切除修复交叉互补基因1和着色性干皮病基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性的关系研究

目的探讨切除修复交叉互补基因1(ERCC1)、着色性干皮病基因(XPD)多态性与晚期非小细胞肺癌(NSCLC)患者含铂二药方案化疗敏感性的关系。方法采用PCR-RFLP方法检测130例以铂类药物为基础化疗方案的晚期NSCLC患者ERCC1 118C/T、C8092A与XPD Asn312Asp、Lys751Gln基因多态性,分析其与化疗敏感性的关系。结果化疗2个周期后,130例患者的客观缓解率(ORR)为33.8%(44/130),其中部分缓解(PR)44例(33.8%),疾病稳定(SD)54例(41.6%),疾病进展(PD)32例(24.6%)。ERCC1 118C/T+T/T基因型化疗ORR(52.4%)是C/C基因型(41.8%)的3.300倍[95%CI(1.104,9.864),P=0.003]。XPD Asp312Asn、Lys751Gln(或Gln751Gln)基因型化疗ORR(62.5%)是其他基因型的(29.2%)的3.922倍[95%CI(1.320,11.649),P=0.010]。ERCC1 118C/T(或T/T)、XPD Asp312Asn与Lys751Gln(或Gln751Gln)基因型化疗ORR(58.0%)是ERCC1 118C/C、XPD Asp312Asp与Lys751Lys基因型的(31.8%)的3.571倍[95%CI(1.082,11.793),P=0.032]。应用SHEsis分析软件发现以其他单体型组为参照,A-C单体型化疗ORR显著提高(P=0.039)。结论 ERCC1 118C/T和XPD Asp312Asn、Lys751Gln多态性与晚期NSCLC患者铂类药物化疗敏感性密切相关。     

切除修复交叉互补基因2与非小细胞肺癌铂类化疗敏感性的研究进展

全世界肺癌的发病率及病死率为恶性肿瘤的首位,且仍旧持续增加,严重威胁着人类生命安全.而非小细胞肺癌(NSCLC)患者占所有肺癌的80％以上,约85％的患者病情确诊时已处于中晚期,故铂类药物联合第三代标准化疗方案成为主要治疗措施[1-2].切除修复交叉互补基因2 (ERCC2)作为一种DNA解螺旋酶,为RNA聚合酶Ⅱ(TFⅡH)组分,参与碱基切除修复(BER)和核苷酸切除修复(NER)过程[3].而ERCC2基因的单核苷酸多态性(SNP)可抑制TFⅡH的活性,导致修复、转录缺陷异常,进而影响ERCC2蛋白表达及DNA损伤修复能力[4].人体内多种SNP决定对应修复酶的活性差异,故对DNA修复能力就表现出个体差异,影响患者对化疗药物敏感性[5].目前ERCC2基因的SNP研究热点主要集中在Asp312Asn、Lys751Gln.LI等[6]分析ERCC2基因多态性对长春瑞滨联合顺铂化疗敏感性,结果显示ERCC2 Lys751Gln基因型的化疗敏感性为Lys751Lys的0.4倍.金珊珊等[7]荟萃国内外文献资料,显示携带ERCC2 Asp312Asn/Lys751Gln基因肺癌患者敏感性较高.而PEREZ-RAMIREZ等[8]发现携带ERCC2 Asp312Asn/Lys751Gln基因与肺癌发病风险相关,且与患者种群、吸烟及危险环境有关.鉴于目前国内外晚期NSCLC患者的ERCC2与铂类药物化疗敏感性相关性的结论,本研究探讨它们之间调控机制,以期构建预测NSCLC铂类化疗药物疗效的基因组学体系,为指导临床晚期NSCLC患者铂类药物个体化治疗提供科学依据.     

XPD基因遗传多态性与肺癌易患性关系的Meta分析

目的系统评价人类着色性干皮病D组(XPD)基因多态性Lys751GIn及Asp312Asn与肺癌的关联。方法检索中英文数据库查找涉及ERCC2/XPD基因多态性Lys751Gln及Asp312Asn与肺癌易患性关系的病例对照研究,提取数据进行Meta分析。选用比值比(OR)和95%置信区间(95%CI)作为合并效应量。结果共32篇纳入研究,累计病例组肺癌人数为19 542例,对照组非肺癌人数为25 078例。312Asn/Asn、751Gln/Gln及751Lys/Gln基因型携带者肺癌易患性明显升高(Asn/Asn比Asp/Asp:OR=1.140(95%CI 1.014~1.281),P=0.028;Gln/Gln比Lys/Lys:OR=1.294(95%CI 1.154~1.451),P<0.001;Lys/Gln比Lys/Lys:OR=1.149(95%CI 1.064~1.241),P<0.001)。结论 ERCC2/XPD基因的单核苷酸多态性Asp312Asn和Lys751Gln作为肺癌发病的危险因素与肺癌易患性相关。     

