Interphotoreceptor Retinol-Binding Protein Ameliorates Diabetes-Induced Retinal Dysfunction and Neurodegeneration Through Rhodopsin

Patients with diabetes often experience visual defects before any retinal pathologies are detected. The molecular mechanism for the visual defects in early diabetes has not been elucidated. Our previous study reported that in early diabetic retinopathy (DR), rhodopsin levels were reduced due to impaired 11-cis-retinal regeneration. Interphotoreceptor retinol-binding protein (IRBP) is a visual cycle protein and important for 11-cis-retinal generation. IRBP levels are decreased in the vitreous and retina of DR patients and animal models. To determine the role of IRBP downregulation in the visual defects in early DR, we induced diabetes in transgenic mice overexpressing IRBP in the retina. IRBP overexpression prevented diabetes-induced decline of retinal function. Furthermore, IRBP overexpression also prevented decreases of rhodopsin levels and 11-cis-retinal generation in diabetic mice. Diabetic IRBP transgenic mice also showed ameliorated retinal oxidative stress, inflammation, apoptosis, and retinal degeneration compared with diabetic wild-type mice. These findings suggest that diabetes-induced IRBP downregulation impairs the regeneration of 11-cis-retinal and rhodopsin, leading to retinal dysfunction in early DR. Furthermore, increased 11-cis-retinal–free opsin constitutively activates the phototransduction pathway, leading to increased oxidative stress and retinal neurodegeneration. Therefore, restored IRBP expression in the diabetic retina may confer a protective effect against retinal degeneration in DR.     

Updates on bacterial resistance and empirical antibiotics treatment of complicated acute appendicitis in children

Objective: Through historical comparison with our previous study published 10 years ago, this paper aims to provide latest analysis of local bacteriology of acute complicated appendicitis and evaluate the effects of early escalation of potent antibiotics on course of postoperative recovery.Methods: A 5-year retrospective review of all children receiving emergency laparoscopic appendicectomies for acute appendicitis from December 2014 to November 2019 was conducted.Results: 257 cases of acute appendicitis were included, 126 were complicated appendicitis (38 gangrenous, 88 ruptured). 96 had positive peritoneal swab culture, 53 (42.1%) grew resistant bacterial strains, including extended spectrum beta-lactamase producing E. coli (ESBL E. coli), Pseudomonas aeruginosa, against traditional empirical triple antibiotics. The prevalence had significantly increased over the past decade (p = 0.008). In our patients, piperacillin/tazobactam, ertapenem, gentamicin provided coverage of 69.8%, 45.3% and 45.3% respectively. For patients with early escalation of postoperative antibiotics, no statistical significance was identified in terms of postoperative complications (p = 0.883), or duration of antibiotics (p = 0.0615).Conclusion: Growing prevalence of resistant strains were observed over the decade. Piperacillin/tazobactam provided the best coverage (69.8%) against resistant bacterial strains in our patients. Early escalation of antibiotics failed to reduce postoperative complications and antibiotics duration.Type of Study: Clinical Research, Retrospective Historical Comparative StudyLevel of Evidence: Level III     

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

加味双柏凝胶贴膏质量研究及安全性考察

目的：建立加味双柏凝胶贴膏中黄柏、冰片、大黄的薄层色谱法（TLC）,对其质量稳定性进行考察,并初步评价加味双柏凝胶贴膏敷贴的用药安全性。方法：通过TLC对加味双柏凝胶贴膏处方中的黄柏、冰片、大黄进行鉴别,采用加速试验、长期试验和影响因素试验考察其稳定性,试验以新西兰兔为模型进行多次皮肤刺激试验,以Hartley豚鼠为模型进行主动皮肤过敏试验和豚鼠Buehler试验,观察凝胶贴膏的皮肤刺激作用和致敏作用。结果：TLC中色谱斑点清晰、特征明显且阴性对照无干扰。3批产品在长期试验和加速试验中均具有较好的稳定性,加味双柏凝胶贴膏对新西兰兔皮肤无刺激性,对豚鼠皮肤无过敏性。结论：建立的TLC可作为加味双柏凝胶贴膏的质量控制方法,加味双柏凝胶贴膏是一种较安全的新型外用制剂且制剂质量稳定可控。     

后路经椎间隙截骨的临床分型及应用

【摘要】 目的：介绍脊柱后路经椎间隙截骨术（trans-intervertebral space osteotomy,TIO）的技术理念、临床分型和应用策略。方法：根据TIO技术特点、手术操作过程中截骨切除范围所涉及的解剖结构,将其分为3大类型及2种扩大（+）型：围绕椎间盘及关节突关节为Ⅰ型,扩大至楔形切除椎间隙一侧终板为Ⅱ型（头尾双侧终板则为Ⅱ+型）。扩大至楔形切除椎间隙一侧椎弓根为Ⅲ型（双侧椎弓根则为Ⅲ+型）;收集2003年1月~2012年12月接受后路经椎间隙截骨术治疗的30例胸腰椎侧后凸畸形患者的临床资料,其中男12例,女18例,年龄29~69岁（51.4±10.4岁）。由5位脊柱外科医师先后对患者的临床资料进行独立评估与分型（间隔2周）,进行Kappa一致性检验以分析其可信度及可重复性。结果：30例患者中行Ⅰ型TIO 15例,Ⅱ型TIO 6例,Ⅱ+型TIO 3例,Ⅲ型TIO 4例,Ⅲ+型TIO 2例。观察者间一致性的Kappa系数0.806~0.953;观察者内一致性的Kappa系数为0.837~0.953,可信度及可重复性满意。结论：经椎间隙截骨临床分型实用可靠,可作为理论基础用于比较不同研究中经椎间隙截骨技术的手术效果,有利于指导脊柱侧后凸畸形的截骨矫形治疗。     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Effects of bariatric surgery on patients with obesity and polycystic ovary syndrome: a meta-analysis

BackgroundBariatric surgery is effective for polycystic ovary syndrome (PCOS), while the exact mechanism remains unclear.ObjectivesTo assess the impact of bariatric surgery on PCOS patients and further explore the possible mechanism.SettingA meta-analysis.MethodsWe searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before November 2020.ResultsTwenty-one studies met our inclusion criteria, and we identified 552 patients with PCOS study. Results showed that the prevalence of preoperative PCOS, menstrual irregularity, hirsutism, type 2 diabetes (T2D), hypertension, infertility, and depression significantly decreased after bariatric surgery. Levels of total testosterone, fasting insulin, and luteinizing hormone (LH) decreased and estradiol increased, while levels of follicle-stimulating hormone (FSH) and LH/FSH did not show significant changes during the 3-month follow-up. There were decreases in testosterone and fasting insulin levels when the postoperative follow-up time was 6 months or ≥12 months. Levels of fasting blood glucose and triglycerides were significantly reduced after 6 months or ≥12 months of bariatric surgery. High-density lipoprotein (HDL) and sex hormone-binding globulin (SHBG) significantly improved ≥12 months after bariatric surgery.ConclusionSymptoms of PCOS and related complications are significantly alleviated after bariatric surgery. In addition, we found a significant improvement on anomalous secretion of gonadotropins, glucose metabolism, and lipid metabolism in patients with PCOS after bariatric surgery.