The activation of the sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species (ROS) levels. Clinical trials have demonstrated that Zhongfeng Xingnao Liquid (ZFXN) ameliorates post-stroke cognitive impairment (PSCI). However, the underlying mechanism, particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway, remains unclear. This study employed an oxygen-glucose deprivation (OGD) cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation (2VO). The effects of ZFXN on learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro. Results indicated that ZFXN significantly increased the B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax) ratio, reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)⁺ cells, and markedly improved cognition, synaptic plasticity, and neuronal function in the hippocampus and cortex. Furthermore, ZFXN exhibited potent antioxidant activity, evidenced by decreased ROS and malondialdehyde (MDA) content and increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels. ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential (MMP), Tom20 fluorescence intensity, adenosine triphosphate (ATP) and energy charge (EC) levels, and mitochondrial complex I and III activity, thereby inhibiting mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity and elevated SIRT1, nuclear Nrf2, and HO-1 levels. Notably, these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro. In conclusion, ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
Sirtuin 1/genetics* ; Animals ; NF-E2-Related Factor 2/genetics* ; Cognitive Dysfunction/genetics* ; Male ; Rats, Sprague-Dawley ; Rats ; Humans ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Heme Oxygenase-1/genetics* ; Stroke/complications* ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Neuroprotective Agents

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.

Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P＜0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P＜0.001),and a significantly lower serum level of PGE2(Z=-4.909,P＜0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P＜0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P＜0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To investigate the impacts of atrial high-rate episodes (AHRE) on the risks of new onset of atrial fibrillation and all-cause mortality in elderly patients over 90 years old after cardiac dual-chamber pacemaker implantation.Methods:This study was a retrospective study. Patients aged 90 years and above who were implanted with cardiac dual-chamber pacemakers and followed up in the People′s Liberation Army General Hospital from January 2017 to June 2022 were enrolled and divided into AHRE≥6 h group and AHRE<6 h group according to the onset time of AHRE. The primary endpoint was new onset of atrial fibrillation, and the secondary endpoints were all-cause mortality and cardiovascular mortality. Kaplan-Meier survival curve was poltted, and log-rank test was used to compare the differences in the incidence of new onset of atrial fibrillation, all-cause death and cardiovascular death between AHRE≥6 h and AHRE<6 h groups. Multivariate Cox survival analysis was used to investigate the factors affecting new onset of atrial fibrillation, all-cause death and cardiovascular death in elderly patients aged 90 years and above with dual-chamber pacemaker implantation.Results:A total of 169 patients were enrolled, aged (93.95±3.28) years, including 18 females (11%). The median follow-up time was 28.9 months. There were 87 and 82 patients in AHRE≥6 h group and AHRE<6 h group, respectively. Kaplan-Meier survival curve analysis showed that the incidence of new onset of atrial fibrillation (log-rank P<0.001), all-cause death (log-rank P=0.004) and cardiovascular death (log-rank P=0.026) in AHRE≥6 h group was significantly higher than that in AHRE<6 h group.After adjusting for traditional risk factors, multivariate Cox survival analysis showed that AHRE≥6 h was an independent risk factor for new onset of atrial fibrillation ( HR=4.046, 95% CI 2.402-6.814, P<0.001) and all-cause mortality ( HR=1.668, 95% CI 1.119-2.487, P=0.012) in elderly patients over 90 years old with cardiac dual-chamber pacemaker implantation. However, AHRE≥6 h had no effect on cardiovascular mortality ( P>0.05). Anemia ( HR=3.098, 95% CI 1.342-7.153, P=0.008) and heart failure with reduced ejection fraction ( HR=3.028, 95% CI 1.181-7.763, P=0.021) were both independently associated with cardiovascular mortality. Conclusions:AHRE is common in cardiac dual-chamber pacemakers recipients aged 90 years and above, and AHRE≥6 h can be used as a predictor of new onset of atrial fibrillation or all-cause mortality in these patients.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To observe the effect of human mesenchymal stem cells(hMSCs)conditioned medium(CM)co-cultured with the human liposarcoma SW872 cells on the proliferation and migration of the tumor cells,and to discuss the effect of hMSCs CM on the liposarcoma cells and the possible mechanism.Methods:The hMSCs were cultured in vitro and transfected with either lentiviral vector control shNS(control group)or lentiviral shRNA targeting Yes-associated protein(YAP)(shYAP-hMSCs group)by lentiviral methods.The expression levels of YAP mRNA and protein in the hMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The CM was then harvested.The SW872 cells were cultured in vitro and divided into control group(normal culture),hMSCs CM group,and shYAP-hMSCs CM group.The proliferation activities of the cells in various groups were detected by CCK-8 assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the scratch healing rates of the cells in various groups were detected by cell scratch assay;the expression levels of YAP,matrix metallopeptidase-9(MMP-9),and cyclin D1 proteins in the cells in various groups were detected by Western blotting method.Results:Compared with control group,the expression levels of YAP mRNA and protein in the cells in shYAP-hMSCs group were decreased(P＜0.01),indicating the successful establishment of a stable transfected cell line.The CCK-8 assay results showed that compared with control group,the proliferation activity of the cells in hMSCs CM group was increased(P＜0.05),and the proliferation activity of the cells in shYAP-hMSCs CM group was decreased(P＜0.01).The flow cytometry results showed that compared with control group,there was no significant change in the apoptotic rate of the cells in hMSCs CM group(P＞0.05),while the apoptotic rate of the cells in shYAP-hMSCs CM group was increased(P＜0.01).The cell scratch assay results showed that compared with control group,the scratch healing rate of the cells in hMSCs CM group was increased(P＜0.05),and the scratch healing rate of the cells in shYAP-hMSCs CM group was decreased(P＜0.01).The Western blotting results showed that compared with control group,there were no significant differences in the expression levels of YAP,MMP-9,and cyclin D1 proteins in the cells in hMSCs CM group(P＞0.05),while the expression levels of YAP,MMP-9,and cyclin D1 proteins in the cells in shYAP-hMSCs group were decreased(P＜0.05 or P＜0.01).Conclusion:The hMSCs regulate the proliferation and migration of the human liposarcoma SW872 cells,and its mechanism may be related to the expression of YAP.

