尿源干细胞及其外泌体治疗肾脏病的作用北大核心

背景:尿源干细胞为尿液中存在的间充质干细胞,具备自我增殖与多向分化的潜能,由于其本身存在于泌尿系统,并且很可能来源于肾脏组织,相较于其他间充质干细胞存在先天的优势,因此尿源干细胞及其外泌体可能具备对于肾脏病的特殊干预作用。目的:综述尿源干细胞及其外泌体的生物学特性,以及二者在肾脏病领域的应用进展,以期为临床肾脏疾病的治疗提供新思路。方法:以“urine-derived stem cell*,urine-derived stromal cell*,urine-derived mesenchymal stem cell*,urine-derived mesenchymal stromal cell*,urine-derived progenitor cell*,kidney diseases,acute kidney injury,diabetic nephropathies,kidney failure,chronic,tissue engineering,organoids”为检索词检索PubMed数据库,以“尿源干细胞,急性肾损伤,慢性肾病,糖尿病肾病,组织工程,类器官”为检索词检索CNKI数据库,发表时间限定为2000年1月至2021年10月。检索后严格按照纳入和排除标准进行人为筛选,最终纳入31篇文献进行综述。结果与结论:①尿源干细胞作为泌尿系统来源的间充质干细胞,具备间充质干细胞共有的特性。此外,其在肾脏病领域是一种有效的干预措施和适宜的种子细胞来源;②尿源干细胞及其外泌体在急性肾损伤动物及细胞模型上,可以显著缓解肾功能损害和组织学损伤,抑制炎症、细胞凋亡和氧化应激;在慢性肾脏病(包括糖尿病肾病)方面,尿源干细胞及其外泌体可以延缓肾功能进展及组织学改变,抑制炎症细胞浸润及纤维化,发挥对足细胞的保护作用;此外,其在肾脏组织工程与再生医学领域的应用也同样具有广阔的前景;③虽然尿源干细胞及其外泌体在肾脏病领域的研究尚处于初始阶段,但已体现出较大的潜力和价值,在未来有望成为临床肾脏病治疗的有效手段之一。     

小胶质细胞极化介导炎症反应在脊髓损伤中的作用

背景:小胶质细胞极化参与脊髓损伤后的炎症反应,并在其中发挥关键作用。相关研究表明,有效诱导小胶质细胞从M1促炎表型向M2抗炎表型极化,可以减轻脊髓损伤后的炎症反应,促进组织的修复再生和神经功能的恢复。目的:文章对小胶质细胞的功能和极化、小胶质细胞极化对脊髓损伤的影响及其潜在调控策略以及脊髓损伤后炎症反应进行综述。方法:检索PubMed、Web of Science和中国知网数据库,英文检索词为“microglia,polarization,spinal cord injury,inflammation”,中文检索词为“小胶质细胞、极化、脊髓损伤、炎症”,按纳入和排除标准共纳入80篇文献进行总结。结果与结论:①由小胶质细胞介导的稳定而持续的炎症反应,对脊髓损伤的预后至关重要。②在生理条件下,小胶质细胞处于M0静止表型,但在脊髓损伤后,小胶质细胞活化,进而极化成M1促炎表型,导致神经组织修复能力降低和出现持续性神经炎症。③在脊髓损伤的炎症反应过程中,调控小胶质细胞向M2表型极化或至少向M2表型倾斜,有利于抑制氧化应激反应、调节突触重塑、促进轴突再生和血管生成,是一种有效的调控策略。④截止到目前的研究表明,间充质干细胞、外泌体、临床药物、天然产物、miRNAs和靶点分子可调控小胶质细胞在M1和M2表型之间的转换,这为脊髓损伤后神经组织的修复提供了一种新的思路,未来需进一步研究小胶质细胞在脊髓损伤过程中调控极化的详细机制。     

Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

Single dose inactivated hepatitis A vaccine: Rationale and clinical assessment of the safety and immunogenicity

