1.Effect of Wenpi tongluo kaiqiao formula against neuronal necroptosis in mice with Alzheimer’s disease and its mechanism
Xiaomin ZHU ; Wei CHEN ; Yulan FU ; Guifeng ZHUO ; Yingrui HUANG ; Ying ZHANG ; Lin WU
China Pharmacy 2025;36(9):1046-1051
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.
2.Anti-vascular dementia effect of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission
Yulan FU ; Wei CHEN ; Guifeng ZHUO ; Xiaomin ZHU ; Yingrui HUANG ; Jinzhi ZHANG ; Fucai YANG ; Ying ZHANG ; Lin WU
China Pharmacy 2025;36(15):1859-1865
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.
3.Study on the mechanism of Yifei xuanfei jiangzhuo formula against vascular dementia
Guifeng ZHUO ; Wei CHEN ; Jinzhi ZHANG ; Deqing HUANG ; Bingmao YUAN ; Shanshan PU ; Xiaomin ZHU ; Naibin LIAO ; Mingyang SU ; Xiangyi CHEN ; Yulan FU ; Lin WU
China Pharmacy 2024;35(18):2207-2212
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.
4.Differential value of CT radiomics in papillary renal cell carcinoma and clear cell renal cell carcinoma
Xu LIN ; Yankun GAO ; Xiaomin ZHENG ; Xingwang WU
Journal of Practical Radiology 2024;40(1):74-78
Objective To construct a radiomics nomogram combining clinical and a radiomics signature for distinguishing type Ⅱpapillary renal cell carcinoma(pRCC)from atypical clear cell renal cell carcinoma(ccRCC).Methods Clinical and CT data of patients with pathologically confirmed type Ⅱ pRCC(62 cases)and atypical ccRCC(56 cases)were analyzed.A random sample was divided into a training set(82 cases)and a test set(36 cases)in a ratio of 7∶3.Clinical factors were screened to construct clinical factor models.A total of 1 595 radiomics features of tumors were extracted from the corticomedullary phase CT images and based on the most effective features to construct a radiomics signature and calculate the radiomics score(Rad-score).A radiomics nomogram was constructed by combining the Rad-score and independent clinical factors.Receiver operating characteristic(ROC)curve was used to assess the clini-cal usefulness of the models.Decision curve analysis(DCA)was used to assess the difference between the models.Results The radiomics signature showed good discrimination in training set area under the curve(AUC)0.894[95%confidence interval(CI)0.834-0.947]and test set AUC 0.879(95%CI 0.774-0.963).The AUC of the clinical factors model in training set and test set were 0.725(95%CI 0.646-0.804)and 0.698(95%CI 0.567-0.819).The AUC of the radiomics nomogram in training set and test set were 0.901(95%CI 0.840-0.953)and 0.901(95%CI 0.809-0.975).DCA demonstrated the radiomics nomogram outmatched the clinical factors model and radiomics signature in the aspects of clinical usefulness.Conclusion Radiomics nomogram based on enhanced CT can provide good prediction of type Ⅱ pRCC and atypical ccRCC preoperatively,improve the diagnostic accuracy and provide guidance for future clinical treatment.
5.Status quo of pain catastrophizing in patients with diabetic peripheral neuropathic pain and influencing factors analysis
Ziqiang LI ; Guifen FU ; Yanping ZHANG ; Xiang LI ; Xin ZHANG ; Lin ZENG ; Qiuping ZHENG ; Xiaomin XIAN ; Miao WANG
Chongqing Medicine 2024;53(22):3389-3395,3400
Objective To investigate the status quo of pain catastrophizing(PC)in the patients with di-abetic peripheral neuropathic pain(DPNP),and to analyze the influencing factors to provide reference for for-mulating clinical preventive intervention strategies.Methods A total of 206 patients with DPNP admitted and treated in the People's Hospital of Guangxi Zhuang Autonomous Region were selected as the research sub-jects by convenience sampling method.The general data questionnaire,Numerical Rating Scale(NRS),Pain Catastrophizing scale(PCS),Perceived Social Support Scale(PSSS)and diabetes distress scale(DDS)were used to conduct the investigation.Results The incidence rate of PC in 206 cases of DPNP patients was 44.66%(92/206),and the total score of PCS was(30.10±5.16)points.The results of multiple linear regres-sion analysis showed that the gender,duration of diabetes(≥10 years),multiple drug use,number of compli-cations(>5),NRS score,PSSS score and scores of DDS dimensions were the main influencing factors of PC(all P<0.05),which could explain 92.3%of the total variation of PC.Conclusion The PC incidence rate in the patients with DPNP is high.Clinical healthcare workers should pay attention to the evaluation of PC in these patients,and formulate the scientific and effective targeted intervention measures according to the main influen-cing factors to help the patients to reduce the pain burden in order to reduce the level of PC.
