COX-2基因启动子区-765G/C多态性与昆明地区汉族人2 型糖尿病的相关性研究

目的 探讨环氧化酶2(COX-2)基因启动子区-765G/C 多态性与昆明地区汉族人2 型糖尿病(T2DM)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法,对200 例T2DM 患者、100 例健康对照者(NC)的COX-2 基因-765G/C 多态性进行检测;比较分析两组间基因型频率和等位基因频率及相关资料.结果 (1)基因型频率和等位基因频率在两组的差异无统计学意义.(2)T2DM 患者中,-765GG 型携带者的空腹血糖水平、餐后2 h 血糖水平和糖化血红蛋白百分比水平与非GG 型携带者相比,差异有统计学意义.结论 在昆明地区汉族人群中虽COX-2 基因-765G/C 多态性与T2DM 发病无明显相关,但-765GG 基因型能影响T2DM 患者血糖水平.     

湖北汉族人群RBP4基因多态性803G/A位点与T2DM的相关性研究

目的 调查湖北汉族人群中的视黄醇结合蛋白4(RBP4)基因多态性(-803G/A位点)分布情况,并探讨RBP4基因多态性(-803G/A位点)与2型糖尿病(T2DM)的相关性.方法 应用基因测序技术对湖北128例T2DM患者和131例正常人RBP4基因-803G/A位点进行研究,同时结合血糖、血脂水平来探讨两者之间的关系.结果 T2DM组中基因型分布为:GG型40.5%,AG+AA型59.5%;对照组中分布为:GG型62.3%,AG+AA型37.7%.T2DM组中等位基因频率A和G分别为36.2%和63.8%;对照组中分别为18.7%和81.3%.T2DM患者AA基因型频率和A等位基因频率均明显高于正常对照组(P＜0.05).与对照组比较,T2DM组中GG基因型血清TG与 Lp(a)水平差异均有统计学显著性意义(P＜0.01);AG基因型血清 Lp(a)水平差异有统计学显著性意义(P＜0.01).结论 湖北汉族人群中的RBP4基因-803G/A多态性可能与T2DM的发生相关.     

血管紧张素转换酶2基因A9570G多态性与2型糖尿病合并冠心病的相关性研究

目的:研究血管紧张素转化酶2(angiotensin Ⅰ converting enzyme 2,ACE2)基因A9570G多态性与2型糖尿病(type 2diabetes,T2DM)合并冠心病(coronary artery disease,CHD)的相关性.方法:选择广东地区无血缘关系的T2DM患者共262例,所有患者按是否并发CHD分为T2DM CHD组扣T2DM组,对照组100例为健康体检者,应用聚合酶链反应和限制性内切酶片段长度多态性的方法检测ACE2基因A9570G多态性.综合分析ACE2基因A9570G多态性与T2DM并发CHD的关系.结果:在男性,对照组和T2DM组等位基因频率及基因型构成差异均无统计学意义(X2=0.024,P=0.876),但T2DM CHD组G等位基因频率及G基因型频率高于对照组及T2DM组,差异有统计学意义(X2=4.781,P=0.029及X2=4.933,P=0.026);在女性,3组间等位基因频率及基因型构成差异均无统计学意义(X2=0.037,P=0.981及X2=1.243,P=0.871).根据不同基因型对T2DM CHD组患者进行亚组分析发现,在男性,G基因型患者冠脉病变的Genisini积分高于A基因型者,差异有统计学意义(t=2.243,P=0.029);在女性,则未观察到这种差异(F=1.156,P=0.324).结论:ACE2基因A9750G多态性可能与男性T2DM并发CHD的遗传易感性相关.并且与其冠脉痛变程度有一定关系.     

HSL基因启动子-60C>G多态性与2型糖尿病高脂血症的相关性研究

目的探讨激素敏感性脂肪酶(HSL)基因启动子-60C>G多态性与2型糖尿病(T2DM)高脂血症患者血浆脂质水平的相关性。方法采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)和DNA测序法对94例健康对照者、77例T2DM高脂血症患者的HSL基因启动子-60C>G多态性进行分析,并检测空腹血糖和血脂水平。结果试验组空腹血糖和TC、TG、LDL-C水平均显著高于健康对照组,HDL-C水平明显低于健康对照组(P<0.05);两组均未发现HSL基因-60GG纯合型,试验组CG杂合型频率较健康对照组高,G等位基因频率也较健康对照组高,但两组间的基因型频率和等位基因频率差异均无统计学意义(P>0.05);试验组CC型血浆TC、TG、LDL-C水平均明显高于健康对照组CC型、CG型(P<0.05),HDL-C水平明显低于健康对照组CC型(P<0.05);试验组和健康对照组组内CC型和CG型血脂水平差异均无统计学意义(P>0.05)。结论 HSL基因启动子-60C>G多态性与湖北地区汉族人群中T2DM高脂血症的血脂水平无明显关联。     

