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.

[摘 要] 目的：探究半乳糖凝集素-9（Gal-9）对胰腺癌细胞的侵袭与迁移功能的促进作用及其机制。方法：基于公开单细胞转录组数据分析胰腺癌中免疫检查点分子的表达谱，结合Western blotting和ELISA验证Gal-9在胰腺癌细胞及临床相关模型中的表达与分泌特征。建立C57BL/6小鼠胰腺原位移植瘤模型，通过免疫组化、免疫荧光染色和流式细胞术分析Gal-9对肿瘤细胞增殖及其对瘤内CD8+ T细胞浸润与功能状态的影响。Gal-9重组蛋白及肿瘤细胞条件培养基（CM）处理肿瘤相关成纤维细胞（CAF），Western blotting、RT-qPCR和免疫荧光检测CAF中Ⅰ型胶原表达变化。免疫共沉淀、免疫荧光染色和Western blotting分析Gal-9与CD44的相互作用及JAK2/STAT3通路相关蛋白的表达。构建过表达Gal-9胰腺癌细胞与CAF共移植的裸鼠皮下荷瘤模型，结合天狼星红和马松染色评估小鼠肿瘤组织中胶原沉积情况。脱细胞外基质法提取CAF中沉积的细胞外基质（ECM）蛋白；通过细胞划痕、Transwell迁移及侵袭实验，检测CAF来源Ⅰ型胶原对胰腺癌细胞侵袭、迁移功能的影响，并通过siRNA干扰Gal-9表达进行功能反向验证。结果：与经典免疫检查点分子PD-L1和CTLA-4相比，Gal-9在胰腺癌中显著高表达（P < 0.000 1）。体内实验表明，Gal-9促进肿瘤生长（P < 0.001），上调Ki-67表达，同时减少肿瘤内CD8⁺ T细胞浸润并诱导肿瘤组织中TIM-3⁺细胞比例升高，Granzyme B、IFN-γ及TNF-α表达下降（P < 0.05）。体外实验显示，外源性Gal-9及肿瘤细胞来源的CM均可上调CAF中Ⅰ型胶原表达（P < 0.001）。机制研究表明，在CAF中抗Gal-9抗体免疫沉淀复合物中检测到CD44，且JAK2/STAT3蛋白表达水平增加。CAF来源的Ⅰ型胶原处理胰腺癌细胞后，肿瘤细胞的迁移和侵袭数量增加。相反，肿瘤细胞中敲低Gal-9表达后，CAF来源Ⅰ型胶原水平下降，同时肿瘤细胞侵袭和迁移数量下降。结论：胰腺癌来源的Gal-9具有双重作用：一方面，通过促进肿瘤细胞增殖和诱导CD8+ T细胞耗竭促进肿瘤进展；另一方面，通过结合CAF上的CD44受体，激活JAK2/STAT3信号通路，刺激CAF合成并分泌Ⅰ型胶原，进而增强胰腺癌细胞的侵袭迁移能力。

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Organ transplantation is an effective treatment for end-stage organ failure, but postoperative infections and rejection reactions are key factors affecting the survival of the patients. Recently, the incidence of human parvovirus B19 (B19V) infection following transplantation has increased. B19V is a non-enveloped virus that primarily infects the upper respiratory tract and exhibits significant tropism for erythroid progenitor cells in the bone marrow, leading to the lysis of erythrocytes and hematological abnormalities. After B19V viremia, it may further infect other cells, triggering inflammatory responses and tissue damage. B19V infection may lead to chronic anemia in organ transplant patients, thereby affecting the success of the transplant and the survival of the patients. Therefore, it is essential to diagnose and monitor B19V infection post-transplantation. Due to the immunosuppressive therapy following transplantation, traditional serological detection methods, such as IgM and IgG antibody tests, are often unreliable. In contrast, molecular biological detection, especially real-time fluorescent quantitative PCR technology, provides more accurate results. However, the diversity of B19V genotypes may lead to the missed detection of some genotypes. Thus, it is necessary to use different detection techniques to improve the diagnostic accuracy of B19 virus infections. Additionally, there is a need to explore more precise diagnostic methods to enhance the early identification and management of B19V infection, further improving the survival and life quality of the patients.

