1.Effect of Dingzhi Xiaowan on PI3K/Akt/mTOR/HIF-1α Pathway in Post-stroke Cognitive Impairment Model Mice
Han ZHANG ; Yu WANG ; Xiaoqin ZHONG ; Zhenqiu NING ; Dafeng HU ; Minzhen DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):1-11
ObjectiveTo investigate the effect of Dingzhi Xiaowan (DZXW) in post-stroke cognitive impairment (PSCI) model mice. MethodsThe cerebral ischemia-reperfusion injury model of mice was established by using the middle cerebral artery occlusion method. Forty C57BL/6 male mice were randomly divided into the sham operation group, model group, low-dose DZXW group (1.43 g·kg-1), and high-dose DZXW group (2.56 g·kg-1), with 10 mice in each group. Both the sham operation group and the model group were treated with equal amounts of normal saline by gavage, and the above four groups of mice were gavaged once a day for 30 consecutive days. Morris water maze test was used to evaluate the learning memory ability of mice. Serum levels of amyloid precursor protein (APP), amyloid 42 (Aβ42), acetylcholinesterase (AChE), and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay (ELISA). Deoxyribonucleotide end transferase-mediated nick end labelling (TUNEL) assay was applied to detect the degree of apoptosis in the mouse's hippocampal neurons. Western blot was used to detect the protein expression of phosphoinositol-3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), hypoxia-inducible factor 1-alpha (HIF-1α), B-cell lymphoma 2 (Bcl-2) homologous structural domain protein (Beclin1), sequestosome 1 (p62), microtubule-associated protein light chain 3 (LC3), Bcl-2, and Bcl-2-associated X protein (Bax) in hippocampal tissue. Prussian blue staining was used to detect iron deposition in hippocampal tissue. Transmission electron microscopy was taken to observe the ultrastructure of the mouse's hippocampal neurons. ResultsCompared with the sham operation group, the latency, APP, Aβ42, AChE, TUNEL positivity, ferric ion deposition, HIF-1α, Beclin1, Bax, and LC3Ⅱ/Ⅰ were significantly increased in the model group (P<0.01), while the number of crossing platforms, SOD, p-PI3K, p-Akt, p-mTOR, p62, and Bcl-2 were significantly decreased (P<0.01). Compared with the model group, the latency, APP, Aβ42, AChE, TUNEL positivity rate, ferric ion deposition, HIF-1α, Beclin1, Bax, and LC3Ⅱ/Ⅰ were significantly reduced in the DZXW groups (P<0.05), while the number of crossing platforms, SOD, p-PI3K, p-Akt, p-mTOR, p62, and Bcl-2 were significantly higher (P<0.05). ConclusionDZXW can alleviate cognitive impairment induced by oxidative stress-aggravated hippocampal neuronal damage in PSCI model mice by modulating the PI3K/Akt/mTOR/HIF-1α autophagy signalling pathway.
2.Prediction of premature mortality of major chronic and non-communicable diseases and exploration of influencing factors in Anhui Province
Qin HE ; Yan ZHANG ; Xiuya XING ; Dan DAI ; Qianyao CHENG ; Wei XU ; Zhenqiu ZHA ; Rui LI ; Yeji CHEN ; Huadong WANG ; Zhirong LIU
Chinese Journal of Epidemiology 2024;45(5):700-707
Objective:To analyze and predict the future trend of the premature mortality of major chronic and non-communicable diseases in Anhui Province, evaluate the implementation of the "Healthy China 2030" Plan, and explore its influencing factors.Methods:Using data from death-cause surveillance and statistical yearbooks in Anhui, the trend prediction and analysis on influencing factors were conducted by using methods such as time series accumulation and logarithmic linear Joinpoint regression, principal component regression.Results:In Anhui, 28.10% of the deaths were premature ones, of which 84.40% were attributed to chronic and non-communicable diseases. In premature deaths attributed to chronic and non-communicable diseases, the deaths caused by malignant tumor and cardiovascular disease accounted for 45.88% and 41.65% respectively. The prediction results showed that the premature mortality of major chronic and non-communicable diseases would decrease in Anhui in the future, and by 2030, the goal in the "Healthy China 2030" Plan would be reached only in rural area. To reduce premature death, it is necessary to pay attention to the prevention and control of malignant tumor and cardiovascular disease. Men in urban area are the key population. Factors that reflect urban infrastructure had a significant impact on premature mortality of major chronic non-communicable diseases, such as garden and green space area per capita. Factors such as concentration of PM 2.5 had a negative impact on premature mortality of chronic non-communicable diseases, while factors such as garden and green space area per capita had a positive impact. Conclusions:Disease burden caused by chronic and non-communicable diseases, such as malignant tumor, exits in Anhui. Men in urban area are key population in the prevention and control of chronic and non-communicable diseases in the future.
