Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Aim To investigate the effects of the fangchinoline derivative LYY-32 on the biological prop-erties of the BLM642-1290 DNA helicase,in order to lay a foundation for further research on its antitumor activity.Methods Fluorescence polarization assay,malachite green-phosphate and ammonium molybdate colorime-try,and fluorescein-labeled DNA gel electrophoresis experiments were conducted to study the effects of fangchinoline derivative LYY-32 on the DNA binding activity,ATPase activity,and DNA unwinding activity of BLM642-1290 DNA helicase.The effects of LYY-32 on the DNA unwinding activity of DNA helicase in cells were studied using fluorescent techniques and time-lapse microscopy.Ultraviolet spectral scanning was used to investigate the effects of LYY-32 on the confor-mation of the BLM642-1290 DNA helicase.Results At a concentration of 10 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to dsDNA was 53.17％.At a concentration of 5 μmol·L-1,the inhibition rate of LYY-32 on BLM642-1290 DNA helicase binding to ssDNA was 88.49％.The inhibition rate of LYY-32 on the ATPase activity of BLM642-1290 DNA he-licase was 89.3％at a concentration of 50 μmol·L-1.When the concentration of LYY-32 exceeded 5μmol·L-1,its inhibition rate on the DNA unwinding activity of BLM642-1290 DNA helicase was 100％.LYY-32 also significantly inhibited the DNA unwinding ac-tivity of DNA helicase in cells.However,LYY-32 had no effect on the conformation of BLM642-1290 DNA heli-case.Conclusion The DNA binding activity,AT-Pase activity,and DNA unwinding activity of BLM642-1290 DNA helicase could be significantly inhibi-ted by the fangchinoline derivative LYY-32.