目的 观察新疆石河子地区绝经后女性2型糖尿病(T2DM)患者糖、脂、骨代谢特征及骨密度(BMD)情况,探讨该人群中低密度脂蛋白受体相关蛋白5(LRP5)基因rs3736228、rs3781586位点的基因多态性及突变与糖、脂、骨代谢指标的关系。方法 将新疆石河子地区2016年10月—2017年10月社区、医院门诊及住院绝经后女性按照纳入标准和排除标准选取136例为研究对象,根据患者病史、糖耐量实验及骨密度仪测定骨密度分4组,糖耐量正常与骨量正常组(A组),糖耐量正常与骨量异常组(B组),T2DM与骨量正常组(C组),T2DM与骨量异常组(D组)。测定并记录患者年龄、绝经年限等基线资料,计算体质指数(BMI)等,并检测糖代谢指标(空腹血糖等)、骨代谢指标(血Ca等)、脂代谢指标(甘油三酯等)。采用MALDI-TOF-MS法测定LRP5基因该两个位点基因多态性并进行统计分析。结果 ①糖代谢指标:与A组比较,C组、D组FPG、HbA1c均高于A组(P<0.01)。脂代谢指标:与A组比较,B组、D组TG低于A组(P<0.05)。骨代谢指标:与A组比较,B组、D组BMD(L1-4)、BMD(股骨颈)低于A组(P<0.01)。②LRP5基因该两个位点SNP基因分型分布符合Hardy-Weinberg遗传平衡定律(P>0.05);同时,该两个位点不同基因型的分布频率和等位基因频率在组间的比较经Pearson Chi-Square检验后发现暂无显著差异(P>0.05)。③LRP5基因rs3736228位点:A组,与CC型(野生型)相比,CT/TT型(突变型)甘油三酯(TG)降低(P<0.05),BMD(L1-4)降低(P<0.05);C组,与CC型(野生型)相比,CT/TT型(突变型)高密度脂蛋白(HDL-C)升高(P<0.01),磷(P)升高(P<0.05);LRP5基因rs3781586位点:B组,与GG型(野生型)相比,GT/TT(突变型)高密度脂蛋白(HDL-C)升高(P<0.05)。结论 在新疆石河子地区绝经后女性2型糖尿病人群中,LRP5基因rs3736228、rs3781586位点的基因多态性可能与糖代谢无关,但LRP5基因rs3736228位点的突变可能与脂代谢(TG、HDL-C)、骨代谢(P、BMD)有关,rs3781586位点的突变可能与脂代谢(HDL)有关。

Objective To observe the characteristics of glucose, lipid and bone metabolism and bone mineral density (BMD)in postmenopausal women with type 2 diabetes mellitus (T2DM)in Shihezi district of Xinjiang province, and to investigate the relationship in the polymorphism and mutation of rs3736228 and rs3781586 of LRP5 gene and glucose,lipid and bone metabolism indexes in this population. Method A total of 136 postmenopausal Han women, who were related in the outpatient department, community, and hospital after hospitalization in Shihezi district of Xinjiang province from October 2016 to October 2017, were selected as the study subjects by the inclusion criteria and exclusion criteria.According to the patient's medicalhistory, glucosetolerance test results and bone mineral density (BMD), they were divided into 4 groups: normal glucose tolerance and normal bone mass (group A), normal glucose tolerance and abnormal bone mass (group B), type 2 diabetes and normal bone mass (group C), and type 2 diabetes mellitus and abnormal bone mass (group D). Baseline data such as patient's age, menopause years were measured and recorded, and body mass index (BMI)was calculated. Simultaneously, glucose metabolism indicators including fasting blood glucose (FBG, etc), bone metabolism indicators (blood Ca, etc), lipid metabolism indicators(triglycerides, etc)were detected. The polymorphisms of rs3736228 and rs3781586 of LRP5 gene were determined by Maldi-Tof-Ms and those data were analyzed statistically. Results ①Glucose metabolism index: compared with group A: FPG and HbAlc in group C, group D were all higher than group A (P<0.01). Lipid metabolism index: compared with group A, TG in group B and group D was lower than that in group A (P<0.05). Bone metabolism index: compared with group A, BMD (L1- 4)and BMD (femoral neck)in group B and group D were lower than those in group A (P<0.01). ②The distribution of SNP genotypes at rs3736228, rs3781586 of LRP5 conformsed to the Hardy-Weinberg genetic equilibrium law (P>0.05). The distribution frequency and allele frequency of LRP5 genotypes rs3736228, rs3781586 were compared among the groups. Pearson chi-square test showed no significant difference (P>0.05). ③Rs 3736228 locus of LRP5 gene:in group A, compared with CC (wild type), CT/TT (mutated type)triglyceride (TG)decreased (P<0.05), BMD (L1- 4)decreased (P<0.05). In group C, compared with CC (wild type), CT/TT (mutated type)high-density lipoprotein (HDL-C)increased (P<0.05), phosphorus increased (P<0.05). Rs 3781586 locus of LRP5 gene: in group B, compared with GG (wild type), GT/TT (mutated type)high-density lipoprotein (HDL-C)increased (P<0.05).Conclusion In the Xinjiang Shihezi district among postmenopausal women with type 2 diabetes, rs3736228, rs3781586 loci of LRP5 gene polymorphism may be irrelevant to glucose metabolism, but the mutation of rs3736228 of LRP5 gene locus may be related to lipid metabolism and bone metabolism (TG, HDL-C, BMD, P), and the mutation of rs3781586 may be related to lipid metabolism (HDL-C).

