1.Research progress on the mechanisms linking and intervention of adolescent depression and lipid metabolism disorders
Ruhui LI ; Jianfei ZENG ; Bing WANG ; Qin WANG ; Ying ZHANG
Sichuan Mental Health 2026;39(2):175-182
In recent years, the incidence of depression among adolescents has increased significantly, becoming a serious global public health problem. There is a close relationship between adolescent depression and lipid metabolism abnormalities. However, the mechanisms underlying this association have not been fully elucidated. This article provides a review of the mechanisms and interventions linking adolescent depression and lipid metabolism abnormalities, aiming to offer new ideas for interventions in adolescent depression. Using computerized searches of the China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, and Web of Science, studies on the mechanisms and interventions related to adolescent depression and lipid metabolism were collected, with the search period extending up to October 10, 2025. Two researchers independently conducted literature screening and extracted basic information from the included studies. A total of 12 original studies were included. The results indicate that adolescent depression is associated with certain lipid metabolites. Neurobiological factors, immune inflammation, oxidative stress, and gut microbiota imbalance play important roles in this association. In addition, lipid metabolites such as omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have a significant ameliorating effect on adolescent depression. [Funded by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (number, SZGSP013); Shenzhen Science and Technology Program (number, 20210617155253001)]
2.FAH promotes glioblastoma progression by activating the PI3K/AKT/mTOR signaling pathway
Shihao LI ; Bing ZHAO ; Tieniu YANG ; Jinliang YANG ; Yongliang ZHANG ; Zhongsen LI ; Shunli LI ; Ning CHEN ; Jianbiao WANG ; Jia LI ; Qingfang MA
Acta Universitatis Medicinalis Anhui 2026;61(4):662-676
ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase (FAH) in the progression of glioblastoma (GBM). MethodsDifferential expression analysis was performed on the TCGA-GBM, GSE4290, and GSE116520 datasets. Weighted gene co-expression network analysis (WGCNA) was used to identify key modules, and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments, and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets (P<0.05). WGCNA revealed that the turquoise module was most strongly associated with tumor purity, stromal score, immune score, and ESTIMATE score (P<0.001). Compared with normal tissues, three prognostic genes (CTSD, FAH, and THBD) were upregulated in GBM and correlated with immune infiltration (P<0.05). FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues, and its expression was significantly associated with age stratification and TP53 mutation (P<0.05). CCK-8 assay results showed that, compared with the shNC group, the proliferative activity of GBM cells in the shFAH group was reduced (P<0.001). Transwell migration and invasion assays demonstrated that, relative to the shNC group, the numbers of migrated and invaded cells in the shFAH group decreased (P<0.05). Western blot analysis revealed that the protein expression levels of PI3K, p-AKT, and p-mTOR in the shFAH group decreased compared with those in the shNC group (P<0.05). In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group (P<0.001). ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.
3.Secular trends in energy and macronutrient intake across different occupational groups in nine provinces of China, 1989–2018
Yu WU ; Jiguo ZHANG ; Liusen WANG ; Lixin HAO ; Chang QU ; Yumeng SONG ; Zhihong WANG ; Huijun WANG ; Bing ZHANG ; Hongru JIANG ; Gangqiang DING
Journal of Environmental and Occupational Medicine 2026;43(2):145-152
Background With China's socio-economic development, the dietary structure of Chinese residents has gradually shifted from a traditional Eastern pattern characterized by high carbohydrate intake to a relatively high-fat Western dietary model, alongside a growing burden of chronic diseases. However, dietary changes may vary across different occupational groups. Objective To analyze the long-term trends in dietary energy and three major macronutrient intake among various occupational groups aged 18-59 years in nine provinces of China from 1989 to 2018, providing a scientific basis for developing occupation-specific dietary intervention strategies. Methods Based on 11 waves of data (1989–2018) from the China Health and Nutrition Survey (CHNS),
4.Cardiometabolic risk factor trends across different occupational groups in nine provinces of China, 2009–2018
Yu WU ; Hongru JIANG ; Lixin HAO ; Liusen WANG ; Weiyi LI ; Shaoshunzi WANG ; Zijian WANG ; Zhihong WANG ; Huijun WANG ; Bing ZHANG ; Lili CHEN ; Gangqiang DING
Journal of Environmental and Occupational Medicine 2026;43(2):153-159
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
5.Change trend of compound obesity among different occupational groups in nine provinces of China from 1993 to 2018
Lixin HAO ; Yu WU ; Liusen WANG ; Lili CHEN ; Boya ZHAO ; Zhongting LU ; Zhihong WANG ; Bing ZHANG ; Hongru JIANG ; Huijun WANG
Journal of Environmental and Occupational Medicine 2026;43(2):160-167
Background The global prevalence of obesity is on the rise and is closely associated with various chronic non-communicable diseases such as cardiovascular diseases and diabetes. There is a relative lack of long-term dynamic studies on compound obesity among occupational populations. Objective To explore the changing trends of compound obesity among different occupational groups aged 18–59 years in nine provinces (autonomous regions, municipalities) of China from 1993 to 2018, and to provide a scientific basis for formulating targeted weight management strategies for occupational populations. Methods A total of
6.Association between changes in body mass index and hypertension among different occupational groups
Zhongting LU ; Lili CHEN ; Hongru JIANG ; Lixin HAO ; Liusen WANG ; Weiyi LI ; Yu WU ; Huijun WANG ; Bing ZHANG ; Jiguo ZHANG ; Zhihong WANG
Journal of Environmental and Occupational Medicine 2026;43(2):168-173
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
7.Preventive treatment of latent tuberculosis infections in schools clusters in Hefei during 2022-2024
GUO Ce, ZHANG Qiang, QIAN Bing, CHEN Shuangshuang, HE Yuqin, XU Rui, LI Zhen, ZHAO Cunxi, WU Jinju
Chinese Journal of School Health 2026;47(3):421-424
Objective:
To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools.
