Objective To explore the feasibility of 7.0T MR scanner in mouse aorta atherosclerosis models.Visualising the TN-C in atherosclerotic plaque by immunohistochemistry and its correlation with CD68 to provide experimental basis for the feasibility of TN-C in targeted MRI.Methods ApoE-/- mice and wild type C57 mice were fed on high fat diet to establish aorta atherosclerosis model (n=10),the aorta were observed by MRI after 14 weeks.The aorta specimens were taken to stain with HE to observe the pathological changes.The plaque was stained with oil red O,anti-TNC and TN-C antibody respectively to observe the fat,CD68 and TN-C in plaque.Results 7.0 MRI showed the aortic wall of the experimental group was thicker,high signal on T1 WI and PDWI,and low signal on T2 WI after 14 weeks.The histopathlogic examination showed the intima was obviously thicker,and the lumen was ir-regulary narrow.Both of CD68 and TN-C were highly expressed in plaque,and the distribution of TN-C correlated with CD68.In the control group,no case showed hyper-signal in the vessel wall of aorta or narrow lumen by MRI,and the histopathlogy showed no for-mation of atherosclerotic plaque in the aorta.Conclusion Aorta atherosclerotic plaque can be established through high fat diet on ApoE-/- mouse,and 7.0 MR can successfully detect it.TN-C is high expressed in AS plaque and the expression is correlated with CD68,which may suggest that they may collaborate in the development of AS.Detecting TN-C could be useful for the further study of atherosclerotic plaque.

Objective To isolate,culture,and identify the synthetic phenotype vascular smooth muscle cells (VSMC) and identify the specific marker protein (tropomyosin-4,TPM-4) of synthetic phenotype.To employ the immune molecular imaging technique to develop MRI of probe targeted with TPM-4 antibody VSMC in vitro.Methods The synthetic phenotype VSMC and endothelial cells (EC) were isolated and cultured in vitro,respectively.Immunocytochemistry (ICC) staining for α-smooth muscle actin (SMA) and Ⅷ factor was performed for cell identification,respectively.The high expression level of TPM-4 protein was tested by immunofluorescence double staining.The MRI molecular probe was built by chemical cross-linking,TPM-4 conjuncted probe (TPM4-USPIO) as the experimental group,IgG conjuncted probe (IgG-USPIO) as the negative group,unconjuncted probe (USPIO) as the control group,and PBS as the blank group.The synthetic VSMC were incubated with probes within experimental group,negative group,control group,respectively,and EC were incubated with experimental group as another control group.Prussian blue staining was employed to analyze the specific-targeting and MTT assay was used to test bioactivity of the probe under different concentrations (0,5,10,20,40 μg/ml) in vitro.7.0 T MRI scanner was used to detect the magnetic properties.With 7.0 T MRI scanner,the T2WI images of different probes labeled synthetic VSMC and different concentration gradient (1 × 103,5 × 103,1 × 104,5 × 104)TPM4-USPIO labeled cells were obtained and analyzed.T2 signal and MTT data among groups were compared using single factor analysis of variance (ANOVA) and LSD test.Results The synthetic phenotype of VSMC were isolated and cultured successfully,and the VSMC could express the TPM-4 protein.The synthetic phenotype VSMC had a high level of the protein expression.The probe was made successfully.The T2 relaxivity of TPM4-USPIO and IgG-USPIO were 0.0350 × 106,0.0316 × 106 mol/s,respectively,with high stability as USPIO (0.0292 × 106 mol/s).Prussian blue staining results showed that the experimental group probe could specifically bind to the synthetic VSMC.MTT results showed that iron concentration within 40 μg/ml or less had no effect on VSMC proliferation activity.The T2 WI of experimental group showed lower signal than the control group.The T2 relaxivity was (116.67 ± 2.08) ms,which was less than the control group [(217.67 ±2.52),(219.33 ±2.08)ms,respectively] and the blank group [(205.33 ± 1.53)ms](F =1670.43,P ＜ 0.01).The T2 relaxivity of the different concentration gradient labeled cells (1 × 103 、1 × 104 、1 × 105) were (184.33 ± 2.08),(169.67 ± 1.15),(116.67 ± 2.08) ms,respectively (F =684.35,P ＜0.01).No significant difference of the T2WI gradual signal dim was found between cells with the same order concentration(P ＞ 0.05).Conclusions The synthetic phenotype of VSMC can be obtained by PDGF-BB treatment.TPM4-USPIO probe is efficient,specific and targeted at combination with synthetic VSMC.The T2WI signal changed obviously under high field MRI scanner,which provides a new way for molecular imaging research.

