BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

Pulmonary hypertension (PH), marked by sustained elevation of pulmonary artery pressure, imposes a heavy burden on the right ventricle and may culminate in right heart failure. Its pathogenesis is multifaceted, encompassing endothelial dysfunction, vascular smooth muscle proliferation, inflammation, thrombosis, and genetic factors. Animal models serve as core tools for exploring PH mechanisms and therapies, each with unique strengths and limitations. The single-dose monocrotaline (MCT) model is one of the most commonly used experimental animal models of PH and is widely applied in mechanistic studies, drug screening, and efficacy evaluation; it offers simplicity and cost-effectiveness, can induce PH within a short period, yet its pathophysiology differs to some extent from human idiopathic PH. In contrast, the Sugen5416 combined with chronic hypoxia model better mimics PH progression by placing animals under hypoxic conditions to induce pulmonary vasoconstriction and vascular remodeling, but it requires a longer modelling time, and the degree of hypoxia has a substantial impact on experimental outcomes. Beyond these two commonly used modeling approaches, a variety of emerging techniques have been applied in PH research; gene-editing technologies enable precise investigation of specific gene functions in PH. Additionally, induced pluripotent stem cell-based 3D organoid technology allows for individualized modelling while preserving patients' genetic information for precise clinical translation. Each model or technology can simulate different aspects of the pathological processes of human PH, and their findings provide key insights into the nature of the disease and serve as an important platform for the development of novel therapeutic targets. This paper comprehensively describes various animal models and emerging technologies used in PH research, analyzing their characteristics, applications, and limitations, with the aim of providing experimental and technical support for the development of new therapeutic strategies and drugs.

Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

Objective:To construct a "local-systemic" dual-track prediction model integrating the resistance index (RI) score of bilateral sacroiliac joints and the systemic immune-inflammation index (SII), and to evaluate its predictive efficacy for the active stage of ankylosing spondylitis (AS).Methods:A total of 205 patients with ankylosing spondylitis (AS) from the Second Hospital of Lanzhou University between April 2022 and April 2025 were retrospectively enrolled and categorized into an active group ( n=113) and a remission group ( n=92). Hematological parameters and ultrasound data were collected. The resistance index (RI) of the synovial area in bilateral sacroiliac joints was measured by Doppler ultrasound and scored as follows: RI < 0.5: 3 points; RI 0.5~0.55: 2 points; RI > 0.55: 1 point; undetectable blood flow: 0 points. A total bilateral RI score (range 0 to 6) was calculated. The systemic immune-inflammation index (SII) was derived as (neutrophils× platelets)/lymphocytes. Normality was tested for all continuous variables; normally distributed data were compared using the t-test, while non-normally distributed data were analyzed with the Mann-Whitney U test. Categorical variables were compared using the χ2 test or analysis of variance.Variable selection was performed using Lasso regression, and a multivariate logistic regression model was developed to assess predictive performance. Results:The proportion of patients with a bilateral RI total score≥5 was significantly higher in the active group compared to the remission group (50 of 113, 44.3% vs 2 of 92, 2.2%, χ2=55.63, P<0.001). Multivariate logistic regression analysis, after adjustment for confounding variables, identified the SII [ OR(95% CI)=1.01(1.00, 1.01), P<0.001], bilateral RI total score [ OR(95% CI)=1.67(1.29, 2.26), P<0.001], erythrocyte sedimentation rate [ OR(95% CI)=1.19(1.11, 1.30), P<0.001], and mean corpuscular hemoglobin concentration [ OR(95% CI)=1.09(1.03, 1.17), P<0.001] as independent risk factors for active AS. Conversely, lymphocyte count [ OR(95% CI)=0.42(0.18, 0.92), P=0.030] and globulin [ OR(95% CI)=0.89(0.80, 0.99), P=0.040] were significantly associated with protective effects. The bilateral RI total score demonstrated the strongest predictive effect, with each 1-point increase associated with a 67% elevation in the risk of active disease. ROC curve analysis indicated that the area under the curve (AUC) for predicting whether AS is in the active disease phase was 0.94 for the combined model (SII+bilateral RI total score), compared with 0.93 for the SII-alone model and 0.92 for the bilateral RI total score-alone model, demonstrating superior predictive performance of the combined model (SII+bilateral RI total score). An online prediction tool has been developed based on the combined model. Conclusion:The dual-track prediction model, which integrates local joint hemodynamic characteristics and systemic immune-inflammatory status, facilitates a multidimensional assessment of the risk of active AS and provides an objective basis for early identification.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

