Objective To investigate the relationship between serum resistin,leptin and adiponectin with microangiopathy in the patients with type-2 diabetes mellitus(T2DM).Methods One hundred and twenty patients with T2DM in our hospital were selected and divided into the non-microangiopathy group (NON-MAP,60 cases) and microangiopathy group (MAP,60 cases) according to whether complicating microangiopathy.Other 60 individuals undergoing healthy physical examination were selected as the normal control group(NC).Fasting serum resistin,adiponectin and leptin levels were detected in each group.Fasting blood glucose,insulin and blood lipid levels were also detected.The insulin resistance was evaluated by using insulin resistance index(HOMA-IR).Results The levels of serum resistin,leptin,free fat acid(FFA) and hs-CRP in the NON-MVP group and MVP group were signifi cantly higher than those in the NC group,while the adiponectin level was sigrnificantly lower than that in the NC group,the difference was statistically significant(P＜0.05).The correlation analysis showed that serum resistin and leptin levels had positive correlation with hs-CRP,FFA,HOMA-IR and TG(P＜0.05),and had negative correlation with HDL-C(P＜0.05);the adiponectin level was negatively correlated with hs-CRP,FFA,HOMA-IR and TG,while positively correlated with HDL-C(P＜0.05);serum resistin and leptin levels had positive correlation,both had significantly negative correlation with adiponectin;with serum resistin,leptin and adiponectin as the dependent variables,the multiple stepwise linear regression analysis showed that HOMA-IR and waist to hip ratio had maximal influence on them.Conclusion Serum resistin and leptin levels increase and adiponectin level decrease in T2DM patients suggests that serum resistin,leptin and adiponectin are correlated with T2DM occurrence as well as microangiopathy occurrence.

Objective:To construct the pleiotrophin (PTN )overexpression vector,and to explore the effect of PTN on the decidualization of uterine stromal cells in the mice.Methods:The specific primers containing restriction enzyme cutting sites were designed according to the PTN gene sequences published in GenBank for PCR amplification.The amplified fragment of PTN was recovered from the agarose gel and cloned into the pGEM-T vector.The pGEMT-PTN was cut by double enzyme digestion and ligated into pcDNA3.1 (+)to construct the PTN overexpression plasmid.After transfection with PTN overexpression plasmid,the expression levels of PTN mRNA in the uterine stromal cells and the expression levels of decidualization markers Prl8a2 and Prl3c1 were detected by qRT-PCR method.The uterine stromal cells transfected with pcDNA3.1 (+)empty vector were used as control group. Results:The results of identification by double enzyme digestion indicated that the bands of PTN overexpression plasmid were consistent with those of the target gene,and the clone sequencing results suggested that it had 100% homology with mouse PTN gene sequence published in GenBank.Compared with control group, the expression levels of PTN,Prl8a2 and Prl3c1 mRNA in mouse uterine stromal cells in PTN overexpression group were significantly increased (P < 0.05).Conclusion:PTN overexpression could increase the expression levels of decidualization markers in mouse uterine stromal cells,indicating that PTN might play an enhancement effect during uterine decidualization in the mice.

This study aimed to use the sika deer as a model to study the influence of IGF-1 on the expression of Col Ⅰ in antler chondrocytes.The chondrocytes were separated from sika deer antlers,cultured and were treated with recombinant human IGF-1 protein (rIGF-1),both rIGF-1 and PQ401,and transfected with IGF-1 over-expression plasmid or IGF-1 siRNA,respectively.The expression of Col Ⅰ which,a well-known marker for chondrocytes dedifferentiation,was detected by real-time PCR.The results showed that administration of rIGF-1 to antler chondroctyes resulted in an obvious decrease of Col Ⅰ mRNA levels,while PQ401 pretreatment could dramatically attenuate the effects of rIGF-1 on the expression of Col Ⅰ mRNA.After transfection with IGF-1 over-expression plasmid,the expression of Col Ⅰ mRNA was obviously reduced in antler chondrocytes compared with control.Conversely,knockdown IGF1 with specific siRNA could increase the expression of Col Ⅰ in antler chondrocytes.These results indicate that IGF-1 may play an important role in process of antler chondrocyte dedifferentiation.

Objective:To explore the effect of sulforaphane (SFN) preconditioning on the cold myocardial ischemia-reperfusion injury (IRI) in the rats through PI3K/Akt signaling pathway.Methods:Sixty-four health male Sprague-Dawley (SD) rats were randomly divided into cold IRI group,SFN group,LY (LY294002) + cold IRI group,and LY+SFN group (n=16).The allogeneic heterotopic heart transplantation model was established by donor heart into recipient abdomen.The myocardium tissue was taken 24 h after reperfusion for the detection of histological changes using HE staining.The expression levels of Akt,p-Akt,Bax and Bcl-2 proteins were detected by immunohistochemistry and Western boltting methods.Results:The morphological results showed that the myocardium tissue damage was serious in cold IRI group and LY+cold IRI group,it was light in SFN group;the myocardium tissue damage of the rats in SFN+ LY group was ranged between cold IRI group and SFN group.Compared with IRI group,the expression levels of p-Akt protein and Bcl-2 protein in SFN group were increased (P＜0.05),and the expression level of Bax protein was decreased (P＜0.05).After treatment of blockage LY294002,compared with LY-+-cold IRI group,the expression level of p-Akt protein in LY-+-SFN group was not statistically significant (P＞0.05),the expression level of Bcl2 protein was increased (P＜0.05),the expression levels of Bax protein was decreased),and the ratio of Bcl-2/Bax was also increased (P＜0.05).Conclusion:SFN may attenuate cold IRI of heart transplantation through PI3K/Akt signaling pathway in the rats.

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.