Pleiotropic genomic variants at 17q21.31 associated with bone mineral density and body fat mass: a bivariate genome-wide association analysis

Osteoporosis and obesity are two severe complex diseases threatening public health worldwide. Both diseases are under strong genetic determinants as well as genetically correlated. Aiming to identify pleiotropic genes underlying obesity and osteoporosis, we performed a bivariate genome-wide association (GWA) meta-analysis of hip bone mineral density (BMD) and total body fat mass (TBFM) in 12,981 participants from seven samples, and followed by in silico replication in the UK biobank (UKB) cohort sample (N = 217,822). Combining the results from discovery meta-analysis and replication sample, we identified one novel locus, 17q21.31 (lead SNP rs12150327, {"type":"entrez-nucleotide","attrs":{"text":"NC_000017.11","term_id":"568815581"}}NC_000017.11:g.44956910G > A, discovery bivariate P = 4.83 × 10⁻⁹, replication P = 5.75 × 10⁻⁵) at the genome-wide significance level (ɑ = 5.0 × 10⁻⁸), which may have pleiotropic effects to both hip BMD and TBFM. Functional annotations highlighted several candidate genes, including KIF18B, C1QL1, and PRPF19 that may exert pleiotropic effects to the development of both body mass and bone mass. Our findings can improve our understanding of the etiology of osteoporosis and obesity, as well as shed light on potential new therapies.Subject terms: Genome-wide association studies, Gene expression profiling     

企业员工应对方式与心理健康之间的关系

目的：验证不同应对方式对心理健康的单独与共同影响。方法：对4745名被试用分层回归的方法分析不同应对方式对心理健康的单独影响和交互作用。结论：单独使用“消极应对”的应对方式,对心理健康水平存在不利影响;而单独使用“积极应对”的应对方式能在一定程度上改善心理健康水平。“消极应对”与“积极应对”两种应对方式结合使用能显著改善心理健康水平,比单独使用这两种应对方式对心理健康更有利。     

Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case report with p53 gene mutation analysis

Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the family of perivascular epithelioid cell tumors and is typically composed of blood vessels, adipose tissue, and smooth muscle- like cells, which are characteristically positive for HMB-45. Results of recent studies suggest that p53 mutation may play an important role in AML progression. Here, we describe a locally destructive renal AML in a patient with tuberous sclerosis. The tumor consisted of mostly epithelioid cells with marked nuclear pleomorphism and frequent mitoses and was positive for HMB-45. The diagnosis of atypical epithelioid AML was made. Codon alteration in the p53 gene was not detected, despite focal p53 immunoreactivity and single nucleotide polymorphism at exon 6. Our finding indicates no definite link between p53 abnormalities and the atypical appearance of AML. To the best of our knowledge, this is the second renal AML case investigated for p53 mutations.     

病毒载量和T淋巴细胞计数在HIV感染者临床治疗疗效观察中的应用

目的 研究病毒载量检测和CD4^ 计数在评价人类免疫缺陷病毒(HIV)感染者疗效中的应用效果。方法 对HIV感染者临床病例73例进行了实验室和临床观察，其中包括6例鸡尾酒治疗病例、36例中药试验性治疗病例及31例未进行治疗的感染者。主要实验室指标包括血浆病毒载量及T淋巴细胞亚群计数。结果 在进行治疗后3个月时联合治疗组的病毒载量明显低于其他两组，并且在其后保持在很低的水平，CD4^ 计数水平明显高于其他两组并在其后持续升高。在整个观察期间，中药治疗组的病毒载量检测和CD4^ 计数水平与未治疗组差异无显著性，但在临床症状观察中中药治疗组较未治疗组有明显改善。结论 病毒载量检测和CD4^ 计数试验是评价抗HIV治疗疗效的有效方法。     

采用永磁悬浮的永久性左心室辅助装置

研制出一台采用永磁轴承的左心室辅助装置（LVAD）。该装置包括一个定子和一个转子，采用径向驱动方式；转子包括驱动磁钢和叶轮，电机定子线圈和泵壳组成定子。装置设计采用了一种特殊结构的永磁轴承。转子的位置测量表明，转子稳定悬浮的前提条件是必须有较高的转速（大于3250r／min）且流量大于1L/min。用猪血为介质所做的液动力测试表明，当转速达到3500r／min～4000r／min时，血泵输出流量达到4L/min～6L/min，输出压力达到100mmHg。该装置重200g，最大处直径为40mm。     

Toward a durable impeller pump with mechanical bearings

Our former work demonstrated that our impeller pump could support the circulation of experimental animals for several months without harm to blood elements or organ function. The termination of the experiments was mostly related to wear of the mechanical bearing and thrombosis along the bearing. To solve the bearing problem, we investigated a magnetic bearing in our lab, which resulted in some new problems, such as complicated design and control, considerable energy consumption, and lesser reliability. Progress in developing an impeller pump for long-term application has recently been achieved. Instead of using a sliding bearing system, we devised a rolling bearing system. Its service life is more than 10 years because of a wearproof roller made of ultra high molecular weight polythene. To avoid thrombus formation, we introduced a special purge system to the bearing, allowing the saline with heparin to be infused through the bearing into the pump. The bearing, therefore, keeps working in the saline, and no thrombus will be formed. Animal experiments demonstrated that a 30 ml fluid infusion per hour is enough to prevent thrombus formation. With these improvements, the impeller pump has continuously run for 8 months, and no bearing wear can be measured. The device, weighing 150 g, is fully implantable, consumes approximately 9.6 watts, and delivers a 9L/min blood flow against a 120 mm Hg mean pressure and reaches a highest total efficiency of 24.7% for the motor (including the controller) and pump. The system can produce both pulsatile and nonpulsatile flow according to requirements.     

医院实施ISO9001质量管理体系内部审核的探讨

医疗机构实施ISO9001,其目的是为了提高医疗服务质量,满足病人一切明确和隐含的需求。那么,内审是否发挥作用,直接关系管理体系的有效性。文章对此进行了初步的探讨,即:①明确内审的目的是检查体系满足标准要求的程度;②建立正规的内审机构,要选拔责任心强、综合素质高的人担任内审员;③编制合理且有特色的内审计划,是内审有效性的关键;④适当增加专题审核;⑤医院最高管理者应重视内审结果。     

神经营养素受体在人外周血T细胞中表达的研究

目的 研究人外周血CD4^ /CD8^ T细胞4种神经营养素受体基因的转录。方法 应用尼龙手法分离出T细胞，磁式细胞分离法（MACS）分离CD4^ /CD8^ T细胞亚群，再以RT－PCR法研究4种神经营养素受体在两种T细胞亚群上的表达。结果 未经刺激的CD4^ /CD8^ T细胞亚群不表达任何神经营养素受体。经PHA或PPD刺激后，CD4^ /CD8^ T细胞亚群表达trkA,CD8^ T细胞亚群表达trkC；而在各种状态下的T细胞上均未见表达trkB及p75^NGFR。结论神经营养素受体在两种T细胞亚群中有不同的表达格局，提示不同T细胞亚群受神经营养素调节的模式可能各不相同。     

Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。