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.

Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective To investigate the current status of work readiness and its influencing factors among patients returning to work after lung cancer surgery. Methods A retrospective study was conducted on young and middle-aged postoperative lung cancer patients who were treated at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to September 2023 and returned to their jobs. Data were collected through a general information questionnaire, readiness for return-to-work scale (RRTW), general self-efficacy scale (GSES), and simplified coping style questionnaire (SCSQ). Univariate and multivariate logistic regression analyses were used to explore the factors affecting the work readiness of patients returning to work. Results A total of 219 patients were included, with 59 males and 160 females aged 18-60 years. Among the postoperative lung cancer patients returning to work, 73.1% were in the active maintenance stage of return-to-work readiness with a RRTW score of (17.59±1.48) points, and 26.9% were in the uncertain maintenance stage with a RRTW score of (16.22±1.50) points. Multivariate logistic regression analysis showed that patients aged≤30 years (OR=52.381), employees of enterprises and institutions (OR=7.682), agricultural, pastoral, fishery, forestry laborers (OR=15.665), positive coping (OR=5.043), those with higher self-efficacy (OR=1.157) and engaged in physically demanding work (OR=2.449) had higher return-to-work readiness, while patients with≥2 children (OR=0.055), self-payment (OR=0.044), and those working more than 40 hours per week (OR=0.122) had lower return-to-work readiness. Conclusion The return-to-work readiness of young and middle-aged postoperative lung cancer patients needs to be improved, and occupation, job nature, main coping styles, general self-efficacy and other factors are associated with return-to-work readiness.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

Objective:To investigate the clinical effect of transposition of gracilis muscle flap in repairing urethral perineal fis-tula after Miles operation.Methods:The clinical data of 3 patients with urethral perineal fistula treated in the Second Affiliated Hos-pital of Zhejiang University from September 2023 to November 2024 were analyzed retrospectively.All patients were male,aged from 59 to 68 years(mean 63 years).All patients underwent Miles operation because of low rectal cancer.Urethral perineal fistula occurred after 2 months to 13 years of the operation.The underlying comorbidities included diabetes(2/3),preoperative chemoradiotherapy(1/3),and chemotherapy alone(1/3).The endourethral fistula was located in the apical and membranous part of the prostate,with a diameter of 1.5-2.0 cm and a mean of 1.7 cm.Suprapubic cystostomy was performed one month before operation.In all 3 cases,perineal inverted"Y"incision was taken under general anesthesia to expose urethral fistula,cut off necrotic tissue and suture urethral fistula.The gracilis muscle of the right thigh was taken and turned through the perineal subcutaneous tunnel.and 6 stitches were suture at the urethral fistula.Results:The operations of all 3 patients were completed successfully.The follow-up period ranged from 2 months to 12 months,with an average of 8 months.There was no case of urinary incontinence after removal of catheter 3 weeks after operation.In two patients,urethrography was reviewed 1 month after surgery to show no fistula residue and urethral stenosis,and the fistula was removed.In one patient with a history of radiotherapy,urethrography was reviewed 1 month after surgery to show a small amount of contrast overflow around the urethra,and urethrography was reviewed again 3 months after surgery to show no contrast over-flow around the urethra.All the 3 patients had no disturbance of movement of the right lower limb,and the pain of different degrees of thigh incision was acceptable and basically relieved half a month after operation.Conclusion:Gracilis muscle flap is one of the ef-fective methods for repairing urethral perineal fistula after Miles operation,which has a precise surgical result and few complications.

