BACKGROUND: The effect of air pollution on annual change rates in grip strength and body composition in the elderly is unknown. OBJECTIVES: This study evaluated the effects of long-term exposure to ambient air pollution on change rates of grip strength and body composition in the elderly. METHODS: In the period 2016-2020, grip strength and body composition were assessed and measured 1-2 times per year in 395 elderly participants living in the Taipei basin. Exposure to ambient fine particulate matters (PM_2.5), nitric dioxide (NO₂), and ozone (O₃) from 2015 to 2019 was estimated using a hybrid Kriging/Land-use regression model. In addition, long-term exposure to carbon monoxide (CO) was estimated using an ordinary Kriging approach. Associations between air pollution exposures and annual changes in health outcomes were analyzed using linear mixed-effects models. RESULTS: An inter-quartile range (4.1 µg/m³) increase in long-term exposure to PM_2.5 was associated with a faster decline rate in grip strength (-0.16 kg per year) and skeletal muscle mass (-0.14 kg per year), but an increase in body fat mass (0.21 kg per year). The effect of PM_2.5 remained robust after adjustment for NO₂, O₃ and CO exposure. In subgroup analysis, the PM_2.5-related decline rate in grip strength was greater in participants with older age (>70 years) or higher protein intake, whereas in skeletal muscle mass, the decline rate was more pronounced in participants having a lower frequency of moderate or strenuous exercise. The PM_2.5-related increase rate in body fat mass was higher in participants having a lower frequency of strenuous exercise or soybean intake. CONCLUSIONS Among the elderly, long-term exposure to ambient PM_2.5 is associated with a faster decline in grip strength and skeletal muscle mass, and an increase in body fat mass. Susceptibility to PM_2.5 may be influenced by age, physical activity, and dietary protein intake; however, these modifying effects vary across different health outcomes, and further research is needed to clarify their mechanisms and consistency.
Humans ; Hand Strength ; Aged ; Male ; Female ; Environmental Exposure/adverse effects* ; Follow-Up Studies ; Taiwan ; Air Pollution/adverse effects* ; Particulate Matter/adverse effects* ; Muscle, Skeletal/drug effects* ; Air Pollutants/adverse effects* ; Ozone/adverse effects* ; Aged, 80 and over ; Adipose Tissue/drug effects* ; Body Composition/drug effects* ; Nitrogen Dioxide/adverse effects*

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Objective Inflammation and fibrosis are key features of diabetic nephropathy(DN).Triptolide(TP)exhibits anti-inflammatory and anti-fibrotic properties,though its mechanisms of action in DN remain unclear.CREKA(Cys-Arg-Glu-Lys-Ala)is a pentapeptide that specifically binds to fibronectin(FN),and the CREKA-modified liposome(CREKA-Lip)represents a novel FN-targeted drug delivery system.This study aimed to investigate the role of TP in diabetic db/db mice and determine whether encapsulation within CREKA-Lip enhances therapeutic efficacy while reducing the multi-organ toxicity of TP.Methods Eight-week-old diabetic db/db mice received tail vein injections twice weekly with vehicle,free TP,or CREKA-Lip/TP for 10 weeks.Urine and serum parameters were measured,and kidney,heart,liver,and testis tissues were collected for pathological evaluation.Protein-protein interaction networks were constructed using Cytoscape and its plug-ins to identify core targets and elucidate the therapeutic mechanism of TP against DN.Inflammatory,fibrotic,apoptotic,and lipid metabolism markers were evaluated in the kidneys of diabetic mice with DN and in high glucose-treated mouse mesangial cells and podocytes using qPCR,Western blot,immunohistochemistry,and immunofluorescence assays.Results TP administration reduced fasting blood glucose levels and glomerular mesangial expansion in diabetic mice.TP significantly suppressed renal inflammation,fibrosis,and apoptosis while enhancing lipid metabolism.Integration of network pharmacology,molecular docking,and transcriptomics revealed that TP ameliorated DN by inhibiting the JAK2-STAT1 signaling pathway.In vitro,TP inhibited high glucose-induced phosphorylation of JAK2 and STAT1,reduced collagen production in mesangial cells,decreased apoptosis,and improved lipid metabolism in podocytes.Moreover,CREKA-Lip/TP exhibited superior efficacy compared with free TP,with a more sustained reduction in urine albumin-to-creatinine ratio and greater inhibition of mesangial expansion.Notably,CREKA-Lip/TP treatment did not induce systemic toxicity.Conclusion TP improves renal inflammation,fibrosis,apoptosis,and lipid homeostasis,thereby ameliorating DN by inhibiting JAK2-STAT1 activation.Targeted delivery of TP via FN-binding CREKA-Lip enhances therapeutic efficacy while minimizing multi-organ toxicity.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.