LADA China Study is the first nation-wide muliicenter study for adult onset latent autoimmune diabetes (LADA) in Chinese.We have published the data on Diabetes in 2013.In this article,we briefly introduce the results and the significance to clinical practice.

Incretin-based therapies are now being widely used in type 2 diabetes as a new type of antidiabetic drugs,with their efficacy and safety having been confirmed.However,there are relatively few researches carried out in type 1 diabetes.A variety of clinical studies (mainly in type 2 diabetes) have shown that incretin-based therapy could effectively improve glucose control.In this article,the clinieal application of incretin-based therapy in type 1 diabetes will be reviewed and commented from the prospective of clinical studies,combined with animal experiments.

Type 1 diabetes mellitus(T1DM) is a chronic autoimmune disease.Prospective studies carried out in T1 DM pre-diabetic relatives have shown that the process of β-cell degeneration can take place before the disease manifests itself clinically.Scholars have made several breakthroughs in immune therapy for T1 DM.This paper will make a review of the latest progress in the antigen-specific,antibody-based,cell-based,and other immunotherapies of T1DM.

Objective To investigate the significance of serum IP-10 levels in different types of diabetic patients. Methods Serum IP-10 level in 78 cases with type 1 diabetes,49 cases with type 2 diabetes and 33 cases of healthy controls was measured with ELISA assays. Type 1 diabetic patients were divided into classic type 1 diabetes (n=39) and latent autoimmune diabetes in adults (LADA,n=39) according to their disease process,and they were also divided into autoimmune type 1 diabetes (n=58) and idiopathic type 1 diabetes (n=20).Type 2 diabetic patients,according to carotid intima-media thickness (IMT),were divided into patients with (n=24) or without atherosclerosis (n=25). Results 1) Serum IP-10 levels were not statistically different among type 1 diabetes,type 2 diabetes and healthy controls. 2) Serum IP-10 concentrations in autoimmune type 1 diabetes with positive islet autoantibody were higher than those in healthy controls(184.96?104.48pg/ml vs 146.10?74.61pg/ml,P=0.03);while there were no difference in type 1 diabetes with variable disease durations. 3) No difference in IP-10 levels was found between type 2 patients with(173.5?69.6pg/ml) and without atherosclerosis (188.5?79.7 pg/ml). Conclusions Serum IP-10 level is augmented in autoimmune type 1 diabetes.

Objective To optimize the radioligand assays for glutamic acid decarboxylase antibody (GAD-Ab), tyrosine phosphatase antibody (IA-2A) and insulin autoantibody (IAA) and to facilitate their application in clinical practice. Methods The radioligand assays established in our laboratory were optimized in several aspects, including the mode and time of antigen-antibody incubation, pH value of TBST buffer, times of washing, and type of centrifuge. The sensitivity and specificity of the optimized assays were calculated by the Diabetes Antibody Standardization Program (DASP, 2003). And the results were compared to those measured with domestic radioimmune assay kits. Results The optimal condition for radiligand assay were as followed: incubating the antigens of GAD-Ab and IA-2A with serum by rotating slowly for 24 hours and IAA for 72 hours respectively; washing the precipitation complex of GAD-Ab and IA-2A with TBST buffer (pH value 7 2～7 4) 4 times and IAA 5 times respectively; and applying the horizontal type of centrifuge. The results from DASP demonstrated that sensitivity and specificity of the optimized assays were 82% and 98% respectively for GAD-Ab, and 64% and 100% for IA-2A. The proportion of consistency between our results for 82 IAA gradient index of optimized assay and those measured with domestic radioimmune kits was 89%. The extensive analysis showed that the consistency reached 100% for those with IAA index less than 0 04 or more than 1 00, and the inconsistency was for the bordline positive ones (index 0 04～1 0). Conclusion The optimized radioligand assays for islet autoantibodies are high sensitivity and specificity, and are applicable in clinical practice.

