Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

ObjectiveTo analyze the clinicopathological features of patients with comorbidities of chronic hepatitis B （CHB） and steatotic liver disease （SLD）， to investigate the impact of hyperglycemia on the risk of liver fibrosis and end-stage liver diseases （ESLD）， and to provide a basis for the clinical management of such population. MethodsA total of 668 adult patients with CHB-SLD confirmed by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2011 to December 2019 were enrolled， and a retrospective cohort was established with the time of liver biopsy as the baseline and the onset of ESLD as the endpoint. All patients were followed up to March 31， 2024. Propensity score matching （PSM） was performed at a ratio of 1∶4 to balance baseline features between groups， resulting in 82 patients in the hyperglycemia group and 281 in the non-hyperglycemia group. The two groups were compared in terms of metabolic profiles， laboratory markers， and histopathological features. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for advanced fibrosis （AF）， and the Kaplan-Meier survival analysis and the Cox proportional-hazards regression model were used to determine the influencing factors for the development of ESLD. ResultsCompared with the non-hyperglycemia group， the hyperglycemia group had a significantly higher number of factors for metabolic disorders， a significantly higher degree of hepatic steatosis， and a significantly higher detection rate of AF （all P<0.05）. The multivariate Logistic regression analysis showed that hyperglycemia was a risk factor for AF （odds ratio = 1.753， 95% confidence interval ［CI］： 1.017　—　3.023， P=0.043）. The survival analysis showed that hyperglycemia increased the risk of ESLD （χ²=4.340， P=0.037）. The multivariate Cox regression analysis confirmed that hyperglycemia was a significant metabolic risk factor for ESLD in patients with AF （adjusted hazard ratio=3.208， 95%CI： 1.201　—　8.568， P=0.020）. ConclusionHyperglycemia can increase the risk of AF and ESLD in CHB-SLD patients. Clinical monitoring and active management should be strengthened for patients who have already developed AF and hyperglycemia.

Objective: To investigate the status and influencing factors of latent tuberculosis infection (LTBI) among enterprise employees in Wenzhou City, Zhejiang Province, so as to provide evidence for optimizing tuberculosis prevention and control strategies in enterprises. Methods: From August 2024 to September 2025, a convenience sampling method was used to select employees from 26 enterprises in Wenzhou City as the study participants. Demographic information, enterprise scale, and industry type were collected by reviewing enterprise employee management files. Interferon-gamma release assays were used to detect Mycobacterium tuberculosis infection and screen for LTBI. Factors affecting LTBI among enterprise employees were identified using a multivariable logistic regression model. Results: A total of 6 476 participants were surveyed, including 3 674 males (56.73%) and 2 802 females (43.27%). The median age was 37.00 (interquartile range, 20.00) years. A total of 994 cases of LTBI were detected, with a detection rate of 15.35%. Multivariable logistic regression analysis showed that male (OR=1.397, 95%CI: 1.211-1.612), age ≥45 years (45-<60 years, OR=1.919, 95%CI: 1.649-2.234; ≥60 years, OR=4.425, 95%CI: 3.170-6.177), household registration outside Zhejiang Province (OR=1.928, 95%CI: 1.577-2.357), employment in small or medium-sized enterprises (medium-sized, OR=1.663, 95%CI: 1.392-1.988; small-sized, OR=1.665, 95%CI: 1.358-2.040), and working in the manufacturing industry (OR=1.799, 95%CI: 1.147-2.822) were associated with a higher risk of LTBI among enterprise employees. Conclusions The detection rate of LTBI among enterprise employees in Wenzhou City was relatively low. Male employees, those aged ≥45 years, those with household registration outside Zhejiang Province, those working in small or medium-sized enterprises, and those in the manufacturing industry were identified as high-risk populations for LTBI.

