The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis.

Although the polymorphisms of PTPN22 and the variants of CTLA-4 have been reported to be the susceptibility genes, which increased risk of latent autoimmune diabetes in adults (LADA), the results remained inconclusive. The aim of this meta-analysis was to evaluate the association between the polymorphisms of two genes and LADA. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. Data from ten studies published between 2001 and 2013 were pooled for two polymorphisms: rs2476601 in the PTPN22 gene and rs231775 in the CTLA-4 gene. Data extraction and assessments for risk of bias were independently performed by two reviewers. Fixed-effect model and random-effect model were used to pool the odds ratios; meanwhile, heterogeneity test, publication bias and sensitive analysis were explored. The minor T allele at rs2476601 and the minor G at rs231775 carried estimated relative risks (odds ratio) of 1.52 (95 % CI 1.29-1.79) and 1.39 (95 % CI 1.11-1.74), respectively. These alleles contributed to an absolute lowering of the risk of all LADA by 4.88 and 14.93 % when individuals do not carry these alleles. The estimated lambdas were 0.49 and 0.63, suggesting a codominant model of effects was most likely for two genes. In summary, our systematic review has demonstrated that PTPN22 rs2476601 and CTLA-4 rs231775 are potential risk factors for LADA. An updated meta-analysis is required when more studies are published to increase the power of these polymorphisms and LADA.

[Effects of intrauterine cigarette smoking exposure on expression of 3-mercaptopyruvate sulfurtransferase in medulla oblongata of neonatal rats].

OBJECTIVE: To investigate the expression of 3-mercaptopyruvate sulfurtransferase (3MST) in medulla oblongata of neonatal rats and effects of intrauterine cigarette exposure on its expression. METHODS: Sprague Dawley pregnant rats were randomly divided into 2 groups, control group and cigarette smoke exposure group (n = 8). 3MST mRNA and protein expression in medulla oblongata of neonatal rats were analysed by RT-PCR and Western blot, respectively, and the expression of 3MST in the neurons of respiratory-related nuclei in medulla oblongata of neonatal rats was investigated with immunohistochemical technique. RESULTS: The RT-PCR and Western blot analyses showed that 3MST mRNA and protein were expressed in the medulla oblogata of neonatal rats and intrauterine cigarette exposure promoted their expression (P < 0.05). Immunohistochemical staining indicated that 3MST existed in the neurons of pre-Bötzinger complex (pre-BötC), hypoglossal nucleus (12N), ambiguous nucleus (Amb), facial nucleus (FN) and nucleus tractus solitarius (NTS) in control group of the animals and the mean optical densities of 3MST-positive neurons in the pre-BötC, 12N, Amb and FN, but not NTS, were significantly increased in cigarette smoke exposure group (P < 0.05). CONCLUSIONS: 3MST exists in the neurons of medullary respiratory nuclei of neonatal rats and its expression can be up-regulated by intrauterine cigarette exposure, suggesting that the 3MST-H2S pathway may be involved in protection of medullary respiratory centers against injury induced by intrauterine cigarette exposure.

Active targeted therapy for metastatic collecting duct carcinoma of the kidney: a case report and review of the literature.

Collecting duct carcinoma (CDC) is a rare and aggressive renal cell carcinoma (RCC) with extremely poor prognosis, which has been shown to have a poor response to several kinds of systemic therapy. Targeted agents have greatly changed the therapeutic landscape in advanced RCC. Nonetheless, patients with CDC are always excluded from the prospective trials with targeted therapies due to its rarity. We present a case of metastatic CDC that responded favorably to the multiple tyrosine kinase inhibitor, sorafenib, achieving a partial response in both lungs and retroperitoneal lymph nodes metastases. We also reviewed the limited number of reports of metastatic CDC treated with targeted agents and found that 33.33 % (4/12) of patients had favorable clinical activity. These suggest that targeted therapy should be considered for the treatment of metastatic CDC and its prospective evaluation is encouraged.

[Association of glycosylated hemoglobin A1c control with the complications in type 2 diabetic patients].

OBJECTIVE: To investigate the status of glycosylated hemoglobin A1c (GHbA(1c)) control in type 2 diabetic patients and its relation to diabetic complications. METHODS: A total of 676 patients with type 2 diabetes were investigated for GHbA(1c) level and the diabetic complications. The patients were divided into two groups with GHbA(1c) >7% and GHbA(1c)< or =7%, and the relation of GHbA(1c) with the complications was analyzed. RESULTS: The rate of good GHbA(1c) control (GHbA(1c)< or =7%) was 35.1% (237/676) in these patients, and 64.9% (439/676) of the patients showed poor GHbA(1c) control (GHbA(1c)>7%). The rates of hypertension and cerebralovascular complications were significantly higher in patients with GHbA(1c)>7% than in those with GHbA(1c)< or =7% (69.9% vs 55.7%, and 21.8% vs 8.9%, respectively, P<0.001), but the rate of coronary heart disease was comparable between the two groups (18.7% vs 17.3%, P>0.05). The patients with poor GHbA(1c) control had significantly higher incidences of diabetic peripheral neuropathy and fatty liver than those with good GHbA(1c) control (46.0% vs 35.0%, and 36.9% vs 25.3%, respectively, P<0.01), but no significant differences were found in the incidences of diabetic nephropathy (18.7% vs 16.5%), diabetic retinopathy (30.8% vs 27.4%) or diabetic feet (5.0% vs 3.8%) between the two groups (P>0.05). CONCLUSION: Type 2 diabetic patients have generally low rate of successful GHbA(1c) control, which can be associated with the occurrence of diabetic complications, suggesting the necessity of more rigorous diabetic health education and GHbA(1c) monitoring in these patients.