Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head （ANFH）. The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroidinjection group （S.G.） and the controlled group （C.G.） are examined, including the weight of rabbits, the hematological examination and the three-dimensional stnactures. It is found that the plasma levels of cholesterol （CHO）, high-density lipoprotein （HDL） and low-density lipoprotein （LDL） in S.G. are lower than those in C.G. when the triglyceride （TG） increased in the S.G.; but the bone mineral content （BMC） and the structural model index （SMI） of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography （CT） scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

Objective： To evaluate the utility of zinc transporter-8 （ZnT8） in the improvement of type 1 diabetes mellitus （T1DM） diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in TI DM. Data Sources： A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows： ＂ZnTS,＂ ＂type 1 diabetes,＂ ＂latent autoimmune diabetes in adults,＂ ＂type 2 diabetes,＂ ＂islet autoantibodies,＂ ＂zinc supplement,＂ ＂T cells,＂ ＂[3 cell,＂ ＂immune therapy.＂ We also searched the reference lists of selected articles. Study Selection： English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed. Results： The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 （ZnTSA） and ZnTS-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy. Conclusions： ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.

Diagnostic criteria of latent autoimmune diabetes in adults(LADA):a review and reflection

Diabetes has become a major public health problem in China nowadays.There are almost 97 million diabetic patients nationwide.Latent autoimmune diabetes in adults(LADA)is a subtype of autoimmune diabetes.Although it has been reported for about 20 years,the diagnostic criteria of this disease remain controversial.The discussion mainly focused on serum autoantibodies,period of insulin need and age of diagnosis.Besides,β cell function,metabolic parameters,genetic factors and cell immunity may also contribute to the formulation of the criteria.Here,we aim to review and discuss the diagnostic criteria of latent autoimmune diabetes in adults.

Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial

Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.

Glutamic acid decarboxylase 65 autoantibody levels discriminate two subtypes of latent autoimmune diabetes in adults

Objective To compare the clinical characteristics between type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults ( LADA) with different titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two distinct subtypes of LADA.Methods Sera of 750 patients with an initial diagnosis of T2DM from central south of China were screened for GADA using a radioligand assay. The distribution and frequency of GADA levels were described. Two hundred and ninety-five patients were divided into the T2DM group (n =233) and the LADA group ( n = 62) to compare the age of onset, body mass index, HbA1c, C-peptide, hypertension, dyslipidemia and chronic diabetic complications. Furthermore, LADA patients with different GADA titers were subdivided to analyze the same indexes as the above.Results The prevalence of LADA (defined as GADA≥0. 05, namely GADA positive) was 9. 7% in the 750 initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients were younger at their ages of onset, had lower C-peptide and body mass index, and also had less cases with hypertension and with dyslipidemia. However, only patients with high titer of GADA had poorer beta cell functions and less diabetic complications compared to T2DM and low GADA titer of LADA patients. Patients with low GADA titer were similar to T2DM patients, except that they were prone to develop ketosis more frequently.Conclusions Two clinically distinct subtypes of LADA can be identified by GADA levels in patients initially-diagnosed as type 2 diabetes. Patients with high titer of GADA (GADA≥0. 5) subsequently develope more insulin dependency, which are classified as LADA-type 1; while those with lower GADA titer (0.05≤GADA < 0. 5) and having clinical and metabolic phenotypes of type 2 diabetes are classified as LADA-type 2.

Adiponectin:a versatile player of innate immunity

Adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders.Macrophages and monocytes are representative components of the innate immune system,and their proliferation,plasticity,and polarization are a key component of metabolic adaption.Innate-like lymphocytes such as group 2 innate lymphoid cells(ILC2s),natural killer T(NKT)cells,and gamma delta T(gd T)cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases.Adiponectin senses metabolic stress and modulates metabolic adaption by targeting the innate immune system under physiological and pathological conditions.Defining the mechanisms underlying the role of adiponectin in regulating innate immunity is crucial to adiponectin-based therapeutic intervention.

Latent autoimmune diabetes in adults： evidences for diabetes spectrum？

In 1936, Himworth first investigated insulin resistance and non-insulin resistance in diabetes. Then the terminology ＂type 1 diabetes （T1D）＂ and ＂type 2 diabetes （T2D）＂ were first used in 1951. In 1999, the World Health Organization （WHO） announced the classification of diabetes： as we all known, T1D and T2D.1 This classification is widely accepted and used. However, in clinical practice, it is quite often to find some patients cannot be simply diagnosed as T1D or T2D.

Gene expression changes in patients with fulminant type 1 diabetes

Background Fulminant type 1 diabetes （F1D） is a complex disease. Microarray analysis was used to identify gene expression changes and obtain understanding of the underlying mechanisms. Methods Microarray analysis was performed on peripheral blood mononuclear cells from six F1D patients and six matched healthy subjects. Real-time polymerase chain reaction was used to verify the differentially expressed genes. NK cell activity was detected by methyl thiazoleterazolium assay. Results Microarray analysis identified 759 genes differing in expression between F1D patients and controls at a false discovery rate of 0.05. Expression of TLR9, ELF4 and ILIRAP were verified and consistent with changes in microarray results. NK cell activity was decreased in FID. With use of a knowledge base, differentially expressed genes could be placed within different pathways with predicted functions including interleukin-1, and tumor necrosis factor-a signaling. Conclusions These results identify several genes indicating possible mechanisms in FID. NK cell dysfunction resulting from changes in expression of TLR9, ELF4 and IL1RAP, and pathways of interleukin-1 and tumor necrosis factor-a sianalino miaht be involved in F1D throuoh inducino B-cell dysfunction.

FGF23 associated bone diseases

Recently,fibroblast growth factor 23(FGF23)has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism.In this review,we summarized the FGF superfamily,the mechanism of FGF23 on phosphate and vitamin D metabolism,and the FGF23 related bone disease.

Hypoadiponectinemia predicts impaired endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients： an 8-year prospective study

Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study. Methods In the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation. Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline （r=0.150, P=0.043） and at year 8 （r=0.339, P=0.001）, whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 （P=0.001）. Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.