Cellular basis of diabetic nephropathy: V. Endoglin expression levels and diabetic nephropathy risk in patients with Type 1 diabetes

Endoglin is an accessory receptor molecule that, in association with transforming growth factor β (TGF-β) family receptors Types I and II, binds TGF-β1, TGF-β3, activin A, bone morphogenetic protein (BMP)-2 and BMP-7, regulating TGF-β dependent cellular responses. Relevant to diabetic nephropathy, endoglin, expressed in vascular endothelial and smooth muscle cells, fibroblasts, and mesangial cells, negatively regulates extracellular matrix (ECM). The aim of this study was to evaluate endoglin expression in cultured skin fibroblasts from patients with Type 1 diabetes with and without diabetic nephropathy. Kidney and skin biopsies were performed in 125 Type 1 diabetic patients. The 20 with the fastest rate of mesangial expansion (estimated by electron microscopy) and proteinuria (“fast-track”) and the 20 with the slowest rate and normoalbuminuria (“slow-track”), along with 20 controls were studied. Endoglin mRNA expression was assessed by microarray and quantitative real-time polymerase chain reaction (QRT-PCR) and protein expression by Western blot. Age and sex distribution were similar among groups. Diabetes duration was similar (20±8 vs. 24±7 years), hemoglobin A1c lower (8.4±1.2% vs. 9.4±1.5%), and glomerular filtration rate higher (115±13 vs. 72±20 ml/min per 1.73 m²) in slow-track vs. fast-track patients. Microarray endoglin mRNA expression levels were higher in slow-track (1516.0±349.9) than fast-track (1211.0±274.9; P=.008) patients or controls (1223.1±422.9; P=.018). This was confirmed by QRT-PCR. Endoglin protein expression levels correlated with microarray (r=0.59; P=.044) and QRT-PCR (r=0.61; P=.034) endoglin mRNA expression. These studies are compatible with the hypothesis that slow-track Type 1 diabetic patients, strongly protected from diabetic nephropathy, have distinct cellular behaviors that may be associated with reduced ECM production.     

用IS6110限制性片段长度多态性方法分析中国南方部队结核分支杆菌DNA指纹特征

目的：分析南方部队结核病患者和当地患者中结核分支杆菌分离株DNA指纹特征，探讨南方部队结核病的分子流行病学特征。方法：用限制性内切酶PvuⅡ消化结核分支杆菌DNA，后用琼脂糖凝胶电泳，再用Southern免疫转印，用[α^32P]-dCTP标记的DNA IS6110序列中的245bp片段作探针，进行杂交后得到限制性片段长度多态性图谱，结合一般流行病学资料加以分析比较。结果：共检测185株结核分支杆菌分离株。检测菌株的IS6110拷贝数范围为1～22。部队患者和当地患者的IS6110拷贝数分布差异无显著姓。部队患者结核菌分离株的IS6110拷贝数主要集中在6～20个，当地分离株主要集中在7～20个；全部菌株指纹特征分成8个组，部队分离株和当地分离株均主要集中在Ⅰ、Ⅱ、Ⅲ 3个组里。耐药菌株指纹特征在各组中的分布与敏感菌株差异有显著性；患者是否接种卡介苗在各组中的分布差异无显著性。结论：南方部队患者与当地患者结核菌分离株在遗传关系上较接近，在基因水平上相关程度较强。提示部队结核病的发生与当地结核分支杆菌菌株的传播密切相关。     

Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials

IntroductionPomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma.MethodsA comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I² index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I² ≥ 50%).ResultsPooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I² = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%.ConclusionThree-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.     

Langerhans Cell Histiocytosis Mimicking Periapical Pathology in a 39-year-old Man

Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of Langerhans-type dendritic cells, with more than 50% of cases of LCH seen in children younger than 15 years of age. The most common clinical presentation of LCH is solitary or multiple bony lesions. The jaws are affected in approximately 10%–20% of cases, with a strong predilection for the mandible. The maxilla is involved in only 1% of head and neck cases. When the jaws are involved, lesions of LCH may mimic periapical pathology as seen in patients requiring endodontic therapy or bone loss as seen in periodontal disease. We report the case of a 39-year-old man with LCH involving the posterior maxilla. This is a rare presentation of LCH with respect to both location and patient age. Clinicians should consider LCH when developing a differential diagnosis of an apical radiolucency of vital teeth or teeth that fail to respond to endodontic therapy and be aware of its clinical and radiographic mimics.     

Recurrent hemarthrosis after total knee arthroplasty caused by the impingement of a remnant lateral meniscus: A case report

A case of recurrent hemarthrosis initially presenting after the fifth postoperative month is described. Because of recurrent pain and swelling, the patient underwent an arthroscopy 14 months after total knee arthroplasty (TKA). A remnant posterior lateral meniscus was found to be impinged between the femoral component and the tibial liner, and there was oozing from the hypertrophied synovium around the remnant meniscus. The remnant meniscus and the synovium were carefully cauterized and completely excised. Following the arthroscopy, hemarthrosis has not recurred. A remnant lateral meniscus may be a cause of recurrent hemarthrosis after TKA. Accordingly, in cases of recurrent hemarthrosis after TKA, exploration by arthroscopy should be considered.     

