AIM: To investigate variation patterns of corneal biomechanical parameters and binocular symmetry among children of different genders aged 8-16 years.METHODS:A retrospective study was conducted, and children who underwent optometric examinations at the ophthalmology department of our hospital were enrolled between January 2022 and December 2024. Measurements included the flat keratometry(K1), steep keratometry(K2), and mean curvature(Km)of the anterior corneal surface, horizontal visible iris diameter(HVID), central corneal thickness(CCT), corneal endothelial cell density(CECD), average cell size(ACS), coefficient of variation(CV), and hexagonality(HEX). Corneal parameters and binocular differences were compared between genders and across age groups.RESULTS:A total of 621 children(1 242 eyes)were enrolled in this study, including 284 males(568 eyes), 337 females(674 eyes), 528 children aged 8-12 years(1 056 eyes), and 93 children aged 13-16 years(186 eyes). In children aged 8-16 years, the K1, K2, Km and CV of both eyes, as well as the interocular CCT differences in boys were significantly lower than those in girls(all P<0.05), while the HVID and HEX of both eyes, as well as the CCT of the left eye in boys were significantly higher than those in girls(all P<0.05). Children aged 8-12 years had significantly higher K1, Km, CECD and HEX in both eyes, and significantly lower ACS in both eyes than those aged 13-16 years(all P<0.05). K1, K2, Km, CECD and HEX in both eyes were negatively correlated with age(P<0.05); ACS in both eyes was positively correlated with age(P<0.001); K1 and Km of the right eye were positively correlated with the CECD of the right eye(P<0.05), and K1 and CCT of the left eye were positively correlated with the CECD of the left eye(P<0.05).CONCLUSION:Significant gender differences exist in corneal parameters among children aged 8 to 16 years, while binocular symmetry remained stable.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

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.

By analyzing the current status of randomized controlled trials （RCTs） on functional dyspepsia （FD） and irritable bowel syndrome （IBS） comorbidity， we identified several critical issues which include insufficient repor-ting of FD and IBS subtypes， inadequate risk assessment of drug combination， lack of composite， objective， and long-term outcomes， and weak evidence support for clinical practice guidelines. It is suggested that future clinical research on FD-IBS comorbidity should further strengthen the application of real-world studies. The use of composite outcomes and long-term follow-up is recommended to improve the quality of evidence， while greater attention should be paid to patients' preferences and self-management to enhance the applicability of findings. Based on the existing issues in clinical studies of traditional Chinese medicine （TCM） for FD-IBS comorbidity， we propose to consolidate the foundation of TCM-specific efficacy evaluation to better reflect the advantages of syndrome differentiation and treatment， optimize real-world study designs to better support clinical decision- making， and introduce intelligent objective evaluation technologies to improve the objectivity and accuracy of TCM clinical efficacy assessment.

By analyzing the current status of randomized controlled trials （RCTs） on functional dyspepsia （FD） and irritable bowel syndrome （IBS） comorbidity， we identified several critical issues which include insufficient repor-ting of FD and IBS subtypes， inadequate risk assessment of drug combination， lack of composite， objective， and long-term outcomes， and weak evidence support for clinical practice guidelines. It is suggested that future clinical research on FD-IBS comorbidity should further strengthen the application of real-world studies. The use of composite outcomes and long-term follow-up is recommended to improve the quality of evidence， while greater attention should be paid to patients' preferences and self-management to enhance the applicability of findings. Based on the existing issues in clinical studies of traditional Chinese medicine （TCM） for FD-IBS comorbidity， we propose to consolidate the foundation of TCM-specific efficacy evaluation to better reflect the advantages of syndrome differentiation and treatment， optimize real-world study designs to better support clinical decision- making， and introduce intelligent objective evaluation technologies to improve the objectivity and accuracy of TCM clinical efficacy assessment.