ERCC基因多态性与骨肉瘤的生存相关性

目的探讨骨肉瘤患者及正常人群 (excision repair cross-complementing, ERCC) 基因ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2Lys751Gln (rs13181) 单核苷酸多态性与骨肉瘤患者对顺铂的反应和生存状况的关系.方法 2011年1月至2015年12月住院收治的骨肉瘤患者161例及正常人群163例, 静脉血2 m L, 用实时逆转录聚合酶链式反应方法 (real time quantitative polymerase chain reaction, RT-PCR) 比较骨肉瘤患者及正常人群ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2 Lys751Gln (rs13181) 基因型及等位基因分布频率.对骨肉瘤患者按不同的临床因素 (年龄、性别、病理类型、肿瘤部位、Enneking外科分期、肿瘤转移及治疗方法) 进行分组, 比较各组基因型频率及等位基因频率, 分析基因多态性与各临床因素的关系.结果 (1) ERCC1Asn118Asn (rs11615) 和ERCC1 Gln504Lys (rs3212986) , ERCC2Asp312Asn (rs1799793) 和ERCC2Lys751Gln (rs13181) 基因型有CC、CT、TT型, 骨肉瘤患者及正常人群基因型频率 (CC、CT、TT) 及等位基因频率 (C、T) 比较差异均无统计学意义 (P=0.590, P=0.544) ; (2) 对于ERCC1 Asn118Asn, 与野生型C/C相比, 突变型T/T与较高的无病生存率显著相关, 校正OR值 (95%CI) 0.37 (0.150.85) .ERCC2 751 A/A基因型表现为骨肉瘤患者生存率增加 (HR=0.45, 95%CI 0.110.88) .没有证明ERCC1 Gln504Lys与ERCC2Asp312Asn的多态性和骨肉瘤预后相关.结论 ERCC基因ERCC1 Asn118Asn118T/T和ERCC2 Lys751Gln A/A多态性与骨肉瘤无病生存率 (SFS) 相关, 可以用作顺铂治疗的骨肉瘤患者临床预后的标志物.而ERCC1 Gln504Lys (rs3212986) 、ERCC2 Asp312Asn与骨肉瘤无病生存率 (SFS) 无相关性.     

ERCC1、XPD和BRCA1基因多态与晚期非小细胞肺癌患者铂类药物化疗效果的相关性

目的探讨核苷酸切除修复系统(NER)的3个重要基因切除修复交叉互补基因1(ERCC1)、着色性干皮病基因D(XPD)和乳腺癌易感基因1(BRCA1)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者铂类药物化疗效果的相关性。方法对124例接受含铂类药物化疗的晚期NSCLC患者进行临床疗效评价。采用TaqMan探针法对ERCC1Asn118Asn(rs11615)、XPD Lys751Gln(rs13181)和BRCA1 Ser1613Gly(rs1799966)进行基因型分析。比较不同基因型与铂类药物化疗效果的关系。结果BRCA1 Ser1613Gly遗传多态与铂类药物化疗临床受益显著相关(P=0.014),携带Gly等位基因的患者临床受益率明显高于野生型患者(P=0.006)。没有发现ERCC1 Asn118Asn和XPD Lys751Gln与临床受益的相关性。这3个基因多态存在一定联合作用,携带变异等位基因(ERCC1 T,XPD Gln和BRCA1 Gly)的数目越多,化疗临床受益率越高(P=0.036)。结论NER系统中的BRCA1 Ser1613Gly遗传多态与晚期NSCLC患者铂类药...     

XPD751基因多态性与晚期非小细胞肺癌化疗敏感性及毒性的相关性探讨

目的探讨人类着色性干皮病D组基因(XPD)与接受含铂方案化疗的晚期非小细胞肺癌(NSCLC)患者的近期疗效及毒副反应的关系。方法经病理确诊的晚期非小细胞肺癌患者62例,接受含铂方案化疗至少2周期后评价疗效,采用TaqMan探针实时荧光定量聚合酶链反应(PCR)法和直接测序法对患者外周血XPD第751位密码子进行多态性分析,分析各基因型与晚期非小细胞肺癌患者近期疗效及毒副反应的的相关性。结果 XPD751基因多态性与NSCLC患者对铂类药物化疗的有效率无关(P>0.05,95%CI=0.2924~4.3594,OR=1.1290)。携带XPD751Lys/Gln基因型患者其消化道反应较携带Lys/Lys基因型患者明显(P<0.05)。而在血液学方面的差异无统计学意义(P>0.05)。结论 XPD751基因多态性与NSCLC患者对铂类药物化疗的敏感性无关,而对预测其毒副反应有一定价值。     

