BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

OBJECTIVES: To investigate the effect of age-friendly social and family care environment on the long-term care (LTC) services for the disabled elderly people. METHODS: A questionnaire-based survey was conducted among disabled elderly people in three cities of Zhejiang province from June to August 2022, involving 311 subjects from Ningbo city (LTC service insurance pilot site, insured group) and 542 subjects from Hangzhou and Quzhou cities (uninsured group). The service provisions, including ensuring daily activities, preventive healthcare, and satisfying spiritual comfort, were compared among the groups. The family friendly care environment was evaluated with the Family Function Scale and assistance of daily activities, financial support and emotional comfort. The social friendly care environment was measured with the revised WHO recommended age-friendly city environmental framework, including accessibility guarantee environment, information dissemination environment, social participant environment, and life security environment. After controlling for covariates such as sociodemographic, elderly care status, and health risk characteristics, the impact of environment on the effectiveness of service provision of LTC insurance was explored by multiple logistic regression analysis. The mediating and moderating effects were tested to explore the role of age-friendly care environment. A fixed effects model was used to test the service provision effects of LTC insurance policy. RESULTS: Disabled elderly with LTC insurance had a higher proportion of their preventive health care and spiritual comfort needs met. Additionally, a multifactorial analysis found a significant positive association between LTC insurance and meeting the spiritual comfort needs. Compared with insured group (Ningbo city), disabled elderly people in Hangzhou urban area (OR=0.45, 95%CI:0.27-0.74, P<0.01) and Quzhou rural area (OR=0.21, 95%CI:0.12-0.37, P<0.01) were more likely to feel unsatisfied with spiritual comfort. The results of mediation analysis showed that the scores of accessibility guarantee environment (OR=1.22, 95%CI:1.02-1.45, P<0.05), information dissemination environment (OR=1.19, 95%CI:1.02-1.39, P<0.05), and social participation environment (OR=1.40, 95%CI:1.17-1.67, P<0.01) in a socially friendly care environment were positively correlated with the satisfaction rate of mental comfort services. The results of the moderation effect analysis indicated that a socially friendly care environment (OR=1.46, 95%CI:1.16-1.84, P<0.01) could compensate for the difference in effectiveness between insured (Ningbo) and uninsured (Hangzhou and Quzhou) areas of LTC insurance. A fixed effect model confirmed the policy chain of LTC insurance policy-social friendly care environment-mental health service satisfaction. CONCLUSIONS The implementation of LTC insurance has improved service accessibility, making disabled elderly people feel "seen and valued", and generating psychological and spiritual satisfaction. Accelerating the establishment and improvement of the LTC insurance system requires systematic design, especially emphasizing the supportive role of a socially friendly care environment, and promoting it in urban and rural areas according to the local conditions.
Humans ; Aged ; Persons with Disabilities ; Surveys and Questionnaires ; Long-Term Care ; Female ; Male ; China ; Social Environment ; Middle Aged ; Aged, 80 and over

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

OBJECTIVES: To investigate the effect of hypaphorine (HYP) on Crohn's disease (CD)‑like colitis in mice and its molecular mechanism. METHODS: Thirty male C57BL/6J mice were equally randomized into WT, TNBS, and HYP groups, and in the latter two groups, mouse models of CD-like colitis were established using TNBS with daily gavage of 15 mg/kg HYP or an equivalent volume of saline. The treatment efficacy was evaluated by assessing the disease activity index (DAI), body weight changes, colon length and histopathology. The effect of HYP was also tested in a LPS-stimulated Caco-2 cell model mimicking intestinal inflammation by evaluating inflammatory responses and barrier function of the cells using qRT-PCR and immunofluorescence staining. GO and KEGG analyses were conducted to explore the therapeutic mechanism of HYP, which was validated in both the cell and mouse models using Western blotting. RESULTS: In the mouse models of CD-like colitis, HYP intervention obviously alleviated colitis as shown by significantly reduced body weight loss, colon shortening, DAI and inflammation scores, and expressions of pro-inflammatory factors in the colon tissues. HYP treatment also significantly increased the TEER values, reduced bacterial translocation to the mesenteric lymph nodes, liver, and spleen, lowered serum levels of I-FABP and FITC-dextran, increased the number of colonic tissue cup cells, and upregulated colonic expressions of MUC2 and tight junction proteins (claudin-1 and ZO-1) in the mouse models. In LPS-stimulated Caco-2 cells, HYP treatment significantly inhibited the expressions of pro-inflammatory factors and increased the expressions of tight junction proteins. Western blotting showed that HYP downregulated the expressions of the key proteins in the TLR4/MyD88 signaling pathway in both the in vitro and in vivo models. CONCLUSIONS HYP alleviates CD-like colitis in mice possibly by suppressing intestinal epithelial inflammation and improving gut barrier function.
Animals ; Male ; Mice, Inbred C57BL ; Crohn Disease/drug therapy* ; Mice ; Humans ; Caco-2 Cells ; Intestinal Mucosa/metabolism* ; Colitis/drug therapy* ; Disease Models, Animal ; Inflammation ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Intestinal Barrier Function