Aim To investigate the mechanism of ac-tion of Qingre Zhixue granules in the treatment of IgA vasculitic nephritis(IgAVN)based on network phar-macology and animal experiments.Methods The ac-tive ingredients and targets of Qingre Zhixue granules were screened out by TCMSP database.The disease targets of IgAVN were retrieved by Disgenet,Gene-cards OMIM and TTD databases.The intersection tar-gets were obtained by WeChat online database,and the information was imported into Cytoscope 3.7.1 soft-ware and STRING analysis platform to construct a drug-active component-therapeutic target network.Based on the core targets,GO and KEGG pathway enrichment a-nalysis was performed through the Metascape database to select key targets and core active components.The results of network pharmacology were verified by ani-mal experiments.The animal model of IgAVN was con-structed by the combination of disease and syndrome.The urine red blood cells and 24-hour urine protein of IgAVN model rats after intervention of Qingre Zhixue granules were detected.HE staining and IgA immuno-fluorescence deposition of renal tissue were observed.Western blot and qRT-PCR were used to detect the ex-pression of core targets in renal tissue.Results Net-work pharmacology showed that 109 active ingredients,402 drug targets,1 285 disease targets and 113 inter-section targets were obtained.The core targets screened by protein interaction and network topology a-nalysis were IL6,TNF,VEGFA,etc.The core drug ingredients were quercetin,paeoniflorin,luteolin,kaempferol and baicalein.A total of 2 545 gene func-tions were enriched by GO,and 164 gene pathways were enriched by KEGG.Qingre Zhixue granules could treat IgAVN by regulating TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,Toll receptor signaling path-way,NF-κB signaling pathway and apoptosis.Animal experiments showed that compared with the blank group,the urine red blood cells and 24-hour urine pro-tein quantification in the model group increased(P＜0.05);the expression of serum IL-6,TNF-α and VEGF-α increased(P＜0.05).HE staining showed glomerular mesangial proliferation,capillary lumen ste-nosis,accompanied by a small amount of inflammatory cell infiltration,glomerular IgA immunofluorescence deposition;the expression of TNF-α,p-p65,p-p38 protein and TNF-α mRNA in renal tissue increased(P＜0.05).After the intervention of Qingre Zhixue gran-ules,urine red blood cells and 24-hour urine protein decreased(P＜0.05).The changes of renal HE stai-ning were improved and glomerular IgA deposition was reduced.TNF-α,p-p65,p-p38 protein and TNF-αmRNA in renal tissue decreased(P＜0.05).Conclu-sions The active ingredients such as quercetin,peony glycoside and luteolin Qingre Zhixue granules regulate TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway and reduce IL-6,TNF-α and VEGF-α in the treatment of IgAVN.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To investigate the effect of traditional Chinese medicine chronic disease management model based on empowerment theory in patients with chronic heart failure(CHF).Methods:A total of 115 CHF patients admitted in Guangdong Provincial Hospital of Chinese Medicine between January 2020 and December 2021 were se-lected.Patients received traditional Chinese medicine chronic disease management model based on empowerment theory according to voluntary principle,and were followed up for 12 months.Exercise capacity,scores of Tradition-al Chinese Medicine Symptom Grading and Quantification Scale,Hospital Anxiety and Depression Scale(HADS)and Minnesota Living with Heart Failure Questionnaire(MLHFQ)were compared between before and after inter-vention.Results:Compared to before intervention,scores of Traditional Chinese Medicine Symptom Grading and Quantification Scale[(6.40±6.11)points vs.(8.88±6.72)points],HADS[(5.95±4.68)points vs.(7.69±5.95)points],MLHFQ[(13.10±10.54)points vs.(25.53±11.16)points]and 3m round-trip movement time[(7.54±1.70)s vs.(8.86±3.65)s]were significantly lower,and right hand grip strength[(27.23±10.49)kg vs.(26.10±9.94)kg]and 6-minute walking distance[(464.79±80.78)m vs.(415.55±79.33)m]were sig-nificantly higher after 12-month intervention(P＜0.05 or＜0.01).Conclusion:The traditional Chinese medicine chronic disease management model based on empowerment theory may improve clinical symptoms of traditional Chi-nese medicine,mental state,exercise capacity and quality of life in patients with chronic heart failure.