OBJECTIVE:To provide basis for the establishment of warfarin individualized administration model that is suitable for Uighurian patients in Xinjiang. METHODS:The genotypes of CYP2C9 and VKORC1 in 200 Uighurian patients in xinjiang were detected and compared with the genotypes and allele frequency of different ethnic populations in world. RESULTS:The frequency of CYP2C9*1/*1 homozygous wild type in Xinjiang Uighurian patients was lower than South Korea,Japan,the United States and Han nationality in China,higher than Turkey;the frequency of *1/*2 heterozygous mutant was lower than Turkey,Sweden and the United Kingdom,higher than South Korea,Japan and Han nationality in China;the frequency of *1/*3 heterozygous mutant was higher than Japan,South Korea,Han nationality in China,the United Kingdom and the United States;the frequency of *3/*3 was higher than the populations above(P<0.05). *1 allele in Xinjiang Uighurian patients was lower than Han nationality in China,Ja-pan,South Korea and the United States,higher than Turkey(P<0.05). *2 allele was higher than Han nationality in China,Japan and South Korea,lower than Turkey,Sweden and the United Kingdom(P<0.05). *3 allele was higher than Han nationality in Chi-na,Japan,South Korea,Sweden,the United Kingdom and the United States(P<0.05). The frequency of VKORC1-1639AA in Xinjiang Uighurian patients was higher than the United States Sweden,the United Kingdom,lower than Singapore,Japan,Taiwan China and Han nationality in China. The frequency of type AG was higher than Singapore,Japan,Taiwan China,Han nationality in China. The frequency of type GG was higher than Singapore,Japan,Taiwan China,Han nationality in China,lower than the United States,Sweden and the United Kingdom(P<0.05). Type A allele in Xinjiang Uighurian patients was lower than Han nation-ality in China,Taiwan China,Japan and Singapore,higher than the United States,Sweden and the United Kingdom;type G was higher than Han nationality in China,Taiwan China,Japan and Singapore,lower than the United States,Sweden and the United Kingdom(P<0.05). CONCLUSIONS:The distribution of CYP2C9 and VKORC1 gene polymorphism in Uighurian patients in Xin-jiang are obviously different from Asian,European and American populations.

Objective To investigate the relationship between insulin resistance and endogenous androgens at early and late phase of postmenopause.Methods A total of 105 women with early postmenopause (≤5 years since menopause) and 107 women with late postmenopause (≥ 10 years since menopause) were enrolled in this study.In the mean time,those women were classified into normal weight [body mass index (BMI),BMI ＜24 kg/m2] group and overweight (BMI≥24 kg/m2) group.Sex hormonebinding globulin (SHBG),testosterone (T),dehydroepiandrosterone-sulfate (DHEA-S),fasting blood glucose(FBG),fasting insulin (FINS)levels were measured and then calculated free androgen index(FAI) and homeostatic model assessment of insulin resistance (HOMA-IR).The relationship between sex hormones and insulin resistance was analyzed by partial correlation and multiple linear regression analyses.Results Compared to early postmenopausal women,late postmenopausal women had higher FINS [(7.9 ± 6.6) mU/L versus (6.6 ±4.0) mU/L] and HOMA-IR(2.1 ± 1.9 versus 1.7 ± 1.1),but they had lower DHEA-S [(0.9 ± 0.5) mg/L versus (1.1 ± 0.5) mg/L,all P ＜ 0.05)].Both in early postmenopausal and late postmenopausal groups,overweight women had higher HOMA-IR (early group,2.2 ± 1.0 versus 1.2 ±0.9 ; late group,2.8 ± 2.6 versus 1.6±1.1)and FINS early group[(6.9±2.9) mU/L versus (4.6±2.0) mU/L] ;late group [(10.2 ± 9.3) mU/L versus (6.4 ± 3.6) mU/L] than those at women with normal weight group(all P ＜ 0.05).In early postmenopausal group,overweight women had lower SHBG [(52 ±37) nmol/L versus (71 ±37) nmol/L] and higher FAI(2.5 ±2.1) versus (1.3 ± 1.1) than those at normal weight women group(all P ＜ 0.05).In late postmenopausal group,overweight women had higher DHEA-S (1.0 ± 0.5) mg/L versus (0.8 ± 0.4) mg/L (P ＜ 0.05).The analyses suggested that in early postmenopausal group,SHBG was correlated negatively with FINS and HOMA-IR (β =-0.386,P ＜ 0.05 ;β =-0.553,P ＜0.05),DHEA-S was correlated positively with FBG (β =0.348,P ＜ 0.05) in early postmenopausal group.FAI was correlated positively with FBG in late postmenopausal group (β =0.505,P ＜ 0.05).Conclusions The increased androgenic activities are associated with insulin resistance after of menopause.These correlations are different at different stages of postmenopause,which SHBG levels correlate with high risk of insulin resistance and DHEA-S levels correlates with high blood glucose levels at early postmenopause and FAI correlates with high blood glucose levels at late postmenopause.

