Objective To investigate the mechanism of a dipeptidyl-peptidase-4 (DPP-4) inhibitor, saxagliptin, pro?moting the regeneration of islet beta cells in diabetic rats. Methods The male SD rats were randomly divided into three groups including control group (NC, n=10), diabetes group (DM, n=10) and diabetes treated with saxagliptin group (DM-S, n=10). DM-S group was treated with saxagliptin 1 mg/(kg·d) for twelve weeks. The pancreaticβcell function was analysed by hyperglycemic clamps. Immunohistochemistry with anti-PCNA was performed to observe the proliferation rate of pancreaticβcells. Immunofluorescence double staining with anti-insulin, anti-glucagon, anti-DPP-4 and anti-SDF-1 were performed to observe the expression of insulin, glucagon, DPP-4 and SDF-1 in pancreatic tissue. Western blot assay was performed to test the expression of Akt, p-Akt,β-catenin and free-β-catenin protein, and RT-PCR was performed to test the expressionlevels of c-myc and cyclinD1 mRNA in pancreatic tissue. Results Compared with NC group, there were significantly in?creased blood glucose, decreased islet function andβcell mass in DM group. Compared with DM rats, saxagliptin treatment significantly inhibited the expression of DPP-4, decreased the degradation of SDF-1, stimulated the proliferation ofβcells, and ultimately improved the islet function and histopathological changes of pancreas. Conclusion DPP-4 inhibitor saxa?gliptin can significantly improve islet function, which involved in the inhibition of the expression of DPP-4, the decreased degradation of SDF-1 and the stimulation of the proliferation ofβcells.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) induced weight loss. Methods High fat diet induced obese c57BL/6 mice were divided into normal control group (N, n=8), high fat feeding group (HF, n=32) and GLP-1Ra group treated with GLP-1Ra (liraglutide 200μg/(kg·d) or 400μg/(kg·d) for 8 weeks). Changes of body weight, blood glucose and three acyl glycosides (TG) levels were observed in three groups. HE staining was used to observe the morphological changes. Immunofluorescence staining and real-time PCR were used to mea?sure the expression of UCP-1. Furthermore, the expression of PGC-1αin protein level was observed to explore the possible mechanism of GLP-1Ra induced browning in white fat (WAT). Results After 8-week liraglutide (Lira) administration, the body weights were significantly reduced in obese mice (P<0.05). The levels of blood glucose and TG were significantly high?er in HF group than those in N group, which reduced significantly in Lira (200μg·kg-1) and Lira (400μg·kg-1) administra?tion groups (P<0.05). HE staining showed adipocytes in perirenal and inguinal subcutaneous adipose tissue partly acquired brown-like morphological characteristics. The expression levels of UCP-1 protein and mRNA and PGC-1αprotein were ele?vated in adipse tissues, which increased more in Lira (400) than those in Lira (200, P<0.05). Conclusion GLP-1Ra can induce weight loss through white fat browning by activation of UCP-1.

Objective To investigate the possible mechanisms of glucagon-like peptide 1 receptor agonists (GLP-1Ra) protection against hyperglycemic induced beta cell apoptosis through depression of NOX2-dependent ROS production. Methods The rat model of type 2 diabetes (T2DM) was established by injecting small doses of streptozotocin (STZ) fol?lowed by 8-week high fat diet. The experimental animals were divided into three groups:normal control (N) group, diabetes (T2DM) group and GLP-1Ra group [treated with liraglutide 200 μg/(kg · d)for 12 weeks]. The blood glucose levels were compared before and after modeling, before treatment and 12-week after treatment with GLP-1Ra. The level of glycosylated hemoglobin (HbA1c) was detected by high-pressure liquid chromatography. Automatic biochemical analyzer was used to de?tect levels of aspertate aminotransferase (AST), creatinine (CR) and urea nitrogen (BUN). The apoptotic rates of islets were determined by TUNEL method and cleaved caspase 3 was detected by immunohistochemistry. DCFH-DA fluorescent probe was used to detect reactive oxygen species (ROS) levels of islets. Levels of NADPH oxidase (NOX) catalytic subunit (NOX 2) in islets were measured by immunohistochemistry. Results At the end of the study, glycemic control (average blood glucose/week and HbA1c) and lipid situation were improved significantly in the GLP-1Ra group than those of N group (P<0.05). TUNEL staining and displayed thatβcell apoptotic and cleaved caspase 3 level were significantly decreased in GLP-1Ra group compared to those of T2DM group (P<0.05). ROS levels were significantly decreased in GLP-1Ra group than those of T2DM group before treatment with Apocynin, but no significant difference between GLP1-Ra group and N group (P>0.05). After application Apocynin for inhibition, there were no significant differences between three groups (P>0.05). The level of NOX2 was significantly lower in GLP-1Ra group compared to that of T2DM group (P<0.05). Conclusion GLP-1Ra can inhibit apoptosis ofβcells in diabetes rat, and the depression of NOX2-dependent ROS may be one of the important underly?ing mechanisms.

