BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

BACKGROUND:Filamin B(FLNB)can crosslink the actin cytoskeleton into a dynamic structure that is essential for the directional movement of cells.It can regulate the proliferation,differentiation and apoptosis of chondrocytes.However,the effect of FLNB on osteoblast proliferation,migration and apoptosis has not been reported. OBJECTIVE:To investigate the effect of FLNB on the proliferation,migration and apoptosis of MC3T3-E1 cells. METHODS:The adenoviral vectors for knockdown of FLNB expression(sh-FLNB1,sh-FLNB2,sh-FLNB3)were constructed and infected with MC3T3-E1 cells.After screened by puromycin drug,the efficiency of FLNB knockdown was detected by western blot and RT-PCR.The MC3T3-E1 cell line with the best efficiency of FLNB knockdown was selected as the stable transient cell line of MC3T3-E1 for subsequent experiments.The cells were divided into blank group,mc3t3 group,sh-NC group(empty vector),and sh-FLNB group(sh-FLNB lentivirus).The blank group was cultured in cell-free α-MEM complete medium;the mc3t3 group was cultured in α-MEM complete medium alone;and the sh-NC and sh-FLNB groups were cultured with α-MEM medium containing 2.5 μg/mL puromycin.After 3 days of culture,cell counting kit-8 assay and cell scratch assay were used to detect the proliferation and migration ability of MC3T3-E1;flow cytometry was used to detect cell apoptosis;and RT-PCR was used to detect the expression of apoptosis-related genes. RESULTS AND CONCLUSION:Western blot and RT-PCR results showed that the efficiency of FLNB knockdown was the best in the sh-FLNB3(P<0.000 1),which was used as a stable cell line for subsequent experiments.Cell counting kit-8 data showed that the proliferative ability of MC3T3 cells was significantly weakened after knockdown of FLNB(P<0.05).Cell scratch assay results showed that the migration ability of MC3T3 cells was significantly decreased after knockdown of FLNB.Flow cytometry and RT-PCR results showed that the apoptotic rate of MC3T3-E1 cells increased after knockdown of FLNB,the expression of pro-apoptotic factor Bax increased significantly,and the expression of anti-apoptotic factor Bcl-2 decreased significantly(P<0.05).To conclude,knockdown of FLNB can reduce the proliferation ability of MC3T3-E1 cells,decrease the migration ability of the cells,and increase cell apoptosis.

Objective:To investigate the association between plasma anti-Müllerian hormone(AMH) levels and ischemic stroke.Methods:In this case-control study, 93 ischemic stroke patients were randomly selected as the case group from a study on the prevention and treatment of metabolic syndrome, which was conducted in 2018-2019 in Changshu, Jiangsu Province, while 372 nonischemic stroke patients were selected as the control group according to the principle of 1∶4 matching.An enzyme-linked immunosorbent assay was used to measure plasma AMH levels.The conditional logistic regression model and restricted cubic spline were used to analyze the relationship between AMH levels and ischemic stroke.Results:A total of 465 subjects with an average age of (68.7±7.4)years were included in this study, of whom 215(46.2%)were men and 250(53.8%)were women.According to our conditional Logistic regression analysis, the risk of ischemic stroke was reduced by 44% for every unit increase in the log-AMH level( OR=0.56, 95% CI: 0.37-0.85)in the overall population after multivariate adjustment.Compared with the tertile with the lowest AMH level, the risk of ischemic stroke in the tertile with the highest AMH level decreased significantly( OR=0.37, 95% CI: 0.19-0.69). When subgrouped by sex, the tertiles with the highest AMH levels were associated with a 66% lower risk of ischemic stroke in men( OR=0.34, 95% CI: 0.13-0.88)and a 64% lower risk of ischemic stroke in women( OR=0.36, 95% CI: 0.15-0.87), compared with the tertiles with the lowest AMH levels.The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between plasma AMH levels and ischemic stroke both in the general population and in male or female population( Pvalues for linear trends were 0.0002, 0.008 and 0.007, respectively). Conclusions:Higher plasma AMH levels decrease the risk of ischemic stroke with a dose-response pattern.

Objectives:This study aims to investigate optimal surgical management strategies for pediatric patients diagnosed with volume-overloaded mitral regurgitation. Methods:A comprehensive retrospective analysis was conducted on a cohort of 110 pediatric patients who underwent primary mitral valve repair for volume-overloaded mitral regurgitation at Fuwai Hospital between April 2020 and March 2022.The cohort,with an average age of(14.5±15.1)months and 38.2%males,was divided into standardized group for patients receiving 3-step standardized mitral valvuloplasty(n=69)and annuloplasty group for patients undergoing annuloplasty only(n=41).After propensity score matching,a total of 38 pairs of patients were included,comparing the primary endpoint(functional mitral failure and postoperative heart failure)between the two groups. Results:Over a median follow-up of 26.3(19.8,32.9)months,and with a median echocardiographic follow-up of 11.9(7.5,14.8)months,no death was recorded.Among the cases,one patient(0.8%)necessitated unplanned reoperation;and seven patients(6.4%)experienced a recurrence of moderate-severe mitral regurgitation as observed through echocardiography beyond 6 months post-surgery.Additionally,nine patients developed heart failure at one month post-discharge.Above events were similar between the two groups.Following propensity score matching,patients in the standardized group demonstrated significantly longer cardiopulmonary bypass and aortic cross-clamp times compared to the annuloplasty group(both P＜0.05),other outcomes were similar between the two groups.Subgroup analysis based on age indicated that infants(＜1 year old)in the standardized group exhibited a significantly lower incidence of major endpoint events compared to the annuloplasty group.Additionally,postoperative echocardiography in annuloplasty group indicated that Z score of left ventricular end diastolic diameter was still greater than 2 during the latest follow-up. Conclusions:Patients with volume-overloaded mitral regurgitation in the standardized group exhibited comparable perioperative recovery and postoperative outcomes as in the annuloplasty group.For pediatric patients suffering from volume-overloaded mitral regurgitation,particularly those under one year of age,the standardized surgical approach exhibited reduced rates of heart failure and major endpoint events,and this strategy is more suitable for this patient group.