6.Impact of therapeutic plasma exchange intervention timing and liver injury periodization on the prognosis of pa-tients with exertional heat stroke
Zongzhong HE ; Min WANG ; Yuan ZHUANG ; Jie LIN ; Leiying ZHANG ; Liyang ZOU ; Lingling LI ; Chunya MA ; Xiaomin LIU ; Xiang QUAN ; Ying JIANG ; Mou ZHOU ; Hongjun KANG ; Yang YU
Chinese Journal of Blood Transfusion 2024;37(7):728-733
Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P<0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P<0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.
7.Analysis of mental health literacy and related factors among non-graduating middle school and high school students in Taizhou, Zhejiang Province
Xiaomin HE ; Jingyi WANG ; Haijiang LIN ; Tingting WANG ; Yuting YANG ; Xiaoxiao CHEN ; Chaowei FU
Shanghai Journal of Preventive Medicine 2024;36(12):1174-1181
ObjectiveTo explore the characteristics and major factors influencing mental health literacy (MHL) among non-graduating middle school and high school students in Taizhou, Zhejiang Province, and to provide a reference for the promotion of mental health literacy among adolescents. MethodsFrom September to October 2023, a stratified random cluster sampling method was used to conduct a questionnaire survey among students from three classes each in non-graduating grades in four middle schools and four high schools in Taizhou, Zhejiang Province. The survey included basic demographic information, a Structured Mental Health Literacy Questionnaire (MHLQ), and other psychological scales [Educational Stress Scale for Adolescents (ESSA), Perceived Choice Single Scale (PC), Child Depression Inventory (CDI), Generalized Anxiety Disorder (GAD), The University of California at Los Angeles 3-item Loneliness Scale (UCLA-3) and Multidimensional Scale of Perceived Social Support (MSPSS)]. t-tests, chi-square tests, analysis of variance (ANOVA), and multiple linear regressions were applied for the statistical analysis of the data. ResultsThe mental health literacy average score of 2 094 students was (82.3±15.8) points, with a mean of (4.1±0.8) points. The dimension of belief in mental health rights had the highest score. There were significant differences in the mental health literacy score across different dimensions for students with different household registration, economic levels, academic performance, and father’s education level (P<0.001). Multiple linear regression analysis indicated that rural household registration, lower paternal education level, greater academic pressure, a weaker sense of control over one’s behavior, less social support, and symptoms of loneliness, depression, or anxiety were associated with poorer mental health literacy among the students. ConclusionThe mental health literacy of middle school and high school students in Taizhou is generally good, but there are differences among students with different characteristics. Targeted interventions should be carried out for students from rural areas, with poorer mental health, and less low social support to improve the overall mental health literacy of adolescents.
8.Efficacy and safety of HA-Mg drainage plate implantation in anterior chamber for intraocular pressure control in rabbit eyes
Xiaomin ZHU ; Wangdu LUO ; Yi LIN ; Mingming CAI ; Yi CHEN ; Lin XIE ; Yong WANG ; Xiangji LI
Chinese Journal of Experimental Ophthalmology 2024;42(6):503-510
Objective:To evaluate the safety and efficacy of hydroxyapatite-magnesium (HA-Mg) glaucoma drainage plate after implantation in rabbit eyes.Methods:Twelve New Zealand white rabbits were randomly assigned to HA-Mg drainage implant group and trabeculectomy group using the paired comparison method, with 6 rabbits in each group.The right eyes of rabbits were taken as the experimental eyes, and the left eyes of rabbits were taken as a normal control group.HA-Mg drainage implant group underwent implantation of the HA-Mg drainage plate and the trabeculectomy group underwent trabeculectomy.At 1, 3, and 5 months after surgery, the ocular condition was observed by slit-lamp examination with auxiliary lenses and the fixation of the drainage plate in the anterior chamber and subconjunctiva was measured by ultrasound biomicroscopy.At 5 months after surgery, corneal endothelial cell counts were performed with a corneal endothelial cell counter.The intraocular pressure (IOP) was continuously measured weekly for 21 weeks preoperatively and postoperatively.The flow patency of aqueous humor drainage channel was identified by the injection of trypan blue in anterior chamber.The aqueous humor drainage channels and surrounding tissues were evaluated by hematoxylin-eosin (HE) staining after HA-Mg drainage plate was completely degraded.This study was in accordance with China Animal Welfare Law and the ARVO Statement on the use of animals for ophthalmic research, and animal experiments were conducted in accordance with the Regulations on the Administration of Experimental Animals issued by the National Science Council.The study protocol was reviewed and approved by the Ethics Committee of The Third Affiliated Hospital of Chongqing Medical University (No.Kelun Pre-Examination [2021]14).Results:No systemic or ocular side effects were observed in the experimental animals after surgery.All 6 HA-Mg drainage plates were completely degraded about 4 months postoperatively, among which 4 plates were well-fixed and 2 plates had a minimal rotation, and no plate moved into the anterior chamber.At 5 months after surgery, the number of corneal endothelial cells in the HA-Mg drainage implant group and normal control group was 2 535.2±274.4 and 2 521.0±175.8, respectively, and there was no statistical significance between them ( t=0.073, P=0.857).There were statistically significant differences in IOP among the three groups at different time points before and after surgery ( Fgroup=26.409, P<0.001; Ftime=7.843, P<0.001), in which the IOP in trabeculectomy group and normal control group at different time points after surgery was higher than that in HA-Mg drainage implant group, and the IOP in HA-Mg drainage implant group at different time points after surgery was lower than that before surgery (all at P<0.05).The patency test revealed that the trypan blue could still drain from the anterior chamber to the subconjunctiva 5 months after HA-Mg drainage plate implantation.The scleral linear aqueous humor drainage channel and anterior synechia were observed after drainage plate completely degraded 6 months postoperatively, and no obvious inflammatory cell infiltration was seen. Conclusions:After implantation of HA-Mg drainage plate in rabbit eyes, the intraocular pressure can be effectively lowered and the safety is good.
