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.

This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Objective To investigate the clinical characteristics, diagnosis, treatment and prognosis of rare simultaneous ipsilateral renal multifocal tumors. Methods The clinical data of a patient with clear cell renal cell carcinoma(ccRCC)and primary renal leiomyosarcoma(LMS)with liver metastasis were retrospectively analyzed. Results The 70-year-old male patient was admitted due to space-occupying lesions of the right kidney detected by physical examination for 12 days. CT showed space-occupying lesions in the upper and middle parts of the right kidney, suggestive of renal cell carcinoma or renal angiosarcoma. He underwent radical nephrectomy. Postoperative pathology showed the tumor in the upper pole of the right kidney with morphology of ccRCC(solid acinar clear cells), but immunohistochemical(IHC)results showed CK(+), EMA(+), CD10(-), PAX-8(-)(rare phenotype); the tumor in the middle of the kidney showed LMS characteristics(spindle cells, active mitosis), Vim(+)and SMA(+). Four months after operation, abdominal CT scan revealed liver metastasis. The biopsy confirmed metastatic LMS, with IHC results showing Vim(+), CD10(+), RCC(+), CK8/18(-), CK7(-), SMA(+), and Caldesmon(+). Subsequently, a liver biopsy combined with microwave ablation of the tumor was performed. The patient was treated with tirelizumab and anlotinib, but the tumor still progressed. The patient died 11 months after operation. Conclusion Simultaneous ipsilateral ccRCC and LMS are extremely rare in clinic, and the prognosis is poor. At present, there is no standardized treatment plan. Surgery is the main treatment for simultaneous multifocal tumors. After surgery, the pathological characteristics of the two tumors should be considered to formulate a comprehensive drug treatment strategy targeting at different biological behaviors so as to provide reference for clinical practice.

BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress. OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software,and the Degree algorithm was run to get the key genes.The GSE1919 dataset was obtained from the GEO database as a validation dataset,and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes.In addition,immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored.miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION:Sixty-five differentially expressed genes and five core genes(IL1B,CXCL8,MYC,NFKBIA,JUN)associated with oxidative stress were identified.Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress,interleukin-17,osteoclast differentiation,fluid shear stress and atherosclerosis.The area under the receiver operating characteristic curve for the five core genes exceeded 0.85,indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions,as well as their close association with immune cells.The predicted miRNA was has-miR-3937,and the therapeutic small-molecule drugs were metformin,ionomycin and celecoxib.To conclude,oxidative stress and immune infiltration exist in osteoarthritis,and immune infiltration is involved in activating oxidative stress.The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis,and small molecule drugs are predicted to treat osteoarthritis.