The pregnant woman was 39 years old，G2P1，a fetal goiter was found at 25 weeks at the Second Xiangya Hospital of Central South University，and thyroid function was normal during the pregnancy. Amniocentesis revealed the presence of two DUOX2 mutations in fetal DNA：c.3340delC（P.L1114Sfs56）in exon 25 and c.2654G＞A（p.R885Q）in exon 20，which were determined to be heritable by familial genetic testing. Many fetal and neonatal ultrasounds have shown goiter，rich blood flow in the parenchyma and low postnatal thyroid hormone levels led to the diagnosis of congenital hypothyroidism. The patient was given L-thyroxine 30 μg/d. After 3 months of follow-up，the thyroid function was normal without developmental problems.

Heatstroke,especially in high-temperature and high-humidity environments,is a life-threatening acute heat-injury disease that seriously endangers human health.Timely and effective on-site treatment is crucial for patients'survival and prognosis.Early recognition,rapid assessment,and on-site cooling are the core of pre-hospital treatment of heatstroke.Currently,there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke.Therefore,the"Expert Consensus on Pre-hospital Emergency Management of Heatstroke(2024 edition)"was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care,emergency departments,and intensive care units.This consensus focuses on heatstroke prevention,on-site and ambulance-based treatment,and early emergency room interventions,and puts forward 10 evidence-based recommendations,aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.

Objective To develop a static progressive ankle stretcher for the treatment of functional disorders caused by scar contracture of the Achilles tendon after burn,and to evaluate its application effect.Methods The static progressive ankle stretcher was composed of a plantar support section and a calf support section,which was mainly made of a 3.2 mm-thick medical low-temperature thermoplastic plate,a commercially available 1 mm-diameter steel wire rope,grooved wheels,ice fishing reels with a diameter of about 50 mm,curved folding hinges and a locking threader with a hole diameter of about 1.5 mm.Totally 49 patients with scar contracture after deep Ⅱ to Ⅲ-degree burns of the Achilles tendon admitted to some hospital from March 2021 to January 2023 were prospectively selected and divided into a conventional rehabilitation group(25 cases)and a combined rehabilitation group(24 cases)using a randomized numerical table method.The patients in the conventional rehabilitation group underwent routine scar care such as anti-scarring medication application at home,scar massage,resistance training,joint loosening training in the hospital and compression therapy with the customized compression stockings/pants at the rest of the time,the patients in the combined rehabilitation group were treated with the static progressive ankle stretcher besides the measures taken for the conventional group.The two groups were compared in terms of scarring,ankle function and active dorsiflexion mobility of the ankle joint before and 12 weeks after the treatment,balance and walking ability 4 weeks and 12 weeks after the treatment,adverse events during the treatment and patient satisfaction 12 weeks after the treatment.SPSS 23.0 statistical software was used for data analysis.Results In terms of scarring condition,ankle function and active dorsiflexion mobility of the ankle joint all the patients were improved 12 weeks after the treatment,and the ones in the combined rehabilitation group behaved better than the ones in the conventional group,with the differences being statistically significant(P<0.05).The balance and walking ability 12 weeks after the treatment was better than that 4 weeks after the treatment in the two groups,and the combined rehabilitation group gained advantages over the conventional group in balance and walking ability,with the difference being statistically significant(P<0.05).During the treatment no adverse events due to the static progressive ankle stretcher were found,such as muscle tissue strain,scarred skin rupture,instrument friction and pressure injury.The combined rehabilitation group had higher patient satisfaction than the conventional group 12 weeks after the treatment,with the differences being statistically significant(P<0.05).Conclusion The static progressive ankle stretcher combined with the conventional rehabilitation treatment contributes to improving contracture scar conditions and joint mobility at the Achilles tendon area of the post-burn patients,which helps accelerate the recovery of ankle function after burns and enhance the balance and walking ability of the patients.[Chinese Medical Equipment Journal,2025,46(10):54-59]

