X线交错互补修复基因1和核苷酸剪切修复基因多态性与前列腺癌发病风险的相关性

目的 探讨DNA损伤修复基因X线交错互补修复基因1(XRCCI)、核苷酸剪切修复基因(XPD)基因多态性与前列腺癌发病风险的关系. 方法 以358例前列腺癌患者和312例健康对照者为研究对象,采用聚合酶链反应一限制性片段长度多态技术检测XRCC1 C26304T、G28152A和XPD A35931C位点基因型,以非条件logistic回归分析计算比值比(OR)及95%可信区间(CI),评估不同基因型与前列腺癌风险之间的相关性. 结果 前列腺癌组XRCC1 28152位点AA基因型者47例(13.1%),对照组24例(7.1%),携带此基因型者患前列腺癌风险显著增加(OR 1.924,95%CI=1.126～3.288,P=0.017).2组间XRCC1 C26304T和XPD A35931C位点基因型分布差异无统计学意义.3个基因位点联合分析结果 显示,个体携带XRCCI 28152AA型及XPD 35931AC+CC型者发生前列腺癌风险显著增加(OR=3.087,95%CI 1.081～8.813;OR=3.376,95%CI 1.067～10.683,OR 3.216,95%CI=1.439～7.188,P=0.004).以患者年龄、PSA值、Gleason评分以及临床分期分层分析结果 显示,携带XRCC1 28152AA及XPD 35931AC+CC基因型者发病年龄明显低于携带野生基因型者(P<0.05). 结论 中国汉族人群XRCCl和XPD基因多态与前列腺癌发病有关,尤其是较年轻者.     

干扰素-γ基因多态性与内蒙古汉族IgA肾病临床特征和预后的相关性研究

目的探讨IgA肾病患者干扰素-γ基因＋874位点单核苷酸多态性与临床特征和预后的关系。方法采用序列特异性引物聚合酶链反应技术检测IgA肾病组和对照组干扰素-γ基因＋874位点单核苷酸多态性,并进行随访。比较两组的基因型分布,分析基因型与临床特征和预后的关系。结果（1）IgA肾病组AA基因型及A等位基因频率显著高于对照组。（2）IgA肾病组中不同基因型发病时的血压、24h尿蛋白定量有显著性差异。（3）TT型患者肾功能减退显著快于AA型。结论（1）干扰素-γ基因＋874位点单核苷酸多态性,AA基因型可能是IgA肾病的易感基因。（2）该位点单核苷酸多态性可能影响IgA肾病患者的24h尿蛋白定量和血压水平。（3）目前还不能认为该位点单核苷酸多态性是影响IgA。肾病患者进展和预后的独立危险因素。     

乳腺癌MDR1基因多态性与其表达及化疗血液毒性的关系

目的：探讨乳腺癌多药耐药基因MDR1基因多态性与其表达及与化疗血液毒性之间的关系。 方法：提取92例乳腺癌患者外周静脉血DNA,利用限制性片段长度多态性（PCR-RFLP）技术检测MDR1外显子（exon）26（C3435T）位点的多态性,并用RT-qPCR方法检测该92例患者癌组织及其中26例配对癌旁组织MDR1 mRNA的表达。根据患者的临床资料,分析C3435T位点多态性与化疗血液学毒性的关系。 结果：92例乳腺癌中, C3435T位点CC,CT,TT 3种基因型分别占21.7%（20/92）,62.0%（57/92）和16.3%（15/92）,所有乳癌组织中均有不同程度的MDR1 mRNA表达,但各基因型间MDR1 mRNA表达水平差异无统计学意义（F=0.173,P=0.841）;癌组织MDR1 mRNA表达水平明显高于其对应的癌旁组织[（3.83±5.27） vs. (1.81±4.42),t=2.522,P=0.018]。C3435T各基因型患者中性粒细胞减少反应差异有统计学意义,CC型中性粒细胞减少（III~IV度）的发生频率（5.0%）明显低于CT和TT型（26.3%和46.7%;χ2=8.075,P=0.018,95%CI=0.017~0.022）,而白细胞减少、贫血、血小板减少等方面各基因型间无统计学差异（均P>0.05）。 结论：乳腺癌患者MDR1基因C3435T位点多态性与MDR1基因表达水平无明显关系,CT和TT型患者化疗后发生中性粒细胞减少症的风险较大。     

