Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2

A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. To develop a more potent IBV DNA vaccine formulations, a monocistronic vector encoding the nucleocapsid protein of IBV and a bicistronic vector separately encoding the nucleocapsid protein and immune-stimulatory interleukin-2 were constructed. When the DNA vaccines were administered to the quadriceps muscle of chickens, the induced humoral and cellular responses were evaluated. There was a significant difference in ELISA antibody levels elicited by either monocistronic or bicistronic DNA vaccines. The percentage of CD3+, CD3+CD8+ and CD3+CD4+ subgroups of peripheral blood T-lymphocytes in chickens immunized with bicistronic DNA vaccine were higher than those in chickens immunized with monocistronic DNA vaccine. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. These results demonstrated that bicistronic DNA vaccine is an effective approach to increase IBV DNA vaccine immunogenicity.     

Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction

Background and objective: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. Methods: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. Results: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). Conclusion: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.     

Implications of the new definition of diabetes for health disparities

In July 2009, an international committee announced a new diagnostic criterion for diabetes based on hemoglobin Alc (HbA1c) values. Our objective was to estimate how the new diabetes diagnostic criterion will affect the prevalence of diabetes among different race, age, and gender subpopulations, compared to the previously used fasting plasma glucose (FPG) criterion. We analyzed nationally representative data from The National Health and Nutrition Examination Survey (NHANES), aggregated from 1999 to 2006. We estimated the prevalence of known diabetes (prevalence static across either diagnostic criterion), unknown, and no diabetes (prevalence variable by criterion). We tested statistical significance of prevalence differences for unknown diabetes between the prior diagnostic criterion--FPG of at least 126 mg/dL--and the new diagnostic criterion--HbA1c of at least 6.5%--using conditional logistic regression. We further tested the association of these differences with demographic factors. The new HbA1c diagnostic criterion differentially affects different racial/ethnic groups. For non-Hispanic whites, the prevalence of undiagnosed diabetes was more than halved from 2.6% (95% confidence interval [CI], 2.2-3.1) with FPG diagnosis to 1.3% (95% CI, 1.0-1.7), P<.001 with HbAic diagnosis. For Hispanics and non-Hispanic blacks, the differences in prevalence by the 2 criteria were smaller and nonsignificant. Racial differences by diagnostic criteria were most pronounced among people aged over 55 years. Overall, the new definition of diabetes differentially affects ethnic groups, especially for older people. If the new criterion is widely adopted, over time, we may see an apparent widening of racial/ethnic disparities in diabetes prevalence.     

抗OmpW单克隆抗体的制备与特性鉴定

目的:制备抗副溶血弧菌OmpW的单克隆抗体(mAb),并鉴定其特性.方法:利用生物信息学方法分析多种病原弧菌的OmpW氨基酸序列,原核表达并纯化制备r-OmpW.以r-OmpW作为免疫抗原制备鼠mAb,以五种病原弧菌为筛选抗原.采用Western blot、流式细胞术(FCM)、间接ELISA法鉴定mAb的特性.结果:生物信息学分析表明OmpW是弧菌内高度保守的外膜蛋白.成功筛选到3株杂交瘤细胞株,其中,杂交瘤细胞株S5C10分泌的mAb的Ig亚类(型)为IgG3,腹水mAb效价达4.6×104.该mAb同时识别副溶血弧菌、溶藻弧菌、哈维氏弧菌、鳗弧菌和创伤弧菌,而与荧光假单胞菌、温和气单胞菌、嗜水气单胞菌、豚鼠气单胞菌及大肠杆菌无明显的交叉反应.结论:制备的mAb可特异性识别上述5种病原弧菌,为进一步建立广谱弧菌的免疫学检测方法提供了工具.     

乳腺小叶肿瘤组织学亚型及其分子病理学研究进展

第5版WHO乳腺肿瘤分类(2019), 将小叶瘤变定义为"起源于终末导管小叶单位(terminal ductal lobular units)失黏附上皮细胞的不典型增生, 伴或不伴有终末导管的派杰样播散"。小叶瘤变包括不典型小叶增生(atypical lobular hyperplasia)和小叶原位癌(lobular carcinoma in situ)。根据细胞形态将小叶原位癌细分为经典型小叶原位癌、旺炽型小叶原位癌和多形性小叶原位癌3种组织学亚型。近年来, 随着分子病理学不断发展, 对组织学形态特征的认识不断深入, 加深了对小叶瘤变及其亚型的研究和分析。本文将对小叶肿瘤各组织学亚型的临床病理学特征和分子病理学等方面进行综述。     

Venetoclax alone or in combination with other regimens treatment achieve deep and sustained remission of relapsed/refractory chronic lymphocytic leukemia: a meta-analysis

Clinical and Experimental Medicine - Recently, the use of novel targeted drugs significantly improved the overall response rate (ORR) and survival of patients with relapsed/refractory chronic...