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.Mediating effect of activities of daily living between pain and depressive symptoms in Chinese elderly
Shan JIANG ; Huaiju GE ; Wenyu SU ; Shihong DONG ; Weimin GUAN ; Qing YU ; Huiyu JIA ; Wenjing CHANG ; Jinglei ZHANG ; Kang ZHANG ; Guifeng MA ; Wentao WEI
Journal of Public Health and Preventive Medicine 2025;36(4):12-16
Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.
3.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.
4.Analysis of laboratory indicators such as vitamin D and blood lipids and pregnancy outcomes in pregnant women with preeclampsia
Xiaolan LIU ; Yuxia ZHANG ; Guifeng DING
Chongqing Medicine 2024;53(4):493-497
Objective To explore the relationship among serum vitamin D,calcium ion,blood lipid lev-els and preeclampsia in pregnant women,and analyze the pregnancy outcomes of pregnant women with pre-eclampsia.Methods A total of 166 pregnant women with preeclampsia who underwent pregnancy examina-tion and delivered in Urumqi Municipal Maternal and Child Health Care Hospital from January 1,2021 to Jan-uary 1,2023 were selected as the observation group,and 200 healthy pregnant women during the same period were selected as the control group.The levels of serum vitamin D,calcium ion,phosphorus ion,blood lipid in-dicators,uric acid,and creatinine were detected in the two groups,and the pregnancy complications and preg-nancy outcomes were observed.The influencing factors of preeclampsia were analyzed by using multivariate logistic regression model.Results The levels of serum vitamin D,calcium ion,and high density lipoprotein in the observation group were lower than those in the control group,and the levels of serum uric acid and creati-nine were higher than those in the control group,with statistical significance(P<0.05).The incidence of fetal growth retardation,placental abruption,oligohydramnios,cesarean section,low birth weight infants,premature delivery,and postpartum hemorrhage in the observation group were significantly higher than those in the con-trol group(P<0.05).Multivariate logistic regression analysis showed that serum vitamin D(OR=15.141,95%CI:1.831-125.204,P=0.012),calcium ion(OR=4.625,95%CI:2.654-8.059,P<0.001),high-den-sit y lipoprotein(OR=0.395,95%CI:0.235-0.666,P<0.001),creatinine(OR=1.034,95%CI:1.005-1.063,P=0.020)and uric acid(OR=1.006,95%CI:1.003-1.010,P<0.001)were independent factors for the occurrence of preeclampsia in pregnant women.Conclusion The levels of serum vitamin D,calcium ions,blood lipids,uric acid and creatinine may be correlated with the occurrence of preeclampsia.
5.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.
6.The mediating effect of mother-infant attachment on the relationship between maternal body image during pregnancy and postpartum depression
Yiyun YANG ; Hui ZHOU ; Zhu ZHU ; Congshan PU ; Yiting WANG ; Yingying ZHANG ; Xiaona YAN ; Guifeng HU
Chinese Journal of Practical Nursing 2024;40(1):58-63
Objective:To investigate the current status of maternal body image during pregnancy, mother-infant attachment and postpartum depression and explore the mediating effect of mother-infant attachment on maternal body image during pregnancy and postpartum depression, in order to effectively reduce the incidence of postpartum depression and provide reference and guidance for alleviating depressive symptoms.Methods:A total of 362 pregnant women admitted to obstetric wards in Women′s Hospital of Nanjing Medical University were selected for a cross-sectional investigation by applying the Edinburgh Postnatal Depression Scale, the Body Image in Pregnancy Scale and the Maternal Postnatal Attachment Scale by convenient sampling from July to September 2022. Model 4 in the SPSS macro program PROCESS was used to test the mediating effect of maternal infant attachment between body image and postpartum depression.Results:Totally 362 valid questionnaires were retrieved including 194 individuals aged ≤30 years old and 168 individuals aged >30 years old. The scores of maternal body image during pregnancy, mother-infant attachment and postpartum depression were (89.24 ± 15.56), (71.40 ± 8.05), 7.50 (4.00, 11.00) points.Conclusions:Body image during pregnancy can not only directly predict postpartum depression, but also indirectly predict postpartum depression through the mediating effect of mother-infant attachment. In order to prevent or reduce the occurrence of postpartum depression, nursing staff should carry out intervention research based on influencing the path of postpartum depression from the perspective of positive psychology.