Objective To investigate the antitumor activity of the procaspase-3 activator SM-1 in BGC-823 cells in vivo and in vitro and the mechanisms.Methods The inhibitory effects of SM-1 on proliferation of BGC-823 cells were evaluated using MTT method, the cell apoptosis rate was detected by flow cytometry, and the expression of caspase-3 protein and procaspase-3 mRNA was detected by Western blotting and RT-PCR, respectively.SM-1 Antitumor activity was evaluated using the xenograft of BGC-823 cells in nude mice.Results SM-1 effectively inhibited the proliferation in vitro and in-duced apoptosis of BGC-823 cells in a dose-dependent manner.After treatment with SM-1 for 48 h, the protein expression levels of caspase-3 and mRNA expression levels of procaspase-3 were increased.SM-1 significantly inhibited growth of BGC-823 xenograft tumor at the 300 mg/kg dose and the inhibition rate was 56.3%(P<0.05).Conclusion SM-1 can significantly inhibit the tumor growth of BGC-823 cells in vivo and in vitro.The mechanism is possibly related to the activation of procaspase-3 and induced apoptosis of tumor cells.

Objectives:To assess bowel function and quality of life in patients with ulcerative colitis (UC)after ileal pouch anal anastomosis (IPAA).Methods:Clinical data of 37 UC patients after IPAA between 2014 and 2017 were retrospectively analyzed at Sir Run Run Shaw Hospital School of Medicine Zhejiang University. The IBDQ and Bowel Function questionnaire were used for analyzing correlation between clinical variables and quality of life or bowel function.Results:Laparoscopic operation was performed in 12 cases at stage 2 and 25 cases at stage 3. Postoperative defecation of stage 3 patients were better than that of stage 2 ( t=6.72, P<0.05). The number of daily defecation in age >45-year-old group was more than that in <45-year-old ( t=3.49, P<0.05), and the rate of evening stool seepage in the older group was higher than in the younger group( t=5.28, P<0.05). The total score of intestinal symptoms of IBDQ in patients of pouchitis was lower than that without pouchitis ( r=0.330, P<0.05). The total score in age >45 in terms of systemic symptoms ( r=0.349, P<0.05) and emotional function ( r=0.379, P<0.05) was higher than age <45. Conclusions:Outcomes of UC patients after IPAA are satisfactory, bowel function and quality of life is related with age, and stage of IPAA affect postoperative defecation.