2型糖尿病遗传易感性与CAPN-10基因多态性的相关性研究

目的探讨2型糖尿病(T2DM)遗传易感性与CAPN-10基因多态性的关系。方法采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术对100例T2DM患者(病例组)和100例健康者(对照组)CAPN-10基因SNP19(rs3842570)、SNP43(rs3792267)和SNP63(rs5030952)多态性位点进行基因分型。结果病例组CAPN-10基因43位点的GG基因型频率和G等位基因频率显著高于对照组,差异有统计学意义(P<0.05);19位点和63位点的基因型频率、等位基因频率在病例组与对照组分布差异均无统计学意义(P>0.05)。结论 CAPN-10基因SNP43(rs3842570)位点与T2DM的发生有相关性,而SNP19(rs3842570)和SNP63(rs5030952)位点则与T2DM的发生无相关性。     

环氧合酶-2基因-1195G>A多态性位点与缺血性脑卒中患者阿司匹林抵抗的相关性

目的:探讨环氧合酶-2(COX-2)基因-1195 G>A多态性位点与缺血性脑卒中(IS)患者阿司匹林抵抗(AR)的相关性。方法:纳入中国北方汉族IS患者210例,根据血小板聚集率分为阿司匹林敏感(AS)组147例,非AS组63例。采用扩增阻碍突变系统(ARMS)结合TaqMan探针的实时荧光定量PCR方法检测-1195 G>A多态性。结果:-1195G>A位点基因型、显性模型分布频率在AS组及非AS组中差异均无统计学意义(P>0.05);非AS组中-1195G>A位点(GA+AA)基因型频率及A等位基因频率高于AS组,差异均有统计学意义(x2=4.96,P=0.03;x2=5.50,P=0.02);多因素分析提示,与GG基因型相比,COX-2的-1195G>A位点(GA+AA)基因型发生AR可能性更大(OR=2.41,95%CI为1.09~5.37,P=0.03)。结论:COX-2基因-1195G>A位点遗传变异与可能IS患者发生AR相关,可能是AR发生的一个遗传易感性位点。     

线粒体DNA 5178C/A多态性与2型糖尿病关系的研究

目的研究线粒体DNA5178C/A多态性与2型糖尿病(T2DM)及其并发症的关系。方法采用聚合酶链反应(PCR)与PCR产物直接测序的方法,对2型糖尿组(220例)及正常对照组(126例)进行基因分析。结果 5178C基因型与5178A基因型的T2DM患者在性别、发病年龄、体重指数、血糖、血脂等水平差异无统计学意义,但T2DM患者中5178C基因型并发视网膜病变的频率要高于5178A基因型(P0.05)。结论线粒体DNA5178C/A多态性可能与T2DM患者并发视网膜病变负相关。     

单核细胞趋化蛋白1基因多态性与2型糖尿病的相关性研究

目的探讨中国西北地区汉族人群中2型糖尿病(T2DM)与单核细胞趋化蛋白1(MCP-1)-2518(A/G)基因多态性的关系。方法测量41例正常对照者和57例2型糖尿病患者相关临床生化指标,并采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术,观察MCP-1-2518(A/G)基因多态性,研究其与2型糖尿病的关系。结果2型糖尿病组与正常对照组的MCP-1等位基因和基因型频率比较差异无统计学意义(P>0.05);多因素Logistic回归分析显示,MCP-1 G等位基因为2型糖尿病的保护因素(OR=0.015,CI=0.005~0.437),且有统计学意义(P<0.05)。结论正常对照组与2型糖尿病组MCP-1-2518(A/G)基因多态性差异无统计学意义,尚不能认为在中国西北汉族人群中MCP-1基因多态性与2型糖尿病之间有相关性,但G等位基因可能为2型糖尿病的保护因素,它的存在降低2型糖尿病的患病率。     

β2-肾上腺素能受体基因多态性与慢性心力衰竭后室性心律失常的关系

目的探究β2-肾上腺素能受体基因多态性与慢性心力衰竭后室性心律失常的关系。方法聚合酶链式反应法(PCR)对115例慢性心力衰竭后室性心律失常患者(观察组)及90例健康体检正常人员(对照组)进行β2-肾上腺素能受体基因多态性检测,比较两组β2-肾上腺素能受体基因多态性位点16Arg/Gly、27Gln/Glu、178Arg A/C基因型、等位基因频率,并分析不同性别、心功能分级、原发性疾病类型与β2-肾上腺素受体基因型的关系。结果观察组27Gln/Glu基因型中G/C型、等位基因G频率均显著高于对照组,差异有统计学意义(P<0.05),多态性位点16Arg/Gly、178Arg A/C基因型、等位基因频率方面两组比较均无显著差异(P>0.05);不同性别、原发性疾病类型患者β2-肾上腺素能受体27Gln/Glu基因型、等位基因频率比较差异均无统计学意义(P>0.05);多位点27Gln/Glu基因型G/C心功能分级显著高于CC型(P<0.05)。结论β2-肾上腺素能受体基因多态性位点27Gln/Glu与慢性心力衰竭后室性心律失常发生有关,特别是G/C型,为其发生易感基因,且与心功能分级相关。     

