1.Histological characteristics of elastase-induced mouse abdominal aortic aneurysm in regression stage
Meng LI ; Haole LIU ; Panpan WEI ; Kexin LI ; Haibin WU ; Haiwen HOU ; Enqi LIU ; Yankui LI ; Sihai ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):119-125
Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147%and 155%,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.
2.Creation and translational relevance of abdominal aortic aneurysm animal models
Congcong XIA ; Haole LIU ; Haiwen HOU ; Enqi LIU ; Sihai ZHAO
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):530-538
Population aging in China has led to an increase in the incidence of abdominal aortic aneurysm(AAA).AAA rupture is one of the most severe life-threatening diseases,with high mortality.The main histopathological features of AAA include elastin degradation,smooth muscle cell depletion,extracellular matrix digestion,and mural leukocyte accumulation.Clinically,drug therapy is still lacking,and open/endovascular repair remains the most effective treatment strategy for AAA management.Notably however,the detailed molecular mechanism of AAA remains unclear,representing an important bottleneck affecting the development of potential drug targets.Animal models are the most powerful tools for clarifying the pathogenesis of AAA,and although some medium-to-large laboratory animal models(e.g.,rabbits,guinea pigs,dogs,pigs)have been established for AAA studies,rodent models(mice and rats)are still the main models used in this field.Current method of inducing AAA include intra-infrarenal aortic infusion of elastase,subcutaneous infusion of angiotensin Ⅱ,periaortic calcium chloride painting,and decellularized aortic xenografting;however,AAA tends to stabilize in most models after ceasing pre-induced stimulation(medical or surgical),and there remains a need for ideal animal models that maintain continuous aortic dilation and even rupture.AAA animal models are helpful for elucidating the pathogenesis of AAA,screening new drug targets,and promoting clinical translation.This review aims to discuss the application of current AAA modeling method and their translational relevance.
3.Macrophage MED1 deficiency promotes the development of atherosclerosis in female ApoE and LDLR knockout mice
Ergang WEN ; Jie GAO ; Yiming DING ; Miaoye BAO ; Yuankun ZHANG ; Yali ZHANG ; Sihai ZHAO ; Enqi LIU ; Liang BAI
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):89-94
【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE-/-), LDLR knockout (LDLR-/-), MED1fl/fl, and macrophage MED1 knockout (MED1△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1△Mac/ApoE-/-) mice and their littermate controls (MED1fl/fl/ApoE-/-). ② LDLR knockout (LDLR-/-) mice receiving bone marrow from MED1△Mac (MED1△Mac→LDLR-/-) or MED1fl/fl (MED1fl/fl→LDLR-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1fl/fl/ApoE-/- control group and MED1△Mac/ApoE-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1△Mac/ApoE-/-mice. Moreover, compared with that in MED1fl/fl→LDLR-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1△Mac→LDLR-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.
4.Clinical Efficacy of Danzhi Jiangtang Capsules on Patients with Type 2 Diabetes Mellitus Complicated with Lower-extremity Macroangiopathy and Serum Levels of Hcy and Cys C
Jiping WU ; Zhaohui FANG ; Ruimin LU ; Jindong ZHAO ; Sihai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):102-108
ObjectiveTo observe the clinical efficacy of Danzhi Jiangtang capsules with the functions of replenishing Qi, nourishing Yin, and dredging collaterals on patients with type 2 diabetes mellitus (T2DM) combined with lower-extremity macroangiopathy and serum levels of homocysteine (Hcy) and cystatin C (Cys C). MethodA total of 80 eligible patients who were treated in the department of endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2017 to December 2019 were randomized into the treatment group (40 cases) and control group (40 cases). Both groups received the basic therapies for diabetes and Danzhi Jiangtang capsules (oral) was added to the treatment group. The levels of glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial glucose (2 hPG), fasting C-peptide (C-P), and 2-hour postprandial C-peptide (2 hC-P), triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) and