Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective To explore the effect of different treatment methods on prognosis in elderly patients with lower extremity arterial occlusive disease.Methods A total of 352 elderly patients with lower extremity arterial occlusive disease admitted in our hospital from May 2020 to May 2022 were enrolled,and according to their willingness and characteristics of lower extremity le-sions,they were divided into balloon dilation group(142 patients),stent implantation group(145 patients)and conservative treatment group(65 patients).All patients were followed up for 13-24 months.The incidences of major adverse cardiovascular events(MACE),including all-cause death,acute myocardial infarction,acute ischemic stroke,and major adverse lower limb events(MALE),including lower extremity pain at rest,ulcers or skin defects,gangrene,reocclusion,and amputation were observed and recorded.The clinical data and prognosis were compared and ana-lyzed of the three groups.Kaplan-Meier survival curves were drawn.Results The incidence of all-cause mortality was significantly lower in the stent implantation group than the conservative treatment group(9.7％vs 23.1％,P＜0.01).The incidence of MALE was obviously lower in the stent implantation group and the balloon dilatation group than the conservative treatment group(4.8％and 9.2％vs 24.6％,P＜0.01).Conclusion Endovascular therapy can reduce the risk of all-cause death and MALE occurrence in elderly patients with lower extremity arterial occlusive disease who are suitable for interventional therapy.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective: To describe the current situation of leisure time physical activity, sedentary behavior, and sleep duration of children and adolescents aged 6-14 in Beijing, and provide a reference basis for guiding school age children to carry out reasonable physical activities and formulating effective intervention measures. Methods: A multistage stratified cluster random sampling method was used to investigate the nutritional and health status of 3 460 students in the first,third,fifth and seventh grades. Through the questionnaire surveys, the basic information of children and families and the activity information of children physical activity, sedentary behavior, and sleep were collected and statistically analyzed. Results: The results showed that the median time of children daily leisure time physical activity (LTPA) was 20.0 (8.6, 38.6) min, children in suburb areas (18.6 min) and seventh grade (14.3 min) had shorter LTPA time( Z/H =5.12，119.11， P <0.01). The average daily sleep duration of children was (8.71 ± 0.76) h, the proportion of school age children with insufficient sleep reached 54.7%. With an increase in grades, the incidence of insufficient sleep increased significantly ( χ 2=407.13， P <0.01). The median daily sedentary time of children was 195.7(145.0, 255.7 ) min, and 84.5% of children engaged in more than two hours of sedentary behavior every day. Urban (202.9 min) and obese children (210.4 min) had longer sedentary behavior time, and with the increase in grade, the daily sedentary behavior time of children gradually increased ( Z/H =5.04，14.83，637.98， P <0.01). Conclusion Children and adolescents aged 6-14 years in Beijing have less LTPA time, too much sedentary time, and insufficient sleep duration. Grade is an important factor affecting physical activity, sedentary behavior, and sleep duration of children, and body shape may be related to their sedentary behavior and sleep time.It is suggested that targeted policies should be adopted for children of different grades to increase their physical activity and reduce their sedentary behavior to promote their healthy development.

Humans ; Animals ; Mice ; NF-kappa B/metabolism* ; Crohn Disease/drug therapy* ; Dextran Sulfate ; Colitis/metabolism* ; Macrophages/metabolism* ; Adenosine Triphosphate/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/metabolism*

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

Objective:To evaluate the role of the sodium leak channel (NALCN) in the hippocampal dentate gyrus (DG) in the social behavior of mice.Methods:Thirty-nine male wild-type C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were used in this study. Three mice were sacrificed to verify the expression and co-expression of NALCN with neuronal nuclear antigen (NeuN) in the hippocampal DG using the immunofluorescent staining. The remaining 36 mice were divided into 2 groups ( n=18 each) by the random number table method: control group (group C) and NALCN gene knockdown group (group KO). NALCN-shRNA virus was injected in group KO, and scrambled-shRNA virus was injected in group C. The three box social test and open field test were performed at 3 weeks after the virus injection. Mice were sacrificed under anesthesia after the behavioral test, hippocampal tissues were collected, and the injection location of the virus was verified with a fluorescence microscope, and the NALCN protein and mRNA expression in the hippocampal DG was detected by Western blot and real-time polymerase chain reaction, respectively. Results:NALCN and NeuN co-expressed a lot on the same neuron in the hippocampal DG of mice, indicating that NALCN was widely expressed on the neurons in the hippocampal DG. Compared with group C, the expression of NALCN and mRNA in the hippocampal DG was significantly down-regulated, and the social novelty preference disappeared ( P<0.05), and no significant change was found in the social ability and each parameter in the open field test in group KO ( P>0.05). Conclusions:NALCN in the hippocampal DG is involved in the regulation of social memory in mice, and the down-regulated expression of NALCN can lead to the loss of social novelty preference in mice.

