Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.     

丹蛭降糖胶囊通过mTOR/S6K1信号通路对糖尿病肾病大鼠的干预作用研究

目的研究丹蛭降糖胶囊对糖尿病肾病大鼠的肾脏病理改变和足细胞自噬水平的影响,初步探讨其相应的作用机制。方法选取GK大鼠40只,采用醋酸脱氧皮质酮-盐皮下注射联合高脂饲料喂养诱导糖尿病肾病模型。造模成功后随机分为模型组、丹蛭降糖胶囊低剂量组[0.54 g/(kg·d)]、高剂量组[1.08 g/(kg·d)]、缬沙坦组[10 mg/(kg·d)],每组10只。另选取10只同周龄正常Wistar大鼠作为正常组。模型组和正常组给予等容积生理盐水。连续灌胃10周后检测空腹血糖(FBG)、血肌酐(SCr)、尿素氮(BUN)和尿微量蛋白(U-mAlb)。Western Blot检测肾小球p-mTOR、p-S6K1、Beclin-1、LC3和Nephrin蛋白的表达,HE染色和PAS染色后于光镜下观察肾脏病理变化,电镜下观察各组亚细胞形态结构变化。结果与正常组比较,模型组FBG、SCr、BUN、U-mAlb水平升高(P<0.01);与模型组比较,丹蛭降糖胶囊低、高剂量组和缬沙坦组U-mAlb水平降低(P<0.01)。模型组可见肾小球基底膜增厚,系膜基质沉积,足细胞损伤,各用药组均有不同程度改善,丹蛭降糖胶囊高剂量组足细胞内有较多自噬体形成。与正常组比较,模型组p-mTOR、p-S6K1的表达增高,Nephrin、Beclin-1和LC3的表达水平降低(P<0.01);与模型组比较,各用药组p-mTOR、p-S6K1的表达下降,Nephrin、Beclin-1和LC3的表达增高(P<0.01)。丹蛭降糖胶囊高剂量组和缬沙坦组Beclin1、LC3Ⅱ/LC3Ⅰ水平较丹蛭降糖胶囊低剂量组升高(P<0.05)。结论丹蛭降糖胶囊具有减轻糖尿病肾病大鼠U-mAIb、足细胞损伤及相关肾脏病理改变的作用,其机制可能与抑制mTOR/S6K1信号通路进而提高足细胞的自噬活性有关。     

新形势下八年制医学教育的再思考

新形势下，健康中国建设和我国卫生事业发展迫切需要具有国际竞争力的医学科学家和领军人才。在现行医学教育体系中，培养具有国际竞争力的未来医学科学家和领军人才是八年制医学教育的必然选择。创新八年制医学人才培养模式应汲取长学制试办经验，直面现存问题，聚焦创新能力和创新精神，构建以研究为基础的八年制医学人才培养模式，确立“目标引领、厚植基础、面向临床、聚集创新”的办学原则，为我国卫生事业培养具有国际竞争力的未来领军人才。     

综合医院发热门诊应对新型冠状病毒肺炎的应急管理

目的 探讨综合医院发热门诊应对新型冠状病毒感染肺炎的应急管理方法及效果。 方法 加强发热门诊的管理，包括优化发热预检分诊工作流程、合理布局发热门诊、修订发热门诊工作职责与流程指引、合理调配人力资源、加强相关人员培训、严格落实院感防控措施、提供后勤保障、加强健康宣教与管理。 结果 接诊患者13 761例次，采集咽拭子591例次，静脉输液11 973例次，氧气吸入998例次。 结论 加强综合医院发热门诊管理，能有效提高护理人员对新型冠状病毒肺炎疫情的应对能力，保障护理安全。     

Bismuth Sodium Titanate Based Materials for Piezoelectric Actuators

The ban of lead in many electronic products and the expectation that, sooner or later, this ban will include the currently exempt piezoelectric ceramics based on Lead-Zirconate-Titanate has motivated many research groups to look for lead-free substitutes. After a short overview on different classes of lead-free piezoelectric ceramics with large strain, this review will focus on Bismuth-Sodium-Titanate and its solid solutions. These compounds exhibit extraordinarily high strain, due to a field induced phase transition, which makes them attractive for actuator applications. The structural features of these materials and the origin of the field-induced strain will be revised. Technologies for texturing, which increases the useable strain, will be introduced. Finally, the features that are relevant for the application of these materials in a multilayer design will be summarized.     

Intermittent Internal Fixation With a Locking Plate to Preserve Epiphyseal Growth Function During Limb-Salvage Surgery in a Child With Osteosarcoma of the Distal Femur: A Case Report

Limb shortening is a problem associated with surgery for osteosarcoma of the lower extremity in adolescents, as the tumors frequently occur near the epiphysis. Herein we report the use of a less invasive stabilization system (LISS) and an intermittent fixation method to preserve the growth function of epiphysis in an 11-year-old patient with an osteosarcoma of the distal femur.The 11-year-old male presented with left knee enlargement and pain for 2 weeks, and magnetic resonance imaging (MRI) and biopsy were consistent with osteosarcoma of the left distal femur. After preoperative chemotherapy, en bloc tumor resection was performed with margins based on MRI findings preserving the epiphyseal growth plate, the tumor cavity was filled with inactivated bone and bone cement, and a LISS was used to stabilize the femur. Aggressive postoperative chemotherapy was given. Approximately 105 weeks after surgery radiography showed that the distal end of the plate had moved superior to the epiphysis along with bone growth. Locking screws were placed in the distal part of the LISS plate to stabilize the re-implanted bone, and external fixation was not needed.The patient was able to walk with the crutches 1 week postoperatively, and bear weight on the extremity 6 weeks postoperatively. At 6 years after surgery, the patient''s height had increased 52 cm, shortening of the affected limb was only 1 cm, and the circumference of the affected limb was 2 cm smaller than that of the contralateral limb. There was no significant discomfort in the affected limb, and there was no gait abnormality. The patient could jump and run, and could participate in sports including basketball and badminton to the same degree as his peers.In summary, the novel method of bone reconstruction and fixation provided good results in a child with an osteosarcoma of the distal femur. This fixation method preserves the osteogenic function of the epiphysis and restored bone integrity simultaneously, and provides good functional recovery.     

8种寄生虫病例分析

本文报道并分析8例寄生虫病例,其中包括脑裂头蚴病、眼部裂头蚴病、肺吸虫幼虫移行症、肺吸虫病、钩虫病、肝吸虫病、包虫病和广州管圆线虫病各1例。8例寄生虫病均有不同程度的误诊,其中6例在寄生虫抗体筛查检测阳性后得以确诊。因此,寄生虫病应引起临床医生的重视,抗体筛查有助于发现寄生虫病例。     

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.