serum levels of Hcy and Cys C were measured and the traditional Chinese medicine(TCM) syndrome scores were calculated before and after treatment in the two groups. ResultAfter 12 weeks of treatment, levels of HbA1c, FPG, and 2 hPG were lower than those before treatment in the two groups (P<0.05). Levels of C-P (P<0.05) and 2 hC-P were higher than those before treatment in the two groups. After treatment, levels of HbA1c, FPG, and 2 hPG in the treatment group were lower than those in the control group (P<0.05), while levels of C-P and 2 hC-P showed no significant difference between two groups. After treatment, the levels of TG, TC, and LDL-C were lower than those before treatment (P<0.05) and HDL-C level was higher than that before treatment (P<0.05) in both groups. After treatment, levels of TG and LDL-C in the treatment group were lower than those in the control group (P<0.05), and levels of TC and HDL-C demonstrated no significant difference between two groups. After the treatment, the TCM syndrome score was lower than that before the treatment in both groups (P<0.05) and lower in the treatment group than in the control group (P<0.05). The overall effective rate of the treatment group was higher than that of the control group (χ2=7.585, P<0.05). The levels of Cys C and Hcy were lower than those before treatment in the two groups (P<0.05) and lower in the treatment group than in the control group (P<0.05). Doppler echocardiography of the lower limbs showed no obvious improvement in the control group after treatment. However, for the treatment group, slight decrease in intima-media thickness of the lower limb arteries and a slight reduction in the plaque area were observed, but the difference was not statistically significant. ConclusionDanzhi Jiangtang capsules has definite therapeutic effect on T2DM combined with lower-extremity macroangiopathy, which can improve glucolipid metabolism and reduce serum levels of Hcy and Cys C. This study can serve a reference for the prevention and treatment of T2DM combined with macroangiopathy.
5.Spatio-temporal characteristics of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020
Hemei ZHANG ; Sihai GAO ; Xiangyang CHEN ; Zhenmiao YE ; Jun LI ; Lina ZHAO ; Dehua SU ; Wenxue HU ; Jiangyi LAI ; Wanjun CHEN
Journal of Preventive Medicine 2022;34(5):483-486
Objective:
To analyze the spatio-temporal distribution characteristics of new HIV/AIDS cases at ages of 50 years and older in Wenzhou City from 2006 to 2020, so as to provide insights into precise control of AIDS.
Methods :
The data of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020 were collected from the China Information System for Disease Control and Prevention. The temporal and spatial distribution characteristics of new HIV/AIDS cases at ages of 50 years and older were identified using global and local spatial autocorrelation analyses and spatial-temporal scan analysis.
Results:
Totally 1 917 new HIV/AIDS cases aged 50 years and older were detected in Wenzhou City from 2006 to 2020, and there were 179 new HIV/AIDS cases in 58 townships ( streets ) from 2006 to 2010, 643 cases in 113 townships ( streets ) from 2011 to 2015 and 1 095 cases in 147 townships ( streets ) from 2016 to 2020, respectively. The distribution of new HIV/AIDS cases appeared positive spatial autocorrelations from 2006 to 2010 ( Moran's I value=0.05, Z=1.976, P=0.046 ), from 2011 to 2015 ( Moran's I value=0.08, Z=2.314, P=0.028) and from 2016 to 2020 (Moran's I value=0.18, Z=3.956, P=0.003 ). Spatial-temporal scan analysis identified two clusters. The primary cluster mainly covered 70 towns ( streets ) in Lucheng Distrct, Ouhai District, Longwan District, Economic and Technical Development Region, Rui' an City and Pingyang County of Wenzhou City from January 1, 2014 to December 31, 2020, with a cluster radius of 34.30 km [log likelihood ratio ( LLR )=192.84, RR=2.60, P<0.001], and the secondary cluster was located in Hongqiao Township of Yueqing City from January 1, 2009 to December 31, 2015, with a cluster radius of 0 ( LLR=90.60, RR=7.27, P<0.001 ).
Conclusions
The number of new HIV/AIDS cases aged 50 years and older appeared a tendency towards a rise in Wenzhou City from 2006 to 2020, with spatial clusters that were predominantly identified in urban areas, Rui' an City and Pingyang County of Wenzhou City.