ERCC1、XPD、XPC单核苷酸多态性与局部晚期宫颈癌新辅助化疗敏感性的相关性

目的：探讨DNA修复切除修复交叉互补基因1（ERCC1）、人类着色性干皮病D组基因（XPD）、人类着色性干皮病C组基因（XPC）基因多态性与局部晚期宫颈癌（LACC）铂类为基础的新辅助化疗（NACT）敏感性的关系。方法：经病理学确诊的LACC患者114例,所有病例化疗前抽取静脉血并提取DNA,采用聚合酶链式反应-限制性片段长度多态性分析（PCR-RFLP）技术检测单核苷酸多态性（SNPs）,比较不同基因型与NACT疗效的关系。结果：携带ERCC1 Asn118Asn C/T基因型的化疗敏感率高于C/C基因型,差异有统计学意义（P＜0.05）,携带C/T基因型化疗敏感性比C/C基因型增加4.48倍（OR=4.480;95%CI=1.436～13.976）。携带XPD Lys751Gln A/A基因型化疗敏感性高于A/C基因型,但差异无统计学意义（P＞0.05）。XPC Lys939Gln基因型与化疗敏感性差异无统计学意义（P＞0.05）。结论：ERCC1 Asn118Asn多态性可以预测以铂类为基础的LACC患者化疗疗效。     

XPD 基因多态性与晚期非小细胞肺癌患者铂类化疗获益的Meta分析

目的 采用Meta分析的方法评价XPD基因多态性与晚期非小细胞肺癌患者铂类化疗获益的关系,为临床用药和个体化治疗提供参考.方法 计算机检索PubMed、CNKI、CBM和万方中文数据库,按照制订的纳入与排除标准筛选关于XPD基因多态性与晚期非小细胞肺癌患者铂类化疗获益相关性的病例对照研究或者队列研究,检索时限为数据库建库至2012年9月.获得所需的数据、评价纳入研究方法学质量,使用RevMan5.4.1进行统计分析.结果 共纳入文献15篇,文献质量评价结果显示纳入研究质量良好.Meta分析发现:①野生型Lys/Lys患者与突变型Lys/Gln及Gln/Gln患者的铂类化疗敏感性没有显著性差异,合并优势比为1.26(95％可信区间0.96～1.66).②野生型Lys/Lys患者与突变型Lys/Gln及Gln/Gln患者生存风险比没有显著性差异,合并风险比值为1.06(95％可信区间0.81～1.37).③以人种分组的亚组分析发现XPD Lys751Gln多态性在不同人种中与患者接受铂类药物的远期获益无关.结论 XPD Lys751Gln与晚期非小细胞肺癌患者对铂类药物化疗获益无关.但因为纳入研究的数量有限,仍应开展更多高质量、大样本的随机对照试验加以验证.     

XPD/ERCC2多态性与晚期结直肠癌对奥沙利铂敏感性关系

目的 了解XPD/ERCC2 Lys751Gln (C→A,35931) 多态性与晚期结直肠癌对奥沙利铂为主化疗敏感性的关系.方法 70例Ⅳ期结直肠癌病人化疗前取静脉血并提取DNA,以real-time PCR法对XPD/ERCC2基因进行单核苷酸多态性(SNP)分型.对病人行奥沙利铂化疗,观察客观缓解率,比较不同基因型与化疗效果的关系.结果 XPD/ERCC2 Lys751Gln基因位点在本研究人群中的突变类型及频率为:C/C55.72%,C/A 35.71%,A/A 8.57%.70例结直肠癌病人化疗有效率(CR+PR+SD)为54.29%,C/C与C/A+A/A基因型在化疗有效组(CR+PR+SD)和无效组(PD)之间分布的差异有统计学意义(χ2=7.926,P<0.05).结论 XPD/ERCC2 Lys751Gln基因多态性与晚期结直肠癌病人接受奥沙利铂一线化疗后的临床疗效有关.     

ＸＰＤ７５１基因多态性与晚期ＮＳＣＬＣ对ＧＰ方案化疗的敏感性

目的:研究DNA修复基因XPD751基因多态性与晚期非小细胞肺癌(NSCLC)对吉西他滨/顺铂(GP)方案化疗敏感性的关系.方法:收集经病理学确诊的晚期NSCLC 116例,所有病例化疗前抽静脉血,提取白细胞DNA,用多聚酶链反应--限制性片段长度多态性(PCR-RFLP)分析技术检测XPD751基因型,所有患者均为GP方案化疗.结果:①在肺癌患者中,XPD751 Lys/Lys、Lys/Gln和Gin/Gin基因型分别为94例(81.0%)、20例(17.2%)和2例(1.8%).经化疗后,44例患者有效,总有效率37.9%.②XPD751 Lys/Lys、Lys/Gln和Gin/Gin基因型有效率分别为39.4%、25.0%、100.0%,三者相比差异无统计学意义(X2=4.775,P=0.093).与携带Lys/Gln基因型患者相比,Lys/Lys基因型者对GP方案化疗效果无显著增加,调整性别、每龄、临床分期和细胞学类型后的OR=1.09,95%CI:0.95-1.51.③携带Lys/Lys基因型患者的恶心呕吐反应和脱发程度均高于Lys/Gln和Gin/Gin基因型患者(X2=4.032,P=0.045;X2=4.344,P=0.037).结论:XPD751基因多态性与晚期NSCLC对Gl方案化疗的敏感性无显著相关,但可作为预测GP方案化疗毒副反应的指标.     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.