3.Spatial and temporal distribution characteristics research of esophageal cancer in China
Shaoping LAI ; Haimei SU ; Yawen LIU ; Mengqi ZHANG ; Zhenqiu HUANG ; Jiaxin LIU ; Hong HUANG
Chinese Journal of Oncology 2024;46(7):657-662
Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P<0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P<0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.
4.Correlation between acetabular development and spinopelvic parameters in patients with developmental dysplasia of the hip
Tianye LIN ; Wensheng ZHANG ; Xiaoming HE ; Mincong HE ; Ziqi LI ; Zhenqiu CHEN ; Qingwen ZHANG ; Wei HE ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2024;28(6):857-861
BACKGROUND:The majority of studies on developmental dysplasia of the hip focus on hip malformations,but there are few reports on the effects of acetabular dysplasia on the spine. OBJECTIVE:To investigate the compensation of spinopelvic parameters in coronal and sagittal views in patients with developmental dysplasia of the hip,and to explore the correlation between acetabular development and spinopelvic parameters. METHODS:A total of 101 patients with developmental dysplasia of the hip admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2018 to June 2022 were selected as the trial group,and 114 healthy subjects were selected as the control group during the same period.The spinopelvic parameters of the subjects were measured through the full-length X-ray films of the coronal and sagittal spines:lumbar lordosis,anterior pelvic tilt,thoracolumbar kyphosis,Cobb angle,and the distance between the C7 plumb line and the center sacral vertical line,sacral slope,pelvic incidence,and thoracic kyphosis.The differences in spinopelvic parameters were compared between the two groups.In addition,the differences in spinopelvic parameters in patients with unilateral,bilateral and different Crowe classifications of developmental dysplasia of the hip were compared.Pearson correlation analysis was used to explore the correlation between Sharp angle and spinopelvic parameters. RESULTS AND CONCLUSION:(1)In the sagittal view,the lumbar lordosis in the trial group was significantly lower than that in the control group(P<0.05).The pelvic tilt and kyphosis angle of the thoracolumbar segment in the trial group were significantly greater than those in the control group(P<0.05).In the coronary position,the Cobb angle and the distance between the C7 plumb line and center sacral vertical line in the trial group were significantly greater than those in the control group(P<0.05).There was no significant difference in the remaining spinopelvic parameters between the two groups(P>0.05).(2)The lumbar lordosis of patients with bilateral developmental dysplasia of the hip was significantly lower than that of patients with unilateral developmental dysplasia of the hip(P<0.05).The pelvic tilt,thoracolumbar kyphosis,Cobb angle and the distance between the C7 plumb line and center sacral vertical line in bilateral developmental dysplasia of the hip patients were significantly greater than those in unilateral developmental dysplasia of the hip patients(P<0.05).(3)The lumbar lordosis decreased with the increase of Crowe classification severity(P<0.05).The pelvic tilt increased with the severity of the Crowe classification(P<0.05).(4)Pearson correlation analysis showed that Sharp angle was negatively correlated with lumbar lordosis(P<0.05),while Sharp angle was positively correlated with anterior pelvic tilt,Cobb angle,C7 plumb line and center sacral vertical line(P<0.05).(5)It is concluded that the pelvic tilt,thoracolumbar kyphosis,Cobb angle and the distance between the C7 plumb line and center sacral vertical line increase,while lumbar lordosis decreases in developmental dysplasia of the hip patients.The degree of acetabular dysplasia was significantly correlated with lumbar lordosis,pelvic tilt,Cobb angle,C7 plumb line and center sacral vertical line.