结肠癌易感性与细胞毒性T淋巴细胞相关抗原4的关系

目的:探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因外显子49位点及启动子1661位点单核苷酸多态性(SNP)及临床病理参数与青岛地区人群结肠癌的发病的关系。方法:采用聚合酶链反应-限制性片段长度多态分析(PCR-RFLP)检测来自青岛地区人群结肠癌患者及对照组中位CT-LA-4+49A/G,-1661A/G基因多态性的分布,并研究多态性与结肠癌临床病理参数的关系。结果:1)CT-LA-4+49A/G:与AA基因型携带者相比,AG及GG基因型人群罹患结肠癌的风险都显著增加(P=0.00),携带GG基因型罹患结肠癌的风险明显增加5.12倍,且男性、吸烟结肠癌患者携带AG及GG基因型明显增加;2)CTLA-4-1661A/G:以AA基因型为对照,AG+GG基因型携带者的患病风险显著增高,为对照组的2.50倍(P=0.001),多态性与结肠癌患者的性别、年龄、肿瘤分化程度及TNM分期无相关性。结论:CTAL-4+49A/G及-1661A/G基因多态性与结肠癌的遗传易感性相关,性别、吸烟与否也是影响因素。     

巨噬细胞清道夫受体单核苷酸多态性与前列腺癌易感及患者预后的相关性分析

目的探讨分析巨噬细胞清道夫受体(MSR1)单核苷酸多态性与前列腺癌易感及患者治疗预后的相关性。方法选择2017年3月至2019年5月在本院治疗的前列腺癌患者103例设为前列腺癌组,再选取同期在本院健康体检的男性受试者97例设为对照组。检测两组受试者MSRI基因r918位点及rs1904577位点的基因多态性分布情况,并分析前列腺癌化疗相关因素及MSRI基因rs918.rs1904577位点与前列腺癌患者生存预后的关系。结果两组受试者MISRI基因rs918位点基因型GG、AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.364.7.941;两组受试者MSRI基因rs1904577位点基因型GG,AG.AA比较,差异具有统计学意义(P<0.05),携带AG、AA基因型者相对于携带GG基因型者罹患前列腺癌的OR值分别为1.819.8.228。对可能影响患者化疗疗效的各因素进行单因素及多因素logstie回归分析,其中T分期.CGleason评分以及MSRI基因rs1904577位点基因型进人回归模型(P<0.05),是影响患者化疗疗效的重要因素。MSR1基因rs918位点CG以及AG+AA基因型前列腺癌患者生存情况比较,差异无统计学意义(P>0.05)。MSRI基因rs1904577位点GG基因型前列腺癌患者生存情况显著优于AG+AA基因型患者(P<0.05)。结论MSR1基因ns918位点和rs1904577位点单核苷酸多态性与前列腺癌易感性相关,其中rs1904577位点单核苷酸多态性与患者化疗的疗效及生存预后有关。     

PRM1基因SNP位点-190C-＞A多态性对精子畸形率的影响

目的:探讨鱼精蛋白基因1(protamine 1,PRM1)单核苷酸多态性(SNP)与畸形精子症的关系。方法:收集畸形精子症不育患者(病例组,n=157)和精子形态正常男性(对照组,n=37)精液样本,进行形态学分析并提取基因组DNA,应用Sequenom MassARRAY SNP分型技术对PRM1基因-190C->A SNP位点(rs2301365)进行基因分型,比较病例组与对照组基因型的分布差异及病例组不同基因型间精子形态参数的差异。结果:病例组中,基因型CC、CA、AA的分布频率及个体数分别为38.9%(61)、44.6%(70)、16.6%(26),对照组为45.9%(17)、51.4%(19)、2.7%(1),病例组AA基因型分布频率显著高于对照组(P<0.05)。病例组等位基因C、A的分布频率分别为57.6%、42.4%,对照组为71.6%、28.4%,病例组等位基因A的频率与对照组差异无显著性(P>0.05)。病例组基因型CC与CA、AA、CA+AA在精子形态学参数的比较,差异无统计学意义(P>0.05)。结论:PRM1基因SNP位点-190C->A可能与中国汉族畸形精子症男性不育存在相关,该位点可能导致精子形态异常,但所致形态异常并无部位上的特异性。     

