In recent years, the rising prevalence of obesity and its associated metabolic syndromes has emerged as a critical global public health concern. Sustained weight loss exceeding 10% of total body weight has been shown to ameliorate obesity-related comorbidities, including type 2 diabetes mellitus, hypertension, and hepatic steatosis. Recently, the potential of brown adipose tissue (BAT) to improve metabolism has garnered significant attention. However, evidence regarding weight loss therapies that promote BAT activation remains limited in preclinical models and is even scarcer in clinical studies, partly due to the paucity of appropriate BAT assessment techniques. This review aims to explore the potential impact of various weight loss therapies on BAT, with the goal of providing novel insights and strategies for the treatment of obesity.

Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Occupational hazards pose a major public health challenge that seriously endangers the health of the working population. As a statutory key component of occupational health work, occupational health risk assessment urgently requires more attention. Currently, commonly used occupational health risk assessment methods exhibit notable deficiencies such as insufficient comprehensive assessment capabilities and limited applicability. The absence of assessment methods that accurately align with occupational health practices has constrained the depth and breadth of occupational health risk assessment in China, resulting in inadequate risk identification and significant deficiencies in social service provision, decision-making support, and health protection. Meanwhile, under the current assessment system, the occupational health big data obtained from risk assessments, occupational health examinations, biological monitoring, and other sources suffer from issues such as fragmented resources and low utilization rates. As a result, existing systems are unable to effectively support critical operational needs, including accurate risk early warning, timely risk response, and refined risk management. This study systematically reviewed the common occupational health risk assessment methods and the current status of occupational health risk assessment and big data applications in China, identified existing shortcomings, proposed a comprehensive risk assessment and risk prediction-early warning scheme based on the application of occupational health big data. The scheme is expected to provide theoretical foundations and methodological references for advancing comprehensive risk assessment of occupational health through big data analytics, and to enhance the level of occupational health management, thereby safeguarding worker health and promoting sustainable socioeconomic development.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

OBJECTIVE: To develop a user-friendly visualization application for the automatic annotation of Human Phenotype Ontology (HPO) terms based on large language models and retrieval-augmented generation (RAG) technology, and to validate its performance in an authoritative case dataset. METHODS: By integrating the domestic open-source large language model DeepSeek-V3 with RAG technology, an interactive web application was deployed on the Streamlit cloud platform. Using only the latest official HPO dataset as the data source, the lightweight sentence-embedding model BAAI/bge-small-en-v1.5 was employed to construct a FAISS vector index. During the online phase, a four-step closed-loop process is automatically completed: multilingual translation, phenotype phrase extraction, RAG candidate retrieval, term mapping, and official database validation. 121 English case reports publicly released by BMJ Case Reports and Oxford Medical Case Reports (with a gold-standard HPO set of 1 794 terms) were selected for application validation. Precision, recall, and F1 score were calculated and compared horizontally with traditional dictionary tools, standalone large language models, and the similar application "RAG-HPO". Finally, replace the model with the more advanced ChatGPT-5 and evaluate its performance on the newly extracted dataset. RESULTS: An HPO term automatic annotation visualization application named PhenoRAG, based on large language models and RAG technology, was successfully developed. Users can access it directly via a web link. Across the 112 cases, a total of 2 150 HPO terms were generated; 2,064 (96.0%) were fully validated by the official database, with a hallucination rate of 1.3% and an HPO ID-name mismatch rate of 2.7%. After deduplication, 1,906 terms remained for testing. The overall precision was 63.65%, recall was 67.34%, and F1 was 65.44%, significantly outperforming traditional annotation tools (F1: 0.45-0.49, P < 0.001). Although PhenoRAG's F1 was lower than that of RAG-HPO (F1 = 0.78, P < 0.001), which relies on a manually constructed synonym database of 54 000 entries plus the HPO dataset, it requires no additional dictionary maintenance and can be used without any background in computer programming. Moreover, after switching to the GPT-5 model, PhenoRAG exhibited no hallucination rate on the new dataset, and its F1 score significantly increased (P = 0.038). CONCLUSION Without constructing a synonym database, the PhenoRAG achieved high-accuracy automatic mapping from clinical text to standard HPO terms. It features a low usage threshold, free access, and a Chinese-language interface, and can directly serve rare disease diagnosis, genetic counseling, and research scenarios in China and worldwide, warranting further clinical promotion and multicenter validation.
Humans ; Phenotype ; Biological Ontologies ; Language ; Software ; Large Language Models