Objective To evaluate the effects of turmeric volatile oil (TVO) combined with cisplatin on the proliferation and apoptosis of a human cutaneous squamous cell carcinoma cell line A431,and to explore their mechanisms.Methods Some cultured A431 cells at exponential growth phase were divided into several groups to be treated with 5,10,20,40 and 80 mg/L TVO,as well as high-glucose Dulbecco's modified Eagle's medium (DMEM) containing 1％ dimethyl sulfoxide (DMSO,control group),respectively.After 24-hour treatment,cell counting kit 8 (CCK8) assay was performed to estimate the proliferative activity of A431 cells in the above groups.Some other A431 cells were divided into 4 groups:control group treated with high-glucose DMEM containing 1％ DMSO,TVO group treated with 40 mg/LTVO,cisplatin group treated with 10 mg/L cisplatin,and TVO + cisplatin group treated with 40 mg/L TVO and 10 mg/L cisplatin.After 24-hour treatment,CCK8 assay was performed to estimate the cellular proliferative activity,inverted microscopy to observe changes in cell morphology,fluorescence microscopy to detect cell apoptosis after acridine orange (AO)/ethidium bromide (EB) double-staining,colorimetry to evaluate the activity of Caspase-3 and Caspase-9,and Western blot analysis to determine the protein expression of Caspase-3 and p-glycoprotein.Results After 24-hour treatment with 5,10,20,40 and 80 mg/L TVO,the cell proliferation rates were inhibited by (12.83 ± 6.4)％,(16.27 ± 11.4)％,(21.61 ± 9.1)％,(33.11 ± 2.0)％ and (46.00 ± 3.3)％ respectively,and the inhibition rates were all significantly higher in these groups than in the control group (4.03％ ± 1.4％,all P ＜ 0.05).The 50％ inhibitory concentration (IC50) of TVO at 24 hours was (61.66 ± 1.03) mg/L.Compared with the control group,the proliferation inhibition rates significantly increased in the TVO group,cisplatin group and TVO + cisplatin group (all P ＜ 0.05),suggesting that the combination of TVO and cisplatin showed synergistic inhibitory effects with a combination index of 1.366.Moreover,A431 cells turned round to different extents and became apoptotic in the TVO group and cisplatin group,and the TVO + cisplatin group showed obviously decreased number of cells and a large number of cell debris.The TVO + cisplatin group also showed significantly increased activity of Caspase-3 (1.520 ± 0.115) and Caspase-9 (2.760 ± 0.297) as well as protein expression of Caspase-3 (1.482 ± 0.016) compared with the TVO group (Caspase-3 activity:1.117 ± 0.095;Caspase-9 activity:1.259 ± 0.059;Caspase-3 protein expression:1.156 ± 0.006,all P ＜ 0.01) and cisplatin group (Caspase-3 activity:1.381 ± 0.089;Caspase-9 activity:1.829 ± 0.171;Caspase-3 protein expression:1.296 ± 0.021,all P ＜ 0.01),but significantly decreased p-glycoprotein expression (0.528 ± 0.014) compared with the TVO group (1.311 ± 0.011,P ＜ 0.01) and cisplatin group (1.169 ± 0.012,P ＜ 0.01).Conclusion TVO combined with cisplatin can synergistically inhibit the proliferation of A431 cells and induce cell apoptosis,which may be associated with activation of the caspase system and decreased expression of pglycoprotein.