Abstract Latent tuberculosis infection (LTBI) refers to a specific immune state after Mycobacterium tuberculosis infection, affecting approximately one quarter of the global population and contributing to 85%-90% of active pulmonary tuberculosis cases. At present, the tuberculin skin test and interferon-gamma release assay are the main detection methods for LTBI, yet both have certain limitations, and there is no unified standard for LTBI diagnosis. With the rapid advancement of molecular biotechnology and artificial intelligence, technologies such as RNA sequencing, proteomics and machine learning have opened up new perspectives for LTBI diagnosis. RNA sequencing and proteomics can reveal the complexity and diversity of gene and protein expression profiles under LTBI status, and improve diagnostic accuracy by identifying specific biomarkers. Machine learning can establish diagnostic models through algorithm training, so as to provide rapid diagnosis and personalized decision support for LTBI screening. This paper reviews the current diagnostic situation, novel detection techniques of LTBI and the application of machine learning in auxiliary diagnosis of LTBI, aiming to provide theoretical references for the diagnosis of LTBI.

Objective: To investigate the status of latent tuberculosis infection (LTBI) and tuberculosis preventive treatment (TPT) among HIV/AIDS cases in Wenzhou City, Zhejiang Province, and to analyze the influencing factors of LTBI, so as to provide the evidence for optimizing active tuberculosis screening and early intervention strategies. Methods: Study subjects were HIV/AIDS cases who received antiretroviral therapy and CD4+T lymphocyte count testing at designated HIV treatment hospitals from October 2024 to August 2025. The interferon-gamma release assay was used for LTBI screening. Data on HIV/AIDS cases, including gender, age, and other variables, were collected through the Surveillance System of China Information System for Disease Control and Prevention. A multivariable logistic regression model was used to analyze the influencing factors for LTBI among HIV/AIDS cases. Results: A total of 3 719 HIV/AIDS cases were included, including 2 983 males (80.21%) and 736 females (19.79%). The study population was predominantly aged 40-<65 years, with 1 948 individuals accounting for 52.38%. LTBI was detected in 399 cases, with a detection rate of 10.73%. Among LTBI cases, 103 received TPT, representing a TPT rate of 25.81%. Multivariable logistic regression analysis showed that HIV/AIDS cases who were male (OR=1.796, 95%CI: 1.326-2.431), aged ≥40 years (40-<65 years, OR=1.895, 95%CI: 1.424-2.523; ≥65 years, OR=2.365, 95%CI: 1.575-3.551), non-Wenzhou household registration (OR=1.462, 95%CI: 1.150-1.857), with education level below junior college (primary school and below, OR=1.578, 95%CI: 1.023-2.394; junior high school, OR=1.725, 95%CI: 1.161-2.562; high school/technical secondary school, OR=1.639, 95%CI: 1.066-2.518), CD4+T lymphocyte count ≥500 cells/μL (OR=2.642, 95%CI: 1.420-4.915), and at the HIV infection stage (OR=1.322, 95%CI: 1.022-1.709) had a higher risk of LTBI. Conclusions The detection rate of LTBI and the TPT rate among LTBI cases are relatively low among HIV/AIDS cases in Wenzhou City. Gender, age, household registration, education level, CD4+T lymphocyte count, and disease stage are influencing factors for LTBI in HIV/AIDS cases.