Methods:
Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test.
Results:
Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05).
Conclusions
In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.
8.Design, synthesis and biological evaluation of lactate dehydrogenase A inhibitors
Tiande BING ; Jiabao HU ; Xiaojin ZHANG
Journal of China Pharmaceutical University 2026;57(1):34-45
Human lactate dehydrogenase A (LDHA) is an NADH-dependent oxidoreductase that catalyzes the conversion of pyruvate to lactate, playing a crucial role in the aerobic glycolysis of tumor cells. Additionally, LDHA is responsible for catalyzing the conversion of glyoxylate to oxalate in the liver, excessive accumulation of which leads to hyperoxaluria. Representative LDHA inhibitors reported to date include GNE-140, NCATS-SM1441, and CHK-336. In this study, NCATS-SM1441 was used as the lead compound. Based on the analysis of its cocrystal binding mode with LDH, the key carboxythiazole and aromatic pharmacophores were retained, while the original substituted pyrazole linker was replaced with urea linker moieties to simplify the structure. As a result, nine urea derivatives were designed and synthesized. Subsequently, on the basis of structure-activity relationship and molecular docking studies, nine target triazole compounds were further designed. Ultimately, triazole compound 25 was found to exhibit the most potent LDHA inhibitory activity (IC50 = 1.59 μmol/L) in vitro. Molecular dynamics simulations were employed to analyze the interactions between compound 25 and key amino acid residues. Finally, the prediction of physicochemical properties and the evaluation of cell viability were performed for compound 25. The study provides an experimental basis for future development of novel LDHA inhibitors with improved drugability.
9.Research priorities on physical and mental comorbidity among children and adolescents in Zhejiang Province
Chinese Journal of School Health 2026;47(4):498-501
Objective:
To identify research priorities on physical and mental comorbidity among children and adolescents in Zhejiang Province, so as to provide a theoretical base for improving their physical and mental health.
Methods:
In May 2025, 77 experts in the fields of health and education from 11 cities in Zhejiang Province were selected by convenient sampling method to participate in the first round of expert consultation. In June, 2025, snowball sampling was used to expand to 194 experts for the second round of consultation, and it was convenient to select 21 students from primary schools to high schools in Zhejiang Province and 29 parents to empower the evaluation criteria. It applied the Child Health and Nutrition Research Initiative (CHNRI) method in a structured process, which encompassed the definition of the research field, generation of research ideas, scoring, and quantitative ranking of priorities. Research ideas were evaluated against 6 predefined criteria: effectiveness, safety, answerability, feasibility, sustainability, and scientific significance.
Results:
After 2 rounds of structured consultations, 81 research ideas on physical and mental comorbidity among children and adolescents were established and classified into 7 subthemes: epidemiological characteristics and influencing factors, optimization of primary service systems and policies, comprehensive intervention strategies for physical and mental comorbidity, biological mechanisms and clinical research, the impact of education and environment on physical and mental health, special populations and social support, and digital and technology driven disease prevention and intervention. The top 10 research priorities primarily centered on the subdomain of "epidemiological characteristics and influencing factors" (5 items). The top 3 research priorities were "the association between outdoor activity duration and the incidence of common diseases (including mental disorders) among children and adolescents" "the impact of outdoor activity duration on the physical and mental health of adolescents" "comprehensive intervention strategies for myopia, obesity, and their comorbidities among children and adolescents".
Conclusion
The framework of priority issues in the field of psychosomatic comorbidity of children and adolescents in Zhejiang Province based on CHNRI method provides a reference for optimizing the allocation of provincial research resources.
10.MCC950 Targeted Inhibition of TXNIP-NLRP3 Axis-mediated Podocyte Pyroptosis in Diabetic Nephropathy
Hong ZHENG ; Zhong-Cheng MO ; Hang LIU ; Xi-Zhang PAN ; Bing WEI
Progress in Biochemistry and Biophysics 2026;53(2):418-430
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.


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