1.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
ObjectiveTo explore the feasibility, evaluation methods and metabolic differences of high-fat diet(HFD) combined with myocardial ischemia-reperfusion injury(MIRI) to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome(PBSBCS). MethodsThirty-two SD rats were randomly divided into the sham operation, HFD, MIRI, and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet(regular chow), while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery, while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography, including left ventricular ejection fraction(EF), left ventricular fractional shortening(FS), cardiac output(CO), and stroke volume(SV). Serum levels of creatine kinase(CK), CK-MB, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), lactate dehydrogenase(LDH), endothelin-1(ET-1), endothelial nitric oxide synthase(eNOS), tumor necrosis factor-α(TNF-α), interleukin-18(IL-18), oxidized LDL(ox-LDL), and cardiac troponin T(cTnT) were measured by biochemical assays and enzyme-linked immunosorbent assay(ELISA). Myocardial histopathology was evaluated via hematoxylin-eosin(HE) staining, while myocardial infarction and no-reflow area were assessed using 2,3,5-triphenyltetrazolium chloride(TTC), Evans blue, and thioflavin staining. Changes in syndrome characteristics[body weight, tongue surface red-green-blue [RGB] values, and pulse amplitude] of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). ResultsCompared with the sham operation group, the HFD and MIRI+HFD groups showed significant increases in body weight(P<0.01), RGB values and pulse amplitude decreased in the HFD, MIRI and MIRI+HFD groups, TC, TG, LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups, while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased, serum eNOS level decreased, and CK-MB, LDH, and cTnT activities increased in the HFD, MIRI and MIRI+HFD groups(P<0.05, P<0.01). Whole blood viscosity was increased in the HFD group at medium shear rate, and in the MIRI and MIRI+HFD groups at low, medium and high shear rates(P<0.05, P<0.01). Platelet aggregation rate increased in the MIRI and MIRI+HFD groups, accompanied by elevated ET-1, TNF-α, and IL-18 levels, reduced cardiac function indices, expanded myocardial no-reflow and infarction areas, and increased serum CK, CK-MB, LDH, and cTnT activities(P<0.05, P<0.01). Compared with the MIRI group, the HFD and MIRI+HFD groups showed significant increase in body weight, TC, TG, LDL-C and ox-LDL levels, and significant decrease in HDL-C content(P<0.01). The MIRI+HFD group showed decrease in RGB values and pulse amplitude, and an increase in whole blood viscosity, platelet aggregation, blood perfusion peak time, myocardial no-reflow and infarction areas, elevated ET-1, TNF-α and IL-18 levels, decreased eNOS content, EF and SV, increased serum CK, CK-MB and cTnT activities, and worsened myocardial pathology(P<0.05). Compared with the HFD group, the MIRI+HFD group showed similar aggravated trends(P<0.05, P<0.01). Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury, and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices, effectively simulating clinical features of coronary heart disease(CHD), which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.
2.Establishment and Evaluation of Rat Model of Myocardial Ischemia-reperfusion Injury with Phlegm and Blood Stasis Blocking Collaterals Syndrome Based on Metabolomics
Longxiao HU ; Jiabei GAO ; Weihao MA ; Jieming LU ; Yunxiao GAO ; Yue YUAN ; Qiuyan ZHANG ; Xiaoxiao CHEN ; Yali SHI ; Jianxun LIU ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):41-51
ObjectiveTo explore the feasibility, evaluation methods and metabolic differences of high-fat diet(HFD) combined with myocardial ischemia-reperfusion injury(MIRI) to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome(PBSBCS). MethodsThirty-two SD rats were randomly divided into the sham operation, HFD, MIRI, and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet(regular chow), while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery, while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography, including left ventricular ejection fraction(EF), left ventricular fractional shortening(FS), cardiac output(CO), and stroke volume(SV). Serum levels of creatine kinase(CK), CK-MB, triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), lactate dehydrogenase(LDH), endothelin-1(ET-1), endothelial nitric oxide synthase(eNOS), tumor necrosis factor-α(TNF-α), interleukin-18(IL-18), oxidized LDL(ox-LDL), and cardiac troponin T(cTnT) were