A novel cysteine-sparing G73A mutation of NOTCH3 in a Chinese CADASIL family

neurogenetics - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia....     

输尿管支架管结壳患者尿液菌群的分布特点

目的探讨输尿管支架管结壳患者尿液菌群的分布特点。方法选取2018年10月至2019年3月在山东省立第三医院、山东大学齐鲁医院、济南市中心医院和济南市济钢医院就诊的35例输尿管支架管置入术后患者。纳入标准:年龄18~65岁;输尿管镜碎石术后留置内支架管4周。排除标准:尿液细菌培养阳性;严重肉眼血尿;近期口服抗生素;存在明显残石患者。本研究采用横断面研究方法(临床研究注册号为ChiCTR1800020025),根据有无支架管结壳将患者分为结壳组23例和无结壳组12例。收集拔管当日患者尿液行细菌16s DNA检测。使用UPARSE、UCHIME和RDP calssifier等软件分析两组患者尿液菌群分布特点,明确两组患者尿液中细菌种类总数、细菌丰度,以及丰度占比较大的细菌类别,比较两组患者尿液细菌种类、数量及细菌丰度的差异,明确结壳组患者尿液中丰度占比较大的细菌菌属。结果两组患者的年龄、性别、体质指数、置管侧别、内支架管型号及结石成分差异均无统计学意义(P>0.05)。16s DNA检测结果显示,结壳组丰度占比>1%的菌属数量为11个,丰度占比>0.01%的菌属数量为74个;无结壳组丰度占比>1%的菌属数量为7个,丰度占比>0.01%的菌属数量为11个,两组丰度占比>1%的菌属数量比较差异有统计学意义(t=5.12,P=0.000)。结壳组中菌属丰度占比前3位分别为乳杆菌属(23.1%)、拟杆菌属(18.8%)和未分级拟杆菌属(17.1%),非结壳组中菌属丰度占比前3位分别是为埃希菌-志贺菌属(32.2%)、肠球菌属(24.9%)和假单胞菌属(18.2%)。两组间差异最大的3种细菌是乳杆菌属(P=0.010),拟杆菌属(P=0.004)和未分级拟杆菌属(P=0.004)。结论支架管结壳患者尿液中细菌种类和数量都明显多于非支架管结壳患者。拟杆菌属细菌在支架管结壳患者尿液中的细菌种类丰度较大。     

子宫内膜功能亢进性疾病的“异病同治”诊治研究思路＊

笔者根据现代临床子宫内膜的病理演变过程结合中医“异病同治”理念，提出“子宫内膜功能亢进性疾病”概念，涵盖5种常见的子宫内膜疾病：无排卵性异常子宫出血（Abnormal Uterine Bleeding Ovulatory dysfunction，AUB-O），子宫内膜息肉（Endometrial Polyp，EP），子宫内膜异位症（Endometriosis，EMs），子宫腺肌病（Adenomyosis，AM），子宫内膜癌（Endometrial Carcinoma，EC）。基于文献的汇总，分析得到此类疾病的子宫内膜病理演变与中医病因病机的关联性，为寻找关键通路、创新性治疗此类疾病提供了重要的参考方向，对深化中医妇科学常见疾病的共性病因病机提供了理论依据和探索思路。     

Evaluation of a deep learning model on coronary CT angiography for automatic stenosis detection

PurposeThe purpose of this study was to evaluate a deep-learning model (DLM) for classifying coronary arteries on coronary computed tomography -angiography (CCTA) using the Coronary Artery Disease-Reporting and Data System (CAD-RADS).Materials and methodsThe DLM was trained with 10,800 curved multiplanar reformatted (cMPR) CCTA images classified by an expert radiologist using the CAD-RADS. For each of the three main coronary arteries, nine cMPR images 40° apart acquired around each arterial circumference were then classified by the DLM using the highest probability. For the validation set composed of 159 arteries from 53 consecutive patients, the images were read by two senior and two junior readers; consensus of the two seniors was the reference standard. With the DLM, the majority vote for the nine images was used to classify each artery. Three groups (CAD-RADS 0, 1–2, or 3–4–5) and 2 groups CAD-RADS 0–1–2 or 3–4–5 (<50% vs. ≥50% stenosis) were used for comparisons with readers and consensus. Performance of the model and readers was compared to the consensus reading using the intraclass coefficient (ICC) and Cohen's kappa coefficient at the artery and patient levels.ResultsWith the three groups at the artery level, the ICC of the DLM was 0.82 (95% CI: 0.75–0.88) and not significantly different from those of 3/4 readers; accuracy was 81%. With the binary classification, Cohen kappa coefficient of the DLM was 0.85 (95% CI: 0.69–0.94) and not significantly different from that of 3/4 readers; accuracy was 96%. At the patient level, sensitivity and specificity were 93% and 97% respectively, and the negative predictive value was 97%.ConclusionThe DLM detected ≥50% stenoses with performances similar to those achieved by senior radiologists.     