目的 利用分析各种浓度环氧化酶-2(COX-2)特异度抑制剂塞来昔布对食管癌EC109细胞系的作用,进而对COX-2蛋白表达的影响及对细胞凋亡能力的作用,进一步探讨塞来昔布对食管癌细胞凋亡的作用及机制。方法 使用0 μmol/L、20 μmol/L、60 μmol/L、100 μmol/L四个浓度的塞来昔布处理EC109细胞24 h,酶联免疫吸附剂测定(ELISA)法测定COX-2蛋白表达;流式细胞仪测定EC109细胞凋亡情况。结果 与0 μmol/L塞来昔布组比较,20 μmol/L、60 μmol/L、100 μmol/L塞来昔布组EC109细胞内COX-2蛋白表达不断降低(1.581±0.116;1.226±0.089,0.846±0.076,0.521±0.082)(P<0.05);而细胞凋亡率逐步上升(1.700±0.557,13.400±1.735,18.766±1.301,28.100±1.997)(P<0.05)药物浓度依赖于梯度。结论 塞来昔布是一种COX-2抑制剂,可能以浓度梯度的形式抑制COX-2蛋白的表达,从而促进EC109细胞的凋亡。

Objective The effects of celecoxib, a specific COX-2 inhibitor at various concentrations, on EC109 cell line of esophageal cancer were analyzed, and the effect and mechanism of celecoxib on apoptosis of esophageal carcinoma cells were further studied. Methods EC109 cells were treated with celecoxib at concentrations of 0 μmol/L, 20 μmol/L, 60 μmol/L and 100 μmol/L for 24 h. The protein of COX-2 in EC109 cells was determined by enzyme-linked immunosorbent assay (ELISA). Assay of EC109 cell apoptosis were determined by flow cytometry. Results Compared with the 0μmol/L celecoxib group, the expression of COX-2 protein in EC109 cells of 20μmol/L, 60μmol/L, 100μmol/L celecoxib group gradually decreased(1.581±0.116; 1.226±0.089, 0.846± 0.076, 0.521±0.082) (P<0.05); and the apoptotic rate gradually increased (1.700±0.557; 13.400±1.735, 18.766±1.301, 28.100±1.997) (P<0.05) in a drug concentration gradient-dependent manner. Conclusion The COX-2 inhibitor celecoxib may inhibit the expression of COX-2 protein in a concentration gradient and promote the apoptosis of esophageal cancer EC109 cells.