Intensive attention has been drawn to macrophages in obesity after the discovery of macrophage infiltration in adipose tissue. This review updates of adipose tissue macrophages in the immune-pathophysiology of obesity, including new progression on the adipose tissue macrophages phenotype and the potential of beige fat induction by M2 macrophage, which inspires a novel therapy for obesity and insulin resistance.

Objective To investigate the effect of rosiglitazone on the CD4+regulatory T cells in the patients with latent autoimmune diabetes in adults(LADA).Methods The CIM+T cells from IADA patients were isolated with anti-CD4-dynal magnetic beads.The expression of Foxp3 mRNA,along with peroxisome proliferators activator receptors gamma(PPARγ)mRNA and TGF-131 mRNA was determined.The effect of rosiglitazone on CD4+T cells was measured,after treated with rosiglitazone for 48 h.Cell viability was assessed by Mtit assay.The proliferation was assayed with 3 H-TdR.Two-color staining(anti-CD4,anti-CD25)flow cytometric analysis was employed to measure the percentage of CD4+CD25+T cells of Deriph eral blood.Resuits PPARγmRNA was expressed in peripheral CD4+T lymphocytes.RosiglitazoBe inhibited phytohemagglutinin(PHA)-induced human CD4+T cell proliferation in dose dependence.The percentage of CD4+CD25+T cells showed no significant change after the peripheral blood culture with 1 μmol/Land 10μmot/L rosiglitazone.10 μmol/L of rosiglitazone induced Foxp3 mRNA expression in vitro (3.27fold,P<0.05),whereas TGF-β1 mRNA expression did not change.Furthermore,only 1 μmol/L of rosiglitazone could promote Foxp3 mRNA expression if adding IL-2(10 U/m1)in cultures(3.48 fold.P

Objective To establish the amplified luminescent proximity homogeneous assay(AlphaLISA) for the detection of Sendai virus.Methods The antigen concentration,serum concentration and the donor beads/acceptor beads ratio used in the AlphaLISA method were optimumized by the phalanx experiments, then the antibodies of Sendai Virus in 40 rat sera were detected by the established AlphaLISA method and ELISA detection method.The results were compared and the differentia between the two methods was confirmed by IFA.Results The optimum concentration of SV bio-peptide in AlphaLISA assay was 250 nmol/L, the best proportion of donor beads/acceptor beads ratio was 1 ∶1, using the concentration of 20 μg/mL and the serum dilution was 1∶10000.7 of the 40 rat sera were detected SV positive by ELISA, the positive rate was 17.5%, 8 of the 40 rat sera were determined SV positive by AlphaLISA, and the positive rate was 20.0%, the AlphaLISA positive serum was confirmed by IFA.Conclusions We preliminary established the Amplified Luminescent Proximity Homogeneous Assay(AlphaLISA) for the detection of Sendai virus.The sensitivity of the method is comparable to classical ELISA method, but this method use less serum samples and without washing steps.The method has some advantages in degeneracy and accuracy.

Objective To screen and determine the effective silencing targets of β2-microglobulin(B2m)gene at the cellular level in marmoset.Methods By homology comparison of the b2m gene in human and the B2m gene in marmoset, choose homology small hairpin RNA(shRNA)sequences targeting marmoset B2m gene were designed, We choose homology small hairpin RNA(shRNA)sequences targeting designed B2m gene to make homology analysis, and insert into lentivirus-based gene silencing constructs FUGW-TDT.The vectors were transfected into HEK293T cells induced by polyethylenimine(PEI).The suppression of B2m mRNA was detected by real-time PCR.Results Two gene-silencing sequences were screened that lied in 290~310 bp and 665~685 bp of the marmoset B2m mRNA, and have statistical significance in the silencing rate:(46.54±7.91)% (P < 0.05) and(83.22±4.37)%(P < 0.0001).Conclusions Two effective silencing target sequences are screened at cellular level, which can be further used in studies on gene silencing in marmoset.

In this paper, some items about the microbes listed in the current National Standard of Laboratory Animals were reviewed, including their host spectrum, impact of infection on the animals, their interference on research works and their epidemiology in laboratory animals.This paper may provide some clues for the update of our National Standard of Laboratory Animals.