJECTIVE To explore the effect of fluconazole on proteomics of Trichosporon asahii so as to reveal the responding process of T.asahii to fluconazole stress and the resistance mechanisms to azoles on the protein level.METHODS T.asahii AS 2.2174 was chosen as the research subject,the minimum inhibitory concentration(MIC)of fluconazole was determined by broth microdilution assay.The protein abundance of T.asahii was detec-ted by means of tandem mass tag(TMT)technique combined with liquid chromatography-tandem mass spectrom-etry(LC-MS/MS)before and after the treatment with fluconazole(1× MIC).The differentially expressed pro-teins(DEPs)were identified based on the screening standards of fold change ≥1.20 or ≤0.83 and P<0.05.Gene ontlogy(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed for the DEPs so as to understand the biological property of the DEPs and the major biological pathways that the DEPs in-volved in.Finally,the targeted validation was carried out for the targeted differentially expressed proteins by using multiple reaction monitoring(MRM).RESULTS The MIC of fluconazole to T.asahii AS 2.2174 was 8 μg/ml.Totally 196 DEPs were identified,including 93 upregulated DEPs and 103 downregulated DEPs.The function en-richment analysis showed that the DEPs mainly participated in synthesis and metabolism of sterols,drug metabo-lism,stress response,energy metabolism and intertranslation.The targeted DEPs showed the consistent expres-sion trends in MRM target validation and TMT-LC-MS/MS.CONCLUSIONS The protein abundance of T.asahii has remarkable change under the fluconazole stress.The bioinformatics analysis reveals the complicated molecular mechanisms of T.asahii in response to the fluconazole stress,which may offer valuable ideas for understanding the drug resistance to azoles and developing new drug targets.
5.Report of tigecycline-induced adverse reactions in 574 patients
Ranran DONG ; Hao LIU ; Man ZHU ; Jintang NING ; Ao GAO
Chinese Journal of Nosocomiology 2025;35(16):2525-2528
OBJECTIVE To statistically analyze and detect signals for the adverse drug reactions(ADRs)related to tigecycline based on the ADR spontaneous reporting system,so as to provide reference for the prevention of medi-cation risks of tigecycline.METHODS ADR reports of tigecycline were extracted from the ADR spontaneous repor-ting system of the hospital from Oct.2013 to Mar.2024.Statistical analysis was conducted by Microsoft Excel and Free Statistics 2.1.1.The data mining and analysis were performed using the reporting odds ratio(ROR),the proportional reporting ratio(PRR)and the composite criteria of UK Medicines and Healthcare products Regulato-ry Agency(MHRA).RESULTS Among the 574 ADR reports with tigecycline as the primarily suspected drug,elderly patients accounted for over 50%.The ADRs mainly occurred within one week after medication administra-tion,involving 12 organ systems and 57 adverse reaction signals.Through comprehensive analysis using three methods,20 positive risk signals related to tigecycline were identified,mainly affecting the gastrointestinal system,hepatobiliary system and hematological system.The top 5 frequent ADR signals were nausea,vomiting,diarrhea,thrombocytopenia and hyperbilirubinemia.According to the ROR method,the top five ranked ADR sig-nals were hyperbilirubinemia(ROR=330.55),hepatocellular injury(ROR=110.22),elevated amylase(ROR=78.90),cholestasis(ROR=73.32),and decreased fibrinogen(ROR=43.65).CONCLUSIONS The adverse reac-tions of tigecycline mainly occur during the initial stage of medication,and special caution is required when used in elderly patients.High-intensity risk signals for ADRs are hyperbilirubinemia,liver injury,and others related to hematological system and gastrointestinal system.Close monitoring of these ADRs and timely intervention are necessary during medication.
