OBJECTIVE -To investigate whether long-term optimal glycemic control can be achieved without medication by transient continuous subcutaneous insulin infusion (CSII) and the possible mechanisms responsible for this remission.RESEARCH DESIGN AND METHODS -Newly diagnosed type 2 diabetic patients (n ϭ 138, fasting glucose Ͼ11.1mmol/l) were hospitalized and treated with CSII for 2 weeks. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, HbA 1c , lipid profiles, proinsulin, insulin, and C-peptide were measured before and after CSII. Patients were followed longitudinally on diet alone after withdrawal of insulin.RESULTS -Optimal glycemic control was achieved within 6.3 Ϯ 3.9 days by CSII in 126 patients. The remission rates (percentages maintaining near euglycemia) at the third, sixth, twelfth, and twenty-fourth month were 72.6, 67.0, 47.1, and 42.3%, respectively. Patients who maintained glycemic control Ͼ12 months (remission group) had greater recovery of ␤-cell function than those who did not (nonremission group) when assessed immediately after CSII. Homeostasis model assessment of ␤-cell function (HOMA-B) and the area under the curve (AUC) of insulin during IVGTT were higher in the remission group (145.4 Ϯ 89.6 vs. 78.5 Ϯ 68.5, P ϭ 0.002, and 1,423.4 Ϯ 523.2 vs. 1,159.5 Ϯ 476.8 pmol ⅐ l Ϫ1 ⅐ min Ϫ1 , P ϭ 0.044). Change in acute insulin response was also greater in the remission group than that in the nonremission group (621.8 Ϯ 430.4 vs. 387.3 Ϯ 428.8 pmol ⅐ l Ϫ1 ⅐ min Ϫ1 , P ϭ 0.033).CONCLUSIONS -Short-term intensive insulin therapy can induce long-term glycemic control in newly diagnosed type 2 diabetic patients with severe hyperglycemia. The improvement of ␤-cell function, especially the restoration of first-phase insulin secretion, could be responsible for the remission. Diabetes Care 27:2597-2602, 2004␤ -Cell dysfunction and decreased insulin sensitivity are the main pathophysiological defects responsible for the development of hyperglycemia (1). With continuous presence of insulin resistance, progressive loss of ␤-cell function is the crucial defect. The continuous decline in ␤-cell function is affected by glucotoxicity generated by hyperglycemia and lipotoxicity due to lipolysis (2). The vicious cycle of elevated glucose further impairs and possibly destroys ␤-cells, finally stopping insulin production completely (3). Therefore, optimal metabolic control, especially early intensive glycemic control, plays a role in the prevention of progressive ␤-cell dysfunction and worsening of diabetes. Many reports have shown (4 -6) that induction of normoglycemia in type 2 diabetes resulted in both improved ␤-cell function and insulin resistance. Ryan, Imes, and Wallace (7) recently reported that, in severe newly diagnosed type 2 diabetic patients, a 2-to 3-weeks' course of intensive insulin therapy by multiple daily insulin injection could successfully lay a foundation for prolonged good glycemic control. So the potential benefits of early, aggressive intervention with insulin treatment to...

Mitochondrial (mt) genome data have been proven to be informative for animal phylogenetic studies but may also suffer from systematic errors, due to the effects of accelerated substitution rate and compositional heterogeneity. We analyzed the mt genomes of 25 insect species from the four paraneopteran orders, aiming to better understand how accelerated substitution rate and compositional heterogeneity affect the inferences of the higher-level phylogeny of this diverse group of hemimetabolous insects. We found substantial heterogeneity in base composition and contrasting rates in nucleotide substitution among these paraneopteran insects, which complicate the inference of higher-level phylogeny. The phylogenies inferred with concatenated sequences of mt genes using maximum likelihood and Bayesian methods and homogeneous models failed to recover Psocodea and Hemiptera as monophyletic groups but grouped, instead, the taxa that had accelerated substitution rates together, including Sternorrhyncha (a suborder of Hemiptera), Thysanoptera, Phthiraptera and Liposcelididae (a family of Psocoptera). Bayesian inference with nucleotide sequences and heterogeneous models (CAT and CAT + GTR), however, recovered Psocodea, Thysanoptera and Hemiptera each as a monophyletic group. Within Psocodea, Liposcelididae is more closely related to Phthiraptera than to other species of Psocoptera. Furthermore, Thysanoptera was recovered as the sister group to Hemiptera.

MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms.

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Although improvements in therapeutic strategies were achieved, the outcome remains poor for most patients with metastatic or recurrent osteosarcoma. Therefore, it is imperative to identify novel and effective prognostic biomarker and therapeutic targets for the disease. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts >200 nucleotides that lack protein coding potential. Many lncRNAs are deregulated in cancer and are important regulators for malignancies. Nine lncRNAs (91H, BCAR4, FGFR3-AS1, HIF2PUT, HOTTIP, HULC, MALAT-1, TUG1, UCA1) are upregulated and considered oncogenic for osteosarcoma. Loc285194 and MEG3 are two lncRNAs downregulated and as tumor suppressor for the disease. Moreover, the expressions of LINC00161 and ODRUL are associated with chemo-resistance of osteosarcoma. The mechanisms for these lncRNAs in regulating development of osteosarcoma are diverse, e.g. ceRNA, Wnt/β-catenin pathway, etc. The lncRNAs identified may serve as potential biomarkers or therapeutic targets for osteosarcoma.