OBJECTIVETo investigate the association between L296Q polymorphism in the cholesterol ester transfer protein(CETP)gene and type 2 diabetes mellitus(T2DM)and blood lipids.

METHODSPlasma glucose and lipid levels were measured in a total of 303 subjects recruited from the West China Hospital of Sichuan University. The subjects were divided into 4 groups according to the levels of plasma glucose and triglyceride, namely T2DM with hypertriglyceridemia group, group of T2DM with normal triglyceride, group of hypertriglyceridemia without DM and group of normal controls, respectively. Genotypes of L296Q polymorphism in the CETP gene of all subjects were analyzed by real-time fluorescent quantitative PCR(FQ-PCR).

RESULTSNo significant differences were observed in the frequencies of genotypes LL and LQ and the 296Q allele among the four groups (chi-square=3.459, P>0.05; chi-square=3.155, P>0.05, respectively), nor the frequencies of genotypes LL and LQ between the T2DM and non-T2DM, or plasma lipid levels between the 296Q allele carriers and those of genotype LL.

CONCLUSIONNo association was found between the L296Q polymorphism in the CETP gene and T2DM as well as plasma lipid levels in various groups of Chinese in this study.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Cholesterol Ester Transfer Proteins ; genetics ; Diabetes Mellitus, Type 2 ; blood ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA

This investigation was directed to the metabolic syndrome and the islet beta-cell secretory function in the first-degree relatives (FDR) of type 2 diabetic patients in Sichuan province. A large cohort study was designed. Totally 1929 subjects were investigated. They were in two groups: FDR group comprising 505 first-degree relatives of type 2 diabetic patients, and Control group comprising 1424 controls without positive family history of Diabetes. Blood pressure, weight, waist, plasma glucose, lipids and insulin were measured. HOMA-IR and HOMA-beta indexes were used to evaluate insulin resistance and beta-cell secretion function. The insulin sensitivity index (ISI) and glucose disposition index (DI) were also used to evaluate insulin resistance. After adjustment for age and sex, HOMA-IR increased, ISI, DI and HOMA-beta decreased in FDR group when compared with controls (P < 0.05). The incidence of co-existed three or more metabolic disorders and metabolic syndrome was higher in FDR group than that in control group (P < 0.05). In FDR group, HOMA-IR increased, HOMA-beta, DI and ISI decreased while the number of co-existing metabolic disorders increased. But when the number of co-existing metabolic disorders > or = 4, HOMA-IR increased no longer and ISI decreased no more. Metabolic disorders occurred more frequently in FDR of diabetic patients than those in individuals without positive family history. As the number of co-existing metabolic disorders increased, the beta-cell secretion function and insulin sensitivity became worse. Our study indicated that it is necessary to keep on monitoring the metabolic index in FDR of type 2 diabetes and provide early preventive interventions.
Adult ; China ; epidemiology ; Cohort Studies ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; Islets of Langerhans ; physiopathology ; Male ; Metabolic Syndrome ; epidemiology ; genetics ; Middle Aged ; Surveys and Questionnaires

[摘 要] 目的：重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌（PHC）的有效性和安全性。方法：回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较，采用Kaplan-Meier法进行生存分析，从中估计中位总生存期（OS），然后采用Log-Rank检验进行比较；采用单因素Cox回归分析预测影响OS的因素。结果：本研究共纳入43例PHC患者，一线治疗患者的客观缓解率（ORR）为23.3%（7/30），二线及以上治疗患者的ORR为15.4%（2/13）。两组患者的疾病控制率（DCR）分别为83.3%（25/30）和61.5%（8/13），中位无进展生存期（PFS）分别为5.0个月（95% CI 3.2，6.8）和4.0个月（95% CI 1.7，6.3）（P=0.514），中位OS分别为13.0个月（95% CI 11.2，14.8）和9.0个月（95% CI 2.8，15.2）（P=0.179）。在43例患者中，33例（76.7%）存在3级或以上的治疗相关不良反应（AE）；最常见的AE为血小板计数下降（14.0%）、高血压（9.3%）和蛋白尿（9.3%）。Cox单因素回归分析显示，Child-Pugh分级是影响PHC患者预后的独立危险因素[HR=0.324，95% CI （0.146，0.716），P<0.05]。结论：卡瑞利珠单抗联合阿帕替尼可显著改善PHC患者的OS、ORR和DCR，AE可控。