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 value of serum thymidine kinase 1(TK1),hypoxia-inducible fac-tor-1α(HIF-1α)and squamous cell carcinoma antigen(SCC)in the diagnosis and prognosis of esophageal cancer.Methods A total of 105 patients with esophageal cancer treated in the Qinhuai Medical Zone of East-ern Theater General Hospital from February 2019 to October 2021 were selected as the study group,and 80 healthy subjects were selected as the control group during the same period.The serum levels of TK1,HIF-1αand SCC were compared between study group,control group and patients with different pathological charac-teristics.Patients with esophageal cancer were followed up for 3 years,and the overall survival(OS)and pro-gression-free survival(PFS)were recorded.Receiver operating characteristic curve was used to analyze the di-agnostic efficiency of serum TK1,HIF-1α and SCC combined detection for esophageal cancer,Pearson correla-tion analysis was used to analyze the correlation between the serum indicators,and Kaplan-Meier survival a-nalysis was used to analyze the OS and PFS of patients with different serum levels of TK1,HIF-1α and SCC.Multivariate COX regression was performed to analyze prognostic factors.Results Compared with the control group,the serum TK1,HIF-1α and SCC levels in the study group increased(P＜0.05).The area under the curve(AUC)of serum TK1,HIF-1α,SCC alone and combined for diagnosis of esophageal cancer were 0.893,0.744,0.841,0.922,respectively,and their combined diagnoses of esophageal cancer had the largest AUC.Se-rum TK1,HIF-1α and SCC in patients with different TNM stages and differentiation stages were significantly different(P＜0.05).Serum TK1,HIF-1α and SCC in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05).Serum TK1 was positively correlated with HIF-1α and SCC levels in patients with esophageal cancer(P＜0.05).The survival functions of OS and PFS in TK1,HIF-1αand SCC low expression group were better than those in high expression group(P＜0.05).Multivariate COX regression analysis showed that low differentiation and lymph node metastasis were independent risk factors for poor prognosis in esophageal cancer patients(P＜0.05).Conclusion Serum levels of TK1,HIF-1α and SCC are increased in patients with esophageal cancer,the combined diagnosis of the three is effective.The high expression of TK1 and HIF-1αand SCC will shorten OS and PFS.

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.

Objective To study the shielding effect of water body on γ spectrometer during underwater measurements.Methods A mathematical model of water immersion was constructed for the 3-inch(ф76.2 mm×76.2 mm)lanthanum bromide detector.The totipotent peak count rate of 10 typical γ characteristic energies under different radius water sphere conditions was calculated by MCNP software,and the relationship was established.Results The effective radii of γ photons of different energies based on the 3-inch lanthanum bromide detector was obtained.The relation of energy and effective radius was established,and the effective radius of Tl-208@2614keV was 102.99 cm.Conclusion The quantitative relationship between photons of different energies of a typical 3-inch lanthanum bromide detector and effective radius had been established theoretically,which provides a theoretical basis for measuring and analyzing radioactive water body by γ spectrometer.

BACKGROUND:Up to now,there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages.It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE:To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous(ARCO),thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS:This study used a retrospective study design.A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database,and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria.Patient age,gender,body mass index,and blood laboratory test results were collected.Blood laboratory tests included low-density lipoprotein,total cholesterol,triglycerides,high-density lipoprotein,apolipoprotein β,apolipoprotein α1,uric acid,total protein quantitative,alkaline phosphatase,activated partial thromboplastin time,prothrombin time,prothrombin time International Normalized Ratio,prothrombin time activity,fibrinogen quantitative,coagulation time of thrombin,D-dimer,total iron binding capacity,and platelet count.The indicators of patients with different age groups and different ARCO stages were compared,and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION:(1)There were statistical differences in total cholesterol,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer among ARCO stages in the young group(P<0.05).Among young patients in ARCO stage II,total cholesterol levels were higher than those in ARCO stage III(P<0.05).Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III(P<0.05).Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II(P<0.05).(2)There were statistically significant differences in high-density lipoprotein,coagulation time of thrombin,and D-dimer among ARCO stages in the middle-aged group(P<0.05).Among middle-aged patients in ARCO stage IV,high-density lipoprotein levels were higher than those in ARCO stages II and III(P<0.05).Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III(P<0.05).D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III(P<0.05).(3)The uric acid,activated partial thromboplastin time,D-dimer,and platelet count in the elderly group showed statistically significant differences(P<0.05).The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group(P<0.05),while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group(P<0.05).The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group(P<0.05).The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group(P<0.05).(4)Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head.(5)It is indicated that total cholesterol,high-density lipoprotein,uric acid,prothrombin time,prothrombin time International Normalized Ratio,and D-dimer are statistically significant among patients with different ARCO stages.Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head,while D-dimer,uric acid,overweight,and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head.