Objective To establish a reference range for specific thyroid function during pregnancy and to explore the influencing factors of hypothyroxinemia during pregnancy.Methods A retrospective analysis of 2 996 cases of thyroid function in the pregnant women who were with single pregnancy and without thyroid diseases and family history of those diseases.Results (1) Establish a unified reference range for specific thyroid function during pregnancy;the early,middle,and late trimesters thyrotropin (TSH) ranges were 0.02-6.39,0.16-6.23,0.64-6.59 mU/L,respectively,while free thyroxine (FT4) ranges were 11.32-23.00,9.39-18.92,8.54-16.73 pmol/L respectively.The specific reference ranges of Han and Uygur pregnant women were established separately.There was no difference in the detection rates of various thyroid diseases when using their respective reference ranges and the unified reference range of the hospital (P ＞ 0.05).(2) The detection rate of various thyroid diseases (except subclinical hyperthyroidism) of our subjects with China guideline reference range was significantly higher than the reference range with the hospital (P＜0.05).(3) The detection rates of hypothyroxinemia in all pregnant women with FT4 cut points of P2.5 and P5 were 4.3％ and 7.4％,respectively,of which the Han population was 4.3％ and 7.1％,respectively,and the Uygur population was 4.3％ and 7.9％,respectively.(4) Comparing the mean age,gestational age,median urine iodine,and thyroid antibody positive rate between the hypothyroxinemia group and the control group,only the mean age and gestational age were different (P＜0.05);Logistic binary regression analysis showed that age was the risk factor for hypothyroxinemia during pregnancy (OR =1.035,95％ CI 1.006-1.066,P ＜ 0.05).Conclusions The Han and Uygur pregnant women in this area both can use the thyroid reference range of our hospital during pregnancy.The establishment of thyroid reference range may avoid over-diagnosis of thyroid disease during pregnancy.Age is a possible influencing factor of hypothyroxinemia during pregnancy.

Objective:To observe the dynamic changes of thyroid hormone levels and thyroid autoimmune antibodies in pregnant women in Xinjiang Uygur Autonomous Region during pregnancy, and to investigate the significance of repeated screening of thyroid function in different gestational ages.Methods:A retrospective study was carried out of pregnant women who completed thyroid function screening in Clinic, People's Hospital of Xinjiang Uygur Autonomous Region from January 2015 to December 2017, and the test results of thyroid stimulating hormone (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TGAb) were collected and analyzed of their changes during pregnancy. Pregnant women were divided into 2 different gestational age groups by the age limit of 30, the changes of thyroid dysfunction rate with pregnancy were analyzed, and the clinical significance of repeated screening in different pregnancy stages was discussed. Results:Changes of thyroid-related indicators with pregnancy: first, second, and third trimesters were 404,725, and 767 cases, respectively; TSH level in the third trimester (2.76 mU/L) was significantly higher than those in the first and second trimesters (2.55, 2.36 mU/L, P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the FT 4 and FT 3 levels decreased gradually with pregnancy ( P < 0.05); the positive rate of TPOAb was significantly higher in the first and second trimesters than that in the third trimester ( P < 0.05), there was no significant difference between the first trimester and the second trimester ( P > 0.05); the positive rate of TGAb decreased gradually with pregnancy ( P < 0.05). Comparison of abnormal rate of TSH in different gestational ages: the first, second, and third trimesters were 352, 664, 735 cases, respectively; the abnormal rate of TSH in the overall study was statistically significant at different stages of pregnancy (χ 2=31.627, P < 0.05), the first trimester was significantly higher those in the second and third trimesters ( P < 0.05). In pregnant women aged ≥30 years old, the abnormal rate of TSH in the first trimester was significantly higher than those in the second and third trimesters ( P < 0.05); in pregnant women aged < 30 years old, the abnormal rate of TSH in the first trimester was significantly higher than that in the third trimester ( P < 0.05). There were no significant differences in the abnormal rate of TSH in the first, second, and third trimesters between the < 30 years old group and ≥30 years old group ( P > 0.05). Comparison of abnormal rate of FT 4 in different gestational ages: there were no significant differences in the FT 4 abnormal rate among different pregnancy groups in the overall, < 30, ≥30 years old groups (P > 0.05). In early pregnancy, the abnormal rate of FT 4 in the ≥30 years old group was higher than that in the < 30 years old group ( P < 0.05); in second and third trimesters, there were no significant differences between the two age groups ( P > 0.05). Conclusions:Screening for thyroid function in the first trimester of pregnancy is important for women of different ages. Except for women with abnormal thyroid function who have not been treated during the first trimester, the rest may not need to be screened again. Pregnant women aged ≥30 years old may have a higher risk of thyroid dysfunction than those < 30 years old.

ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg^-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg^-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg^-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.