Development and validation of a novel 133-plex forensic STR panel (52 STRs and 81 Y-STRs) using single-end 400 bp massive parallel sequencing

International Journal of Legal Medicine - Short tandem repeats (STRs) are the preferred genetic markers in forensic DNA analysis, routinely measured by capillary electrophoresis (CE) method based...     

Chromic-P32 phosphate treatment of implanted pancreatic carcinoma： Mechanism involved

AIM: To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. METHODS: Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. RESULTS: The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F= 4.14-105.36, P<0.01). MVD were 38.5±4.0,28.0±2.9,17.0±2.9,8.8±1.5, 5.7±2.3 and 65.0±5.2 (t=11.9-26.1,P<0.01),respectively. Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group.The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation induced apoptosis,the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.     

TNF-α-Secreting B Cells Contribute to Myocardial Fibrosis in Dilated Cardiomyopathy

Purpose

Excessive inflammation responses mediated by CD4⁺ T cells contributes to myocardial fibrosis in dilated cardiomyopathy (DCM) resulting from viral myocarditis. Recently, some scholars discovered that B cells harbored an abnormal pro-inflammatory capacity besides the production of autoantibodies. Thus, we aimed to explore whether and which type of B cells act on myocardial fibrosis in DCM.

Methods

A total of 56 newly hospitalized DCM patients were studied, and among these, 17 patients accepted the gadolinium enhanced cardiovascular magnetic resonance imaging (MRI) for myocardial fibrosis evaluations.

Results

B cell functions including the frequency and proliferation were significantly elevated in DCM patients. After screening the important cytokines including IL-1β, IL-6, IL-10, IL-17, TNF-α and TGF-β produced in these B cells by flow cytometry, we found that only the TNF-α-secreting B cells were obviously increased. Furthermore, the TNF-α protein secretion and mRNA levels were also enhanced in LPS-stimulated B cell isolated from DCM patients. In addition, 10 patients (59 %) with increased TNF-α-secreting B cells showed late enhancement and boosted serum procollagen type III compared with the other 7 patients (41 %) whose enhancement could not be detected. Moreover, the frequencies of TNF-α-secreting B cells were negatively correlated with LVEF and positively correlated with LVEDD, NT-proBNP and procollagen type III in all of the DCM patients.

Conclusions

Our study firstly suggested that TNF-α-secreting B cells were involved in myocardial fibrosis, which revealed the new pathogenic mechanism of B cells in DCM, and therapeutic targets against these cells might be valuable.     

Texture Analysis of Three-Dimensional MRI Images May Differentiate Borderline and Malignant Epithelial Ovarian Tumors

ObjectiveTo explore the value of magnetic resonance imaging (MRI)-based whole tumor texture analysis in differentiating borderline epithelial ovarian tumors (BEOTs) from FIGO stage I/II malignant epithelial ovarian tumors (MEOTs).Materials and MethodsA total of 88 patients with histopathologically confirmed ovarian epithelial tumors after surgical resection, including 30 BEOT and 58 MEOT patients, were divided into a training group (n = 62) and a test group (n = 26). The clinical and conventional MRI features were retrospectively reviewed. The texture features of tumors, based on T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging, were extracted using MaZda software and the three top weighted texture features were selected by using the Random Forest algorithm. A non-texture logistic regression model in the training group was built to include those clinical and conventional MRI variables with p value < 0.10. Subsequently, a combined model integrating non-texture information and texture features was built for the training group. The model, evaluated using patients in the training group, was then applied to patients in the test group. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the models.ResultsThe combined model showed superior performance in categorizing BEOTs and MEOTs (sensitivity, 92.5%; specificity, 86.4%; accuracy, 90.3%; area under the ROC curve [AUC], 0.962) than the non-texture model (sensitivity, 78.3%; specificity, 84.6%; accuracy, 82.3%; AUC, 0.818). The AUCs were statistically different (p value = 0.038). In the test group, the AUCs, sensitivity, specificity, and accuracy were 0.840, 73.3%, 90.1%, and 80.8% when the non-texture model was used and 0.896, 75.0%, 94.0%, and 88.5% when the combined model was used.ConclusionMRI-based texture features combined with clinical and conventional MRI features may assist in differentitating between BEOT and FIGO stage I/II MEOT patients.     

外周血白细胞端粒长度和线粒体基因拷贝数对急性心肌梗死的诊断预测价值以及相关机制的探讨

目的 探究外周血白细胞端粒长度(LTL)和线粒体基因拷贝数(mtDNA?CN)对急性心肌梗死(AMI)的预测价值,并从端粒酶逆转录酶(TERT)和线粒体氧化损伤的角度探讨其相关机制.方法 选取AMI患者80例,并选同期行冠脉造影检查且结果显示冠脉大致正常者80例作为对照.收集研究对象的临床资料和空腹全血,以qPCR法检测外周血LTL、TERT mRNA、mtDNA?CN和线粒体氧化损伤程度,采用Spearman相关分析评估上述指标间的相关性.采用多因素Logistic回归分析LTL和mtDNA?CN与AMI发生风险的关系,以受试者工作曲线(ROC)评价LTL和mtDNA?CN对AMI诊断的预测价值.结果 AMI组患者外周血LTL、TERT mRNA表达水平和mtDNA?CN均显著低于对照组,线粒体氧化损伤水平显著高于对照组,差异均具有统计学意义(P<0.05).在AMI组和对照组中,LTL分别与TERT mRNA的表达水平和mtDNA?CN呈显著正相关,与线粒体氧化损伤水平呈显著负相关(均P<0.05).在AMI组中,mtDNA?CN与线粒体氧化损伤水平呈显著负相关(P=0.03),但在对照组中两者相关性无统计学意义(P=0.20).Logistic回归分析结果表明,长LTL和高mtDNA?CN是AMI的保护因素;ROC曲线分析结果表明,LTL、mtDNA?CN以及两者联合预测AMI的曲线下面积(AUC)分别为0.748、0.704、0.767.结论 外周血LTL和mtDNA?CN对AMI具有一定的预测诊断价值.AMI患者外周血LTL的缩短可能与TERT mRNA表达的降低有关,外周血白细胞线粒体氧化损伤水平的升高可能是mtDNA?CN降低和LTL缩短的重要原因.