Insulin Action,Regional Fat,and Myocyte Lipid: Altered Relationships with Increased Adiposity

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Research Methods and Procedures: Myocyte triglyceride content (¹H‐magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 ± 7.8 years) with a broad range of adiposity (BMI 28.6 ± 4.1 kg/m², range 20.1 to 37.6 kg/m²). Results: Relationships between insulin‐stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut‐point, insulin‐stimulated glucose disposal correlated negatively to all regional body fat measures (all p ≤ 0.004), serum triglycerides and free fatty acids (p < 0.02), and both soleus intramyocellular lipid (p = 0.003) and vastus lateralis triglyceride (p = 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin‐stimulated glucose disposal in more overweight men (r = ?0.576, p = 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut‐points or measures of adiposity. Discussion: Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.     

五种豆科种子胚乳细胞的微观结构的比较

运用光学显微镜和电子显微镜分别对胡芦巴、野皂荚、皂荚、瓜尔豆、塔拉豆等五种豆科种子内胚乳细胞的形态、大小、壁厚等微观结构进行了观察比较。研究结果表明：五种种子内胚乳细胞壁几乎完全由胶状的透明的半乳甘露聚糖所填充,细胞的形态、大小差异较大,瓜尔豆、塔拉豆的内胚乳细胞呈球形或近球形;胡芦巴内胚乳细胞为多角形或多角椭圆形,它们细胞壁界限清晰,细胞排列整齐有规律;皂荚、野皂荚则为不规则的长椭球形,细胞壁彼此连接成片,界限模糊。一般地说：当细胞壁壁厚小于4μm时,胚乳胶粉中的水不溶物含量较低,1％浓度的胶液的粘度较高,而当壁厚大于4μm时,情况反之。本文的研究目的是为植物胶生产、加工提供一定的细胞学方面的依据。     

Fed-batch cultivation ofEscherichia coli YK537 (pAET-8) for production ofphoA promoter-controlled human epidermal growth factor

Secretion of the expressed heterologous proteins can reduce the stress to the host cells and is beneficial to their recovery and purification. In this study, fed-batch cultures ofEscherichia coliYK537 (pAET-8) were conducted in a 5-L fermentor for the secretory production of human epidermal growth factor (hEGF) whose expression, was under the control of alkaline phosphatase promoter. The effects of feeding of glucose and complex nitrogen sources on hEGF production were investigated. When the fed-batch culture was conducted in a chemically defined medium, the cell density was 9.68 g/L and the secreted hEGF was 44.7 mg/L in a period of 60 h. When a complex medium was used and glucose was added in pH-stat mode, the secreted hEGF was improved to 345 mg/L. When the culture was fed with glucose at a constant specific rate of 0.25 gg⁻¹h⁻¹, hEGF reached 514 mg/L. The effects of adding a solution containing yeast extract and tryptone were further studied. Different rate of the nitrogen source feeding resulted in different levels of phosphate and acetic acid formation, thus affected hEGF expression. At the optimal feeding rate, hEGF production achieved 686 mg/L.     

血痕Chelex 100抽提DNA用于人类TNF-α基因启动子区SNP分型

建立快速、简便的血样本采集及DNA抽提方法,可用于大规模的分子流行病学调查及群体遗传学研究。采用无菌纱布为载体取血,Chelex100快速抽提DNA,用TaqMan MGB探针对人类TNF-α基因启动子区-857（C／T）位点进行SNP分型。344份血样均得到明确的分型结果,获得的荧光信号强,本底低。深圳地区汉族群体-857位点基因型频率分别为：cc为0.78,ct为0.21,tt为0.01。血痕Chelex100抽提DNA为大规模血样本的采集,DNA的抽提提供了有效的手段。     

DDX39 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with clear cell renal cell carcinoma

DEAD-box protein 39 (DDX39) has been demonstrated to be a tumorigenic gene in multiple tumor types, but its role in the progression and immune microenvironment of clear cell renal cell cancer (ccRCC) remains unclear. The aim of the present study was to investigate the role of DDX39 in the ccRCC tumor progression, immune microenvironment and efficacy of immune checkpoint therapy.The DDX39 expression level was first detected in tumors in the public data and then verified in ccRCC samples from Changzheng Hospital. The prognostic value of DDX39 expression was assessed in the Cancer Genome Atlas (TCGA) and ccRCC patients from Changhai Hospital. The role of DDX39 in promoting ccRCC was analyzed by bioinformatic analysis and in vitro experiments. The association between DDX39 expression and immune cell infiltration and immune inhibitory markers was analyzed, and its value in predicting the immune checkpoint therapy efficacy in ccRCC were evaluated in the public database. DDX39 expression was elevated in Oncomine, GEO and TCGA ccRCC databases, as well as in Changzheng ccRCC samples. In TCGA ccRCC patients, increased DDX39 expression predicted worse overall survival (OS) (p<0.0001) and progression-free interval (PFI) (p<0.0001), and was shown as an independent predictive factor for OS (p=0.002). These findings were consistent with those from Changhai ccRCC patients. In addition, GO and GSEA analysis identified DDX39 as a pro-ccRCC gene. In vitro experiments confirmed the role of DDX39 in promoting ccRCC cell. Finally, DDX39 was found to be positively correlated with a variety of immune inhibitory markers, and could predict the adverse efficacy of immune checkpoint therapy in TIDE analysis. In conclusion, Increased DDX39 in ccRCC patients predicted worse clinical prognosis, promoted ccRCC cell proliferation, migration and invasion, and also predicted adverse efficacy of immune checkpoint therapy.     

Osteochondritis dissecans-like lesions of the occipital condyle and cervical articular process joints in a Saddlebred colt horse

Background

Osteochondritis dissecans (OCD) is a sequela to osteochondrosis, whereby the cartilage superficial to the site of osteochondrosis fractures and gives rise to osteochondral fragments in the affected joint. In this case, both the radiological and computed tomography findings were supportive of classical severe OCD but the histologic findings were not supportive of the diagnosis of OCD.

Case presentation

A 1 year and 6 months old, Saddlebred, colt was presented for evaluation of chronic cervical pain. Standing laterolateral radiographs revealed an osteochondral fragment with corresponding irregular subchondral bone defect at one of the occipital condyle. Computed tomography confirmed the presence of osteochondral fragments at the left occipital condyle and several articular process joints of the cervical spine, with associated subchondral bone defects and sclerosis, suggestive of OCD. However, the lack of ischemic chondronecrosis microscopically was not supportive of a histologic diagnosis of OCD. Therefore, the term ‘OCD-like lesions’ was deemed most appropriate for these cervical lesions.

Conclusion

In the event where imaging features were characteristics of OCD but lack of histologic evidence of ischemic chondronecrosis, the term ‘OCD-like lesion’ is deemed most appropriate.

     

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e‐Delphi consensus, concluded that ‘repigmentation’ and ‘maintenance of gained repigmentation’ are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e‐surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e‐surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.