Objective:To investigate the effect and the neural mechanisms of Apelin-13 on the behavior changes of posttraumatic stress disorder (PTSD) model mice.Methods:Totally 32 SPF grade male C57BL/6J mice aged 6 weeks were divided into 4 groups randomly ( n=8 in each group): control group, model group, normal saline group and Apelin-13 group.The mice model of PTSD was established by single-prolonged stress (SPS) method. The mice in normal saline group and Apelin-13 group were respectively given lateral ventricular microinjection of 0.9% sodium chloride solution (2 μL) and Apelin-13 (1.5 μg/μL, 2 μL)after PTSD modeling. The behaviors of mice were evaluated by open field test, elevated plus maze test and Morris water maze test.The morphological structure and numerical changes of hippocampal neurons were observed by hematoxylin and eosin (HE) staining.The expression of phosphoinositide 3-kinase(PI3K), phosphorylated-PI3K(p-PI3K), protein kinase B(Akt), phosphorylated-Akt (p-Akt), forkhead box O3a (FoxO3a), phosphorylated-FoxO3a(p-FoxO3a), autophagy-related proteins including microtubule-associated protein 1 light chain 3(LC3) and sequestosome 1(p62) were detected by Western blot. SPSS 26.0 software was used for data analysis.The escape latency data of repeated learning training in Morris water maze was conducted by repetitive measurement ANOVA.The comparison of other data among multiple groups was conducted by one-way ANOVA and further pairwise comparisons were conducted by LSD test and Tamhane test. Result:(1) Open field test results showed statistically significant differences in the central area activity distance and residence time in central area among mice in the four groups ( F=15.37, 9.63, both P<0.05). The central area activity distance ((0.06±0.03) m) and residence time ((2.48±1.02) s) of the mice in model group were lower than those of the control group ((0.19±0.05) m, (15.00±8.91) s)(both P<0.05). And the central area activity distance((0.12±0.04)m)and the residence time((13.56±7.64)s)were higher than those of model group((0.06±0.03)m, (2.48±1.02)s)and normal saline group((0.06±0.02)m, (2.82±1.52)s)(all P<0.05). Elevated plus maze test results showed statistically significant differences in the numbers and time entering open arms among the four groups ( F=10.74, 19.12, both P<0.05). The numbers((4.50±2.51) times) and the time ((26.95±17.48) s) entering the open arm of mice in model group were both lower than those of the control group ((13.75±4.71) times, (103.75±42.43)s) and Apelin-13 group ((10.00±5.18) times, (55.98±19.49) s) (all P<0.05). Morris water maze test results showed that in the 4-day learning and training phase, the time and group interaction of escape latency was not significant among the four groups ( F=1.15, P=0.34), but time main effect and group main effect were significant ( F=131.65, 16.98, both P<0.05). On the 2nd to 4th day, mice in model group showed significantly increased escape latency than mice in control group and Apelin-13 group(both P<0.05). And the numbers crossing original platform and the time in the target quadrant of Apelin-13 group were both higher than those of model group and normal saline group (all P<0.05). (2) HE staining results showed that neurons in the hippocampal CA1 and CA3 area of mice in model group and normal saline group were swollen and arranged loosely.The hippocampal neurons in control group and Apelin-13 group were arranged neatly and densely. (3) Western blot results showed statistically significant differences in the protein expression of p-PI3K, p-Akt, p-FoxO3a, p62 and the ratio of LC3Ⅱ/LC3Ⅰ among the four groups ( F=21.37, 37.35, 20.71, 13.26, 37.65, all P<0.05). The protein expression of p-PI3K, p-Akt, p-FoxO3a and p62 in Apelin-13 group((0.92±0.07), (0.90±0.09), (0.89±0.13), (1.03±0.08)) were higher than those in model group((0.59±0.04), (0.50±0.07), (0.49±0.11), (0.68±0.04)) and normal saline group((0.61±0.06), (0.50±0.08), (0.53±0.11), (0.70±0.05))(all P<0.05), and the ratio of LC3Ⅱ/LC3Ⅰ in Apelin-13 group(0.60±0.06) was lower than those in model group(0.92±0.10) and normal saline group(0.99±0.05) (both P<0.05). Conclusion:Apelin-13 can alleviate the anxiety-like behavior and impaired spatial learning and memory in PTSD model mice. The mechanism may be related to the up-regulation of PI3K/Akt/FoxO3a autophagy pathway.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

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.