measured by biochemical assays and enzyme-linked immunosorbent assay(ELISA). Myocardial histopathology was evaluated via hematoxylin-eosin(HE) staining, while myocardial infarction and no-reflow area were assessed using 2,3,5-triphenyltetrazolium chloride(TTC), Evans blue, and thioflavin staining. Changes in syndrome characteristics[body weight, tongue surface red-green-blue [RGB] values, and pulse amplitude] of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). ResultsCompared with the sham operation group, the HFD and MIRI+HFD groups showed significant increases in body weight(P<0.01), RGB values and pulse amplitude decreased in the HFD, MIRI and MIRI+HFD groups, TC, TG, LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups, while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased, serum eNOS level decreased, and CK-MB, LDH, and cTnT activities increased in the HFD, MIRI and MIRI+HFD groups(P<0.05, P<0.01). Whole blood viscosity was increased in the HFD group at medium shear rate, and in the MIRI and MIRI+HFD groups at low, medium and high shear rates(P<0.05, P<0.01). Platelet aggregation rate increased in the MIRI and MIRI+HFD groups, accompanied by elevated ET-1, TNF-α, and IL-18 levels, reduced cardiac function indices, expanded myocardial no-reflow and infarction areas, and increased serum CK, CK-MB, LDH, and cTnT activities(P<0.05, P<0.01). Compared with the MIRI group, the HFD and MIRI+HFD groups showed significant increase in body weight, TC, TG, LDL-C and ox-LDL levels, and significant decrease in HDL-C content(P<0.01). The MIRI+HFD group showed decrease in RGB values and pulse amplitude, and an increase in whole blood viscosity, platelet aggregation, blood perfusion peak time, myocardial no-reflow and infarction areas, elevated ET-1, TNF-α and IL-18 levels, decreased eNOS content, EF and SV, increased serum CK, CK-MB and cTnT activities, and worsened myocardial pathology(P<0.05). Compared with the HFD group, the MIRI+HFD group showed similar aggravated trends(P<0.05, P<0.01). Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury, and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices, effectively simulating clinical features of coronary heart disease(CHD), which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.
3.Study on the effect and burden of precipitation on road traffic injuries in Zhejiang Province
Lihua GUO ; Weiquan ZENG ; Wenjun MA ; Ming ZHAO ; Jianxiong HU ; Na LI ; Jieming ZHONG ; Jingjing LIN
Chinese Journal of Epidemiology 2025;46(4):605-611
Objective:To analyze the effect of precipitation on road traffic injuries (RTI) in Zhejiang Province.Methods:The RTI surveillance and meteorological data from 2009 to 2022 in Zhejiang Province were collected. Based on the time-stratified case-crossover design, the precipitation of case day and control day was compared, and the distributed lag nonlinear model was applied to analyze the correlation of precipitation and RTI. Stratified analyses were conducted to analyze the effect modification of gender, age, injury location, and temperature. An attributable fraction was used to assess the burden of RTI caused by precipitation.Results:A total of 239 970 RTIs were monitored in Zhejiang Province from 2009 to 2022, averaging 46 daily cases. The distributed lag nonlinear model showed that compared with no rain, the risk of RTI increased first and then decreased with the increase of precipitation. The risk of RTI was the highest when the precipitation was 30.99 mm ( OR=1.08, 95% CI: 1.05-1.11). The adverse effects on RTI mainly occurred on the day of precipitation, and it showed insignificant or protective effects with the extension of lag days. 1.34%(95% CI: 1.31%-1.36%) of RTI could be attributed to precipitation. Stratified analysis showed that gender, age, injury location, and temperature may modify the effect of precipitation on RTI. Precipitation caused a heavier burden on RTI in subgroups aged 18-64, females, and occurring on roads and in low temperatures. Conclusions:Precipitation can increase the risk of RTI. People aged 18-64 or females are the key groups for RTI prevention, and prevention and control efforts of precipitation-related RTI should be increased in road and low-temperature environments.
4.Research advances of association between age at natural menopause and diabetes risk: evidence from prospective studies
Meng WANG ; Yunqi GUAN ; Weiwei GONG ; Xiaoyan ZHOU ; Zhimin MA ; Jin PAN ; Mingbin LIANG ; Jieming ZHONG ; Fan WU ; Min YU
Chinese Journal of Epidemiology 2025;46(8):1502-1505
The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.