胰岛素降解酶基因单核苷酸多态性与前列腺癌的关系研究

目的研究胰岛素降解酶(IDE)基因单核苷酸多态性与前列腺癌之间的关系。方法运用TaqMan探针SNP分析法测定192例胰腺癌患者和258例正常对照IDE基因rs4646953和rs2251101两个位点基因型,并分析IDE基因多态性与前列腺癌的关系。结果病例组IDE基因rs4646953位点TT、CT以及CC3种基因型等位基因频率分别为85.4%、14.1%和0.5%;对照组3种基因型等位基因频率分别为88.4%、10.1%和1.6%。病例组rs2251101位点TT、CT以及CC3种基因型频率分别为81.8%、16.7%和1.6%;对照组3种基因型等位基因频率分别为73.6%、23.3%和3.1%。病例组IDE基因rs4646953位点的基因型分布与正常对照组比较未见统计学差异(P=0.348),rs2251101位点病例组CT和CC基因型低于正常对照组(P=0.039)。结论 IDE基因rs2251101位点变异与前列腺癌相关。     

酪氨酸蛋白激酶-2 rs2230724基因多态性与结直肠癌风险相关性研究

目的探讨酪氨酸蛋白激酶-2（JAK2）基因rs2230724多态性与结直肠癌风险的相关性。 方法采用多聚酶链式反应-限制性内切酶片段长度多态性（PCR-RFLP）方法分析110例结直肠癌患者（病例组）和150例非肿瘤患者（对照组）JAK2 rs2230724基因的多态性,并对该多态性与结直肠癌风险的相关性进行评估。采用SPSS 26.0软件进行分析。采用拟合优度χ²检验进行Hardy-Weinberg平衡的检测。两组间的一般资料、基因型和等位基因的频率分布的比较采用Student’s t检验和Pearson χ²检验。采用Logistic线性回归（需要进行校正）分析JAK2 rs2230724基因多态性和结直肠癌风险的相关性,相对危险度用优势比（OR）和95%可信区间（CI）估计。以P<0.05为有统计学意义。 结果病例组A等位基因频率明显高于对照组,A等位基因突变增加50%结直肠癌发病风险（P=0.025,OR=1.50,95%CI=1.05-2.14）。与野生基因型（GG）相比,变异基因型（AG+AA）增加79%结直肠癌发病风险（P=0.043,校正OR=1.79,95%CI=1.02-3.15）。其中,突变纯合子（AA）基因型的携带者结直肠癌的风险增加129%（P=0.034,OR=2.29,95%CI=1.06-4.93）,差异有统计学意义。但是,在添加了校正因素后,差异无统计学意义（P=0.052,校正OR=2.29,95%CI=0.99-5.26）。而且,在分层分析中,在高年龄组（年龄>56）、非吸烟受试者和城市居住者中,该多态性增加结直肠癌风险（P<0.05）。 结论在江苏汉族人群中JAK2基因rs2230724多态性与增加结直肠癌风险相关。     

汉族人群白介素17受体C基因单核苷酸多态性与青少年特发性脊柱侧凸的相关性

【摘要】　目的：探讨白介素17受体C（IL-17RC）基因单核苷酸多态性与中国汉族人群青少年特发性脊柱侧凸（adolescent idiopathic scoliosis,AIS）易感性之间的相关性。方法：收集529例AIS女性患者及512例正常同龄女性青少年的静脉血标本,采用聚合酶链反应－限制性片段长度多态性（PCR-RFLP）方法鉴定和统计两组人群IL-17RC基因rs708567和rs279545多态性位点的基因型及等位基因分布频率;比较两组间不同多态性位点各基因型及等位基因分布频率的差异。结果：研究Power值（81%）大于80%,AIS患者组及正常对照组各多态性位点的基因型分布均符合Hardy-Weinberg遗传平衡定律。AIS组rs708567多态性位点GG基因型和G等位基因的分布频率显著高于对照组GG基因型（90.17% vs. 85.55%,P=0.023）和G等位基因（95.1% vs. 92.8%,P=0.028）的分布频率;携带GG基因型青少年中AIS的发病率约为携带AG基因型青少年的1.5倍（OR值=1.55;95% CI:1.45~3.11）。rs279545多态性位点各基因型及等位基因的分布频率在两组间均无统计学差异。结论：中国汉族人群中IL-17RC基因单核苷酸多态性与AIS的发生相关。     