An epidemiologic study of sleep-disordered breathing in a large sample of Chinese adolescents

Journal of Public Health - Sleep-disordered breathing (SDB) is common among adolescents and is associated with short- and long-term consequences. Data on the prevalence and epidemiologic...     

The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte–macrophage colony-stimulating factor

Research questionDoes Embryogen®/BlastGen™ culture medium improve live birth rates compared with standard culture medium for women undergoing IVF and intracytoplasmic sperm injection (ICSI) with poor prognosis.DesignRandomized clinical trial. A total of 100 couples undergoing IVF/ICSI were randomly allocated to having their inseminated oocytes incubated in either Embryogen®/BlastGen™ sequential culture media or standard Cleavage/Blastocyst sequential culture media for 5 days (ClinicalTrials.gov Identifier: NCT02305420).ResultsNo statistically significant difference in live birth rate was found between the control group and the Embryogen®/BlastGen™ group (17 [34%] versus 11 [22%], respectively) (OR 0.55; 95% CI 0.22 to 1.32; P = 0.18). After adjustment for maternal age, body mass index and fertilization procedure, the blastulation rate reduced (40.6 ± 26.5 versus 24.6 ± 26.7; RR 0.70, CI 0.52 to 0.95; P < 0.05), and grade of the embryo transferred (OR 0.35, CI 0.16 to 0.77; P < 0.01) when Embryogen®/BlastGen™ medium was used.ConclusionA significant reduction in day-5 embryo outcome parameters was found using Embryogen®/BlastGen™ compared with standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations and strict inclusion criteria of this single-centre study, further research is needed to determine the efficacy of Embryogen®/BlastGen™ medium in couples undergoing IVF/ICSI.     

基于机器学习的脑胶质瘤多模态影像分析

脑部胶质瘤是临床中常见的一种原发性脑肿瘤，具有复发率高、死亡率高以及治愈率低的特点。常规临床诊断主要依靠计算机断层扫描(CT)和磁共振成像(MRI)检查技术进行鉴别。随着成像技术和机器学习方法的不断发展，多模态影像智能分析技术已经逐步成为研究热点，在脑胶质瘤的病灶分割测量、肿瘤分级、预后生存周期预测和基因型辨别等方面具有重要的应用前景。本文重点介绍基于机器学习和多模态影像在脑胶质瘤临床辅助诊断和预后评估中的应用进展。     

Regulation of glucose and insulin release following acute and repeated treatment with the synthetic galanin analog NAX-5055

The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems. However there is limited understanding of how individual galanin receptor (GalR1, 2, and 3) subtypes mediate the physiological activity of galanin in vivo. To address this issue we utilized NAX-5055, a systemically available, metabolically stable galanin analog. NAX-5055 displays a preference for GalR1 receptors and possesses potent anticonvulsant activity in vivo, suggesting that NAX-5055 engages central galanin receptors. To determine if NAX-5055 also modulates the activity of peripheral galanin receptors, we evaluated the effect of NAX-5055 on blood glucose and insulin levels in mice. Acute and repeated (once daily for four days) systemic administration of NAX-5055 (4 mg/kg) significantly increased blood glucose levels compared to vehicle treated mice. However, a hyperglycemic response was not observed following systemic administration of NAX-805-1, a scrambled analog of NAX-5055, with critical receptor binding residues, Trp² and Tyr⁹, reversed. These results suggest that chemical modifications independent of the galanin backbone of NAX-5055 are not responsible for the hyperglycemic response. The effect of NAX-5055 on glucose homeostasis was further evaluated with a glucose tolerance test (GTT). Mice administered either acute or repeated (once daily for four days) injections of NAX-5055 (4 mg/kg) displayed impaired glucose handling and reduced insulin response to an acute glucose (1g/kg) challenge. Here we have shown that systemic administration of a centrally active GalR1-preferring galanin analog produces acute hyperglycemia and an inhibition of insulin release in vivo and that these effects are not attenuated with repeated administration. NAX-5055 thus provides a new pharmacological tool to further the understanding of function of both central and peripheral GalR1 receptors in vivo.