To study the therapeutic effect and mechanisms of ethyl syringate(MD) on ulcerative colitis(UC), the MTT assay was used to detect the proliferation inhibition of RAW264.7 cells and HT-29 cells by different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)). UC cell models were constructed by inducing RAW264.7 cells and HT-29 cells with lipopolysaccharide(LPS) and tumor necrosis factor-α(TNF-α). An animal model was established by inducing mice with 2.5% dextran sulfate sodium(DSS) to verify the therapeutic effect of MD on UC. A control group, a model group(LPS or TNF-α), and groups treated with different concentrations of MD(50, 100, 200, 400 μmol·L~(-1)) were set up in this study. Nitric oxide(NO) levels were measured using a NO detection kit. Intracellular reactive oxygen species(ROS) levels were assessed using a laser confocal microscope and ROS kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect changes in the levels of interleukin-6(IL-6), TNF-α, interferon-γ(INF-γ), interleukin-10(IL-10), and myeloperoxidase(MPO) in cells and animal tissues. Western blot was used to detect the expression levels of phosphorylated Janus kinase 2(p-JAK2), Janus kinase 2(JAK2), phosphorylated signal transducer and activator of transcription 3(p-STAT3), signal transducer and activator of transcription 3(STAT3), zonula occludens-1(ZO-1), occludin, and claudin-1 in cells and animal tissues. The results showed that MD can improve the inflammatory response by inhibiting the production of NO and ROS and regulating the expression of inflammatory factors. It significantly reduced the disease activity index(DAI) in mice, improved the shortening of the colon, and repaired intestinal epithelial damage by inhibiting the activation of the JAK2/STAT3 pathway, thereby exerting anti-UC activity.
Animals ; Colitis, Ulcerative/chemically induced* ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Mice ; Humans ; Signal Transduction/drug effects* ; Male ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism* ; Nitric Oxide/metabolism* ; HT29 Cells ; Salicylates/administration & dosage* ; Protective Agents/administration & dosage*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

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.

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the effect of securinine(SEC)on apoptosis of the human colon cancer cell line SW620,and to elucidate its possible mechanism.Methods:The nude mice with subcutaneously transplanted tumor were divided into control group(n=6),oxaliplatin(OXA)group(n=7),and SEC group(n=7).The volume and mass of subcutaneous tumors in the nude mice were measured in various groups,and the tumor inhibitory rates in various groups were calculated.The SW620 cells were treated with different doses(5-120 μmol·L-1)of SEC for 12,24,48,and 72 h,respectively.Cell counting kit-8(CCK-8)assay was used to assess the survival rates of cells in various groups,and the optimal doses of SEC were confirmed.The SW620 cells were divided into control group,20 μmol·L-1 SEC group,40 μmol·L-1SEC group,and 40 μmol·L-1OXA group.TUNEL staining method and flow cytometry were used to detect the apoptotic rates of cells in various groups.JC-1 staining was used to detect the mitochondrial membrane potentials of cells in various groups,and 2',7'-dichlorodi-hydrofluorescin diacetate(DCFH-DA)fluorescence staining and flow cytometry were used to measure the reactive oxygen species(ROS)levels in the cells in various groups.Western blotting method was used to detect the expression levels of cytochrome C,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),mitogen-activated protein kinase p38,phosphorylated p38(p-p38),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)proteins in the cells in various groups.Results:Compared with control group,the volume and mass of subcutaneously transplanted tumors in the nude mice in SEC group were significantly decreased(P＜0.05 or P＜0.01 or P＜0.001);the inhibitory rates of tumor in SEC group and OXA group were 20.42％and 6.50％.The CCK-8 assay results showed that compared with 0 μmol·L-1 SEC,when the SEC dose exceeded 20 μmol·L-1,the survival rates of SW620 cells were significantly decreased(P＜0.001).The optimal condition for subsequent experiments was set as doses of 20 μmol·L-1SEC and 40 μmol·L-1SEC,and duration of 24 h.The TUNEL results showed that compared with control group,the apoptotic rates of cells in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.001).The results of flow cytometry showed that compared with control group,the apoptotic rate in 40 μmol·L-1SEC group was significantly increased(P＜0.001).The JC-1 staining results showed that compared with control group,the mitochondrial membrane potentials of cells in 20 and 40 μmol·L-1 SEC groups were significantly decreased(P＜0.001).Compared with control group,the levels of ROS detected by DCFH-DA fluorescence staining in the cells of 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were significantly increased(P＜0.001),while the level of ROS detected by flow cytometry in 40 μmol·L-1SEC group was significantly increased(P＜0.05).Compared with control group,the expression levels of Bcl-2 protein in the cells in 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were decreased(P＜0.01),while the expression levels of cytochrome C and Bax proteins were increased(P＜0.001).Compared with control group,the ratios of p-JNK/JNK,p-p38/p38 and p-ERK/ERK in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.01 or P＜0.001).Conclusion:SEC can inhibit the proliferation of SW620 cells,increase the cellular ROS levels,reduce the mitochondrial membrane potential,and induce the mitochondrial apoptosis;its mechanism may be related to the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.

Objective:To systematically evaluate the current financing status of Beijing's urban and rural residents'basic medical insurance,analyze equity disparities among different groups under the existing flat-rate financing policy.By simulating the equity changes of various financing schemes with different contribution rates,this study aims to provide foundations for advancing medical insurance financing system reform.Methods:Based on the per capita disposable income and number of insured residents in Beijing's 16 districts from 2018 to 2023,we separately calculated the Gini coefficient,concentration index,and Kakwani index,along with their changes before and after financing adjustments,to assess the funding burden among different insured groups.Using the geometric mean method,we projected per capita disposable income and insured populations for each district in Beijing from 2024 to 2035,simulating various financing schemes under different premium rate systems.Results:From 2018 to 2023,the Gini coefficient of net income after financing consistently exceeded that of original income before financing.The concentration index remained positive and showed an upward trend,while the Kakwani index was negative for all periods.The Gini coefficient after financing slightly decreased for the elderly and working populations with fiscal subsidy support,whereas it remained higher than that for students and children.Under the simulated differentiated rate system,the post-funding Gini coefficient for 2024-2035 was lower than the original value,and the Kakwani index was positive.Conclusions:The current fixed-amount financing mechanism for urban and rural residents'basic medical insurance exhibits regressive characteristics and insufficient fairness,with disparities in equity among different insured groups.It is necessary to establish differentiated financing standards based on differential rates,particularly implementing a financing mechanism with dynamic adjustments according to regional and group income levels,to enhance the fairness of financing for urban and rural residents'basic medical insurance.

Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.