人类纤溶酶原激活物抑制物-1基因多态性与2型糖尿病血管内皮功能的关系

目的 探讨人类纤溶酶原激活物抑制物-1(PAI-1)基因4G/5G多态性与2型糖尿病(T2DM)患者内皮依赖性血管舒张功能(EDF)的关系.方法 采用特异性多聚酶链反应技术检测66例T2DM患者和33例健康对照组PAI-1基因4G/5G多态性;利用B型超声检测T2DM患者EDF;同时检测PAI-1和纤维蛋白原.结果 T2DM患者与健康对照组基因型分布频率均符合Hardy-Weinberg平衡,差异无统计学意义(P0.05).T2DM患者比健康对照组具有更高的PAI-1、纤维蛋白原水平.T2DM患者PAI-1基因4G/4G型PAI-1水平明显高于其他两型,EDF明显低于其他两型(P<0.05).结论 PAI-1基因多态性可能影响T2DM患者的EDF.     

Atomic and electronic structure of solids of Ge2Br2PN,Ge2I2PN,Sn2Cl2PN,Sn2Br2PN and Sn2I2PN inorganic double helices: a first principles study

We report the results of density functional theory calculations on the atomic and electronic structure of solids formed by assembling A₂B₂PN (A = Ge and Sn, B = Cl, Br, and I) inorganic double helices. The calculations have been performed using a generalized gradient approximation for the exchange–correlation functional and including van der Waals interactions. Our results show that the double helices crystallize in a monoclinic lattice with van der Waals type weak interactions between the double helices. In all cases except Ge₂Cl₂PN, the solids are stable with a binding energy between the double helices ranging from 0.06 eV per atom to 0.09 eV per atom and inter-double helices separation of more than 3.33 Å. All the solids are semiconducting. Further calculations have been done by using meta-GGA with a modified Becke–Johnson functional to obtain better band gaps, which are found to lie in the range of 0.91 eV to 1.49 eV. In the case of Ge₂Br₂PN the solid is a direct band gap semiconductor although the isolated double helix has an indirect band gap and it is suggested to be interesting for photovoltaic, and other optoelectronic applications. The charge transfer between the atoms has been studied using Bader charge analysis and the DDEC6 method in the CHARGEMOL program, which suggests charge transfer from the outer helix to the inner helix.

We report the results of density functional theory calculations on the atomic and electronic structure of solids formed by assembling A₂B₂PN (A = Ge and Sn, B = Cl, Br, and I) inorganic double helices.     

Shape-dependent close-edge 2D-MoS2 nanobelts

Atomic-thin MoS₂ materials have attracted increasing attention due to their potentials in numerous fields. However, in 2D-MoS₂ sheets, the edge region usually has unique features differing from the interior region, which has potential application in enhancing catalysts and shape-dependent 2D-nanodevices. However, fabricating it cost-effectively is still very difficult. Here, we present one universal method to obtain various shape-dependent closed-edge 2D-MoS₂ nanobelts only using one simple step, and width of the MoS₂ nanobelts (minimum of 270 nm) were adjustable. Our strategy opens a new fabrication route for closed-edge 2D-MoS₂ nanobelts, and in principle, this method is also suitable for other CVD-grown 2D materials.

A very simple mechanical peeling method to obtain various closed and shape-dependent MoS₂ edge nanobelt.     

Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9

Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively in vivo by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.     

Interleukin-2 (IL-2) immunotherapy

Various forms of immunotherapy have been employed for the treatment of cancer patients during the past 5 years, with recombinant interleukin-2 (IL-2) having been widely used in these treatment regimes. The progress of IL-2 immunotherapy is discussed.     

乳腺癌环氧合酶-2和基质金属蛋白酶-2及其抑制因子的表达

目的 研究环氧合酶(COX)-2、基质金属蛋白酶(MMP)-2及其抑制因子(TIMP-2)在乳腺癌组织中的蛋白表达及其相互关系.方法 建立组织芯片平台,应用免疫组织化学S-P法检测127例乳腺癌组织COX-2、MMP-2和TIMP-2蛋白的表达情况.结果 乳腺癌COX-2、MMP-2和TIMP-2阳性率分别为81.1%(103/127)、96.9%(123/127)和60.6%(77/127);COX-2的表达与乳腺癌腋淋巴结转移和TNM分期均呈正相关(P<0.01,P<0.05),与孕激素受体表达呈负相关(P<0.05);MMP-2蛋白表达与COX-2表达呈显著正相关(r=0.290,P<0.01).结论 乳腺癌COX-2表达状况与肿瘤侵袭转移有密切关系,COX-2可能通过调控MMP-2表达来促进肿瘤侵袭转移.