BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

Objective: To understand the association of physical exercise willingness and insomnia with depressive symptoms among college students, so as to provide reference for improving depressive symptoms of college students. Methods: From October 2022 to April 2023, cluster sampling was used to recruit 11 101 college students from four colleges in Anhui Province. The questionnaire survey was conducted to investigate the willingness to engage in physical exercise, insomnia and depressive symptoms of college students. The multivariate Logistic regression model was used to analyze the association of physical exercise willingness and insomnia with depressive symptoms of college students. Results: The prevalence of depressive symptoms among college students was 9.24%. Multivariate Logistic regression analysis showed that college students who were passive participants/non participants in physical activity, or who experienced insomnia, had a higher likelihood of depressive symptoms compared to those who were active participants or did not experience insomnia ( OR =1.84, 2.07, 4.02, all P <0.01). College students who were passive participants or non participants in physical activity and concurrently experienced insomnia had a higher risk of depressive symptoms compared with those who were active participants or did not experience insomnia ( OR =1.87-8.39, all P <0.01). Gender stratified analysis showed that the combined effect of passive physical exercise and insomnia increased the risk of depressive symptoms in both male ( OR = 1.81 -9.87) and female college students ( OR =1.67-7.39) (all P <0.05). Conclusions Both physical exercise willingness and insomnia are associated with depressive symptoms in college students. In order to improve the depressive symptoms of college students, it is necessary to improve the enthusiasm of physical exercise and strengthen the education of sleep health awareness.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

OBJECTIVE: To analyze the correlation between the expression levels of Tim-3, C-myc and the proportion of T lymphocyte subsets and prognosis in patients with acute lymphoblastic leukemia (ALL). METHODS: The research group selected 60 ALL patients admitted to our hospital from December 2019 to December 2021, while the control group selected 55 healthy volunteers who underwent physical examination in our hospital. The expression levels of Tim-3, C-myc mRNA and the proportion of T lymphocyte subsets in the two groups were detected. The mortality rate of ALL patients was calculated, and the correlation between the expression levels of Tim-3, C-myc, and the proportion of T lymphocyte subsets and pathological features and prognosis was analyzed. RESULTS: Compared with the control group, the levels of Tim-3, C-myc and CD8⁺ in the research group were increased, while the levels of CD3⁺ , CD4⁺ and CD4⁺ /CD8⁺ were decreased (all P < 0.001). The levels of Tim-3, C-myc mRNA, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were correlated with risk classification and extramedullary infiltration (all P < 0.05). The survival rate of patients with low expression of Tim-3, C-myc, and CD8⁺ was higher than that of patients with high expression, while the survival rate of patients with high expression of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ was higher than that of patients with low expression (all P < 0.05). Univariate analysis showed that the deceased patients had higher proportions of extramedullary infiltration and high-risk classification, as well as higher levels of Tim-3, C-myc, and CD8⁺ , while lower levels of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ compared with surviving patients (all P < 0.01). Multivariate logistic regression analysis showed that extramedullary invasion, risk classification, Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were the main factors affecting the prognosis of ALL patients (all P < 0.05). ROC curve analysis showed that the combination of Tim-3, C-myc, and T lymphocyte subsets had higher sensitivity and accuracy in predicting prognosis of ALL patients compared with the single diagnosis of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , and CD4⁺ /CD8⁺ (P < 0.05). CONCLUSION ALL patients show higher levels of Tim-3, C-myc mRNA and CD8⁺ but lower levels of CD3⁺ , CD4⁺ and CD4⁺/CD8⁺. Moreover, the expression levels of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺/CD8⁺ are correlated with extramedullary invasion, high-risk classification and prognosis.
Humans ; Hepatitis A Virus Cellular Receptor 2/metabolism* ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; T-Lymphocyte Subsets ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; RNA, Messenger