pre-miR-146a基因rs2910164位点单核苷酸多态性与胆管癌的关系

目的：探讨pre-miR-146a基因表达及其rs2910164位点多态性与胆管癌的关系。 方法：分别用基因直接测序与定量PCR方法检测70例胆管癌患者的胆管癌组织（胆管癌组）及 39例胆管非肿瘤性疾病患者的胆管组织（对照组）中pre-miR-146a基因rs2910164位点单核苷酸多态性与pre-miR-146a表达,分析不同基因型与pre-miR-146a表达量、胆管癌临床病理及其预后的关系。 结果：胆管癌组的pre-miR-146a基因型分布与对照组有明显差异,前者表现为GG和GC基因型比例明显高于CC基因型,且G等位基因频率明显高于C等位基因（均P<0.05）;对照组GG和GC基因型人群的pre-miR-146a表达量较CC基因型低,但差异无统计学意义（P>0.05）,胆管癌组织pre-miR-146a表达量明显低于对照组胆管组织（P<0.05）;Logistic多元回归分析显示GG和GC基因型可能是胆管癌的危险因素（P=0.052）,分层分析显示GG和GC基因型与胆管癌患者的临床分期和淋巴结转移有关（均P<0.05）;生存分析显示GG和GC基因型胆管癌患者的生存率低于CC基因型胆管癌患者,但差异无统计学意义（P=0.178）。 结论：pre-miR-146a基因rs2910164位点G等位基因频率升高可能是导致pre-miR-146a基因表达降低以及胆管癌发生发展的危险因素。

     

Genetic polymorphism of VEGF: Impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the peritoneal angiogenesis and hyperpermeability in patients on peritoneal dialysis. We hypothesis that VEGF genetic polymorphism may affect the longitudinal change of peritoneal transport and clinical outcome of peritoneal dialysis patients. METHODS: We studied 135 consecutive new peritoneal dialysis patients. VEGF genetic polymorphism at -1154 and -2578 positions were determined by polymerase chain reaction (PCR) methodologies. Standard peritoneal test and dialysis adequacy and transport test (DATT) were performed at the initiation of peritoneal dialysis. After 12 months, DATT was repeated in 83 patients. In 35 patients, VEGF production in vivo was determined by its levels in serum and peritoneal dialysis effluent, and mRNA expression in peritoneal dialysis effluent. Patients were followed for 19.4 +/- 8.5 months for survival study. RESULTS: There was no relation between VEGF genotype and baseline peritoneal transport group. The changes in 24-hour dialysate-to-plasma (D/P) creatinine after 12 months were 0.028 +/- 0.159, -0.013 +/- 0.137, and 0.141 +/- 0.231 for CC, CA, and AA genotype at -2578 position, respectively [one-way analysis of variance (ANOVA), P= 0.028]. The AA genotype had significantly higher increase in 24-hour D/P creatinine than the other genotypes. Similar results were found with the genotype at -1154 position, which had marked linkage disequilibrium with the genotype at -2578 position. Actuarial patient survival was 90.3% and 74.9% at 24 months for CC and CA/AA genotypes at -2578 position, respectively (P= 0.036). After correcting for confounding covariates, the adjusted hazard ratio of death was 3.04 (95% CI, 1.10 to 8.36) for the CA/AA group as compared to CC group. Although baseline serum VEGF level was higher in patients with CC genotype than those with CA/AA genotype at -2578 position (541.5 +/- 322.8 pg/mL vs. 298.8 +/- 209.4 pg/mL, P= 0.012), VEGF mRNA expression in peritoneal dialysis effluent was significantly lower in patients with CC genotype (1.82 +/- 2.77 vs 4.48 +/- 3.28, P= 0.021). VEGF protein level in peritoneal dialysis effluent was also marginally lower in patients with CC genotype, although the difference was not significant. Genotype at -1154 position was not associated with VEGF production in vivo or patient survival. CONCLUSION: We conclude that in peritoneal dialysis patients, the AA genotype of VEGF promoter at -2578 position was associated with progressive increase in peritoneal transport. The CA/AA genotype at -2578 position was also associated with an excess mortality. Our finding also suggests that systemic and local peritoneal VEGF production may be differentially regulated.     

