Objective:To explore the genetic diversity of Mycobacterium tuberculosis (MTB) in different types of tuberculosis and its association with clinical features, providing evidence for precise diagnosis and treatment of tuberculosis. Methods:This cross-sectional study included 103 cases of tuberculosis (38 with simple pulmonary tuberculosis, 43 with tuberculous pleurisy, and 22 with pulmonary combined with extrapulmonary tuberculosis) from Shenzhen Third People′s Hospital from 2015 to 2018. Paired bacterial strains from lung and pleural effusion/extrapulmonary sites were collected. Whole-genome sequencing (WGS) was used for drug resistance prediction, and genetic diversity (π value) was calculated as well as differential genes screening. Statistical analysis included paired t-tests and χ2 tests to compare clinical, bacteriological and genetic diversity features among groups.Results:The simple pulmonary tuberculosis group exhibited significantly higher rates of retreatment (71.7%, 27/38), cavitation (70.4%, 19/27), and multidrug-resistant or rifampicin-resistant (MDR/RR) (60.5%, 23/38) compared to the tuberculous pleurisy group (retreatment 11.9%, 5/42; cavitation 11.9%, 5/42; MDR/RR 16.3%, 7/43) and extrapulmonary tuberculosis group (retreatment 9.1%, 2/22; cavitation 18.2%, 4/22; MDR/RR 13.6%, 3/22) ( P<0.05). The overall π values of the MTB strain genomes in lung [(5.94±3.93)×10 ?5], pleural effusion[(6.22±3.51)×10 ?5], and extrapulmonary tissues [(5.83±3.54)×10 ?5] showed no significant differences ( H=0.10, P=0.94). Differential gene diversity analysis revealed that π value alternating genes related to respiration and intermediate metabolism were prominently high [tuberculous pleurisy 32.4% (11/34) and extrapulmonary tuberculosis groups 31.4% (32/102)], while cell wall-associated genes dominated in the simple pulmonary tuberculosis group (42.9%, 6/14). Drug resistance profiles and mutation spectra were identical across isolates from different sites within the same patient. Conclusion:WGS revealed the MTB diversity among different types of tuberculosis. Difference between pulmonary and extrapulmonary environments may impel the adaptive alternations of the bacterial strains to maintain survival with higher overall genome stability. Drug resistance testing of lung-derived isolates may provide references on extrapulmonary tuberculosis treatment.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To explore the effect of accelerated intermittent theta burst stimulation(aiTBS)on post-stroke depression(PSD).Methods From July,2021 to July,2023,48 PSD patients in Beijing Bo'ai Hospital were randomly assigned to control group(n=16),high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)group(n=16)and aiTBS group(n=16).aiTBS group received left-sided aiTBS treatment at dorsolateral prefrontal cortex(DLPFC),HF-rTMS group received left-sided 10 Hz rTMS treatment at DLPFC,and the control group received left-sided sham stimulation treatment,for three weeks.They were evaluated with the Hamilton Depression Rating Scale(HAMD),Hamilton Anxiety Rating Scale(HAMA)and Beck Depression Inventory(BDI)before and after treat-ment,and one month of follow-up.Results One case dropped down in each group.The inter-group effect,intra-group effect and interaction effect of HAMD,HAMA and BDI scores were all significant(F>3.235,P<0.05).The post-hoc test results showed that the scores of HAMD,HMMA and BDI were lower in HF-rTMS group and aiTBS group than in the control group(P<0.05),and no significant difference was found between HF-rTMS group and aiTBS group(P>0.05).There was significant difference in the effective rate of depression improvement among three groups(χ2=7.834,P=0.019),the effective rate was higher in aiTBS group than in the control group(P<0.017),and no significant dif-ference was found between HF-rTMS group and aiTBS group(P>0.017).Conclusion aiTBS can improve the depression and anxiety symptoms of patients with PSD,with shorter treatment time,compared with HF-rTMS.

Objective:To explore the current implementation status and challenges of family doctor contract services (FDCS) from the perspective of contracted residents.Methods:This qualitative study used purposive sampling to select contracted residents from 11 primary healthcare institutions across five cities in China. Semi-structured interviews were conducted from March to December 2024, covering topics such as awareness of contracting, service experience, health needs, service continuity, and policy recommendations. Thematic framework analysis was applied to organize, code, and summarize the data.Results:A total of 25 contracted residents were interviewed (6 men, 19 women; 11 from central urban areas, 14 from suburban or rural towns; 8 with chronic diseases). Three main themes and ten sub-themes emerged: Theme Ⅰ: Pathways to improved service accessibility (optimized chronic disease management, more efficient referrals, and improved health education). Theme Ⅱ: Structural misalignment between supply and demand (limited specialty services despite patient needs, insufficient coverage and public awareness of home-based medical care, imbalanced human resources, and service disruption due to clinician turnover). Theme Ⅲ: Challenges in service awareness and communication mechanisms (information asymmetry and public misperception regarding FDCS, perverse incentives in administrative performance evaluation, and communication barriers in building patient-doctor trust).Conclusions:While FDCS has shown progress in chronic disease management, referral coordination, and health education, structural supply-demand gaps and communication challenges continue to hinder service quality. Improvements in resource allocation and service models are needed to support high-quality development.

