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 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.

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

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 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 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 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.

ObjectiveTo describe the incidence and distribution characteristics of congenital heart disease in newborns， and to analyze the trend of the notification rate from 2009 to 2018 in Chongming District， Shanghai. MethodsBased on the shanghai birth defects surveillance system， newborns delivered in all medical institutions in Chongming District from 2009 to 2018 were examined for congenital heart disease at birth and followed up to 42 days. The notification rate and trends of various congenital heart diseases were described. ResultsThere were 548 cases of neonatal congenital heart disease in Chongming District from 2009 to 2018， and the notification rate was 20.11‰ （95%CI： 18.47‰-21.85‰）， with statistically significant differences between years during the study period （Z=10.616， P<0.001）. The four most common types of congenital heart disease were patent ductus arteriosus （313， 11.49%）， patent foramen ovale （312， 11.45%）， atrial septal defect （88， 3.64%） and ventricular septal defect （73， 2.68%）. Majority of the congenital heart disease cases were patent ductus arteriosus and patent foramen ovale that could be further closed during growth and development. Isolated patent ductus arteriosus and isolated patent foramen ovale accounted for 18.61% and 23.18% respectively of the total cases. ConclusionThe notification rate of congenital heart disease in Chongming District shows a trend of fluctuating decline followed by an increase. Community follow-up and outcome tracking should be strengthened for children with congenital heart disease， especially those with patent ductus arteriosus or patent foramen ovale.