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.

Background With China's socioeconomic development, significant lifestyle changes have occurred among occupational groups, leading to alterations in cardiovascular metabolic risk factors. However, few studies have examined the secular trends of these risk factors in China's working population. Objective To analyze the trends in cardiovascular metabolic risk factors among the occupational population in nine provinces of China from 2009 to 2018, and to explore the associations between different occupational types and these risk factors, along with their clustering patterns, thereby providing evidence for targeted interventions. Methods This study utilized data from the China Health and Nutrition Survey (CHNS) in 2009, 2015, and 2018. The dataset covered 13274 employed individuals aged 18-59 years. Only participants with complete blood test results and physical measurement data were included in the final analysis. The average annual percentage change (AAPC) in the positive rates of risk factors was calculated using Joinpoint regression to analyze temporal trends. Multinomial logistic regression and binary logistic regression models were employed to examine the cross-sectional associations between occupational types (categorized as white-collar workers, agricultural workers, blue-collar workers, service workers, and others) and nine cardiovascular metabolic risk factors and their clustering (defined as having ≥2 risk factors) in 2018. Results A total of 8451 participants were included. From 2009 to 2018, significant increasing trends (AAPC>0, P<0.05) were observed for overweight, obesity, central obesity, borderline elevated triglycerides (TG), borderline elevated to elevated total cholesterol (TC), borderline elevated low-density lipoprotein cholesterol (LDL-C), elevated blood pressure and hypertension, diabetes. The most rapid increases were found for obesity (AAPC=6.07%, 95%CI: 3.42%, 8.88%), hypertension (AAPC=4.10%, 95%CI: 0.62%, 7.77%), and central obesity (AAPC=3.27%, 95%CI: 1.24%, 5.36%). The clustering rate of risk factors increased from 62.3% in 2009 to 73.2% in 2018 (AAPC=1.87%, 95%CI: 1.02%, 2.73%). The cross-sectional analysis in 2018, after adjusting for confounders, showed that compared with white-collar workers, blue-collar workers had a significantly lower risk of overweight (OR=0.67, 95%CI: 0.48, 0.95), central obesity (OR=0.65, 95%CI: 0.45, 0.92), and borderline high TG (OR=0.54, 95%CI: 0.35, 0.82). In contrast, agricultural workers had a higher risk of hypertension (OR=1.76, 95%CI: 1.14, 2.72). Conclusion Between 2009 and 2015, the burden of most cardiometabolic risk factors increases significantly among the Chinese occupational population, with the rate of increase slowing by 2018. Risks vary across occupational types, among which blue- collar workers report lower target outcomes. Targeted interventions focusing on the rapidly increasing risk factors and high-risk occupational groups are recommended.

Background With rising obesity rates and earlier hypertension onset among occupational populations, there is an urgent need to elucidate the long-term cardiovascular impacts of dynamic body weight patterns. Current evidence lacks trajectory modeling studies examining occupation-specific prevention strategies. Objective To investigate the association between long-term body mass index (BMI) trajectories and incident hypertension risk in Chinese working adults, and to examine occupation-specific heterogeneity in this relationship. Methods A dynamic sub-cohort of 4 413 occupational participants was constructed from ten survey waves (1991–2018) of the China Health and Nutrition Survey (CHNS). Eligible individuals had valid key BMI records at three or more independent follow-ups before the outcome event; the individual baseline was set as the year of their first participation in the survey. Group-based trajectory modeling (GBTM) was used to identify BMI change patterns. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence interval (CI) for hypertension incidence across trajectory groups, with stratified analysis by occupational categories. Results Among 4413 occupational participants, 1441 incident hypertension cases were reported during the follow-up window. Three long-term BMI trajectories were identified: low-stable, moderate-slowly rising, and high-rising. In Model 3 with all selected confounders adjusted, compared with the low-stable group, the moderate-slowly rising group showed a significantly higher risk of incident hypertension (HR=1.28, 95%CI: 1.12, 1.45; P < 0.001), as did the high-increasing group (HR=1.80, 95%CI: 1.45, 2.23; P < 0.001). The stratified analyses revealed occupational differences in the association. Among agricultural workers, the moderate-slowly rising group (HR=1.35, 95%CI: 1.15, 1.57) and the high-rising group (HR=2.00, 95%CI: 1.50, 2.66) both exhibited significantly increased risks of hypertension (P<0.001). Conversely, among white-collar workers, an increased risk of hypertension was observed only in the high-rising group (HR=1.97, 95%CI: 1.23, 3.17; P<0.05). Conclusion Rapid BMI escalation constitutes a significant risk factor for incident hypertension in occupational populations. Targeted long-term weight monitoring and tailored interventions are recommended for high-risk occupations.