5.The pathological progression of steroid-induced osteonecrosis of the femoral head caused by oxidative stress-induced osteoblast ferroptosis
Jiahao ZHANG ; Yuhao LIU ; Chi ZHOU ; Liang MO ; Hanjun FANG ; Zhenqiu CHEN
Chinese Journal of Tissue Engineering Research 2024;28(20):3202-3208
BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.
6.Study on the risk for cerebrovascular disease among subtypes of middle-aged and elderly type 2 diabetes mellitus patients aged between 35‒74 years in Shanghai suburbs
Chengjun ZHANG ; Qiu XIAO ; Zhenqiu LIU ; Chen SUO ; Tiejun ZHANG ; Genming ZHAO ; Yanfeng JIANG ; Kelin XU ; Xingdong CHEN
Shanghai Journal of Preventive Medicine 2024;36(12):1148-1156
ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.
7.Spatial and temporal distribution characteristics research of esophageal cancer in China
Shaoping LAI ; Haimei SU ; Yawen LIU ; Mengqi ZHANG ; Zhenqiu HUANG ; Jiaxin LIU ; Hong HUANG
Chinese Journal of Oncology 2024;46(7):657-662
Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P<0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P<0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.
8.Effects of WeChat-based health education on management of hypertensive outpatients under medical consortium
Guilan SUN ; Mengping HE ; Yuanwen XU ; Liu SU ; Lili SHUANG ; Yuan TIAN ; Lili SONG ; Jin HUANG ; Xiao ZHANG ; Zhenqiu YU
Chinese Journal of Modern Nursing 2020;26(17):2355-2360
Objective:To explore the effects of WeChat-based health education on management of hypertensive outpatients under medical consortium.Methods:Totally 180 hypertensive patients who attended the Multidisciplinary Clinics of Beijing Anzhen Hospital, Capital Medical University, and Datun Community Health Service Center from communities under our medical consortium from November 2018 to April 2019 were selected and divided into the observation group ( n=91) and the control group ( n=89) according to the visit time. Patients in the control group received routine health education, while patients in the observation group received WeChat-based health education under medical consortium for 6 months. The self-management ability (using Hypertension Patients Behavior Rating Scale, HPSMBRS) , treatment compliance (using Therapeutic Adherence Scale for Hypertensive Patients, TASHP) , the 24 h average systolic and diastolic blood pressure, the average systolic and diastolic blood pressure at daytime, and the average systolic blood pressure and diastolic blood pressure at night were compared between the two groups. Results:After the intervention, the diet management, medication management, disease monitoring, exercise management, work and rest and emotional management scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the medication-taking behavior, bad medication-taking behavior, daily activity management behavior and tobacco and alcohol addiction scores were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the 24 h average systolic and diastolic blood pressure, average systolic and diastolic blood pressure at daytime and average systolic and diastolic blood pressure at night decreased in the observation group, and the differences were statistically significant compared with the control group ( P<0.05) . Conclusions:The WeChat platform under medical consortium provides standardized, consistent, continuous and effective health education, which can improve the self-management ability and treatment compliance of hypertensive outpatients, and can effectively control blood pressure levels. It shows sound effects in clinical use.