Objective To explore the animal model of syndrome used in the study of hot flash phenomenon in women.Methods Twenty-four female SD rats were divided randomly into three groups:Con group,Ovx group,and tamoxifen group(n = 8 rats per group).Hot flashes were induced by bilateral oophorectomy and intragastric tamoxifen 10 mg/(kg·d),respectively.Open-field activity,anal temperature,and body surface infrared thermograms were detected on model days 14 and 28.The rats were then killed on day 29 and their uteruses were removed,weighed,and sectioned.Blood estradiol and catecholamine levels were determined by enzyme-linked immunosorbent assay.Gene expression levels of adrenal sex hormone synthetases(Star,Cyp11a1,Cyp17a1,Cyp19a1,Por,Hsd3b2,Hsd17b1)and catecholamine synthetases(Th,Ddc,Dbh,Pnmt)in the adrenal medulla were detected by reverse transcription-polymerase chain reaction.Results Rat body weight was significantly higher in the Ovx group compared with Con group(P<0.01),while body weight increased slowly in the tamoxifen group.The maximum body surface temperature was significantly decreased on day 28 in the Ovx group(P<0.01),the difference between the maximum and minimum abdominal temperatures was significantly increased on day 14(P<0.05),the difference between the maximum and minimum temperatures on the back was significantly increased on day 28(P<0.01),and the open-field activity was decreased(P<0.01).Compared with the sham operation group,the maximum body surface temperature in the tamoxifen group was significantly decreased(P<0.01)but the open-field activity was increased(P<0.01).The uterine index was significantly decreased in both models(P<0.01).Estradiol levels were significantly decreased(P<0.01)and NE and epinephrine were also significantly decreased in the Ovx group compared with Con group(P<0.05),and β-EP was also significantly decreased in Ovx group(P<0.05).Adrenal Cyp11a1 gene expression was significantly increased(P<0.05)while Cyp17a1 and Hsd17b1 gene expression levels were significantly decreased(P<0.05)in bilateral ovariectomized rats compared with Con group.Compared with Con group,gene expression levels of Star and Por were significantly increased(P<0.01)while Cyp17a1 gene expression was significantly decreased(P<0.01)in the tamoxifen group,and Pnmt gene expression was significantly down-regulated in Ovx group(P<0.01).Conclusions Bilateral ovariectomized rats can be used for the study of perimenopausal hot flashes,which resemble kidney Yang and Yin deficiency in traditional Chinese medicine.

Objective To investigate the clinical significance and changes of serum interleukin-4 (IL-4),interferon-γ(IFN-γ) and immunoglobulin E (IgE) levels in infants with spasmodic laryngitis.Methods Serum samples were obtained from 50 children with spasmodic laryngitis and 30 healthy children.The changes of IL-4,IFN-γand IgE levels in serum when hospital admission (acute stage),before discharge (the stage of clinical symptom disappeared) and after 2 months of follow-up were observed.Enzyme-linked immunosorbent assay was used to determine the levels of IL-4 and IFN-γ in serum.Serum IgE level was determined with enzyme-linked fluoroimmuneassay.Results The serum level of IL-4 in patients with spasmodic laryngitis during acute stage were much higher than that in normal control group[(20.65 ±5.87) ng/L vs(8.23 ±2.71) ng/L,t =5.536,P ＜0.05].It was decreased during the stage of clinical symptom disappeared and significantly lower than that during acute stage[(11.07 ± 2.93) ng/L vs (20.65 ± 5.87) ng/L,F =5.258,P ＜ 0.05].The serum level of IFN-γ in patients with spasmodic laryngitis during acute stage were much lower than that in normal control group[(61.38 ±6.36) ng/L vs (108.42 ± 13.56) ng/L,t =4.831,P ＜ 0.05],and it was increased during the stage of clinical symptom disappeared [(95.12 ± 11.63) ng/L] and significantly higher than that during acute stage(F =4.239,P ＜ 0.05).There was no difference between the patients at clinical symptom disappeared stage and normal control group (P ＞ 0.05).Two months after discharge,there was no difference in serum INF-γlevel between the patients [(75.68 ±6.29) ng/L] and that in control group (P ＞ 0.05).The serum level of IgE in patients with spasmodic laryngitis during acute stage were much higher than that in normal control group [(136.63 ± 17.86) ng/L vs (47.16 ± 6.83) ng/L,t =6.685,P ＜ 0.05].It was decreased during the stage of clinical symptom disappeared [(88.07 ± 11.83) μg/L] and significantly lower than that during acute stage(F =5.182,P ＜ 0.05),but higher than that of normal control group (P ＜ 0.05).Two months after discharge [(86.72 ± 7.25) μg/L] it was still higher than that in control group (P ＜ 0.05).Conclusions There is TH1/TH2 imbalance in infants with spasmodic laryngitis.Maybe spasmodic laryngitis is one of the clinical manifestations of atopic diseases.IL-4,IFN-γand IgE may play important roles in immunologic pathogenesis.