Objective To observe the impact of brain-computer interface(BCI)robot combined with task-oriented training(TOT)on hand function and activities of daily living in stroke patients.Methods A total of 40 patients with subacute stroke who were hospitalized in the Department of Rehabilitation Medicine of Anhui No.2 Province People's Hospital from December 2022 to December 2024 were prospectively and consecutively included in this study.The stroke patients were randomly assigned to the experimental group and the control group using the random number table method,with 20 cases in each group.Baseline data were collected from all patients,including gender,age,personal history(smoking,drinking),past medical history(hypertension,diabetes),stroke type(hemorrhagic stroke,ischemic stroke),hemiplegia side(left,right),disease course,stroke location(basal ganglia,internal capsule),and admission assessment indicators(including kinesthetic and visual imagery questionnaire[KVIQ-20]score,mini-mental state examination[MMSE]score and National Institutes of Health stroke scale[NIHSS]score).Both groups of patients received conventional rehabilitation training and TOT.The experimental group then underwent BCI robot training combined with TOT on this basis.Both groups received treatments for 4 weeks,and the upper limb and hand functions of all patients were evaluated using the Fugl-Meyer upper extremity function assessment scale(FMA-UE),the wrist-hand part of the FMA-UE scale(FMA-WH),the Wolf motor function test(WMFT),and the modified Ashworth scale(MAS)before and after the treatment;the hand function related part(feeding[10 score],bathing[5 score],dressing[10 score],grooming[5 score],and toilet using[10 score])of modified Barthel index(MBI)was used to assess the patients'hand dexterity to perform daily activities.Results(1)No statistically significant differences were found in the baseline data between the two groups of patients(all P＞0.05).(2)Before treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(18.75±7.38),(2.95±1.54),(26.90±8.69),(1.10±0.66),and(15.45±1.82)respectively,while those in the control group were(15.90±5.39),(2.25±1.12),(24.15±6.78),(1.25±0.60),and(15.65±3.12)respectively.There were no statistically significant differences in the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI between the two groups before treatment(all P＞0.05).After 4 weeks of treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(27.10±7.76),(5.75±2.97),(40.85±10.19),(0.73±0.57),and(21.15±2.66)respectively,while those in the control group were(21.25±5.29),(4.00±1.49),(31.85±7.60),(0.73±0.64),and(17.40±3.14)respectively.The time main effects(Ftime values were 925.061,138.138,624.635 and 405.986 respectively,all P＜0.01),group main effects(Fgroup values were 4.460,4.562,5.011 and 4.411 respectively,all P＜0.05),and the interaction effects of time and group(Ftime×group values were 44.358,7.356,52.506 and 114.128 respectively,all P＜0.05)of FMA-UE,FMA-WH,WMFT and hand function related score of MBI scores were all significant.The time main effect of MAS scores was significant(Ftime value was 59.478,P＜0.01),while the group main effect(Fgroup value was 0.162,P＞0.05),the interaction effects of time and group(Ftime×group value was 1.652,P＞0.05)were not significant.Conclusion The combined task-oriented training with BCI robots can improve the upper limb and hand functions of stroke patients,enhance their ability to perform daily activities,and the effect is superior to that of single task-oriented training.

Objective To explore the molecular mechanism by which curcumin enhances the anti-tuberculosis function of macrophages through immune metabolic regulation mediated by liver X receptor α(LXRα)/ABCA1.Methods A model was established by infecting THP-1-derived macrophages with attenuated strain of Mycobacterium bovis(M.bovis).The control group,curcumin group,M.pavis group,M.pavis+LXRα agonist(T0901317)group,M.pavis+LXRα inhibitor(GSK2033)group,M.pavis+curcumin group,M.pavis+curcumin+GSK2033 group and M.pavis+curcumin+T0901317 group were set up.The protein and gene expressions of LXRα/ABCA1 were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The accumulation of lipid droplets was analyzed by Oil Red O staining and micro-assay.The lipid content of the supernatant was determined by a biochemical analyzer,and cell proliferation was assessed by the MTT method.Bacterial clearance capacity was evaluated by measuring intracellular bacterial load.Results Curcumin significantly upregulated the protein and gene expression of LXRα/ABCA1 in M.Bovis-infected macrophages,reduced intracellular lipid accumulation and promoted lipid efflux,while enhancing cell proliferation and reducing intracellular bacterial load(P<0.05,P<0.01).LXRα inhibitors could reverse the effect of curcumin,while agonists synergistically enhanced its effect.Correlation analysis showed that the expression of LXRα/ABCA1 in cells was negatively correlated with the intracellular bacterial load,while the lipid level was positively correlated with the intracellular bacterial load(P<0.01).Conclusion Curcumin activates the LXRα/ABCA1 pathway,coordinates the metabolic remodeling of macrophages and the enhancement of immune function,and forms a synergistic effect against tuberculosis,providing an experimental basis for the development of a novel host-directed treatment strategy for tuberculosis based on immune-metabolic regulation.