OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

Objective To explore the influencing factors of type 2 diabetes mellitus(T2DM)merging with diabetic peripheral neuropathy(DPN),and to construct and verify a prediction model based on random forest algorithm.Methods 512 T2DM patients who were hospitalized in our hospital from January 2019 to December 2021 were divided into simple T2DM group(n=292)and T2DM combined with DPN group(DPN,n=220)based on whether or not DPN was present.The general data and biochemical indicators of the two groups were compared.Logistic regression analysis was conducted to identify the influencing factors of DPN in T2DM patients.A random forest model was constructed.Results Compared with the T2DM group,the DPN group showed an increase in weight loss rate,incidence of diabetic retinopathy(DR),WBC and HbA1c(P<0.05),with decrease in DM duration≥10 years,TG and HDL-C(P<0.05).Logistic regression analysis showed that age≥60 years,HbA1c,TG,HDL-C,rate of weight loss,DR were influencing factor for T2DM combined with DPN.The random forest model showed that when the number of trees was 387,the error rate was the lowest.The importance ranking of the influencing factors of T2DM combined with DPN were the rate of weight loss,TG,DR,HDL-C,HbA1c and age≥60 years.Conclusions Age≥60 years,HbA1c,TG,HDL-C,rate of weight loss and DR are influencing factors for T2DM combined with DPN,that can be used for early clinical diagnosis and treatment.

Objective To explore mechanisms of family resilience in children with obstetrical brachial plexus palsy(OBPP)and provide a basis for developing interventions to family resilience.Methods Semi-structured interviews were conduc-ted with 10 primary caregivers,and data were analyzed through content analysis.Results Three themes were distilled,namely,great impact of the injurious event on the family,positive response of the family to the injurious event,and hidden pain that the injurious event brought to the family.Conclusion The overall resilience of families of OBPP children is in a high level.It is es-sential to address the adverse impact of the injurious event on the families,consolidate the positive results of the family's re-sponse to the injury,and promote the restoration and enhancement of the family's function.

Objective To analyze the effects of immediate multi-vessel percutaneous coronary inter-vention(MV-PCI)and staged vascular intervention(Staged-PCI,immediate PCI for culprit-only followed by a delayed treatment of all other lesions)on the prognosis in elderly patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 417 elderly acute STEMI patients who underwent PCI in Baoding First Central hospital from January 2021 to June 2023 were enrolled,and according to different treatment strategies,they were divided into MV-PCI group(87 cases)and Staged-PCI group(330 cases).A propensity score matching(PSM)model was established based on baseline data of the two groups,there were 84 cases in each group.During a mean follow-up period of 13.5 months,with the occurrence of main adverse cardi-ovascular and cerebrovascular events(MACCE)as endpoint,the incidence of MACCE was com-pared between the two groups after PSM.Cox proportional hazard regression model was used to analyze the risk factors of MACCE.Results Before PSM,there were significant differences be-tween the two groups in terms of age,proportions of hypertension,diabetes and hyperlipidemia,family history,stroke history,peripheral artery disease,preoperative SBP,lesion vessels(such as left anterior descending branch and left circumflex branch),and number of non-diseased vessels(P＜0.05).Kaplan-Meier survival curve showed that the incidences of MACCE and all-cause mor-tality were significantly lower in the MV-PCI group than the Staged PCI group(Plog rank＜0.05).Multivariate Cox proportional hazard regression model showed that MV-PCI was a protective prognostic factor for MACCE(HR=0.263,95％CI:0.105-0.659,P=0.004)and all-cause death(HR=0.236,95％CI:0.007-0.722,P=0.016).Conclusion MV-PCI can significantly improve the prognosis of elderly patients with acute STEMI with multivessel disease.

Objective: To investigate gender differences regarding changes of myopia rates among Han Chinese students aged 7-18 years in China, and to provide a scientific basis for precise myopia prevention and control. Methods: The visual acuity data of 871 112 students aged 7-18 years from four national student physical fitness and health surveys in 2005, 2010, 2014 and 2019 were selected to analyze gender differences in myopia rates and myopia rates among male and female students in each age group. Results: The overall myopia rate of students aged 7-18 years in China increased from 2005 to 2019( χ 2=7 265.06, P <0.01), and the myopia rate increased from 47.9%(2005) to 60.1% (2019). Gender differences in myopia rates among students trended to decrease( χ 2=72.24, P <0.01), and showed an inverted "U shaped" distribution from south to north, decreasing first and then increasing. Conclusion The problem of myopia in children and adolescents cannot be ignored, and the difference in myopia rates between male and female students should be taken into account, precise prevention and control of myopia accurately according to gender.

Objective To investigate the effect and underlying mechanisms of miR-124 on the an-giogenesis of brain microvascular endothelial cells(BMEC)after oxygen glucose deprivation/reperfusion(OGD/R).Methods Mouse BMEC were randomly divided into normal control group(con),OGD/R group,OGD/R+overexpression control group(OGD/R+ov-con),OGD/R+miR-124 overexpression group(OGD/R+ov-miR-124),OGD/R+silence control group(OGD/R+si-con),and OGD/R+miR-124 silence group(OGD/R+si-miR-124).Migration distance,number of migrated cells,number of tubule formation,CD31 positive cells,miR-124 level,and mRNA and protein expression levels of 15-lipoxygenase(15-LOX)were observed and compared in all each groups of BMEC.Results OGD/R injury resulted in shorter migration distance,less cell migra-tion and tubule formation,lower miR-124 level(P＜0.05,P＜0.01),but higher expression of 15-LOX at mRNA and protein levels when compared with the con group(3.29±0.24 vs 1.00± 0.00,4.31±0.39 vs 1.00±0.00,P＜0.01).Compared with OGD/R+ov-con group,the OGD/R+ov-miR-124 group had longer cell migration distance,increased migration cells and tubule forma-tion,more CD31-positive cells and enhanced miR-124 level,and decreased 15-LOX mRNA and protein levels(P＜0.05).On the contrary,silence of miR-124 led to opposite results when com-pared with the OGD/R+si-con group(P＜0.05).Conclusion MiR-124 may promote the angio-genesis of BMEC after OGD/R through regulating 15-LOX,which providing potential therapeutic targets for ischemic stroke.

Circadian rhythm is driven by the suprachiasmatic nucleus biological clock, and many life activities and physiological functions are regulated by circadian rhythm, such as central nervous system activity, autonomic nervous system activity, endocrine function, metabolism and immune function. At the molecular level, circadian rhythm is regulated by molecular mechanisms generated by clock genes′ oscillations. Endogenous circadian rhythm is one of the main processes controlling sleep. Circadian rhythm disorder is the most common cause of abnormal sleep-wake cycle, and can also lead to a series of diseases and adverse consequences such as other sleep disorders, abnormal cognitive function, hypertension, diabetes and tumors. Recently, the relationship between circadian rhythm and sleeping awakening has become a hot topic for researchers. In this paper, the research progress of circadian rhythm and circadian rhythm sleep-wake disorders was reviewed.

Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.