6.Comparison of lung shunt fraction and intrahepatic distribution obtained from postoperative 90Y-selective internal radiation therapy and preoperative 99Tc m-MAA images
Hongji YOU ; Min XIONG ; Ao LI ; Zhaozhong WU ; Jingmin FENG ; Licong LIANG ; Liteng LIN ; Kangshun ZHU ; Shengnan JIANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(6):330-334
Objective:To compare the lung shunt fraction (LSF) of 90Y imaging after 90Y-selective internal radiation therapy (SIRT) and preoperative 99Tc m-macroaggregated albumin (MAA) imaging in patients with liver malignant tumors, and compare the volume and visual score of intrahepatic distribution of both nucleins on SPECT/CT images. Methods:A total of 91 patients with liver malignant tumors (78 males, 13 females; age (56.7±13.7)years; 99 cases) who underwent 90Y-SIRT in the Second Affiliated Hospital of Guangzhou Medical University from November 2022 to June 2024 were retrospectively collected. All patients underwent preoperative 99Tc m-MAA simulation and postoperative 90Y distribution verification by whole-body planar scintigraphy and hepatic SPECT/CT imaging. ROIs of the liver and lungs under the anterior-posterior position were delineated on the planar scintigraphy and LSF of 99Tc m-MAA and 90Y were calculated. The volume of interest (VOI) was drawn on the SPECT/CT images to calculate the nuclide distribution volume of both 99Tc m-MAA and 90Y within the liver. Wilcoxon signed rank test was used to compare the difference between two groups. In addition, the liver was divided into five lobes, namely left lateral lobe, left medial lobe, caudate lobe, right anterior lobe and right posterior lobe. Visual assessment of 90Y and 99Tc m-MAA radioactive distribution was performed ( 90Y and 99Tc m-MAA uptakes were graded on a scale of 0-3, where 0 indicated no nuclide accumulation and 3 indicated heavy accumulation). Kappa consistency test was used to analyze the scores of the corresponding lobes between two groups. Results:LSF for 99Tc m-MAA was 11.60%(4.27%, 15.03%), and LSF for 90Y was 11.80%(9.70%, 13.30%), without significant difference ( Z=-1.50, P=0.134). The distribution volume of 99Tc m-MAA within the liver was 542.63(204.00, 818.00)ml, which was significantly different from that of 90Y (688.69(287.00, 954.00)ml; Z=-7.37, P<0.001). Kappa values of the score of each lobe between 99Tc m-MAA imaging and 90Y imaging were 0.469-0.740 (all P<0.001). Conclusions:99Tc m-MAA simulation is reliable for assessing LSF for 90Y-SIRT. The distribution volume of 99Tc m-MAA is generally smaller than that of 90Y, but the consistency of the visual score of radioactive distribution is high. Overall, 99Tc m-MAA may well simulate the distribution pattern of 90Y-SIRT.
7.Application of physical examination information annotation combined with artificial intelligence in CT diagnosis of rib fracture
Ping AO ; Yu-lin ZHANG ; Li ZHU ; Zhi-gang XIU
Journal of Regional Anatomy and Operative Surgery 2025;34(1):41-44
Objective To explore the application value of physical examination information annotation combined with artificial intelli-gence (AI) in CT diagnosis of rib fractures. Methods The clinical data of 100 patients with chest trauma who underwent rib CT examina-tion with physical examination information annotation were collected. The images were analyzed by two physicians in the department of radiology with different seniorities using four methods[diagnosed by physicians independently (group A),diagnosed by physicians combined with physical examination information annotation (group B),diagnosed by physicians under the assistance of AI (group C),and diagnosed by physicians combined with physical examination information annotation under the assistance of AI (group D)]. The diagnostic efficacy and diagnostic time of two radiologists using different methods for rib fractures were compared. Results The sensitivities of two radiologists with different seniorities in the diagnosis of rib fracture in the group A were lower than those in the groups B,C and D (P<0.05),but there was no significant difference in the sensitivity of rib fracture among groups B,C and D (P>0.05). The diagnostic sensitivity of resident physician in the group A was lower than that of the attending physicians (P<0.05),and there was no significant difference in the diagnostic sensitivity of rib fracture in the other groups between the two physicians (P>0.05). There was no statistically significant difference in the false-positive rate of rib fractures among groups between two physicians (P>0.05). There was statistically significant difference in the diagnostic time among groups between two physicians (P<0.05),among which group A took the longest diagnosis time and group C took the shortest. Conclusion The assistance of AI and conbinatin of physical examination information annotation can increase the sensitivity of the physician in the diagnosis of rib fractures,shorten the diagnostic time and improve the work efficiency.