Objective To evaluate the clinical efficacy of Shengqing Jiangzhuo(lifting lucid yang and lowering turbid yin)Acupuncture Method,based on the"turbidity-clearness interaction"theory,combined with western medicine in treating gouty nephropathy(GN)patients with damp-heat accumulation syndrome.Methods A total of 117 patients diagnosed with GN from September 2023 to September 2024 at the First Affiliated Hospital of Guangzhou University of Chinese Medicine Chongqing Hospital were enrolled and randomly divided into three groups,with 39 cases in each group.The western medicine group received Febuxostat Tablets,the control group was given western medicine+conventional acupuncture,and observation group was given western medicine+Shengqing Jiangzhuo Acupuncture Method.All groups received 4 weeks of treatment.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,visual analogue scale(VAS)of pain scores,and laboratory parameters—including serum uric acid(UA),blood urea nitrogen(BUN),creatinine(Scr),estimated glomerular filtration rate(eGFR),β2-microglobulin(β2-MG),24-hour urinary protein(24h-UTP),cystatin C(CysC)were assessed.The erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)were compared before and after treatment.Results(1)The total effective rate was 71.79%(28/39)in the western medicine group,84.62%(33/39)in the control group,and 92.31%(36/39)in the observation group.The observation group demonstrated statistically significant superiority over the western medicine group(P＜0.05),while showing marginally better efficacy than the control group without statistical significance(P＞0.05).(2)After treatment,all three groups exhibited significant improvements in ESR,CRP,and UA levels(P＜0.05).The observation group significantly outperformed the other two groups in reducing ESR and CRP levels(P＜0.05),and was statistically superior to the western medicine group in lowering UA levels(P＜0.05),though no significant difference was observed versus the control group for UA improvement(P＞0.05).The control group showed significantly greater reductions in ESR,CRP,and UA levels than the western medicine group(P＜0.05).(3)After treatment,Scr,BUN,and eGFR levels were significantly improved in all groups(P＜0.05).The observation group achieved significantly better improvements in Scr and eGFR than the other two groups(P＜0.05).However,no statistical difference existed between the control and western medicine groups for Scr or eGFR enhancement(P＞0.05).No intergroup differences were detected in BUN improvement(P＞0.05).(4)Significant differences emerged in β2-MG and CysC levels among all groups after treatment(P＜0.05).Both observation and control groups demonstrated statistically significant improvements in 24-hour 24h-UTP(P＜0.05),whereas the western medicine group showed no significant change(P＞0.05).The observation group significantly outperformed the other groups in reducing 24h-UTP and β2-MG levels(P＜0.05),and was superior to the western medicine group in lowering CysC(P＜0.05),though no difference versus the control group was observed for CysC reduction(P＞0.05).The control group showed no statistical advantage over the western medicine group in improving 24h-UTP,β 2-MG,or CysC(P＞0.05).(5)After treatment,TCM syndrome scores and VAS scores were significantly improved in all groups(P＜0.05).The observation group achieved significantly greater reductions in TCM syndrome scores and VAS scores than the western medicine group(P＜0.05).The control group showed statistically superior VAS score improvement versus the western medicine group(P＜0.05),but no significant differences emerged in TCM syndrome score improvement compared to either group(P＞0.05).No statistical difference existed between observation and control groups for VAS score reduction(P＞0.05).Conclusion Shengqing Jiangzhuo Acupuncture Method,grounded in the"turbidity-clearness interaction"theory,effectively reduces serum UA,controls inflammation,and preserves renal function in damp-heat accumulation type of GN,demonstrating significant therapeutic benefits.

Objective To explore the relationship between axillary artery and axillary vein by combining computed tomography angiography computed tomography angiography(CTA)and computed tomography venography(CTV),and to provide imaging data for establishing an effective blood circulation pathway for vascular injury in clinical transaxillary surgery.Methods The image data of 30 patients who underwent left upper limb and axillary CTA and CTV at the same time were collected.After three-dimensional reconstruction of the images by GE AW4.6 workstation,the course,branch type and variation of axillary artery,the course of axillary vein,the reflux of subordinate branches and the relationship between axillary artery and axillary vein were observed.The length of the whole segment,the length of segment and the inner diameter of the starting point of each segment were measured and statistically analyzed.Results According to the number of branches from the main trunk,the axillary artery was divided into 7 types.According to the variation of the number of blood vessels,the axillary vein was divided into 5 types;The unknown vein branches converge into 32 branches,of which the first segment accounted for 37.5％,the second segment accounted for 46.9％,and the third segment accounted for 15.6％.According to the absence of arterial branches,the relationship between axillary artery and axillary vein was divided into 2 types.Conclusion There are many types of branches of axillary arteries and branches of axillary veins,and the variation types are complex.The changes of branches of axillary arteries affect the distribution of branches of axillary veins.Combined with CTA and CTV images,the relationship between axillary vessels can be reflected clearly and intuitively,which can provide imaging reference for the establishment of new ways of blood supply and reflux in clinical axillary treatment.