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To investigate the main occupational hazards,occupational protection facilities and workers'health examination in 17 plywood manufacturing enterprises in Guangxi,so as to provide valuable basis for ensuring workers'physical and mental health.Methods:A total of 17 plywood enterprises in Guangxi were selected as the observation objects.Through the occupational hazard assessment survey,the occupational hazards in the working environment and the collection of workers'occupational health examination data,the main occupational health problems were comprehensively analyzed and evaluated.Results:The over-standard rates of wood dust,formaldehyde,noise,and high temperature in 17 plywood manufacturing enterprises were 5.6%,28.1%,24.9%,and 29.1%,respectively.The noise in 17 enterprises exceeded standards,the mood dust and formaldehyde in 5 enterprises exceeded standards,and high temperature in 2 enterprises exceeded standards.The coincidence rate of dustproof and poisonproof facilities in production protection was 98.3%,the coincidence rate of heat-proof facilities was 88.2%and the coincidence rate of noise protection facilities was 76.5%.The coincidence rate of wearing and using personal protective equipment was 52.9%,and the coincidence rate of installing eyewash spray devices was 58.8%.The total physical examination rate in 17 enterprises was 42.6%(705/1 654),and the abnormal detection rate of physical examination was 14.6%,among which the abnormal detection rates of hearing,chest X-ray,and lung function were 7.4%,2.1%,and 1.7%,respectively.Conclusions:The main occupational health problems in 17 plywood manufacturing enterprises in Guangxi are wood dust,formaldehyde,noise,and high temperature,especially noise.The prevention and control effects of wood dust and formaldehyde are good,but the prevention and control measures for high temperature and noise need to be further strengthened.

Objective:To analyze the relationship between Twist2 and the prognosis and vascular infiltration of ovarian cancer patients,and to explore the role and mechanism of Twist2 in vascular infiltration of ovarian cancer.Methods:KM plotter was used to explore the correaltion between Twist2 mRNA expression and overall survival(OS),progression free survival(PFS)and post progression survival(PPS)in ovarian cancer.To analyze the cor-relation between Twist2 and vascular infiltration in ovarian cancer using the cancer genomics database cBioPor-tal.In vitro experiment:Transwell method was employed to determine the role of Twist2 in the invasion and migra-tion abilities of ovarian cancer cell CAOV3[blank group,negative control group(siNC group),siTwist2 group].Uti-lizing Realtime-PCR and Western blot to clarify the changes in Twist2 and VEGFC expression in CAOV3 cells af-ter downregulating Twist2 expression at the RNA and protein levels,respectively.Results:①Online data analysis of KM plotter showed that the ovarian cancer patients with high expression of Twist2 were associated with poor prognosis,with OS(HR 1.24,95％Cl 1.01-1.52),PFS(HR 1.39,95％CI 1.14-1.70)and PPS(HR 1.37,95％CI 1.08-1.74)all showing statistical significance(P＜0.05).CBioportal analysis showed that Twist2 mRNA expression was positively correlated with vascular infiltration(r=0.93,P=0.001)and lymphatic infiltration(r=0.89,P=0.009)in ovarian cancer.②Compared with the blank group and siNC group,in vitro experiment Tran-swell assay showed that the invasion and migration ability of ovarian cancer cells in siTwist2 group was significant-ly reduced(P＜0.05).In mRNA and protein level,Realtime-PCR and Western blot showed that compared with the blank group and siNC group,the expression of Twist2,as well as VEGFC,were significantly reduced in the siTwist2 group(P＜0.05).Conclusions:The expression of Twist2 in ovarian cancer is closely related to tumor prognosis and vascular infiltration.After downregulating Twist2,the number of cells that migrate and invade is sig-nificantly reduced,and the expression of VEGFC is reduced.Twist2 can induce migration and invasion of ovarian cancer cells through VEGFC,which may be one of the indicators for prognosis evaluate and targeted therapy of ovarian cancer in future.