9.The value of combined model nomogram based on clinical characteristics and radiomics in predicting secondary loss of response after infliximab treatment in patients with Crohn′s disease
Shuai LI ; Chao ZHU ; Xiaomin ZHENG ; Yankun GAO ; Xu LIN ; Chang RONG ; Kaicai LIU ; Cuiping LI ; Xingwang WU
Chinese Journal of Radiology 2024;58(7):745-751
Objective:To investigate the value of nomogram based on radiomics features of CT enterography (CTE) combined with clinical characteristics to predict secondary loss of response (SLOR) after infliximab (IFX) treatment in patients with Crohn′s disease (CD).Methods:This study was a case-control study. Clinical and imaging data of 155 patients with CD diagnosed at the First Affiliated Hospital of Anhui Medical University from March 2015 to July 2022 were retrospectively collected. The patients were divided into a training set ( n=108) and a testing set ( n=47) in the ratio of 7∶3 by stratified sampling method. All patients were treated according to the standardized protocol and were classified as SLOR (43 in the training set and 18 in the testing set) and non-SLOR (65 in the training set and 29 in the testing set) according to treatment outcome. Based on the data from the training group, independent clinical predictors of SLOR after IFX treatment were screened in the clinical data using univariate and multivariate logistic regression analysis to establish a clinical model. Intestinal phase images were selected to be outlined layer by layer along the margin of the lesion to obtain the volume of the region of interest to extract the radiomics features. The radiomics features were screened using univariate analysis and the minimum absolute shrinkage and selection operator to establish the radiomics model. Multivariate logistic regression analysis was used to build a combined clinical-radiomics model based on the screened clinical independent predictors and radiomics characters, then a nomogram was drawn. The predictive efficacy of the 3 models for SLOR after IFX treatment was assessed by receiver operating characteristic curves, and the area under the curve (AUC) was calculated. The decision curve analysis was applied to evaluate the clinical utility of the models. Results:Disease duration ( OR=1.983, 95% CI 1.966-2.000, P=0.046) and intestinal stenosis ( OR=1.246, 95% CI 1.079-1.764, P=0.015) were identified as the independent predictors of SLOR in the clinical data, and a clinical model was established. Totally 9 radiomics features were included in the radiomics model. The AUCs of clinical, radiomics, and combined models for predicting SLOR after IFX treatment in CD patients were 0.691 (95% CI 0.591-0.792), 0.896 (95% CI 0.836-0.955), and 0.910 (95% CI 0.855-0.965) in the training set, and 0.722 (95% CI 0.574-0.871), 0.866 (95% CI 0.764-0.968), and 0.889 (95% CI 0.796-0.982) in the testing set. Decision curve analysis in the testing set showed higher net clinical benefits for both the radiomics model and combined model than the clinical model, and combined model had higher net clinical benefits than the radiomics model over most threshold probability intervals. Conclusions:CTE-based radiomics model can effectively predict SLOR after IFX treatment in patients with CD, and a combined model by incorporating clinical characteristics of disease duration and intestinal stenosis can further improve the predictive efficacy.
10.Application progress of multi-omics technology in clinical nursing research
Jianmei YANG ; Guiru LIN ; Wanyi OU ; Dongliang CHEN ; Yuanfei WANG ; Aiping WU ; Zumin CHEN ; Ze ZENG ; Xiaomin LU ; Chenli LIN ; Yinji LIANG
Chinese Journal of Nursing 2024;59(16):2044-2048,后插1
The update of multi-omics technology is a key means to promote the rapid development of accurate health model in the whole life cycle.It can formulate dynamic and accurate nursing measures and provide massive data information from the perspective of nursing biology of health and disease.At present,clinical nursing research faces many challenges such as insufficient application and transformation ability of multi-omics technology.This paper introduces the multi-omics technology,reviews the application status of multi-omics technology in cancer nursing,maternal and child nursing,chronic metabolic disease nursing and symptom management,and puts forward the cross integration and prospect of multi-omics technology and nursing research,so as to strengthen the information mining ability of nurses at different levels of health and disease,and provide an important basis for accelerating the clinical transformation of precision nursing.

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