AIM:To analyze the influencing factors of postoperative malignant glaucoma(MG)in patients with primary angle-closure glaucoma(PACG)using logistic regression and decision tree models.METHODS:A retrospective study was conducted on PACG patients who underwent surgery at Eye Hospital of Handan City from March 2020 to March 2025. Patients were divided into two groups: the MG group, who developed MG within 6 mo postoperatively, and the non-MG group. Data were collected from the electronic medical record system. Univariate analysis was performed, followed by multivariate logistic regression to identify independent risk factors. A classification and regression tree model was constructed to visualize the hierarchical relationships among predictors. The predictive performance of the two models was evaluated and compared using receiver operating characteristic(ROC)curve analysis.RESULTS:Totally 182 cases(182 eyes)with PACG were enrolled in this study, including 91 cases(91 eyes)in the MG group and 91 cases(91 eyes)in the non-MG group. In the MG group, there were 53 males and 38 females; 69 cases were aged ≥60 y and 22 cases were aged <60 y. In the non-MG group, there were 47 males and 44 females; 33 cases were aged ≥60 y and 58 cases were aged <60 y. The non-MG group comprised 91 patients, including 47 males and 44 females. Among them, 33 cases were aged ≥60 y, and 58 cases were aged<60 y. The MG group had significantly higher proportions of patients aged ≥60 y, diabetes, moderate-stage PACG, persistent high intraocular pressure(IOP), complete anterior chamber angle closure, lens thickness <4.5 mm, axial length <22 mm, and severe postoperative inflammation compared to the non-MG group(all P<0.01). Multivariate Logistic regression identified the following as independent influencing factors for postoperative MG: age [OR (95%CI)=2.136(1.401-3.255)], PACG stage [OR (95%CI)=2.996(2.044-4.391)], IOP [OR (95%CI)=3.527(1.604-7.755)],anterior chamber angle [OR (95%CI)=4.826(2.498-9.324)], axial length [OR (95%CI)=5.125(1.265-20.771)], and severe postoperative inflammation [OR (95%CI)=2.338(1.478-3.699)](all P<0.05). The decision tree model selected six explanatory variables: age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. Axial length was the primary splitting factor at the root node. The areas under the ROC curve(AUC)for the logistic regression and decision tree models were 0.913(0.863-0.950)and 0.921(0.872-0.956), respectively, with no significant difference between them(Z=0.561, P=0.575).CONCLUSION:Both the logistic regression and decision tree models effectively identify key influencing factors for postoperative MG in PACG patients, including age, PACG stage, IOP, anterior chamber angle status, axial length, and severe postoperative inflammation. The decision tree model offers an intuitive, visual representation of risk stratification, facilitating clinical decision-making. Both models are applicable for clinical risk assessment.