9.Role of bone status in anterolateral portion of femoral head in the progression of osteonecrosis of the femoral head
Qiushi WEI ; Bin FANG ; Zhenqiu CHEN ; Mincong HE ; Xiaojun CHEN ; Fan YANG ; Qingwen ZHANG ; Wei HE
Chinese Journal of Tissue Engineering Research 2019;23(16):2516-2522
BACKGROUND:Mechanical stress plays an important role in the progressive collapse in osteonecrosis of the femoral head.Therefore,the bone structure of weight-bearing area may be the risk factor for collapse.OBJECTIVE:To investigate the relationship between the bone preservation of weight-bearing area and collapse progression in necrotic femoral head.METHODS:Eighty-seven patients (102 hips) with ARCO stage Ⅱ osteonecrosis of the femoral head,diagnosed by MRI,were enrolled.All patients underwent a natural progression.Collapse and bone involvement of the weight-bearing area were viewed by anteroposterior and frog-leg lateral radiographs.According to the location of the necrotic lesion on the anterolateral portion of the femoral head,the necrosis was divided into three types:type 1,the posteromedial and central portions;type 2,part of the anterolateral portion;type 3,the entire anterolateral portion.The collapse rate and the time to collapse in different types were assessed.RESULTS AND CONCLUSION:(1) All patients were followed up for 3-58 months.(2) Of the 60 hips with collapse,46 (76.7%) hip collapse was identified on anteroposterior radiograph.On frog-leg lateral radiograph showing collapsed femoral head could be identified in 57 (95.0%) hips,which was significantly different (P < 0.01).(3) In all 102 hips,the collapse rate in type 3 osteonecrosis of the femoral head was significantly higher than that of type 2 osteonecrosis of the femoral head (P < 0.001),and the time to collapse was markedly shortened.None collapse occurred in all six hips with type Ⅰ osteonecrosis of the femoral head during follow-up.(4) In summary,preservation of anterolateral portion is associated with potential collapse progression in necrotic femoral head.
10.Study on Protective Effects of Pericarpium Trichosanthis Extract on H 9c2 Myocardial Cells Injured by Hypoxia/Reoxygenation and Its Mechanism
China Pharmacy 2019;30(8):1072-1078
OBJECTIVE: To study the protective effects of Pericarpium Trichosanthis extract(TPE) on H9c2 myocardial cells injured by hypoxia/reoxygenation(H/R). METHODS: H/R injury model of H9c2 myocardial cells was established by using sodium dithionite (Na2S2O4) as chemical hypoxia agent. The modeling conditions of different concentrations of Na2S2O4 (0.625-10 mmol/L) and different time of hypoxia (10-60 min) and reoxygenation (2-8 h), as well as the concentration of TPE (12.5-400 μg/mL) were screened. The cultured H9c2 myocardial cells were randomly divided into normal group, model group, TPE different dose groups (TPE low-dose, medium-dose and high-dose groups, 25, 50, 100 μg/mL) and positive control group (quercetin, 25 μmol/L). They were pre-treated with relevant medicine for 24 h, and then H/R injury model was established. Cell viability was measured by MTT assay. The levels of LDH, CK-MB, SOD and MDA in cells were tested by ELISA. Apoptosis of H9c2 myocardial cells were observed by flow cytometry. Western blotting was used to detect the protein expression of Bax and Bcl-2 in cells. RESULTS: The condition of H/R injury modeling included modeling concentration of Na2S2O4 2.5 mmol/L, hypoxia time 30 min, reoxygenation time 4 h. 12.5-400 μg/mL TPE showed no toxicity to H9c2 myocardial cells. After treatment, compared with blank group, survival rate and apoptotic rate of H9c2 myocardial cells in model group were increased significantly; the levels of CK-MB, LDH and MDA were increased significantly, while SOD level was decreased significantly; protein expression of Bax and Bax/Bcl-2 ratio were increased significantly, while that of Bcl-2 was decreased significantly (P<0.05 or P<0.01). Compared with model group, above changes of H9c2 myocardial cells were reversed in all dose groups of TPE (P<0.05 or P<0.01). CONCLUSIONS: TPE can protect H9c2 myocardial cells against H/R injury. Its mechanism may be associated with inhibiting the increase of lipid peroxide, improving the ability of scavenging reactive oxygen free radicals, up-regulating the protein expression of Bcl-2 or down-regulating protein expression of Bax, so as to inhibit the cell apoptosis.

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