6.Comparison of histological characteristics of two experimental mouse abdominal aortic aneurysm models
Weilai FU ; Kangli TIAN ; Congcong XIA ; Haole LIU ; Jiaying SUN ; Daxin CHENG ; Enqi LIU ; Yankui LI ; Sihai ZHAO
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(3):383-389
【Objective】 To compare the histological characteristics of porcine pancreatic elastase (PPE) induced abdominal aortic aneurysms (AAA) and angiotensin Ⅱ (AngⅡ) induced AAA in mice. 【Methods】 In the PPE group, the mouse abdominal aorta segment from the infrarenal abdominal aorta to the iliac artery was isolated and its branch arteries were ligated to avoid leakage during PPE perfusion. We perfused the isolated aorta segment with a PPE solution at a concentration of 1.5 U/mL for 5 min and then closed the abdominal cavity. The diameter of the abdominal aorta was measured before and 14 days after the surgery, and the perfusion segment of the arteries was collected at day 14 after the surgery. The histological characteristics of the aneurysm were analyzed and graded by histological and immunohistochemical methods. In the AngⅡ group, ten apolipoprotein E knockout mice were prepared, and AngⅡ [1 000 ng/(kg·min)] was infused with osmotic pumps for 28 days. The aorta was separated and the aneurysm aorta segment was analyzed. The wild type mice were used as normal health controls. 【Results】 In the PPE group, the diameter of the PPE perfused aorta segments increased and was significantly larger than the basal diameter [(0.52±0.02) mm vs. (1.23±0.11) mm] at day 14 after surgery. All the ten mice developed AAA after PPE application. The histological results showed typical pathological features of AAA in PPE perfused mice, such as elastic fiber breakage, smooth muscle exhaustion, and increased inflammation. Six of the ten mice developed aneurysms after AngⅡ infusion (6/10). The aneurysms/dilatations were mostly in the suprarenal abdominal aorta, but also in the thoracic aorta and aortic arch. The histology analysis showed that the formation of arterial dissection was common after AngⅡ infusion, and the typical vascular “false lumen” was found. The breakage of elastic fibers, the exhaustion of smooth muscle damage, and the inflammatory response were not as typical as the PPE model in AngⅡ perfused animals. 【Conclusion】 The histological characteristics of PPE induced AAA are very typical and well present the inflammatory process in the development of aneurysm. The AngⅡ model is suitable for the study of aneurysms combined with aortic dissection. Both models have their own advantages and can complement each other.
7.Detection and analysis of serum TK1,sICAM-1,miR-210 and CEA in patients with colorectal cancer
International Journal of Laboratory Medicine 2018;39(9):1048-1051,1055
Objective To investigate the expression and significance of serum thymidine kinase-1(TK1), soluble intercellular adhesion molecule-1(sICAM-1),miR-210,and carcinoembryonic antigen(CEA)in pa-tients with colorectal cancer.Methods A total of 200 patients with colorectal cancer treated in the hospital from 2015 to 2017 were enrolled as the observation group and 50 healthy subjects were enrolled as the control group.Serum levels of TK1,sICAM-1,miR-210,and CEA were measured before and after treatment,and the trend of each indicator was analyzed.To analyze the relationship between tumor site,degree of tumor differen-tiation,clinical stage,w hether it is the first patient,lymph node metastasis and miR-210 levels in patients with colorectal cancer.Results The concentrations of sICAM-1,CEA,sTK1 and miR-210 in the observation group were significantly higher than those in the control group(P<0.05).The expression of miR-210 was related to the clinical stage and lymph node metastasis(P<0.05).T he sensitivity,specificity,positive predictive value, negative predictive value and accuracy of the combined tests including serum TK 1,sICAM-1,miR-210 and CEA test were higher than those of the single test,and was also higher than the combined tests of TK1,miR-210 and CEA.The sensitivity of the four combined tests was 75.70%,the specificity was 86.00%,the positive predictive value was 82.00%,the negative predictive value was 88.00%,the accuracy was 92.40%.Conclusion The combined detection of serum TK1,sICAM-1,miR-210 and CEA may have some value in the early diag-nosis of colorectal cancer,and can improve the sensitivity and specificity of colorectal cancer diagnosis.
8.Overexpression of PPARγ induces adipogenic steatosis in mouse primary hepatocytes.
Liang BAI ; Yali ZHANG ; Chen XIE ; Rong WANG ; Sihai ZHAO ; Yuzhi JIA ; Enqi LIU ;
Journal of Zhejiang University. Medical sciences 2016;45(1):68-74
OBJECTIVETo investigate the effects of PPARγ overexpression on steatosis in mouse primary hepatocytes.