In comparison with the classical immunisation schedules (0-1-6 or 0-1-12 months) for hepatitis A, a 0- and 12- or a 0- and 6-month schedule would have important advantages by reducing the number of injections and discomfort and increasing scheduling convenience and patient compliance. It would be convenient if a single dose with enough antigen could protect both rapidly and for at least 12 months, when the booster dose would be given. Several clinical trials have been carried out with an inactivated hepatitis A vaccine containing 1,440 ELU. (1 ml), according to a 0–12 and a 0–6 vaccination schedule. This hepatitis A vaccine is safe and well tolerated. It offers a rapid seroresponse: 14 days after a single dose the seroconversion is 88% (95% C.I.: 84.6–90.9). The 0–12 schedule study showed good persistence of hepatitis A virus (HAV) antibodies with a seroconversion rate of almost 95% at month 12. Booster doses given at 6 or 12 months result in a substantial rise in antibody levels; according to these antibody litres, the 1,440 EL. U. vaccine can be expected to confer comparable duration of protection as the 720 EL. U. vaccine, i.e., 10–20 years. Preliminary data show that tinning of the booster may not be critical for the antibody response. In conclusion, the 1,440 EL. U. hepatitis A vaccine is safe, offers rapid seroconversion, and is highly immunogenic. The persistence of HAV antibodies until month 12 allows a certain flexibility in the administration of the booster: month 6 or 12, and a 0–12 or 0–6 schedule can increase the vaccination compliance. copy; 1994 Wiiey-Liss, inc.     

Primary renal angiosarcoma: A case report and review of the literature

Primary renal angiosarcoma is very rare. To our knowledge, only 15 cases have been reported to date. A 77-year-old Japanese man with a unilateral kidney presented with massive hematuria followed by renal failure. A renal tumor was suspected and a left nephrectomy was performed. The histopathological diagnosis was angiosarcoma of the kidney. A hemorrhagic tumor measuring 10 × 5 cm and clotted blood was found in the modularly area. The atypical tumor cells had a sinusoidal and solid appearance, and showed Immunohistochemically positive reactions for some of the endothelial markers. The patient died about 21 months after the nephrectomy and the autopsy revealed massive metastases to the liver and retroperitoneum. One of the differential diagnoses of the case was anglomyolipoma, because the tumor cells were relatively bland in their histological appearance with entrapped fat cells in the pelvic area. Fifteen case reports with titles that included the term 'hemangiosarcoma/anglosarcoma', 'hemangioendothelloma/endothelloma' or 'vascular sarcoma' of the kidney were reviewed and compared to the present case.     

心理弹性(resilience)研究综述

弹性（resilience）日益为心理学界所关注，已经成为心理学的一个重要研究领域。文章追溯了弹性研究的渊源，介绍了众多研究者对于弹性的认识，回顾了弹性领域研究的进展情况，对以往的研究进行了评价，对以后的研究进行了展望。     

A patient with novel MBOAT7 variant: The cerebellar atrophy is progressive and displays a peculiar neurometabolic profile

Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.     

生物医学前沿中的伦理问题

本文在讨论科学技术与伦理学关系、生命伦理学基本原则以及道德与伦理学之间的异同后,探讨了人的克隆和干细胞研究、基因治疗、生殖遗传学、异种移植、生物医学和临床研究中的伦理问题。     

Vasectomy techniques for male sterilization: systematic Cochrane review of randomized controlled trials and controlled clinical trials

BACKGROUND: The review aimed to compare the effectiveness, safety and acceptability of vasectomy techniques for male sterilization. METHODS: We searched five computerized databases and reference lists of relevant articles and book chapters for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing vasectomy techniques. Two reviewers independently extracted data from eligible articles. RESULTS: Two poor-quality trials compared vas occlusion with clips versus a conventional technique, and four poor-quality trials examined vas irrigation with water versus no irrigation or irrigation with euflavine. No significant differences regarding the primary outcome of time to azoospermia were found. However, one trial reported fewer median number of ejaculations to azoospermia with euflavine rather than water irrigation. An interim report of a high-quality trial comparing vasectomy with and without fascial interposition found more azoospermia with fascial interposition but also more surgical difficulties. CONCLUSIONS: No conclusions can be reached regarding the effectiveness, safety and acceptability of vas occlusion techniques or vas irrigation since only low-quality, underpowered studies were available. Fascial interposition had improved vasectomy success but also increased surgical difficulty. High-quality, adequately reported RCTs are required. More work is also needed in the standardization of follow-up protocols, evaluation of vasectomy success and failure, recanalization and analytical methods.