7.Influencing factors of follow-up compliance of special diet therapy in patients with phenylketonuria in four prefectures of Xinjiang Uygur Autonomous Region
Shangqin ZHOU ; Xi CHEN ; Shuyuan XUE ; Luhan ZHANG ; Guifeng DING
Chinese Journal of Child Health Care 2024;32(2):191-195
【Objective】 To investigate the influencing factors behind the follow-up compliance of patients with low/no phenylketonuria (PKU) for special medical use, in order to provide a basis for regulating the follow-up of PKU patients and ensuring the effectiveness of special diet treatment. 【Methods】 A survey was conducted on PKU patients treated in Urumqi Maternal and Child Health Hospital for over 1 year, from January 2010 to December 2020. Interviews and questionnaires were conducted with their caregivers to collect and analyze the current status of PKU patients undergoing special diet treatment, and to identify the influencing factors behind their compliance with follow-up treatment. 【Results】 Patients who had received neonatal disease screening, neonatal gene diagnosis, and maternal Down′s screening during pregnancy had better compliance, with statistically significant differences (χ2=5.753, 10.993, 9.189, P<0.05). PKU children with parents who had a college education or above showed significantly higher adherence to special diet treatment (χ2=8.321, 7.415, P<0.05). PKU children with parents having a fixed occupation also showed higher compliance, with a statistically significant difference (χ2=20.626, 7.895, P<0.05). Patient age, interval of buying special diet, number of blood samples sent and enrollment of normal age, all had a significant impact on the follow-up compliance of PKU patients with special diet (χ2=19.443, 8.090, 69.482, 12.001, P<0.05). 【Conclusions】 PKU is a treatable genetic metabolic disease. Strengthening health education, formulating standardized follow-up plans and procedures, and improving follow-up treatment compliance are crucial in enhancing the treatment and follow-up effectiveness of PKU patients.
8.The study on the effect of automatic compression synchronous ventilation mode on cardiopulmonary resuscitation in pigs
Guangli CAO ; Guifeng GAO ; Jiefeng XU ; Xuguang WANG ; Feng GE ; Jinjiang ZHU ; Meiya ZHOU ; Shuangwei WANG ; Mao ZHANG
Chinese Journal of Emergency Medicine 2024;33(9):1257-1264
Objective:To establish pig cardiac arrest resuscitation model, and explore the effect of automatic compression synchronous ventilation (ACSV) on cardiopulmonary resuscitation in pigs.Methods:Twelve male white pigs with body weight of (38±3) kg were divided into ACSV group and intermittent positive pressure ventilation (IPPV) group with 6 pigs in each group by random number table method. A porcine cardiac arrest and resuscitation model was prepared with ventricular fibrillation induced by alternating current release via right ventricular electrode for 6 min and compression for 8 min. Mechanical chest external compression depth 5 cm, frequency 100 times/min. The tidal volume of ACSV group was 3 mL/kg and the frequency was 100 times/min. In the IPPV group, the tidal volume was 7 mL/kg and the frequency was 10 times/min. Arterial blood was drawn before resuscitation and at 1, 4 and 7min during resuscitation for blood gas analysis. Coronary perfusion pressure (CPP), end-respiratory carbon dioxide (ETCO 2) and carotid blood flow (CBF) were monitored during resuscitation. Stroke volume (SV) and global ejection fraction (GEF) were recorded by pressure monitoring catheter before and 1, 2 and 4 h after resuscitation. Venous blood samples were collected at each time point and 24 h after resuscitation to detect cardiac troponin I (cTnI), neuron specific enolase (NSE), alamine aminotransferase (ALT), creatinine (Cr), and intestinal fatty acid binding protein (IFABP). Results:(1) During resuscitation, CPP, ETCO 2 and CBF in ACSV group were slightly higher than those in IPPV group, but the differences between groups were not statistically significant. (2) There was no significant difference in pH, PaCO 2, HCO 3- and lactic acid between the two groups during resuscitation. The PaO 2 in ACSV group was higher than that in IPPV group, and the difference was statistically significant at 4 and 7 min. (3) The success rate of resuscitation in both groups was 83.3%, and there was no significant difference in SV and GEF before and after resuscitation. (4) After resuscitation, cTnI, NSE, ALT, Cr, iFABP and other indexes in ACSV group were lower than those in IPPV group, and there were statistically significant differences in cTnI at 24 h after resuscitation, ALT at 2 h and 24 h after resuscitation, and IFABP at 4 h and 24 h after resuscitation (all P<0.05). Conclusions:This study preliminarily suggested that the novel ACSV could significantly improve the oxygen supply level during cardiopulmonary resuscitation in pigs, while keeping the compression efficiency unchanged, avoiding hyperventilation, and reducing multiple organ damage after resuscitation, which is worthy of further study.