Objective To determine the effect of knee extension constraint training on bilateral knee biomechanics and bilateral symmetry in running after anterior cruciate ligament reconstruction(ACLR).Methods A total of 33 male patients with unilateral ACL injuries were randomly assigned to a BRACE group of 14 wearing a brace with limitation of knee extension,a PLACEBO group of 10 wear-ing a brace without limitation of knee extension,and a CONTROL group of 9,wearing no brace.All groups underwent unilateral hamstring-auto graft ACLR surgery,immediately followed by 12-week rou-tine rehabilitation.Between week 13 and 48,both the BRACE and PLACEBO groups wore braces for one hour on Mondays.Then,running biomechanical tests were performed at the ends of Week 12 and Week 48,and the bilateral knee extension/flexion angle,moment and inter-leg difference(ILD)were calculated.One-dimensional statistical parametric mapping(SPM1d)two-way ANOVA with repeated measures on one factor was used to identify differences in bilateral knee biomechanics and ILD among the three groups before and after the intervention.Results There was no significant interaction effect of group and time on bilateral knee flexion angle,knee extension moment,and ILD in running(P>0.05).Moreover,no significant effect of group was found on the bilateral knee biomechanics and ILD in running(P>0.05).Additionally,significant effects of time were observed on bilateral knee flexion angle and extension moment in running.However,bilateral knee flexion angle decreased during termi-nal stance(ACLR leg:89%～100%,P=0.036;non-ACLR leg:94%～100%,P=0.046),while the bi-lateral knee extension moment increased during mid-stance(ACLR leg:17%～59%,P<0.001;non-ACLR leg:38%～61%,P<0.001)between week 12 and 48.Conclusion In this study,no improvement was found in the abnormal knee biomechanics and symmetry during running in male patients after uni-lateral ACL reconstruction through long-term knee extension constraint training.Moreover,within one year after ACL reconstruction,the knee extension moment of the surgical limb increased gradually over time,with no changes in the knee flexion angle of the surgical limb and bilateral knee symme-try,suggesting that abnormal knee biomechanics and bilateral symmetry should be paid attention to in the post-surgery rehabilitation.

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]

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

BACKGROUND:Stage Ⅱ Kümmell's disease has traditionally been treated with percutaneous kyphoplasty,but this approach is associated with a high incidence of complications such as poor postoperative pain relief,suboptimal cement dispersion,and adjacent vertebral fractures.Studies have shown that cement augmentation of the injured vertebra combined with posterior spinal canal decompression and short-segment fixation has a good effect on the treatment of Kümmell's disease with neurological symptoms.OBJECTIVE:To compare the outcomes of cement-augmented short-segment percutaneous pedicle screw fixation with those of percutaneous kyphoplasty for the treatment of stage Ⅱ Kümmell's disease.METHODS:From January 2020 to January 2023,a total of 49 patients with stage Ⅱ Kümmell's disease from Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine were included in this study,with 15 males and 34 females.According to the treatment method,the patients were divided into the trial group(n=23)and the control group(n=26).The patients in the trial group received cement-augmented short-segment percutaneous pedicle screw fixation,and the patients in the control group received percutaneous kyphoplasty.The postoperative complications were recorded,and the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra were compared between the two groups at 1,6,12 weeks,6,and 12 months after surgery.The Oswestry disability index and lumbar visual analog score were compared at 1 week and 12 months after surgery.RESULTS AND CONCLUSION:(1)All patients in the two groups were followed up for more than 12 months after surgery.Five patients in the control group had adjacent vertebral fractures,three patients had severe kyphosis,and one patient in the trial group had postoperative incision complications.(2)Compared with preoperative data,the spinal Cobb angle and the ratio of the anterior edge height of the injured vertebra in both groups were significantly improved after surgery(P＜0.05).The spinal Cobb angle of the trial group was lower than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05),and the ratio of the anterior edge height of the injured vertebra in the trial group was higher than that of the control group at 1,6,12 weeks,6,and 12 months after surgery(P＜0.05).(3)Compared with preoperative data,the Oswestry disability index and lumbar visual analog scale score of the two groups were significantly improved after surgery(P＜0.05).The Oswestry disability index and lumbar visual analog scale score of the trial group were lower than those of the control group at 1 week and 12 months after surgery(P＜0.05).(4)The results show that compared with percutaneous kyphoplasty,cement-augmented short-segment percutaneous pedicle screw fixation for stage Ⅱ Kümmell's disease can better restore the height of the affected vertebra,maintain the shape of the affected vertebra,improve spinal function,and alleviate lumbar pain.