Objective:To investigate the current situation of the fatalism of the disabled elderly in hospital, and to analyze the influencing factors, so as to provide a basis for the later development of targeted intervention programs.Methods:This was a cross-sectional survey study. From December 2 to 29, 2023, the convenience sampling method was used to investigate the disabled elderly hospitalized in 7 tertiary general hospitals in Sichuan Province by the general information questionnaire, the Activity of Daily Living scale and the Fatalism Scale. And its influencing factors were conducted by the multivariate linear regression.Results:A total of 280 questionnaires were distributed in this survey, and 269 questionnaires were effectively recovered, with an effective recovery rate of 96.07%(269/280). There were 136 males and 133 females, aged 60-69 years old with 61 cases, 70-79 years old with 103 cases, ≥80 years old with 105 cases. The score of the fatalism in hospitalized disabled elderly was (48.87 ± 10.02) points, of which the pre-determined dimension score was (18.73 ± 4.17) points, the luck dimension score was (12.75 ± 3.42) points, and the pessimistic dimension score was (17.39 ± 4.72) points. Multivariate linear regression showed that the frequency of visits to relatives and friends and the level of education were protective factors for the occurrence of fatalism (t=-3.02, -2.81, both P<0.05), and economic pressure was a risk factor for the occurrence of fatalism (t=4.35, P<0.01).Conclusions:The fatalistic view of the disabled elderly in the hospital is at a medium level.Medical staff can start from the influencing factors, formulate relevant intervention measures, and improve the level of the patient's fatalism.

Objective:To analyze the clinical advantages of the modified Trocar approach in laparoscopic cholecystectomy (LC) compared to the conventional three-hole approach.Methods:Clinical data of 202 patients undergoing the modified Trocar approach LC (the modified group) at the First Affiliated Hospital of Wenzhou Medical University from January 2015 to September 2023 were retrospectively analyzed, including 84 males and 118 females patients, aged (49.58±13.03) years old. The conventional group enrolled 606 patients, including 245 males and 361 females, aged (50.99±12.55) years old. The operative time, conversion to four-hole approach, postoperative complications, hospital stay, pain score, and satisfaction score were compared between the groups.Results:No severe complications occurred in either group. In modified group, three cases (1.5%, 3/202) required conversion to four-hole approach, while in conventional group, seven (1.2%, 7/606) required conversion, with one case conversed to open surgery ( P>0.05). The operative time in modified and conventional groups were (40.28±13.51) min and (40.38±18.75) min, respectively ( P>0.05). The postoperative pain scores were 2.49±1.23 and 3.02±1.48, respectively ( t=5.05, P<0.001). The average postoperative hospital stays were (2.87±0.93) d and (3.80±1.31) d, respectively ( t=11.05, P<0.001). The postoperative Kiyak satisfaction scores were 4.31±0.66 and 4.15±0.63, respectively ( t=2.93, P=0.004). Conclusion:The safety of modified Trocar approach is comparable to that of conventional three-hole approach. The modified approach showed a shorter postoperative hospital stay, less pain, better scars, and higher patient satisfaction.

Cultural construction in public hospitals is currently confronted with several challenges,including lack of em-phasis,tendencies towards formalism,and a sense of detachment.This paper explores how enhancing the leadership of the Com-munist Party of China in cultural endeavors,elevating the awareness among medical professionals,and instituting a multifaceted approach to cultural work can pave the way for new advancements in the cultural landscape of public hospitals.It also discusses comprehensive enhancements of the medical service system by refining and expanding the channels through which cultural initia-tives are communicated and implemented.Furthermore,the paper underscores the practical value of Xi s thought on culture in guiding the cultural construction of public hospitals in the new era.It delineates new directions and goals for hospital cultural devel-opment,providing a theoretical foundation and practical guidance that can propel public hospitals towards high-quality development.

With the increasing aging process, the number of elderly people with cognitive frailty is gradually increasing, which has a profound impact on the clinical outcomes of the elderly. Early identification and precise intervention of cognitive frailty can delay the occurrence of adverse outcomes. This paper reviews the development and research status of cognitive frailty risk prediction models for the elderly in the community, summarizes and compares the characteristics and basic situation of each prediction model, in order to provide references for improving the early identification and intervention of cognitive frailty among the elderly population in the community.

Objective:To explore the current situation of stigma among disabled elderly inpatients and analyze its influencing factors, so as to provide reference for formulating targeted intervention measures.Methods:This study was a cross-sectional survey. In December 2023, convenience sampling was used to select 428 disabled elderly inpatients from 12 ClassⅢ Grade A hospitals in Sichuan Province as research subjects. General Information Questionnaire and Social Impact Scale (SIS) were used to conduct surveys on patients. Multiple linear regression analysis was used to explore the influencing factors of stigma among disabled elderly inpatients.Results:A total of 428 questionnaires were distributed, and 407 valid questionnaires were collected, with a valid response rate of 95.09% (407/428). SIS score of 407 disabled elderly inpatients was (56.55±8.38). Multiple linear regression analysis showed that the number of diseases, educational level, and self-rating economic pressure were the influencing factors of stigma among disabled elderly inpatients ( P<0.05) . Conclusions:The stigma among disabled elderly inpatients is at a moderate level. Medical and nursing staff should establish a comprehensive prevention and management mechanism based on influencing factors.