8.Effects of prognostic nutritional index on readmission rate, complication rate, mortality and survival in cirrhotic patients
Zichun AO ; Jun XIE ; Weifang ZHU ; Huan LI ; Hui LONG ; Qiang WANG ; Qingming WU
Chinese Journal of Digestion 2025;45(8):534-540
Objective:To investigate the effects of prognostic nutritional index (PNI) on the readmission rate, complication rate, mortality rate and survival of patients with liver cirrhosis.Methods:From January 1, 2020 to December 31, 2022, 395 hospitalized patients with liver cirrhosis at Tianmen Hospital Affiliated to Wuhan University of Science and Technology were retrospectively enrolled. The clinical data were collected from the patients at their first hospitalization (baseline period) and re-hospitalization during follow-up period. The 18-month follow-up was divided into 4 periods, including the first period (from the 0th to the 3rd month), the second one was from the 4th to the 6th month, the third one was from the 7th to the 12th month, and the fourth one was from the 13th to the 18th month of follow-up. The prognostic value of PNI for patients with liver cirrhosis was evaluated through the receiver operating characteristic curve (ROC) of the baseline PNI. The 395 patients were divided into the low PNI group and the high PNI group based on the optimal cut-off value of PNI on the ROC. Patients readmitted during each follow-up period were divided into the PNI improvement group (PNI at follow-up -PNI at baseline>0) and the PNI non-improvement group (PNI at follow-up-PNI at baseline ≤0). Independent sample t-test, one-way analysis of variance (ANOVA), Mann-Whitney U test, chi-square test or Fisher′s exact test were used for statistical analysis. Survival curves depicting the relationship between PNI and overall survival rate of patients with liver cirrhosis were constructed using the Kaplan-Meier method. Results:The ROC analysis indicated that the optimal cut-off value of PNI at baseline was 32.65, with an area under the curve of 0.639 (95% confidence interval: 0.541 to 0.738, P=0.011), with a sensitivity of 0.567 and a specificity of 0.701. There were 269 cases in the high PNI group and 126 cases in the low PNI group. The readmission rate, complication rate and mortality rate in the low PNI group were all higher than those in the high PNI group at the first and fourth follow-up periods (32.5% (41/126) vs. 22.3% (60/269), 31.7% (40/126) vs. 20.4% (55/269), 6.3% (8/126) vs. 1.1% (3/269), 25.0% (29/116) vs. 16.2% (42/260), 25.0% (29/116) vs. 15.4% (40/260), 6.0% (7/116) vs. 1.5% (4/260)), and the differences were statistically significant ( χ2=4.72, 6.00, 6.86, 4.10, 4.95, and 4.24; P=0.030, 0.014, 0.009, 0.043, 0.026, and 0.040). The mortality rates of the PNI improvement group at the first and fourth follow-up periods were both lower than those of the PNI non-improvement group (4.3% (2/47) vs. 16.7% (9/54), 0 (0/24) vs. 23.4% (11/47)), and the differences were statistically significant ( χ2=3.99, Fisher′s exact test; P=0.046 and 0.012). There were no statistically significant difference in the incidence of complications between the PNI improvement group and the PNI non-improvement group at each follow-up period (all P>0.05). The Kaplan-Meier survival curve demonstrated that the average survival time of the high PNI group was longer than that of the low PNI group (17.54 months (95% confidence interval: 17.26 to 17.83 months) vs. 16.74 months (95% confidence interval: 16.96 to 17.52 months), and the difference was statistically significant ( χ2=9.18, P<0.001). The survival rate of the high PNI group at the 18th month of follow-up period was higher than that of the low PNI group (95.2% (256/269) vs. 86.5% (109/126), and the difference was statistically significant ( χ2=9.17, P=0.002). Conclusions:PNI has certain predictive efficacy for the survival period of patients with liver cirrhosis. Low-level PNI may increase the readmission rate, complication rate, and mortality of patients with liver cirrhosis, and shorten the survival period, indicating poor prognosis.
9.Research on coagulation effect of cold atmospheric plasma jet device and its mechanism of action
Yan LI ; Hong-ye ZHENG ; Ao-xi XU ; Ya-jun ZHAO ; Shan-shan JIN ; Xu ZHANG ; Yu-fan WEI ; Yi-heng ZHANG ; Li ZHU ; Xi-ru LI
Chinese Medical Equipment Journal 2025;46(6):20-27
Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]
10.Study on the Hemodynamic Effects of Various Bypass Grafting Techniques for the Left Anterior Descending Artery on the Native Artery and Graft Vessels
Ao HAN ; Gang LIU ; Tao ZHANG ; Yi SHI ; Guangyu ZHU ; Yonghui LIU
Chinese Circulation Journal 2025;40(5):494-500
Objectives:To evaluate the hemodynamic impact of different bypass grafting methods on the left anterior descending(LAD)artery using computational fluid dynamics,providing a theoretical basis for optimizing coronary artery bypass grafting.Methods:A patient-specific 3D coronary model was constructed using SimVascular software,including an in-situ internal mammary artery graft(model 1)and three free grafts of varying diameters(model 2:2 mm internal mammary artery free graft;model 3 and model 4:3 mm and 4 mm great saphenous vein free grafts).The hemodynamic parameters of the native artery and grafts were compared among the four bypass grafting models.Results:All four bypass grafting models supply sufficient blood flow for the severely stenosed LAD.LAD flow was slightly lower in the model 1.Free internal mammary artery grafts showed higher flow and wall shear stress.4 mm great saphenous vein free grafts presented with maximum flow but lowest shear stress,3 mm great saphenous vein free grafts offered better hemodynamic stability.Conclusions:Computational fluid dynamics analysis indicates that free internal mammary grafts could provide superior hemodynamics,while larger grafts result in lower shear stress,which might affect long-term graft patency.These findings thus provide experimental evidences useful for optimizing LAD bypass strategies.

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