Objective:To understand the prevalence of psychoactive substance use and related factors in men who have unprotected sex with men in Zhejiang Province.Methods:Men who have unprotected sex with men were recruited by snowball sampling through men who have sex with men (MSM) social organization in Zhejiang to conduct a cross-sectional investigation from January 2022 to December 2023. The sample size was estimated to be 1 169 individuals. The information about their socio-demographic information, sexual behaviors, psychoactive substance use, and HIV testing were collected through on-site questionnaire survey. Logistic regression analysis model was used to analyze related factors about psychoactive substance use in this population.Results:A total of 1 914 men who have unprotected sex with men were included in the study, the average age of the study subjects was (31.43±10.46) years, and most of them were aged ≤35 years (70.8%, 1 356/1 914). Those with education level of high school or below accounted for 50.1% (960/1 914) and those who were not married accounted for 63.5% (1 216/1 914). Psychoactive substance use in the past 3 months was reported in 19.7% (377/1 914) of the subjects. Multivariate logistic regression analysis showed that the factors associated with psychoactive substance use in the past 3 months included age 26-35 years (a OR=1.65, 95% CI: 1.24-2.19), ≥2 sexual partners in the past 3 months (a OR=2.33, 95% CI: 1.82-2.97), STD diagnosed in the past 3 months (a OR=2.62, 95% CI: 1.45-4.74), and awareness of the HIV infection status of sexual partners (a OR=2.83, 95% CI: 2.12-3.78). Conclusions:The prevalence of psychoactive substance use in men who have unprotected sex with men was high in Zhejiang. It is necessary to strengthen the intervention in this population.

Patient complaints not only reflect the shortcomings of hospital services, but also provide an opportunity for hospitals to improve quality. In July 2023, based on the theory of comprehensive quality management and from the perspective of complaint management, Shanghai General Hospital constructed and launched a " 1 (patient service quality improvement work team)+ X (Shanghai 12320 Health Hotline, various functional departments and clinical medical technology departments of the hospital)" patient service defect management system. This system established a four level organizational structure of patient service quality improvement leadership group-work team-clinical medical technology department work group-all employees. It established mechanisms for acceptance, disposal, improvement, training, evaluation, and rewards and punishments, created a comprehensive service platform, and achieved systematic improvement in patient services. By the end of 2024, the hospital had carried out nearly 200 patient service improvement projects; The daily usage of cloud customer service had exceeded 5 000 people, with an effective response rate of over 94%. In 2024, the response rate for handling work orders through various channels within 48 hours was 90%. This practice had achieved good results in improving the quality of hospital services and enhancing the patient experience, which could provide references for other hospitals to promote the management of patient service defects.

To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.

Objective To study the relationship between serum insulin-like growth factor-1 (IGF-1) and resistin levels and osteoporosis in patients with type 2 diabetes mellitus (T2DM). Methods This study was conducted on 306 T2DM patients admitted to Baoding No.2 Central Hospital from January 2018 to January 2022. According to the detection results of bone mineral density, the patients were divided into osteoporosis group (T≤-2.5) and non-osteoporosis group (T>-2.5). The differences in IGF-1, resistin and bone mineral density were compared between the two groups. Pearson correlation analysis was used to analyze the correlation between serum IGF-1 and resistin levels and bone mineral density in patients with osteoporosis. Receiver operating characteristic (ROC) curve was applied to evaluate the application value of IGF-1 and resistin in predicting osteoporosis in patients with T2DM. Patients with T2DM complicated with osteoporosis were followed up for 2 years, and the occurrence of fractures was assessed. After univariate analysis, multivariate logistic regression analysis was applied to screen the risk factors for fractures in T2DM patients with osteoporosis. Results The incidence rate of osteoporosis in patients with T2DM was 53.59% (164/306). The IGF-1 level and bone mineral density level in the osteoporosis group were lower than those in the non-osteoporosis group, while the level of resistin was higher than that in the non-osteoporosis group (P<0.05). Serum IGF-1 in patients with osteoporosis was positively correlated with bone mineral density, and serum resistin was negatively correlated with bone mineral density (P<0.05). The AUC, sensitivity and specificity of combination of IGF-1 and resistin in predicting osteoporosis were 0.888, 82.93% and 62.68% respectively, which were all higher than those of single factor prediction (P<0.05). The 164 T2DM patients with osteoporosis were followed up for two years, and 15 patients developed fragility fractures, with the incidence of fracture of 9.15% (15/164). Multivariate analysis showed that hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1, and high resistin were risk factors for fractures in patients with T2DM complicated with osteoporosis (P<0.05). Conclusion For patients with T2DM, the incidence rates of osteoporosis and fractures are high. The levels of IGF-1 and resistin are closely related to bone mineral density, which can be combined to predict osteoporosis. Hypoproteinemia, high-intensity exercise, lack of nutritional management, low IGF-1 and high resistin are risk factors for fractures in T2DM patients with osteoporosis. It is necessary to carry out targeted preventive measures in clinical practice to reduce the incidence rate of fractures.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.