Intravitreal anti-vascular endothelial growth factor(anti-VEGF)therapy has been widely used, but the variability in its therapeutic efficacy limits individualized treatment. In recent years, the application of artificial intelligence(AI)has opened up new avenues for personalized treatment response prediction, and its core branches include machine learning(ML)and deep learning(DL). This review systematically retrieved and analyzed 41 relevant studies published up to April 2025. Comprehensive analysis reveals that AI predictive models are evolving from forecasting single endpoints(such as visual acuity or central retinal thickness)to integrating multi-dimensional endpoints(encompassing anatomical, functional, and treatment demand parameters)and generating predictive imaging outputs. In terms of technical approaches, DL models(28 studies, accounting for 68.3%)dominate this field due to their robust image interpretation capabilities, while ML models(10 studies, 24.4%)retain significant value in the analysis of structured clinical data. Cross-disease comparisons indicate that research efforts are most concentrated on age-related macular degeneration(ARMD)and diabetic macular edema(DME), with shared conceptual frameworks for model construction, yet distinct anatomical and functional indicators are prioritized for each disease. Currently, the field confronts several key challenges, including insufficient prospective clinical validation, limited model interpretability(the “black box problem”), and a scarcity of high-quality multi-center datasets. Moving forward, it is imperative to advance real-world validation and develop explainable AI techniques to expedite the clinical translation of these predictive models.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

Primary osteoporosis （POP） is a metabolic bone disease characterized by reduced bone mass， degenerated bone microstructure， and increased bone fragility. Its pathogenesis involves the interaction of multiple factors such as genetics， aging， endocrine， and environment， which remain incompletely elucidated. Mitochondrial dysfunction can lead to insufficient adenosine triphosphate （ATP） production and abnormal accumulation of reactive oxygen species （ROS）， activating oxidative stress and inflammation pathways， thereby inhibiting osteoblast differentiation and promoting osteoclast activation， exacerbating the negative bone metabolism balance in POP. Mitochondrial autophagy， as the core mechanism of mitochondrial quality control， selectively identifies and clears damaged mitochondria to effectively reduce ROS accumulation and energy metabolism disorders， thus maintaining the balance between osteoblast and osteoclast differentiation. It plays a critical role in maintaining bone homeostasis and the prevention and treatment of POP. The traditional Chinese medicine （TCM） theory of Qi transformation shares similarities with the functions of mitochondria in energy generation and substance conversion. The pathological state of Qi deficiency and stagnation may be associated with mitochondrial autophagy dysfunction， and the pathogenic characteristics of combined phlegm and stasis align with the metabolic waste accumulation induced by obstructed autophagy flow. This article explores the correlation of the theory of Qi deficiency and stagnation with mitochondrial autophagy and elucidates its potential role in the pathogenesis of POP. Additionally， considering the pathogenesis features of POP， which involve deficiency causing stagnation and a mixture of deficiency and excess， this article proposes a novel therapeutic approach： tonifying Qi to support the body and unblocking collaterals to resolve stagnation from the perspective of mitochondrial autophagy. This article aims to provide theoretical support and research insights for further exploration of TCM in the prevention and treatment of POP.

Primary osteoporosis （POP） is a metabolic bone disease characterized by reduced bone mass， degenerated bone microstructure， and increased bone fragility. Its pathogenesis involves the interaction of multiple factors such as genetics， aging， endocrine， and environment， which remain incompletely elucidated. Mitochondrial dysfunction can lead to insufficient adenosine triphosphate （ATP） production and abnormal accumulation of reactive oxygen species （ROS）， activating oxidative stress and inflammation pathways， thereby inhibiting osteoblast differentiation and promoting osteoclast activation， exacerbating the negative bone metabolism balance in POP. Mitochondrial autophagy， as the core mechanism of mitochondrial quality control， selectively identifies and clears damaged mitochondria to effectively reduce ROS accumulation and energy metabolism disorders， thus maintaining the balance between osteoblast and osteoclast differentiation. It plays a critical role in maintaining bone homeostasis and the prevention and treatment of POP. The traditional Chinese medicine （TCM） theory of Qi transformation shares similarities with the functions of mitochondria in energy generation and substance conversion. The pathological state of Qi deficiency and stagnation may be associated with mitochondrial autophagy dysfunction， and the pathogenic characteristics of combined phlegm and stasis align with the metabolic waste accumulation induced by obstructed autophagy flow. This article explores the correlation of the theory of Qi deficiency and stagnation with mitochondrial autophagy and elucidates its potential role in the pathogenesis of POP. Additionally， considering the pathogenesis features of POP， which involve deficiency causing stagnation and a mixture of deficiency and excess， this article proposes a novel therapeutic approach： tonifying Qi to support the body and unblocking collaterals to resolve stagnation from the perspective of mitochondrial autophagy. This article aims to provide theoretical support and research insights for further exploration of TCM in the prevention and treatment of POP.