卵巢癌中胰岛素样生长因子-1及其受体表达与临床病理特征的相关性

目的研究卵巢癌中胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)及其受体IGF-1R表达与临床病理特征、手术预后的相关性。方法采用免疫组化检测卵巢癌、卵巢交界性肿瘤、卵巢良性肿瘤中IGF-1、IGF-1R的阳性表达率,分析IGF-1、IGF-1R与临床病理特征、手术预后的相关性。结果卵巢癌中IGF-1、IGF-1R的阳性表达量率分别为65.63%、70.31%,明显高于卵巢交界性肿瘤中IGF-1、IGF-1R的阳性表达量率22.22%、16.67%及卵巢良性肿瘤中IGF-1、IGF-1R的阳性表达量率5.00%、10.00%(χ^2/P=27.548/0.000、31.335/0.000),IGF-1、IGF-1R的mRNA表达量及蛋白表达量也明显高于卵巢交界性肿瘤及卵巢良性肿瘤(F/P=31.922/0.000、26.865/0.000、34.567/0.000、27.667/0.000);国际妇产科协会(federation international of gynecology and obstetrics,FIGO)III^IV期、组织分化程度G2~G3、CA125≥35 U/ml、Ki67阳性的卵巢癌中IGF-1、IGF-1R的阳性表达率明显高于FIGO I^II期、组织分化程度G1、CA125<35 U/ml、Ki67阴性的卵巢癌(IGF-1的χ^2/P=8.505/0.004、4.980/0.026、7.481/0.006、10.907/0.001;IGF-1R的χ^2/P=9.785/0.002、4.950/0.026、7.211/0.007、6.471/0.011);卵巢癌IGF-1阳性患者的总生存时间较IGF-1阴性患者缩短。结论IGF-1、IGF-1R在卵巢癌中高表达,且与病理特征及手术预后的恶化相关。     

Genetic polymorphism of vascular endothelial growth factor: impact on progression of IgA nephropathy

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. METHODS: The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. RESULTS: In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 +/- 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. CONCLUSION: Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.     

术前血清丙氨酸氨基转移酶与天冬氨酸氨基转移酶比值对胃癌患者预后的影响

目的研究胃癌患者肝功能指标丙氨酸氨基转移酶和天冬氨酸氨基转移酶比值(LSR)与临床病理因素的关系及其对预测患者生存期的临床意义。方法采用回顾性病例对照研究的方法。回顾性分析2007年1月至2010年12月期间在哈尔滨医科大学附属肿瘤医院胃肠外科行胃癌手术治疗、且术后病理及随访资料完整的891例进展期胃癌患者的临床资料。病例纳入标准:(1)术前明确诊断为胃癌,排除残胃癌及胃其他肿瘤;(2)术前未行新辅助治疗;(3)不合并其他严重疾病如急性冠心病、肝硬化、慢性肾衰等;(4)行胃癌根治术,排除姑息治疗或开腹探查病例;(5)术后病理资料完全,随访信息完整;(6)死亡原因与胃癌相关。取患者入院时采血结果,利用受试者工作特征曲线(ROC)分别对LSR、血红蛋白、淋巴结转移率、肿瘤最大直径、碱性磷酸酶、谷氨酰转肽酶、总胆红素和乳酸脱氢酶取最佳截点。根据LSR截点分组,分析LSR与临床病理因素之间的关系,对不同LSR组别进行总体生存率的比较。并将相关临床因素和LSR纳入单因素和多因素Cox生存分析。结果LSR的ROC曲线最佳截点为1.43,LSR<1.43组682例,LSR≥1.43例209例。血红蛋白、淋巴结转移率、肿瘤长径、碱性磷酸酶、谷氨酰转肽酶、总胆红素和乳酸脱氢酶的ROC曲线最佳截点分别为130.2 g/L、18.0%、4.75 cm、68.1 U/L、16.55 U/L、5.58μmol/L和135.8 U/L。LSR<1.43组与LSR≥1.43组患者比较,年龄(χ^2=4.412,P=0.036)、肿瘤浸润深度(χ^2=64.306,P<0.001)、组织学类型(χ^2=8.026,P=0.005)、碱性磷酸酶(χ^2=8.217,P=0.004)、谷氨酰转肽酶(χ^2=33.207,P<0.001)、总胆红素(χ^2=14.012,P<0.001)和乳酸脱氢酶(χ^2=63.630,P<0.001)的差异均有统计学意义。LSR<1.43组和LSR≥1.43组1、3、5年生存率分别为70.8%、31.3%、25.0%和64.9%、24.4%、11.3%,两组比较差异有统计学意义(χ^2=10.140,P=0.001)。单因素分析显示,年龄、血红蛋白水平、肿瘤TNM分期、肿瘤浸润深度、淋巴结转移率、淋巴结转移、组织学类型、肿瘤长径、谷氨酰转肽酶、总胆红素和LSR是影响胃癌患者预后的相关因素(均P<0.05);多因素分析显示,肿瘤TNM分期(HR=1.605,95%CI:1.332~1.936,P<0.001)、肿瘤浸润深度(HR=1.299,95%CI:1.168~1.445,P<0.001)、淋巴结转移率(HR=2.400,95%CI:1.873~3.076,P<0.001)、淋巴结转移(HR=1.263,95%CI:1.106~1.478,P=0.007)、肿瘤长径(HR=1.375,95%CI:1.134~1.669,P=0.001)和LSR(HR=1.427,95%CI:1.190~1.711,P<0.001)是影响胃癌患者预后的独立危险因素。结论LSR是胃癌患者预后的独立危险因素,且检测简单易行,是胃癌预后的潜在标志物。因此,在术前综合治理阶段,应尽可能恢复和提高肝功能状态有助于改善胃癌患者预后,延长患者生存时间。     