9.Short-term outcomes of reconstruction of tumorous critical bone defects at femoral shaft with a 3D printed ultra-short stem with a porous structure
Guifeng DU ; Jie WANG ; Xin HU ; Yang WEN ; Linyun TAN ; Minxun LU ; Yuqi ZHANG ; Yong ZHOU ; Yi LUO ; Li MIN ; Chongqi TU
Chinese Journal of Orthopaedic Trauma 2022;24(9):805-811
Objective:To explore the short-term outcomes of reconstruction of tumorous critical bone defects at femoral shaft with a 3D printed ultra-short stem with a porous structure.Methods:From September 2016 to June 2018, 8 patients underwent reconstruction of critical bone defects with a 3D printed ultra-short stem with a porous structure after resection of femoral shaft malignant tumor at Department of Orthopaedics, West China Hospital. There were 4 males and 4 females, with an average age of 36.9 years (from 11 to 61 years). Their preoperative Enneking staging was stage Ⅱb in all. There were 3 osteosarcomas, 2 Ewing sarcomas, 2 chondrosarcomas and one periosteal osteosarcoma. Preoperative CT/MRI image fusion technology was used to define the surgical boundary, design the guide plate and prosthesis, and perform surgical simulation. Tomosynthesis-shimadzu Metal Artefact Reduction technology was used to evaluate osseointegration. Complications and bone oncology prognosis of the patients were documented. The lower limb function of the patients was evaluated using Musculoskeletal Tumor Society (MSTS) 1993 scoring and knee range of motion.Results:The overall follow-up time ranged from 36 to 50 months, averaging 42.8 months. During operation one patient sustained a periprosthesis fracture, the union of which was followed up after wire assisted fixation. There was no local tumor recurrence, lung metastasis or death. The last follow-up revealed good osseointegration and basically isometric lower extremities in all cases. There was no such a complication as aseptic loosening of the prosthesis, deep infection or prosthesis fracture during the follow-up period. At the last follow-up in the 8 patients, the flexion range of the knee joint was 116.2°±9.1°, significantly improved compared with that before operation (98.8°±10.9°), and the MSTS score was (26.2±2.1) points, also significantly improved compared with that before operation [(21.6±1.8) points] ( P<0.05). Conclusions:Reconstruction with a 3D printed ultra-short stem with a porous structure is an accurate operation for femoral shaft tumorous bone defects. With careful preoperative design, intraoperative manipulation and strict postoperative follow-up management, this operation can lead to fine early curative outcomes for long shaft critical bone defects.
10.Clinical characteristics and risk factors of severe and critical influenza in children
Guifeng ZHENG ; Shunhang WEN ; Xiaofang CHEN ; Mengfei YU ; Hailin ZHANG
Chinese Journal of Infectious Diseases 2021;39(5):285-288
Objective:To explore the clinical characteristics and risk factors of severe and critical influenza in children.Methods:The clinical data of 214 inpatient children with severe and critical influenza hospitalized in the Second Affiliated Hospital & Yuying Children′s Hospital of Wenzhou Medical University from January 1, 2016 to December 31, 2019 were retrospectively collected. The clinical characteristics including age, gender, symptoms, signs, underlying diseases, C-reactive protein (CRP), treatment and outcome of children with severe and critical influenza were compared. Chi-Square test was used for statistical analysis. A binary logistic regression model was constructed to analyze the risk factors for critically ill influenza.Results:Of the 214 children, 153 were male (71.5%), 177(82.7%) were under 5 years old. There were 52 children with underlying diseases. Fever occurred in 207 cases. Among the 54 cases that had convulsion during the course of the disease, three developed acute necrotizing encephalopathy. The influenza subtype was mainly type A, accounting for 190(88.79%). A total of 42(19.6%) children were critically ill. The incidence of critical influenza in children with underlying diseases (61.9%, 26/42) was higher than that in severe influenza children (15.1%, 26/172), and the difference was statistically significant ( χ2=40.175, P<0.01). The incidence of critical influenza in children with CRP≥40 mg/L was higher than that of severe influenza in children with CRP ≥40 mg/L (33.3%(14/42) vs 9.3%(16/172)), and the difference was statistically significant ( χ2=16.173, P<0.01). Multivariate logistic regression showed that underlying diseases (odds ratio ( OR)=8.794, 95% confidence interval ( CI) 3.845-20.111) and CRP ≥40 mg/L ( OR=5.050, 95% CI 1.966-12.970) were risk factors for critical influenza. All severe cases were improved and discharged.Among the 42 critically ill children, seven children died. Conclusions:Among the severe and critical influenza in children, the majority of children are under five years old.Underlying diseases and CRP ≥40 mg/L are risk factors for critical influenza.


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