Objective:To construct a "local-systemic" dual-track prediction model integrating the resistance index (RI) score of bilateral sacroiliac joints and the systemic immune-inflammation index (SII), and to evaluate its predictive efficacy for the active stage of ankylosing spondylitis (AS).Methods:A total of 205 patients with ankylosing spondylitis (AS) from the Second Hospital of Lanzhou University between April 2022 and April 2025 were retrospectively enrolled and categorized into an active group ( n=113) and a remission group ( n=92). Hematological parameters and ultrasound data were collected. The resistance index (RI) of the synovial area in bilateral sacroiliac joints was measured by Doppler ultrasound and scored as follows: RI < 0.5: 3 points; RI 0.5~0.55: 2 points; RI > 0.55: 1 point; undetectable blood flow: 0 points. A total bilateral RI score (range 0 to 6) was calculated. The systemic immune-inflammation index (SII) was derived as (neutrophils× platelets)/lymphocytes. Normality was tested for all continuous variables; normally distributed data were compared using the t-test, while non-normally distributed data were analyzed with the Mann-Whitney U test. Categorical variables were compared using the χ2 test or analysis of variance.Variable selection was performed using Lasso regression, and a multivariate logistic regression model was developed to assess predictive performance. Results:The proportion of patients with a bilateral RI total score≥5 was significantly higher in the active group compared to the remission group (50 of 113, 44.3% vs 2 of 92, 2.2%, χ2=55.63, P<0.001). Multivariate logistic regression analysis, after adjustment for confounding variables, identified the SII [ OR(95% CI)=1.01(1.00, 1.01), P<0.001], bilateral RI total score [ OR(95% CI)=1.67(1.29, 2.26), P<0.001], erythrocyte sedimentation rate [ OR(95% CI)=1.19(1.11, 1.30), P<0.001], and mean corpuscular hemoglobin concentration [ OR(95% CI)=1.09(1.03, 1.17), P<0.001] as independent risk factors for active AS. Conversely, lymphocyte count [ OR(95% CI)=0.42(0.18, 0.92), P=0.030] and globulin [ OR(95% CI)=0.89(0.80, 0.99), P=0.040] were significantly associated with protective effects. The bilateral RI total score demonstrated the strongest predictive effect, with each 1-point increase associated with a 67% elevation in the risk of active disease. ROC curve analysis indicated that the area under the curve (AUC) for predicting whether AS is in the active disease phase was 0.94 for the combined model (SII+bilateral RI total score), compared with 0.93 for the SII-alone model and 0.92 for the bilateral RI total score-alone model, demonstrating superior predictive performance of the combined model (SII+bilateral RI total score). An online prediction tool has been developed based on the combined model. Conclusion:The dual-track prediction model, which integrates local joint hemodynamic characteristics and systemic immune-inflammatory status, facilitates a multidimensional assessment of the risk of active AS and provides an objective basis for early identification.

With the improvement of China’s scientific research capabilities， the number of innovative drug enterprises and clinical trials has increased， and disputes over damage compensation have also risen accordingly. It has become a consensus to resolve such disputes through institutionalization. Given the similarities between China and India in terms of population and development level， this study analyzed India’s compensation mechanism for clinical trial damage， including the definition of damage， compensation procedures， and calculation methods. Through a comparison of the mechanisms between China and India， this paper put forward suggestions for improving China’s compensation mechanism for clinical trial damage， that is， clarifying the compensation process for clinical trial damage， the scope and calculation methods of damage compensation， and the compensation ratio corresponding to the correlation between damage and clinical trials. It also proposed to use disability weights to measure the participants’ health status before their enrollment in clinical trials， and to calculate the amount of compensation for disability and death based on their health status.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Prolonged standing work can lead to various lower limb health issues. Footwear, as a convenient and noninvasive intervention, plays a key role in foot protection. The purpose of this review was to evaluate the impact of footwear characteristics on foot comfort among workers engaged in prolonged standing occupations. A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until March 2025 for experimental and observational studies; the review is registered in International Prospective Register of Systematic Reviews (CRD420251003253).Given the diversity of study designs, participant characteristics, and outcome measures, results were synthesized narratively, organizing findings by footwear design factors. The synthesis indicated that soft soles reduce foot impact and fatigue but offer limited support, whereas hard soles enhance stability but may cause localized pressure and discomfort. Sole hardness should balance cushioning and support based on activity: hard soles for standing and soft soles for walking. Insole hardness must be carefully considered as semirigid arch supports can cause discomfort. Most insoles improve pressure distribution by adjusting arch loading, and some enhance intrinsic foot muscles by promoting toe engagement, reducing leg swelling. Custom orthotic insoles outperform standard ones in comfort and balance. Future research should promote interdisciplinary collaboration with footwear designers to explore key design parameters and establish a scientific framework for protective footwear.