5.Study on the effect and burden of precipitation on road traffic injuries in Zhejiang Province
Lihua GUO ; Weiquan ZENG ; Wenjun MA ; Ming ZHAO ; Jianxiong HU ; Na LI ; Jieming ZHONG ; Jingjing LIN
Chinese Journal of Epidemiology 2025;46(4):605-611
Objective:To analyze the effect of precipitation on road traffic injuries (RTI) in Zhejiang Province.Methods:The RTI surveillance and meteorological data from 2009 to 2022 in Zhejiang Province were collected. Based on the time-stratified case-crossover design, the precipitation of case day and control day was compared, and the distributed lag nonlinear model was applied to analyze the correlation of precipitation and RTI. Stratified analyses were conducted to analyze the effect modification of gender, age, injury location, and temperature. An attributable fraction was used to assess the burden of RTI caused by precipitation.Results:A total of 239 970 RTIs were monitored in Zhejiang Province from 2009 to 2022, averaging 46 daily cases. The distributed lag nonlinear model showed that compared with no rain, the risk of RTI increased first and then decreased with the increase of precipitation. The risk of RTI was the highest when the precipitation was 30.99 mm ( OR=1.08, 95% CI: 1.05-1.11). The adverse effects on RTI mainly occurred on the day of precipitation, and it showed insignificant or protective effects with the extension of lag days. 1.34%(95% CI: 1.31%-1.36%) of RTI could be attributed to precipitation. Stratified analysis showed that gender, age, injury location, and temperature may modify the effect of precipitation on RTI. Precipitation caused a heavier burden on RTI in subgroups aged 18-64, females, and occurring on roads and in low temperatures. Conclusions:Precipitation can increase the risk of RTI. People aged 18-64 or females are the key groups for RTI prevention, and prevention and control efforts of precipitation-related RTI should be increased in road and low-temperature environments.
6.Research advances of association between age at natural menopause and diabetes risk: evidence from prospective studies
Meng WANG ; Yunqi GUAN ; Weiwei GONG ; Xiaoyan ZHOU ; Zhimin MA ; Jin PAN ; Mingbin LIANG ; Jieming ZHONG ; Fan WU ; Min YU
Chinese Journal of Epidemiology 2025;46(8):1502-1505
The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.
7.Prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province in 2017
Xiaofu DU ; Xiangyu CHEN ; Jie ZHANG ; Le FANG ; Min YU ; Jianwei XU ; Yamin BAI ; Jing WU ; Jixiang MA ; Jieming ZHONG
Chinese Journal of Preventive Medicine 2019;53(5):464-469
Objective To understand prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province. Methods A multi?stage random cluster sampling method was used to select 3 032 residents aged 50-69 years old in Zhejiang Province. The demographic characteristics, prevalence and control of hypertension were collected through a questionnaire survey, and physical measurement was also performed. The stratified random sampling method was used to detect the level of sodium and potassium in the 24 h urine of 676 subjects. The total amount of 24 h urinary sodium ≥102.55 mmol and the ratio of 24 h urinary sodium and potassium content ≥2 were defined as excessive. Results The prevalence of hypertension (95%CI) was 56.89% (54.39%-59.40%), and the awareness, treatment and control rate of hypertension were 58.25% (55.01%-61.49%), 45.37% (42.10%-48.65%) and 19.75% (17.01%-22.50%), respectively. 78.99% (n=534) of residents had excessive 24 h urinary sodium, and 95.41% (n=360) of residents had excessive ratio of 24 h urinary sodium and potassium. Conclusion The prevalence of hypertension in residents aged 50-69 years old in Zhejiang Province was at a high level, and the control of hypertension was not satisfactory in 2017. Most of residents have excessive level of sodium intake and the level of sodium and potassium intake was not balanced.