Objective:To compare the predictive value of different cardiac ultrasound indexes in mechanical ventilation withdrawal / weaning outcome of intensive care unit (ICU) respiratory failure.Methods:Patients who received mechanical ventilation for >48 hours and were to be withdrawn due to respiratory failure in the Department of Critical Care Medicine, 921st Hospital of the People′s Liberation Army from October 2020 to March 2023 were continuously selected, and their general information, mechanical ventilation conditions, and relevant weaning inspection indicators were recorded. Left ventricular ejection fraction (LVEF), left ventricular outflow tract velocity time integral (LVOT-VTI), left heart Tei index (TI), ratio of early mitral valve diastolic peak blood flow velocity to early mitral ring diastolic peak motion velocity (E/e′) were measured by ultrasound. According to the weaning outcome, the receiver operating characteristic (ROC) curves of different cardiac ultrasound indexes were plotted to evaluate the predictive value of the withdrawal outcome.Results:A total of 83 patients were included, of which 62 were successfully withdrawn and 21 were unsuccessful. There were significant differences in mechanical ventilation time, rapid shallow breathing index (RSBI), LVEF, VTI, left cardiac TI and E/e′ between the successful group and the failed group (all P<0.05). Multivariate regression analysis suggested that mechanical ventilation time and E/e′ were independent factors affecting the outcome of patients with respiratory failure ( OR=0.603, 0.282, all P<0.05). The area under ROC curve of E/e′ predicting mechanical ventilation withdrawal/ weaning failure was 0.844(95% CI: 0.729-0.959), which was superior to the RSBI and other cardiac ultrasound indexes. Conclusions:Echocardiography has predictive value for the outcome of mechanical ventilation of respiratory failure, and E/e′, which reflects the diastolic function of the heart, is the most effective predictor, but it is not suitable for single index prediction.