Objective:To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in penehyclidine hydrochloride-induced reduction of endotoxin-induced acute lung injury (ALI) in mice.Methods:Forty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), ALI group, penehyclidine hydrochloride group (PHC group), and α7nAChR inhibitor MLA group (MLA group). ALI was induced by intraperitoneal injection of lipopolysaccharide 15 mg/kg in anesthetized animals, while normal saline was given instead in group C. In PHC group, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected at 30 min before developing the model. MLA 10 mg/kg was intraperitoneally injected at 10 min before administration of penehyclidine hydrochloride in MLA group. Mice were sacrificed at 6 h after lipopolysaccharide administration, and lung tissues were collected for microscopic examination of the pathological changes (by HE staining) and for determination of the wet/dry weight ratio (W/D ratio), content of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay) and expression of α7nAChR (by Western blot). Results:Compared with C group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was up-regulated in ALI, PHC and MLA groups ( P<0.05). Compared with ALI group, the W/D ratio and contents of TNF-α and IL-1β were significantly decreased, the content of IL-10 was increased, and the expression of α7nAChR was up-regulated in PHC group ( P<0.05). Compared with PHC group, the W/D ratio and contents of TNF-α and IL-1β were significantly increased, the content of IL-10 was decreased, and the expression of α7nAChR was down-regulated in MLA group ( P<0.05). Compared with ALI group, the pathological changes of lung tissues were significantly mitigated in PHC group, while this effect of PHC was partially reversed by α7nAChR inhibitor MLA. Conclusions:α7nAChR is involved in penehyclidine hydrochloride-induced reduction of endotoxin-induced ALI in mice.

Objective:To investigate Helicobactor pylori (H. pylori) infection status and interfamilial transmission pattern in Zhengzhou area. Methods:A cross-sectional study was conducted from September 2020 to march 2021, among 731 individual from 266 families randomly selected from 9 communities of Zhengzhou area. H. pylori infection status was determined by serum antibody tests, and 13C-urea breath test was performed in the previously eradicated population to clarify the current infection status. The individual and familial infection rate, infection status for couples and children and adolescent were analyzed. Results:Among 731 individuals from 266 families, 397 of them were H. pylori positive. The individual infection rate was 54.31% (397/731); among infected individuals 77.83% (307/397) were infected with type Ⅰ strain, 22.67% (90/397) were infected by type Ⅱ strain. Annual household income ( χ2=0.419, 0.410, 0.213, all P>0.05), smoking history (χ 2=0.071, P>0.05), drinking history ( χ2=0.071, P>0.05), dining place ( χ2=0.009, P>0.05), gastrointestinal symptoms ( χ2=0.047, P>0.05), family history of gastric disease ( χ2=0.069, P>0.05), and history of gastric cancer ( χ2=0.004, P>0.05) had no significant differences between H. pylori-positive and -negative groups, but the infection rate in individuals with higher education level was lower ( χ2=4.449, P<0.05). The infection rate was significantly higher in≥18 age groups compared with<18 age groups ( χ2=6.531, 23.362, 20.671, 24.244, 37.948, 14.597 and 5.170, all P<0.05). The familial H. pylori infection rate was 87.59% (233/266), and in 61 families all member were infected (26.18%, 61/233). The positive rate was 23.08% (6/26) in 50 families with children under 18 years when both parents were infected. Among 231 coupled families, both couples were infected in 78 families (33.76%), one couple was infected in 113 families (48.92%), and both couples were not infected in 40 (17.32%). With the increase of marriage time, the infection rate of both spouses increased significantly ( χ2=7.775, 12.662, 15.487, all P<0.05). Conclusions:The distribution of H. pylori infection presents a family cluster pattern, and intrafamilial infection is an important transmission rout of H. pylori. The type I strain of H. pylori is the dominate strain in this area.