Toll-like receptors in Borrelia burgdorferi-induced inflammation

Lyme arthritis, the most common manifestation of late Lyme disease, has been associated with the presence of Borellia burgdorferi in the joint. However, it is still unclear whether the pathogen itself is able to elicit such a sustained inflammatory response, or whether an aberrant immunological reaction of the host is the main driving force. Borrelia antigens, including lipoproteins, flagellin and DNA, are ligands of Toll-like receptors, and can thus elicit a strong stimulation of host cells, such as neutrophils, mononuclear cells and resident tissue cells. Understanding the molecular basis of the signalling events caused by Borrelia lipoproteins will lead to a greater understanding of inflammation in Lyme arthritis and, hopefully, new treatment strategies for chronic antibiotic-resistant disease.     

Case Report: Giant choledochal cyst

We report an adult female with a rare giant choledochal cyst. The patient presented following a normal pregnancy with the classical triad of an abdominal mass associated with jaundice and right upper quadrant abdominal pain. The cyst was excised using an intramural technique and biliary reconstruction achieved with a Roux-en-Y hepaticojejunostomy. Our patient has remained well with no evidence of malignancy over a 12 year review period. The aetiology and current management of this condition are discussed.     

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment

Summary The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 μg/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.     

Open mesh versus non-mesh repair of groin hernia meta-analysis of randomized trials leased on individual patient data

Abstract Background. The EU Hernia Trialists Collaboration was established to provide reliable evaluation of newer methods of groin hernia repair. It involved 70 investigators in 20 countries. Materials and methods. Twenty eligible trials (5016 participants) of open mesh vs. non-mesh groin hernia repair were identified. Meta-analysis was performed using raw individual patient data where possible. Results. Fewer hernia recurrences were reported after mesh repair. There were no clear differences between mesh and non-mesh groups in complications. Overall, those in the mesh groups had a shorter hospital stay, quicker return to usual activities and less frequent persisting pain, but individual trial results varied. Conclusions. The review provides strong evidence that open mesh repair is associated with a reduction in the risk of recurrence of between 50% and 75%. There is also some evidence of quicker recovery and of lower rates of persisting pain following open mesh repair. Electronic Publication     

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.