Genetic Polymorphism of Vascular Endothelial Growth Factor: Impact on Progression of IgA Nephropathy

Background. Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. Methods. The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at ?2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. Results. In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 ± 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. Conclusion. Our preliminary results raise the concern that the CC genotype of the VEGF promoter at ?2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.     

Associations of single nucleotide polymorphisms in the vascular endothelial growth factor gene with the characteristics and prognosis of renal cell carcinomas

OBJECTIVES: Vascular endothelial growth factor (VEGF) is considered to play critical roles in tumor development and progression, especially in renal cell carcinoma (RCC) via von Hippel-Lindau gene inactivation. Although VEGF -2578CC, -1154GG, and -634CC genotypes are reportedly correlated with higher levels of VEGF production, no previous studies have reported on the associations of these polymorphisms with RCCs. This study was aimed to clarify the effects of these functional polymorphisms on RCC progression and prognosis. METHODS: We investigated the associations of three polymorphisms (-2578C/A, -1154G/A, and -634C/G) in the VEGF gene with the clinicopathologic parameters and survival of 213 patients with RCC. The -2578C/A and -634C/G polymorphisms were genotyped using a polymerase chain reaction (PCR) restriction fragment length polymorphism technique and the -1154G/A polymorphism was genotyped by an amplification refractory mutation system PCR technique. RESULTS: The GA+AA genotypes of -1154G/A were weakly associated with smaller tumors, lower tumor stage, and lower stage grouping (p=0.028, p=0.012, and p=0.028, respectively). The CA and CA+AA genotypes of -2578C/A were weakly associated with less frequent lymph node metastasis (p=0.029 and p=0.034, respectively) and were significantly associated with favorable cancer-specific survival (p=0.047 and p=0.048, respectively). There was no apparent clinical effect of the -634C/G polymorphism. CONCLUSIONS: These results suggest that some VEGF genotypes may have effects on RCC progression or prognosis, possibly through altered VEGF expression. This finding might help in clarifying the mechanisms of RCC development and progression.     

Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy

AIMS: Clara cell secretory protein (CC16) is a protein with anti-inflammatory and immunomodulatory properties. Moreover, both CC16 gene knockout and antisense-transgenic mouse models developed glomerulonephritis resembling IgA nephropathy (IgAN). In the present study, we evaluated the influence of the G38A polymorphism in the CC16 gene exon 1 on the development and progression of IgAN. METHODS: Korean patients with biopsy-proven IgAN (n=267) with a minimal follow-up of 4 years (mean +/- SD 103.8 +/- 52.6 months) were recruited. Healthy normal subjects (n=315) were included as controls. The G38A polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: GG, GA and AA genotype frequencies were 36.3, 50.2 and 13.5% in IgAN patients, respectively, and 34.3, 50.2 and 15.5% in controls (chi2 = 0.596, p = 0.742). The G allele frequency was 0.614 in IgAN patients and 0.594 in controls (chi2 = 0.429, p = 0.512). Moreover, the GG genotype frequencies were 40.4% in patients showing stable disease course and 26.6% in those with progressive disease (chi2 = 4.029, p = 0.045). Patients with the GG genotype showed a better outcome by Kaplan-Meier analysis in terms of renal survival (p = 0.043). The CC16 polymorphism remained an independent risk factor for progression after multivariate analysis (Cox regression model, HR for CC16 AA genotype: 2.34, 95% CI 1.19-4.64, p = 0.014). CONCLUSION: Our results suggest that CC 16 gene G38A polymorphism is not associated with the development of IgAN, but that it is an important marker of progression in IgAN.     