Huangqi Guizhi Wuwutang was first documented in ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han Dynasty as the principal formula for treating blood obstruction syndrome. It is composed of Astragali Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Zingiberis Rhizoma Recens， and Jujubae Fructus. This formula exhibits the effects of replenishing Qi， warming meridians， harmonizing blood， and relieving obstruction， being primarily indicated for blood obstruction syndrome characterized by diminished Yin and Yang functions with external manifestations of bodily numbness. Traditional Chinese medicine （TCM） emphasizes strict adherence to pathogenesis while applying tailored therapies， employing consistent treatment approaches for conditions with diverse clinical presentations but shared pathogenesis， which embodies the principle of treating different diseases with the same method. In modern clinical practice， Huangqi Guizhi Wuwutang is widely applied in multisystem disorders presenting with symptoms such as cutaneous numbness， cold-induced pain and stiffness， and soreness and weakness， including diabetic peripheral neuropathy， cervical radiculopathy， rheumatoid arthritis， coronary heart disease， pediatric spastic cerebral palsy， and recovery phases of cerebral infarction， demonstrating proven efficacy. Modern pharmacological studies confirm its anti-inflammatory， antioxidant-stress， hemorheological-improving， immunomodulatory， and neuroprotective effects by regulating multiple signaling pathways such as nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） and nuclear factor erythroid 2-related factor 2 （Nrf2）-antioxidant response element （ARE）， thereby addressing common pathological processes including inflammation， hypercoagulability， oxidative stress， immune dysregulation， and neural injury， highlighting the integrated regulatory advantages of TCM formulas with multi-target， multi-level， multi-component， and multi-pathway mechanisms. According to the theory of treating different diseases with the same method and focusing on three core syndromes of blood obstruction， this article systematically reviews and elucidates the clinical extensions and shared mechanisms of this formula， aiming to provide evidence-based insights for the modern adaptation and precise application of this classical formula in orthopedic and related disciplines for chronic musculoskeletal disorders.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

[Objective]To investigate the role of endothelial microparticles(EMPs)in diabetic macrovascular complications(DMCs),summarize the research progress and analyze the research progress on traditional Chinese medicine(TCM)regulation of EMPs for the prevention and treatment of DMCs.[Methods]Base on the research on the pathological mechanism of DMCs,the biological characteristic of EMPs and their mechanism of action in DMCs in recent years,combined with the experimental and clinical studies on the regulation of EMPs by TCM for disease prevention and treatment,their paper summarizes the action targets of EMPs in regulating the pathological process of DMCs and the resarch progress of TCM intervention,on this basis,the limitations of current research and future prospects are summarized.[Results]EMPs are important biomarkers of endothelial injury,promoting mechanisms such as inflammation,oxidative stress,thrombosis and atherosclerosis,contributes to the pathological progression of DMCs.TCM intervenes in the generation and release of EMPs through mechanisms such as regulating inflammatory responses,alleviating oxidative stress,relieving endothelial dysfunction and promoting vascular repair.This approach helps maintain endothelial homeostasis and plays a crucial role in the prevention and treatment of DMCs.[Conclusion]EMPs play a significant role in the onset and progression of DMCs,serving as potential intervention targets.TCM offers novel therapeutic approaches for the prevention and treatment of DMCs by inhibiting inflammation and oxidative stress,promoting vascular remodeling and repair,and suppressing the formation of thrombosis and atherosclerosis.

Objective To explore the regulation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)-mediated inflammatory response in chronic obstructive pulmonary disease(COPD)by modified Shengxian Decoction through the lung-gut axis.Methods Thirty rats were divided into three groups:Control group,COPD group,and COPD+modified Shengxian Decoction(SXT)group,with 10 rats in each.The COPD model was established using passive smoking combined with intratracheal instillation of lipopolysaccharide(LPS).General symptoms and signs of the rats were monitored during the modeling and intervention periods.Hematoxylin and eosin(HE)staining and immunohistochemistry(IHC)were used to observe lung tissue structure.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in lung tissues.Flow cytometry was used to detect the number of type Ⅱ innate lymphoid cells(nILC2)and type 2 innate lymphoid cells(iILC2)in lung and intestinal tissues.Illumina MiSeq sequencing technology was used to perform 16S rRNA gene sequencing on rat feces to analyze the gut microbiota structure.Gas chromatography-mass spectrometry(GC-MS)was used to determine the content of short-chain fatty acids(SCFAs)in rat feces.Western blotting was used to detect the expressions of related proteins in the PI3K/AKT pathway.Results Compared with the Control group,the COPD group showed significantly reduced lung function indicators,increased heart rate and decreased body mass,while the SXT group showed significant improvement in lung function and general signs(P＜0.05).HE staining showed that the COPD group had lung tissue damage filled with inflammatory cells,while the SXT group had significantly fewer inflammatory cells.IHC results showed that the SXT group had significantly reduced expression of caspase-3 protein(P＜0.05).ELISA results showed that the levels of IL-6 and TNF-α were significantly increased in the COPD group,while the SXT group showed significant improvement in inflammatory damage.The ratio of nILC2 to iILC2 in lung and intestinal tissues was significantly reduced in the COPD group,indicating a significant inflammatory response,while the SXT group showed significant improvement(P＜0.05).The levels of ILC2 cytokines IL-13 and IL-4 were significantly increased in the COPD group,while the SXT group had significantly reduced IL-13 and IL-4 levels.The relative abundance of lung and gut microbiota in the SXT group was significantly higher than that in the Control and COPD groups(P＜0.05).Beta diversity index analysis showed significant differences in species diversity among the three groups(P＜0.05).GC-MS detected six types of SCFAs in rat feces:acetic acid,propionic acid,isobutyric acid,butyric acid,isovaleric acid,and valeric acid.Their levels were lower in the COPD group than in the Control group,but the levels in the SXT group were higher than those in the COPD group.Western blotting results showed that the expressions of p-PI3K,PI3K,p-AKT,AKT,p-NF-κB,and NF-κB proteins were significantly reduced in the SXT group compared to the COPD group(P＜0.05).ELISA results showed that the SXT group had significantly downregulated expression levels of IL-1β and IL-10 compared to the COPD group(P＜0.05).Conclusion Modified Shengxian Decoction can alleviate COPD inflammation.It may mediate the inflammatory response in COPD by inhibiting iILC2 cell activity and expressions of related proteins in the PI3K/AKT signaling pathway through gut microbiota metabolism.