8.Prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province in 2017
Xiaofu DU ; Xiangyu CHEN ; Jie ZHANG ; Le FANG ; Min YU ; Jianwei XU ; Yamin BAI ; Jing WU ; Jixiang MA ; Jieming ZHONG
Chinese Journal of Preventive Medicine 2019;53(5):464-469
Objective To understand prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province. Methods A multi?stage random cluster sampling method was used to select 3 032 residents aged 50-69 years old in Zhejiang Province. The demographic characteristics, prevalence and control of hypertension were collected through a questionnaire survey, and physical measurement was also performed. The stratified random sampling method was used to detect the level of sodium and potassium in the 24 h urine of 676 subjects. The total amount of 24 h urinary sodium ≥102.55 mmol and the ratio of 24 h urinary sodium and potassium content ≥2 were defined as excessive. Results The prevalence of hypertension (95%CI) was 56.89% (54.39%-59.40%), and the awareness, treatment and control rate of hypertension were 58.25% (55.01%-61.49%), 45.37% (42.10%-48.65%) and 19.75% (17.01%-22.50%), respectively. 78.99% (n=534) of residents had excessive 24 h urinary sodium, and 95.41% (n=360) of residents had excessive ratio of 24 h urinary sodium and potassium. Conclusion The prevalence of hypertension in residents aged 50-69 years old in Zhejiang Province was at a high level, and the control of hypertension was not satisfactory in 2017. Most of residents have excessive level of sodium intake and the level of sodium and potassium intake was not balanced.
9. Prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province in 2017
Xiaofu DU ; Xiangyu CHEN ; Jie ZHANG ; Le FANG ; Min YU ; Jianwei XU ; Yamin BAI ; Jing WU ; Jixiang MA ; Jieming ZHONG
Chinese Journal of Preventive Medicine 2019;53(5):464-469
Objective:
To understand prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province.
Methods:
A multi-stage random cluster sampling method was used to select 3 032 residents aged 50-69 years old in Zhejiang Province. The demographic characteristics, prevalence and control of hypertension were collected through a questionnaire survey, and physical measurement was also performed. The stratified random sampling method was used to detect the level of sodium and potassium in the 24 h urine of 676 subjects. The total amount of 24 h urinary sodium ≥102.55 mmol and the ratio of 24 h urinary sodium and potassium content ≥2 were defined as excessive.
Results:
The prevalence of hypertension (95
10.Study on the Effects of HMGB1-mediated Inflammatory Pathway on Liver Injury Induced by Tripterygium wilfordii
Jieming DONG ; Cong'en ZHANG ; Xiaohong YU ; Hao WU ; Zhijie MA ; Kuijun ZHAO
China Pharmacy 2018;29(5):633-636
OBJECTIVE:To study the effects of high-mobility group box 1 protein(HMGB1) -mediated inflammatory pathway HMGB1-Toll like receptor 4 (TLR4) /nuclear transcription factor κ B(NF-κ B)on liver injury of rats induced by Tripterygium wilfordii,and to provide reference for clarify the mechanism of liver injury induced by T.wilfordii. METHODS:Totally 24 SD rats were randomly divided into blank group(normal saline,i. g. ),T. wilfordii group(16 g/kg by crude drug,i. g. )and neutralizer group(16 g/kg T. wilfordii crude drug i. g. after i. p injection of 100 mg/kg Ammonium glycyrrhizinate solution 3 h),with 8 rats in each group. All rats were treated for consecutive 3 weeks. The serum levels of AST and ALT in rats were detected every week. After the end of medication,the serum levels of HMGB1,IL-1β,IL-2 and TNF-α were detected by ELISA method;the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats were detected by Western blot assay. The pathological changes of liver tissue in rats were measured with HE staining method. RESULTS:After 3 weeks of treatment,the serum levels of AST, ALT,HMGB1,IL-1β,IL-2 and TNF-α in rats,the protein expression of HMGB1,NF-κB p65 and TLR4 in liver tissue of rats in T. wilfordii group were significantly higher than blank group and neutralizer group(P<0. 05 or P<0. 01). Hepatocyte edema was found around the central vein of the liver,and circular vacuoles were seen in some hepatic cytoplasm in T. wilfordii group;only varying size of vacuoles were found in a small number of cells in neutralizer group. CONCLUSIONS:T. wilfordii induced liver injury may be associated with the activation of HMGB1-TLR4/NF-κB inflammation pathway.

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