目的 分析石河子地区2型糖尿病(T2DM)合并消化道恶性肿瘤患者的临床特征,探讨T2DM合并消化道恶性肿瘤的影响因素。方法 ①纳入我院2015年至今消化道恶性肿瘤患者为研究对象。根据OGTT结果或既往有无T2DM病史分为三组:健康对照组(A组),消化道恶性肿瘤组(B组),T2DM合并消化道恶性肿瘤组(C组)。②全自动生化分析仪测定血清中糖脂代谢指标,化学发光法测定血清甲胎蛋白(AFP)等肿瘤标志物,分析其临床特征,进行组间比较,并探讨其影响因素。采用SPSS 22.0软件处理数据,并进行方差分析;影响因素采用Logistic回归分析;假设检验水准α＝0.05,双侧检验P<0.05差异有统计学意义。结果 ①基线资料比较显示:A组310例(男女比138/172),年龄(52.96±10.98)岁;B组513例(男女比343/170),胃癌患者居多(26.90%),年龄(62.26±12.34)岁;C组134例(男女比80/54),肝癌患者较多(26.12%),年龄(66.78±10.47)岁;与A组相比,B组与C组男性患者较多,年龄较大。②组间基线资料比较显示:三组的性别、年龄存在统计学差异(P<0.001)。③协方差分析消除影响因素后:与A组相比,B组及C组的TG、 TC、HDL-c降低(P<0.001);FPG、AFP、CEA、CA12-5、CA15-3、CA19-9、CA72-4升高(P<0.01)。④Logistic回归分析后结果显示:FPG为消化道恶性肿瘤发生的独立危险因素(OR=1.204);年龄是消化道恶性肿瘤及T2DM合并消化道恶性肿瘤发生的危险因素(OR=1.072,1.105),HDL-c为消化道恶性肿瘤及T2DM合并消化道恶性肿瘤发生的保护因素(OR=0.200,0.111);结论 老年男性T2DM患者易发生消化道恶性肿瘤。因此,对于高龄男性T2DM患者,尤其是HDL-c降低的情况下,应进行相关筛查,以早期防治消化道恶性肿瘤的发生发展。

Objective To analyze the clinical characteristics of patients with type 2 diabetes mellitus (T2DM)complicated with gastrointestinal malignancy in Shihezi area, and investigate the influencing factors of T2DM complicated with gastrointestinal malignancy. Methods ①Patients with malignant tumors of the digestive tract in our hospital from 2015 to the present have been included in the study. They were divided into three groups based on OGTT results or previous history of T2DM: healthy control group (group A), gastrointestinal malignant tumor group (group B), and T2DM combined gastrointestinal malignant tumor group (group C). ②Automatic biochemical analyzer measured serum glucose and lipid metabolism indicators, chemiluminescence method was used to measure serum alpha-fetoprotein (AFP)and other tumor markers, to analyze its clinical characteristics, make a comparaison between groups, and explore its influencing factors. The data was processed with SPSS 22.0 software and analysis of variance was performed; the influencing factors were analyzed by logistic reg-ression; hypothesis test level = 0.05, and the two-sided test P <0.05 was statistically significant. Results ①Comparison of baseline data showed that 310 cases (male/female 138/172)in group A were (52.96±10.98)years old. In group B, 513 patients (male/female 343/170)were diagnosed with gastric cancer (26.90%), aged (62.26±12.34)years. There were 134 cases in group C (male/female 80/54), with more liver cancer patients (26.12%), and the age was (66.78±10.47)years. Compared with group A, group B and group C had more male patients and were older. ②Comparison of baseline data among groups showed there were statistical differences in gender and age among the three groups (P<0.001). ③After covariance analysis eliminated influencing factors: compared with group A, TG, TC and HDL-c were decreased in group B and group C (P<0.001). FPG, AFP, CEA, CA12-5, CA15-3, CA19-9, and CA72-4 increased (P<0.01). ④Logistic regression analysis results: FPG was an independent risk factor for gastrointestinal malignancy (OR=1.204). Age wss a risk factor for gastrointestinal malignancy and T2DM complicated with gastrointestinal malignancy (OR=1.072, 1.105), HDL-c was the protective factor (OR=0.200, 0.111). Conclusion Elderly male T2DM patients are prone to gastrointestinal malignancies. Therefore, for elderly men with T2DM, especially when HDL-c is reduced, relevant screening should be performed to prevent and control the occurrence and development of gastrointestinal malignant tumors in the early stage.