METHODSPrimary hepatocytes isolated from C57BL/6J mice were infected with either Ad/LacZ or Ad/PPARγ for 48 h. Steatosis of the primary hepatocytes was checked by Oil Red O staining. The mRNA and protein expression of adipocyte-specific genes PPARγ, aP2 and CideA were analyzed by using RT Real-time PCR and Western Blot.
RESULTSPrimary hepatocytes were small and even. Hepatocyte nuclei were round with dispersed chromatin and prominent nucleoli. Accumulated lipid droplets were observed in Ad/PPARγ-infected hepatocytes, but in Ad/LacZ-infected hepatocytes. Moreover, compared with Ad/LacZ-infected hepatocytes, the mRNA expression of PPARγ, aP2, FGF21 and CideA in Ad/PPARγ-infected hepatocytes were significantly induced, the protein expression of PPARγ and its target aP2 strongly increased.
CONCLUSIONover expression of PPARγ induces adipogenic steatosis in mouse primary hepatocytes.
Adipocytes ; metabolism ; Adipogenesis ; Animals ; Cells, Cultured ; Fatty Liver ; metabolism ; pathology ; Genetic Vectors ; Hepatocytes ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; PPAR gamma ; metabolism ; Transfection
9.The Association of Maternal Body Composition and Dietary Intake with the Risk of Gestational Diabetes Mellitus during the Second Trimester in a Cohort of Chinese Pregnant Women.
Qing XU ; Zhi Ying GAO ; Li Ming LI ; Lu WANG ; Qian ZHANG ; Yue TENG ; Xia ZHAO ; Sheng GE ; Hong Jiang JING ; Yong Tao YANG ; Xiao Jun LIU ; Chun Jian LYU ; Lun MAO ; Xiao Ming YU ; Ying Hua LIU ; Ai Jing KONG ; Xue Yan YANG ; Zhao LIU ; Yong ZHANG ; Jin WANG ; Xin Sheng ZHANG ; Chang Yong XUE ; Yan Ping LU
Biomedical and Environmental Sciences 2016;29(1):1-11
OBJECTIVETo investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM).
METHODSA total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity.
RESULTSAge, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM.
CONCLUSIONMaternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.
Adult ; Asian Continental Ancestry Group ; Body Composition ; Body Mass Index ; Cohort Studies ; Diabetes, Gestational ; epidemiology ; Diet ; Diet Surveys ; Feeding Behavior ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Risk Factors
10.Monitoring and analysis on iodine deficiency disorders in the high risk areas of Wenzhou City in 2014
Xiaochun ZHAO ; Dan LIN ; Lili WANG ; Ruoqing SHAN ; Yuanyuan CAI ; Sihai GAO
Chinese Journal of Endemiology 2016;(1):47-50
Objective To understand the dynamic conditions after reaching the stage goal of elimination of iodine deficiency disorders (IDD) in Wenzhou, and to provide a scientific basis for prevention and treatment of IDD. Methods Three counties that the annual consumption rate of qualified iodized salt < 80% in 2014 and had the prevalence of endemic cretinism in history, Cangnan, Taishun and Yongjia, were selected as high risk monitoring areas. Three townships were selected in each area, and two primary schools were selected from each township, and 40 children urine samples were collected in each school (half male and half female) and the age of children were 8-10 years old. And near the location of these primary schools, we randomly selected 10 pregnant women in each village, and estimated the urinary iodine level and salt iodine concentration, respectively. The examination of thyroid by B ultrasound was performed in children by provincial professionals. Urinary iodine was determined using the arsenic cerium catalytic spectrophotometric method (GB/T 13025.7-2012). Salt iodine was determined by direct titration. Results Endemic cretinism case was not found in this survey, total goiter rate of 8-10 years old children was 2.04%(16/783). The median of urinary iodine was 116.1 and 108.2 μg/L, respectively, in 8 - 10 years old children and pregnant women. Iodized salt coverage rate was 90.48%(171/189), the intaking rate of qualified iodized salt was 84.66% (160/189). The concentration of pregnant women urinary iodine and salt iodine was positively correlated (r=0.54, P< 0.05). Conclusions Children's iodine nutrition is in the appropriate level, but pregnant women are in iodine definciency in Wenzhou City.


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