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目的 探讨血清微小 RNA-106（miR-106）、C-C 基序趋化因子配体 2（CCL2）水平与糖尿病视网膜病变 （DR）微血管损伤的关系。方法 选择 2 型糖尿病患者 206 例，根据是否合并 DR 及其视网膜病变程度分为增殖性糖 尿病视网膜病变（PDR）56 例（PDR 组）、非增殖性糖尿病视网膜病变（NPDR）68 例（NPDR 组）、无糖尿病视网膜病变 （NDR）82 例（NDR 组）。采集所有研究对象清晨空腹肘静脉血，采用 RT-qPCR 法检测血清 miR-106，采用 ELISA 法检 测血清 CCL2、IL-6、TNF-α，采用流式细胞术检测外周血循环祖细胞（CPC）、内皮祖细胞（EPC）、循环内皮细胞（CEC）比 例，采用葡萄糖氧化酶法检测空腹血糖（FPG），采用乳胶凝集反应法检测糖化血红蛋白（HbA1c），通过口服葡萄糖耐量 试验检测餐后 2 h 血糖（2 h PG）。比较三组血清 miR-106、CCL2、IL-6、TNF-α 水平及外周血 CPC、EPC、CEC 比例，分析 DR 患者血清 miR-106、CCL2 水平与外周血 CPC、EPC、CEC 比例及血清 IL-6、TNF-α 水平的关系。采用多因素 Logistic 回归模型分析 2 型糖尿病患者进展至 DR 或 PDR 的影响因素。结果 与 NPDR 组、NDR 组比较，PDR 组血清miR-106 水平及外周血 CPC、EPC 比例显著降低，血清 CCL2、IL-6、TNF-α 水平及外周血 CEC 比例显著升高（P 均<0. 05）。与 NDR组比较，NPDR 组血清 miR-106 水平及外周血 CPC、EPC 比例显著降低，血清 CCL2、IL-6、TNF-α 水平及外周血 CEC 比例显著升高（P均 <0. 05）。DR 患者血清 miR-106 水平与外周血 CPC、EPC 比例呈正相关关系，与外周血CEC比例和 血清 IL-6、TNF-α水平呈负相关关系（P均 <0. 05）；血清 CCL2 水平与外周血 CPC、EPC 比例呈负相关关系，与外周血 CEC 比例和血清 IL-6、TNF-α 水平呈正相关关系（P均<0. 05）；血清 miR-106 水平与血清 CCL2 水平呈负相关关系（P< 0. 05）。多因素 Logistic 回归分析显示，CCL2 为 2 型糖尿病患者进展至 DR 或 PDR 的独立危险因素，而 miR-106 则为其 独立保护因素（P均<0. 05）。结论 DR 患者血清 miR-106 水平降低、血清CCL2 水平升高，二者可能通过炎症反应共同 参与 DR 微血管损伤；miR-106、CCL2 是 2 型糖尿病患者进展至 DR 或 PDR 的独立影响因素。 [ABSTRACT FROM AUTHOR]

Objective To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch1 gene rs3124599 and susceptibility to lung cancer in patients with primary lung cancer. Methods A total of 78 patients with primary lung cancer (observation group) and 156 healthy subjects (control group) were enrolled. The morning venous blood of the two groups were taken (2 m L). DNA was extracted by phenol-chloroform extraction and Notch1 gene rs3124599 locus typing was analyzed by PCR-PFLPS technique. The clinical data of the two groups were collected. The correlation between various factors and susceptibility to lung cancer was evaluated by conditional logistic regression analysis. The interaction coefficient (γ) was used to evaluate the interaction between environmental factors and gene polymorphism. Results The distribution frequencies of Notch1 gene rs3124599 genotypes AA,AG,GG in the observation group were 25.6% (20/78),39.7% (31/78),and 34.6% (27/78),which were 37.2% (58/156),44.9% (70/156),and 17.9% (28/156) in the control group; the distribution frequencies of alleles A and G in the observation group were 45.5% (71/156)and 54.5% (85/156),respectively,which were 59.6% (186/312) and 40.4% (126/312) in the control group. The differences of the distribution of genotypes and alleles A and G between the two groups were statistically significant (χ2=6.518,3.987; all P < 0.05). The number of smoking,degree of smoking,and the family history of cancer in the observation group were higher than those in the control group (χ2= 23.890,5.647; P < 0.05). Conditional logistic regression analysis showed that individuals with rs3124599 GG genotype had an increased risk of lung cancer as compared with individuals with rs3124599 AA genotype (corrected OR = 1.596,95% CI: 1.058-2.429). The individuals carrying alleles G gene were 1.193 times more likely to develop lung cancer than those carrying A gene (95% CI: 1.132 to 2.501,P <0.05). The rs3124599 locus AG or GG genotype had positive interaction with smoking (γ = 2.296) and drinking (γ =1.130). When the rs3124599 locus AG/GG genotype was associated with a family history of the tumor,the risk of developing lung cancer increased (OR = 3.751,95% CI = 1.665-18. 034). Compared with rs3124599 genotype AA non-smokers,the risk of lung cancer in smokers or smokers carrying AG/GG increased by 4.495 times and 12.134 times,respectively. Conclusion The mutation frequency of allele G in Notch1 gene rs3124599 is higher in lung cancer patients. The allele G of the Notch1 gene rs3124599 (A/G) may be a risk factor for lung cancer,and it has an interaction with the patient’s family history of cancer and smoking history. [ABSTRACT FROM AUTHOR]