Objective:To explore the current status of perceived vulnerability and its influencing factors among parents of children with type 1 diabetes mellitus (T1DM) .Methods:A convenience sampling method was used to select 220 parents of children with T1DM from the diabetes care and consultation outpatient clinic at Beijing Children's Hospital, Capital Medical University, from June to November 2023. The parents were surveyed using a general information questionnaire, the Parental Perceived Vulnerability Scale, the Family Care Index, and the Parental Illness Uncertainty Scale.Results:A total of 220 questionnaires were distributed, with 192 valid responses. The total score on the Parental Perceived Vulnerability Scale was (13.91±5.39), the total score on the Family Care Index was (5.39±2.73), and the total score on the Parental Illness Uncertainty Scale was (75.36±17.34). Multiple linear regression analysis showed that whether the child was an only child, family monthly income per capita, parents' religious beliefs, family care level, and illness uncertainty were significant influencing factors for perceived vulnerability ( P<0.05), explaining 36.5% of the variance. Conclusions:Healthcare professionals should pay more attention to parents who have only children, have lower family income, and do not have religious beliefs. Interventions aimed at improving family care levels and reducing illness uncertainty may help decrease the perceived vulnerability among parents of children with T1DM.

Objective:To investigate the clinical efficacy of application of Shexiang Tongxin Dropping Pills in patients with coronary heart disease and heart failure due to qi deficiency and blood stasis syndrome. Methods:A prospective study was conducted with 66 patients with coronary heart disease and heart failure, all diagnosed with qi deficiency and blood stasis syndrome, who were admitted to the Department of Internal Medicine at Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine from January 2023 to March 2024. The patients were divided into a control group and an observation group, each consisting of 33 patients, based on the odd or even number of their hospital admission numbers. The control group received conventional treatment with Western medicine, while the observation group received Shexiang Tongxin Dropping Pills in addition to the treatment given to the control group. The clinical effects between the two groups were compared, and changes in heart function, traditional Chinese medicine syndrome scores, and serum biomarkers before and after treatment were collected and compared. Results:The overall response rate in the observation group was 96.97% (32/33), which was significantly higher than that of the control group at 75.76% (25/33) ( χ2 = 4.63, P < 0.05). After treatment, the traditional Chinese medicine syndrome scores in the observation group were significantly lower than those in the control group ( t = 9.03, 6.36, 5.55, 12.34, all P < 0.001). The left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular end-diastolic volume in the observation group were all lower than those in the control group ( t = 3.66, 7.69, 6.53, all P < 0.05). The 6-minute walk test results and left ventricular ejection fraction in the observation group were significantly higher than those in the control group ( t = -5.06, -18.10, both P < 0.001). The levels of N-terminal pro B-type natriuretic peptide, high-sensitivity C-reactive protein, and serum homocysteine in the observation group were all lower than those in the control group ( t = 18.09, 18.61, 10.87, all P < 0.001). Conclusions:Combining Shexiang Tongxin Dropping Pills with conventional treatment for patients with coronary heart disease and heart failure due to qi deficiency and blood stasis syndrome can effectively enhance clinical outcomes, alleviate symptoms, improve heart function, and reduce inflammatory responses.

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders are the 3 major chronic diseases threatening human health, which are closely related and often coexist, significantly increasing the difficulty of disease management. In response, the American Heart Association (AHA) proposed a novel disease concept of “cardiovascular-kidney-metabolic (CKM) syndrome” in October 2023, which has triggered widespread concern about the co-treatment of heart and kidney diseases and the prevention and treatment of metabolic disorders around the world. This review posits that effectively managing CKM syndrome requires a new and multidimensional paradigm for diagnosis and risk prediction that integrates biological insights, advanced technology and social determinants of health (SDoH). We argue that the core pathological driver is a “metabolic toxic environment”, fueled by adipose tissue dysfunction and characterized by a vicious cycle of systemic inflammation and oxidative stress, which forms a common pathway to multi-organ injury. The at-risk population is defined not only by biological characteristics but also significantly impacted by adverse SDoH, which can elevate the risk of advanced CKM by a factor of 1.18 to 3.50, underscoring the critical need for equity in screening and care strategies. This review systematically charts the progression of diagnostic technologies. In diagnostics, we highlight a crucial shift from single-marker assessments to comprehensive multi-marker panels. The synergistic application of traditional biomarkers like NT-proBNP (reflecting cardiac stress) and UACR (indicating kidney damage) with emerging indicators such as systemic immune-inflammation index (SII) and Klotho protein facilitates a holistic evaluation of multi-organ health. Furthermore, this paper explores the pivotal role of non-invasive monitoring technologies in detecting subclinical disease. Techniques like multi-wavelength photoplethysmography (PPG) and impedance cardiography (ICG) provide a real-time window into microcirculatory and hemodynamic status, enabling the identification of early, often asymptomatic, functional abnormalities that precede overt organ failure. In imaging, progress is marked by a move towards precise, quantitative evaluation, exemplified by artificial intelligence-powered quantitative computed tomography (AI-QCT). By integrating AI-QCT with clinical risk factors, the predictive accuracy for cardiovascular events within 6 months significantly improves, with the area under the curve (AUC) increasing from 0.637 to 0.688, demonstrating its potential for reclassifying risk in CKM stage 3. In the domain of risk prediction, we trace the evolution from traditional statistical tools to next-generation models. The new PREVENT equation represents a major advancement by incorporating key kidney function markers (eGFR, UACR), which can enhance the detection rate of CKD in primary care by 20%-30%. However, we contend that the future lies in dynamic, machine learning-based models. Algorithms such as XGBoost have achieved an AUC of 0.82 for predicting 365-day cardiovascular events, while deep learning models like KFDeep have demonstrated exceptional performance in predicting kidney failure risk with an AUC of 0.946. Unlike static calculators, these AI-driven tools can process complex, multimodal data and continuously update risk profiles, paving the way for truly personalized and proactive medicine. In conclusion, this review advocates for a paradigm shift toward a holistic and technologically advanced framework for CKM management. Future efforts must focus on the deep integration of multimodal data, the development of novel AI-driven biomarkers, the implementation of refined SDoH-informed interventions, and the promotion of interdisciplinary collaboration to construct an efficient, equitable, and effective system for CKM screening and intervention.