ObjectiveTo investigate the status and influencing factors of latent tuberculosis infection (LTBI) among close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, and to provide scientific evidence for the development of tuberculosis infection testing and preventive intervention strategies for close contacts of bacteriologically positive patients. MethodsFrom October 2022 to October 2023, patients with bacteriological confirmed pulmonary tuberculosis registered in Jing’an District, Shanghai, and their close contacts were enrolled as the research subjects. The close contacts were screened for tuberculosis infection using the interferon-γ release assay (IGRA). The chi-square test and binary logistic regression model were used to analyze factors influencing LTBI. ResultsA total of 112 close contacts were included, of whom 30 (26.79%) were male and 82 (73.21%) were female. The age ranged from 1 to 86 years, with a median (25th, 75th percentiles) of 47.50 (32.25, 61.00) years. The infection rate of LTBI was 21.43% (24/112), and the incidence of active pulmonary tuberculosis was 2.68% (3/112). Univariate analyses showed that a positive sputum smear of the index case, being a direct relative of the index case, co-living, and not wearing a mask were significantly associated with LTBI (all P<0.05). Multivariate logistic regression analyses showed that the risk of latent infection in close contacts of the index case with a positive sputum smear was 6.50 times higher than in those with a negative sputum smear (95%CI: 1.82‒23.25, P=0.004). ConclusionThe infection rate of LTBI in close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, is relatively high, and close contacts of sputum smear-positive patients face an even higher risk of infection. Therefore, tuberculosis infection screening and follow-up management should be strengthened for this population.

Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with neuromuscular electrical stimulation （NMES） in the treatment of dysphagia in Wilson disease （WD） with combined phlegm and stasis. MethodsA total of 80 WD patients with dysphagia due to combined phlegm and stasis treated in the Department of Encephalopathy， the First Affiliated Hospital of Anhui University of Chinese Medicine were randomized into a control group and an observation group， with 40 patients in each group. In addition， 40 healthy volunteers were recruited as the normal group. The control group was treated with basic copper drainage combined with NMES. The observation group was treated with Gandouling Decoction on the basis of the therapy in the control group. Each course of treatment lasted for 8 days， and the patients were treated for a total of 4 courses. All subjects underwent video fluoroscopic swallowing study （VFSS） before and after treatment. During the examination， contrast agents with 4 different characters were used for the swallowing action， and the passing time was recorded. The TCM syndrome score， water swallow test score， standard swallowing assessment （SSA） score， and 24-h urinary copper level before and after treatment were analyzed. ResultsWhen performing VFSS， the passing time of contrast agents of different characters in the oral stage was longer in the WD group than in the normal group （P<0.01）， while it had no significant difference in the pharyngeal stage. After treatment， the passing time in the oral stage shortened in the control and observation groups （P<0.01）， and the observation group outperformed the control group （P<0.01）. After treatment， both the control and observation groups showed declines in TCM syndrome score and SSA score （P<0.01） and an increase in water swallow test score （P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.01）. In addition， the treatment in the control and observation groups elevated the 24-h urinary copper level （P<0.01）， and the elevation in the observation group was more obvious than that in the control group （P<0.01）. Neither group showed obvious adverse reaction. ConclusionGandouling decoction combined with NMES can significantly ameliorate dysphagia in WD patients with the syndrome of combined phlegm and stasis regarding the TCM syndrome score， water swallow test score， and SSA score， demonstrating definite clinical efficacy and high safety.

OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry (LC-MS) remains a formidable challenge. Herein, a metabolic reaction-based molecular networking (MRMN) strategy is introduced, which enables the "one-pot" discovery of prototype drugs and their metabolites. MRMN constructs networks by matching metabolic reactions and evaluating MS² spectral similarity, incorporating innovations and improvements in feature degradation of MS² spectra, exclusion of endogenous interference, and recognition of redundant nodes. A minimum 75% correlation between structural similarity and MS² similarity of neighboring metabolites was ensured, mitigating false negatives due to spectral feature degradation. At least 79% of nodes, 49% of edges, and 97% of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking (GNPS) platform. Furthermore, an approach of redundant ions identification was refined, achieving a 10%-40% recognition rate across different samples. The effectiveness of MRMN was validated through a single compound, plant extract, and mixtures of multiple plant extracts. Notably, MRMN is freely accessible online at https://yaolab.network, broadening its applications.