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。

BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.

BACKGROUND:Research has demonstrated a close association between ferroptosis and vascular dementia.Tongmai Kaiqiao Pill has a certain effect on improving the cognitive function of vascular dementia patients,but its mechanism is unclear. OBJECTIVE:To explore the interventional effects and molecular mechanisms of Tongmai Kaiqiao Pill for vascular dementia based on the regulation of ferroptosis by the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway. METHODS:Among eighty-four SD male rats,12 rats were used as the sham-operated group,and the rest of them were prepared as a model of vascular dementia by the modified 2-VO method,and then randomly divided into the model group,the Tongmai Kaiqiao Pills high-,moderate-,and low-dosage(27.6,13.8,and 6.9 g/kg)groups,the combined group(Tongmai Kaiqiao Pill high-dosage+ML385,20 mg/kg),and the donepezil hydrochloride group(0.45 mg/kg).The drug was given once a day by intragastric administration.The combined group was also intraperitoneally injected Nrf2 inhibitor ML385,once a day,for 4 weeks.Morris water maze was used to detect the learning memory ability of rats.Hematoxylin-eosin staining was used to observe the histopathological changes in the hippocampus of rats in each group.Colorimetric assay was used to detect the content of reduced glutathione,ferrous ion(Fe2+),and malondialdehyde in the serum of rats.Prussian blue staining was used to detect the iron deposition in the hippocampal tissue of rats.Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Western blot assay was used to detect the protein expression levels of Nrf2,HO-1,GPX4,XCT,and ferritin heavy chain 1(FTH1)in rat hippocampal tissues. RESULTS AND CONCLUSION:(1)In comparison to the sham operation,rats in the model group exhibited a significantly prolonged latency period(P<0.05)and a reduced number of platform crossings(P<0.05).Additionally,the hippocampal tissues of these rats displayed loosely organized structure,deeply stained cell nuclei,and solidified or lysed chromatin.Ferri ions aggregated in CA1 region.There were atrophied mitochondria with dissolved cristae and thickened mitochondrial membranes.Fe2+,malondialdehyde,and reduced glutathione levels in rat serum were found to be elevated(P<0.05).A significant reduction in the expression of GPX4,HO-1,XCT,Nrf2,and FTH1 proteins was detected in the hippocampus(P<0.05).(2)Compared to the model group,the average escape latency of the rats was significantly reduced following intervention with Tongmai Kaiqiao Pills and donepezil hydrochloride(P<0.05),with an increased number of platform crossings(P<0.05).Hippocampal neurons showed significant recovery.Notably,iron aggregation in the CA1 region was significantly reduced,and mitochondrial structure and function were improved.There were significant reductions in Fe2+and malondialdehyde levels,while the levels of GPX4,HO-1,XCT,Nrf2,and FTH1 in rat hippocampal tissues,and reduced glutathione in serum were significantly increased(P<0.05).(3)The high-dose Tongmai Kaiqiao Pills exhibited a treatment effect comparable to that of donepezil hydrochloride(P>0.05),with a significant prolongation of water maze escape latency(P<0.05),a reduced number of platform crossings(P<0.05),and insignificant neuronal pathological changes in the CA1 area.However,the combined group showed increased iron deposition,elevated malondialdehyde and Fe2+levels in blood serum(P<0.05),reduced glutathione content(P<0.05),hippocampal tissue mitochondrial atrophy,and reduced expression of Nrf2,XCT,HO-1,GPX4,and FTH1 proteins(P<0.05).Within a certain range,higher doses of Tongmai Kaiqiao Pills demonstrated a more pronounced effect,comparable to the efficacy of high-dose donepezil hydrochloride.(4)It is concluded that Tongmai Kaiqiao Pills have been shown to mitigate histopathological changes in the rat hippocampus and enhance cognitive function in rats with vascular dementia.The mechanism of action is likely associated with the suppression of ferroptosis through the activation of the Nrf2/HO-1/GPX4 signaling pathway.

BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

Objective To explore the value of high-frequency ultrasound in the detection of metastatic hepatocellular carcinoma and displaying lesion characteristics. Methods A total of 38 paitients with hepatocellular carcinoma satellite lesions within 40 mm of subcutaneous tissue were underwent low-frequency (1-5 MHz) and high-frequency (6-9 MHz) ultrasound. Detection rates and ultrasonic features were compared. Results High-frequency grayscale ultrasound had a higher detection rate (71.1% vs. 36.8%, P＜0.001). Subgroup analysis showed higher detection rates with chemotherapy history (88.9% vs. 33.3%, P＝0.002), fatty liver (71.9% vs 31.3%, P＜0.001) or superficial lesion (within 20 mm, 76.5% vs 41.2%, P＝0.031). High-frequency ultrasound also showed clearer margins (P＝0.004) and more arterial-phase rim enhancement (P＝0.007). Conclusions 6-9 MHz ultrasound detects metastatic hepatocellular carcinoma, especially superficial lesions, more effectively than 1-5 MHz ultrasound and better visualizes characteristics.

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.

Mitochondrial autophagy is a unique mechanism that selectively clears dysfunctional or excess mitochondria,closely related to Alzheimer's disease(AD),which is characterized by aggregated neurotoxic proteins and dysfunctional mitochondria.Numerous recent studies have confirmed that traditional Chinese medicine can have significant therapeutic effects against AD,and its advantages including multi-target,multi-pathway,and multi-action mechanisms have become an important component of AD research.Chinese medicine formulas and monomeric active ingredients,such as Jiannaoyizhi Fang,Danggui Shaoyao Tang,alkaloids,and flavonoids,can regulate mitochondrial autophagy-related signaling pathways and targets,inhibit neuronal mitochondrial autophagy defects,and play a neuroprotective role.This review elaborates on the basic process of mitochondrial autophagy and its related signaling pathways and molecular mechanisms in the pathogenesis of AD,and considers the latest research progress on the use of traditional Chinese medicine to improve AD by regulating mitochondrial autophagy,to provide ideas and references for future basic research and clinical treatment.

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]