Traditional Chinese medicine （TCM） plays an important role in the full-cycle management of primary liver cancer； however， the current evidence-based evaluation system with the main assessment index of objective tumor remission is mainly centered on randomized controlled trials and systematic reviews/meta-analyses and cannot fully reflect the characteristics and advantages of TCM. Based on the current status of TCM efficacy evaluation in the prevention and treatment of liver cancer， this article proposes the construction of a multi-dimensional evaluation system that is oriented by stage-specific treatment goals and integrates outcome indicators with process indicators. Outcome indicators include modern medical endpoints such as overall survival and recurrence-free survival， and process indicators include short-term outcomes such as the improvement in TCM syndrome， patient-reported outcomes， the remission rate of adverse events， and the discontinuation rate of the core regimen. It is emphasized that the development of standardized TCM regimens should follow the order of theoretical connotation， accumulation of proven cases， observational evaluation， and interventional evaluation. Furthermore， it is recommended to incorporate artificial intelligence approaches into this evaluation system， so as to promote the intelligent and precise assessment of TCM efficacy.

Objective To investigate the epidemiological characteristics and changing trend of typhus in Shaanxi Province from 2005 to 2023 to provide a scientific basis for its prevention and control. Methods Excel 2007, SPSS 25.0, Joinpoint 4.9.1.0, and Geoda 1.6 were used for data collection and statistical analysis. Super Map was used for data visualization to describe the changing characteristics of the disease. Results A total of 394 typhus cases were reported in Shaanxi Province from 2005 to 2023. The average annual incidence of typhus was 0.054/100 000, showing a dynamic fluctuation trend(AAPC=-3.3, t=-0.3, P>0.05). The cases were mainly concentrated in Baoji, Hanzhong and Xi′an, accounting for 78.68%. The incidence peak was from May to October, accounting for 64.21% of annual incidence. The epidemic season was from May to October and December. The incidence of the disease was concentrated in the 40-69 age group, accounting for 58.88%, and the sex was 1.07:1. The main occupation was farmers, accounting for 72.08%. The median time from onset to diagnosis was 7 days. Global spatial autocorrelation analysis showed that there were significant spatial autocorrelations in 11 years from 2005 to 2023(P<0.05). Local spatial autocorrelation analysis detected a total of 43“high-high”clustering areas, mainly concentrated in Baoji City. Conclusions The overall incidence of typhus in Shaanxi Province showed a dynamic fluctuation trend, with notable seasonal and regional aggregation. The incidence of typhus was higher in middle-aged and elderly people in rural areas. Surveillance should be strengthened in typhus endemic areas in summer and autumn, and health education should be conducted for key population to form good health habits and reduce the incidence of typhus.

Objective:To investigate immunotherapy effects and mechanism of BCG and recombinant BCG(rBCG)with c-di-AMP as adjuvant on melanoma in mice model.Methods:Melanoma mice model was established by B16F10 cell subcutaneous injec-tion in groin,and treated with 1×106 CFU of BCG and rBCG by adjacent injection of subcutaneous tumor for 3 times,respectively.Survival of melanotic mice,tumor growth and metastasis were observed.Tumor tissues of mice were isolated to prepare cell suspen-sion,and proportion of immune cells were detected by flow cytometry.Transcriptional levels of immune-related genes in tumor tissues were detected by qRT-PCR.Results:Both BCG and rBCG immunotherapy could significantly inhibit growth in melanoma mice and prolong survival time of mice.rBCG showed better inhibition on metastasis than BCG.Both strains significantly reduced proportion of M2-type macrophages and myeloid-derived suppressor cell associated with tumor growth and metastasis.Both two strains promoted infiltration of lymphocytes in tumor tissues,and rBCG significantly increased proportion of B cells in tumor.BCG immunotherapy upregulated transcription levels of metastasis-related cytokines,while rBCG therapy had no effects on transcriptions of these genes.Conclusion:Both BCG and rBCG have immunotherapeutic effects on melanotic mice,and rBCG with c-di-AMP as adjuvant shows better inhibition on tumor metastasis than BCG,which mechanism was related to regulation of immune response in tumor tissues.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.