Background Neck-related work-related musculoskeletal disorders (WMSDs) are a major type of musculoskeletal disorders with a relatively high proportion. Shanghai has a large number of occupational populations; however, the occurrence of WMSDs at neck among the occupational populations across industries in this city has not been reported, and needs to be addressed. Objective To understand the occurrence of neck-related WMSDs and their influencing factors among occupational populations in 8 industries in Shanghai, and to provide a scientific basis for the prevention and control of WMSDs in this population. Methods From February 2024 to February 2025, a cross-sectional survey employed stratified cluster sampling to select 7829 employed workers from 48 enterprises across 8 industries in Shanghai. The study investigated the occurrence of neck-related WMSDs among the participants over the preceding 12 months. Logistic regression analysis was employed to examine the relationships between WMSDs and various occupational factors. Results A total of 7770 questionnaires were collected, yielding an effective response rate of 99.2%. Overall, the positive rate of neck-related WMSDs among the participants was 11.89% (924/7770). Among different industries, the environmental sanitation industry (19.48%), pharmaceutical manufacturing industry (14.57%), and cigarette manufacturing industry (13.66%) had higher prevalence of neck-related WMSDs. Univariate analysis showed that the risk of neck-related WMSDs was higher in the following groups: those with a job tenure ≥5 years in the current position (OR=1.50–1.70), females (OR=1.77), those with higher education levels (master’s degree or above, OR=2.27), and those with worse self-rated health (very poor health, OR=4.38) (P＜0.05). Multivariate logistic regression analysis identified the following independent risk factors for neck WMSDs: environmental sanitation industry (OR=7.30, 95%CI: 4.72, 11.87), higher educational attainment (master’s degree or above: OR=2.16, 95%CI: 1.36, 3.35), worse self-rated health status (very poor: OR=1.95, 95%CI: 1.31, 2.85), work performed in a single workshop (OR=1.36, 95%CI: 1.13, 1.64), understaffing (OR=1.46, 95%CI: 1.25, 1.70), slight neck forward flexion (OR=1.64, 95%CI: 1.32, 2.06), severe neck forward flexion (OR=2.55, 95%CI: 1.97, 3.30), and maintaining a fixed neck posture for a prolonged period (OR=2.28, 95%CI: 1.93, 2.70). Conversely, work rotation (OR=0.75, 95%CI: 0.65, 0.87), adequate rest (OR=0.70, 95%CI: 0.60, 0.82), and severe back flexion (OR=0.63, 95%CI: 0.46, 0.85) were protective factors against neck-related WMSDs. For the nomogram, the area under the curve (AUC)=0.75 (95%CI: 0.74, 0.77), Hosmer-Lemeshow test P=0.764, and Brier score=0.094, indicating that the model had good discrimination and calibration. Conclusion Among the occupational populations in Shanghai, the environmental sanitation industry, pharmaceutical manufacturing industry, and cigarette manufacturing industry are identified as high-risk industries for neck-related WMSDs. Industry affiliation, educational level, work organization patterns, and awkward neck working postures are confirmed as the core influencing factors for the development of neck-related WMSDs. Targeted and comprehensive intervention measures should be formulated focusing on the aforementioned high-risk industries and key influencing factors. Multi-dimensional collaborative efforts, including ergonomic optimization, improvement of labor management systems, and strengthened health education and promotion, should be implemented to effectively control the risk of neck-related WMSDs in the occupational population, and to provide robust statistical evidence for the advancement of regional occupational health prevention and control strategies.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

BACKGROUND:Hydrogen peroxide-based bleach is widely used in clinical tooth whitening treatment,but its mechanism of action has not been uniformly determined so far.OBJECTIVE:To examine the effects of two bleaching agents,neutral 10％carbamide peroxide and neutral 40％hydrogen peroxide,on teeth and explore the mechanism of teeth whitening.METHODS:Forty-five discarded teeth extracted for orthodontic treatment were collected,and the dentin sections were made and polished.After removing the smear layer,they were randomly divided into three groups.The control group(n=15)was placed in deionized water;the carbamide peroxide group(n=15)was placed in a neutral 10％carbamide peroxide solution,and the hydrogen peroxide group(n=15)was placed in a neutral 40％hydrogen peroxide solution.The treatment was continued for 6 hours every day for 1 week.The Raman absolute intensity and Raman relative intensity of the three groups of samples were detected by Raman spectrometer every day,and the fluorescence background intensity(the difference between the Raman absolute intensity and the Raman relative intensity)was calculated.The change trend of the amide peak of the three groups of samples every day was recorded by infrared spectrometer.RESULTS AND CONCLUSION:(1)The relative Raman intensity of the three groups did not change significantly during the 1-7 days of treatment.The fluorescence background intensity of the control group did not change significantly during the 1-7 days of treatment.The fluorescence background intensity of the carbamide peroxide group showed a downward trend during the 1-7 days of treatment.The fluorescence background intensity of the hydrogen peroxide group decreased significantly during the 1-4 days of treatment and did not change significantly thereafter.(2)The peak areas of amide Ⅰ and amide Ⅲ did not change significantly during the 1-7 days of treatment in the control group.The peak areas of amide Ⅰ and amide Ⅲ showed a downward trend during the 1-7 days of treatment in the carbamide peroxide group and the hydrogen peroxide group,and the downward trend was more obvious in the hydrogen peroxide group.(3)The results show that the change in the laser-induced fluorescence background intensity of dentin Raman spectroscopy may be derived from the non-collagen components in dentin,and under the action of whitening agents,it may have a certain adverse effect on tooth tissue.