Evaluation of ganglion cell complex and retinal nerve fiber layer in children with spina bifida using optical coherence tomography

PurposeSpina bifida (SB) is a congenital disorder caused by the incomplete fusion of the embryonic neural tube during spinal cord development. In this study, we used Spectral Domain Optic Coherence Tomography (SD-OCT) for retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) analyses and compared the results of healthy children and SB patients in a similar age group.MethodsOur study was planned prospectively and conducted between June 2017 and July 2019. One hundred eyes of 50 participants, consisting of 28 SB patients and 22 healthy children were included. In all cases, RNFL and GCC measurements were undertaken using SD-OCT. The circumpapillary RNFL analysis was conducted by examining the circular area of 3.45 mm in diameter around the centre of the optic disc. GCC parameters were determined with MM7 protocols by taking 15 vertical sections from a 7-mm macular square centred in the fovea.ResultsThe mean GCC thickness of the participants was 91.120 ± 5.224 µm in the control group and 91.696 ± 7.410 µm in the SB group. The difference between the two groups was not statistically significant (p > 0.05). The mean RNFL thickness was 102.499 ± 11.250 µm in the control group and 99.549 ± 15.235 µm in the SB group. The mean RNFL thickness of the patients in the SB group was lower than that of the control group, but the difference was not statistically significant (p > 0.05).ConclusionsIn this study, the lack of a statistically significant difference in the RNFL and GCC values between the SB and control groups can be attributed to successful clinical management.     

聚合酶链反应扩增指纹多态性快速分型技术在部队结核病分子流行病学研究中的应用

目的 探讨南方部队结核病的分子流行病学规律。方法 设计一对特异性IS6110外向性引物，应用聚合酶链反应(PCR)建立检测结核分支杆菌DNA指纹多态性的方法，分析结核分支杆菌DNA多态性与流行病学的关系。结果 共检测分析了154株结核分支杆菌DNA的指纹多态性。根据这些菌株的指纹多态性特征共分为8个类型，以Ⅰ型(36．4％)、Ⅱ型(31．8％)和Ⅲ型(21．4％)为主，其余各型均少于4％。以20—29岁和30—39岁组在这三型中所占比例最大，分别为31．8％和27．9％。驻城镇部队与驻乡村部队以及结核病患者有无卡介苗接种史，在这三型的分布差异无显著统计学意义(P＞0．05)。但初治与复治患者分离菌株的PCR扩增指纹类型的分布差异有显著统计学意义(P＜0．05)。所检测菌株是否具有耐药性，在这三型中的分布差异也有显著统计学意义(P＜0．05)。菌株耐药主要为单耐异烟肼和利福平，耐药菌株在Ⅰ、Ⅱ、Ⅲ型中所占比例分别是44．4％、29．6％和14．8％。结论 PCR扩增指纹多态性分型技术是一种简便、快速、敏感、特异和重复性好的分型方法，可用于结核病的分子流行病学研究。南方部队结核分支杆菌的传播以Ⅰ、Ⅱ、Ⅲ型为主，应加强此三型菌株流行的监控。     

Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central α2A adrenoceptor

Sepsis-associated encephalopathy (SAE) is a significant clinical issue that is associated with increased mortality and cost of health care. Dexmedetomidine, an α2 adrenoceptor agonist that is used to provide sedation, has been shown to induce neuroprotection under various conditions. This study was designed to determine whether dexmedetomidine protects against SAE and whether α2 adrenoceptor plays a role in this protection. Six- to eight-week old CD-1 male mice were subjected to cecal ligation and puncture (CLP). They were treated with intraperitoneal injection of dexmedetomidine in the presence or absence of α2 adrenoceptor antagonists, atipamezole or yohimbine, or an α2A adrenoceptor antagonist, BRL-44408. Hippocampus and blood were harvested for measuring cytokines. Mice were subjected to Barnes maze and fear conditioning 14 days after CLP to evaluate their learning and memory. CLP significantly increased the proinflammatory cytokines including tumor necrosis factor α, interleukin (IL)-6 and IL-1β in the blood and hippocampus. CLP also increased the permeability of blood-brain barrier (BBB) and impaired learning and memory. These CLP detrimental effects were attenuated by dexmedetomidine. Intracerebroventricular application of atipamezole, yohimbine or BRL-44408 blocked the protection of dexmedetomidine on the brain but not on the systemic inflammation. Astrocytes but not microglia expressed α2A adrenoceptors. Microglial depletion did not abolish the protective effects of dexmedetomidine. These results suggest that dexmedetomidine reduces systemic inflammation, neuroinflammation, injury of BBB and cognitive dysfunction in septic mice. The protective effects of dexmedetomidine on the brain may be mediated by α2A adrenoceptors in the astrocytes.