Abstract On January 22, 2024, Yueqing People's Hospital in Zhejiang Province reported a confirmed PTB case (index case) from an enterprise. Yueqing Center for Disease Control and Prevention conducted an on-site epidemiological investigation in accordance with the China Tuberculosis Prevention and Control Technical Guidelines and the Zhejiang Province Tuberculosis Cluster Infection Response Technical Plan (2022 Edition). Screening for latent tuberculosis infection (LTBI) and case confirmation were performed according to the Diagnosis for Pulmonary Tuberculosis. Two rounds of screening were carried out in March and April 2024, covering 341 individuals. A total of 122 LTBI cases were detected, with an overall detection rate of 35.78%; 23 PTB cases were identified, with an attack rate of 6.74%. The cases were predominantly male and registered residents of Liangshan Yi Autonomous Prefecture, Sichuan Province, both accounting for 65.22%. Cases were concentrated in workshops on the 2nd and 3rd floors of Zone C at the workplace, with the enterprise dormitory as the main residence. Secondary cases were diagnosed mainly between April and May 2024, and all had a clear history of exposure within the enterprise. Global spatial autocorrelation analysis showed spatial clustering of case distribution, with local hotspots identified as the inspection area on the 2nd floor and Line 1 on the 3rd floor of Zone C. There were 11 confirmed PTB cases and 12 clinically diagnosed cases. Four strains were isolated, and whole-genome sequencing analysis revealed that they belonged to Lineage 2 and Lineage 4, with pairwise single nucleotide polymorphism differences all exceeding 12. Based on the epidemiological investigation and laboratory testing, the PTB outbreak in the enterprise was determined to be a cluster outbreak resulting from multi-source importation and close contact transmission of Mycobacterium tuberculosis within the same workshop, dormitory, and household registration group, possibly associated with a concentration of migrant workers, poor ventilation in the workplace, and the lack of pre-employment PTB screening.

Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

ObjectiveTo investigate the expression features of HBsAg and HBcAg in liver tissue and their correlation with HBV serum markers in children with chronic hepatitis B （CHB）. MethodsA total of 257 patients who were consecutively admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to December 2023 and underwent liver biopsy to achieve a confirmed diagnosis of CHB were enrolled in this study. The NIS-Elements system was used to capture the immunohistochemical images of HBsAg and HBcAg in liver tissues， and Image J software was used for quantitative analysis. The one-sample chi-square test was used for within-group comparison of continuous data， and the Pearson/Spearman/Kendall’s Tau-b correlation analysis was used to investigate the correlation between viral antigen expression and serological markers. ResultsAmong the 257 CHB patients， there were 162 children （76 children aged<5 years and 86 children aged 5 — 18 years） and 95 adults. There were significant differences in the expression pattern， area， and intensity of HBsAg and the area and intensity of HBcAg in liver tissue between different age groups and between the children with different HBeAg statuses （all P<0.05）. In the children aged<5 years， HBsAg staining area was significantly negatively correlated with anti-HBs and HBeAg （both P<0.05）and was significantly positively correlated with ALT and AST （both P<0.05）， and HBsAg staining intensity was significantly positively correlated with qHBsAg （P<0.05） and was significantly negatively correlated with anti-HBs （P<0.05）. In the children group， HBsAg staining area was negatively correlated with anti-HBs and HBeAg （both P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg （P<0.05） and was negatively correlated with anti-HBs （P<0.05）. In the adult group， HBsAg staining area was positively correlated with ALT， AST， and liver inflammatory activity （all P<0.05）， and HBsAg staining intensity was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05） and was negatively correlated with liver inflammatory activity and fibrosis degree （both P<0.05）. In the children aged<5 years， HBcAg staining area was positively correlated with qHBsAg and HBV DNA （both P<0.05）， and HBcAg staining intensity was significantly positively correlated with HBV DNA （P<0.001）. In the children aged 5 — 18 years， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）. In the children group， HBcAg staining area was positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.05）， and HBcAg staining intensity was positively correlated with qHBsAg and HBV DNA （both P<0.05）. In the adult group， the area and intensity of HBcAg staining were positively correlated with qHBsAg， HBeAg， and HBV DNA （all P<0.001）， and HBcAg staining area was positively correlated with the serum level of ALT （P=0.043）. ConclusionThe expression levels of HBsAg and HBcAg in liver tissue of children with CHB are significantly correlated with serological markers， and in clinical practice， HBsAg and HBcAg combined with serological markers can help to assess the condition of the liver， determine the immune stage， and provide evidence-based guidance for treatment timing.