横结肠癌网膜弓淋巴结转移的预后价值

目的探讨横结肠癌网膜弓淋巴结转移的预后价值。方法采用倾向评分匹配及回顾性队列研究方法。收集2010年11月至2017年11月福建医科大学附属协和医院收治的371例横结肠癌病人的临床病理资料;男202例,女169例;中位年龄为58岁,年龄范围为21~92岁。病人均由同一组外科医师施行全结肠系膜切除+网膜弓淋巴结清扫术。371例横结肠癌病人中,15例网膜弓淋巴结转移阳性,356例网膜弓淋巴结转移阴性。观察指标:(1)倾向评分匹配情况及匹配后网膜弓淋巴结转移阴性和阳性横结肠癌病人一般资料比较。(2)网膜弓淋巴结转移阴性和阳性横结肠癌病人随访及生存情况。(3)横结肠癌病人预后影响因素分析。采用电话或门诊方式进行随访,了解病人肿瘤转移及生存情况。术后2年内每3个月随访1次,术后2~5年每6个月随访1次,术后5年每年随访1次。随访时间截至2020年1月。倾向评分匹配按1∶4最近邻匹配法匹配。偏态分布的计量资料以M(范围)表示,组间比较采用秩和检验。计数资料以绝对数表示,组间比较采用χ²检验或Fisher确切概率法。采用Kaplan-Meier法计算生存率并绘制生存曲线,采用Log-rank检验进行生存分析。单因素分析和多因素分析采用COX比例风险回归模型,单因素P<0.10的变量纳入多因素分析。结果(1)倾向评分匹配情况及匹配后网膜弓淋巴结转移阴性和阳性横结肠癌病人一般资料比较:371例横结肠癌病人中,55例(网膜弓淋巴结转移阴性44例、网膜弓淋巴结转移阳性11例)配对成功。倾向评分匹配前网膜弓淋巴结转移阴性病人年龄,M分期(0期、1期),术前癌胚抗原分别为60岁(24~92岁),328例、22例,4.1μg/L(0.2~343.7μg/L),网膜弓淋巴结转移阳性病人上述指标分别为67岁(21~79岁),11例、4例,5.0μg/L(0.7~952.4μg/L),两者上述指标比较,差异均有统计学意义(Z=-1.440,χ²=9.031,Z=-2.086,P<0.05)。经倾向评分匹配后网膜弓淋巴结转移阴性病人上述指标分别为58岁(45~67岁),40例、4例,4.0μg/L(2.0~10.0μg/L),网膜弓淋巴结转移阳性病人上述指标分别为67岁(59~71岁),9例、2例,5.0μg/L(8.0~19.0μg/L),两者上述指标比较,差异均无统计学意义(Z=-1.580,χ²=0.105,Z=-0.821,P>0.05)。(2)网膜弓淋巴结转移阴性和阳性横结肠癌病人随访及生存情况:网膜弓淋巴结转移阴性和阳性横结肠癌病人均获得随访,随访时间分别为12~92个月和1~70个月,中位随访时间分别为53个月和30个月。网膜弓淋巴结转移阴性和阳性病人术后发生肝转移分别为3例和2例,两者比较,差异无统计学意义(χ²=0.344,P>0.05);术后发生异时性肺转移分别为1例和3例,两者比较,差异有统计学意义(χ²=4.870,P<0.05);5年疾病无进展生存率分别为82.3%和33.9%,两者比较,差异有统计学意义(χ²=13.366,P<0.05)。(3)横结肠癌病人预后影响因素分析:单因素分析结果为pT分期、pN分期、M分期、网膜弓淋巴结转移是影响横结肠癌病人预后的相关因素(风险比=1.599,5.107,4.511,6.273,95%可信区间为0.467~5.471,1.867~13.971,1.385~14.694,2.052~19.176,P<0.05)。多因素分析结果显示:pN分期、M分期、网膜弓淋巴结转移是横结肠癌病人预后的独立影响因素(风险比=6.399,6.163,4.024,95%可信区间为2.028~20.189,1.666~22.800,1.177~13.752,P<0.05)。结论横结肠癌网膜弓淋巴结转移阳性病人术后发生异时性肺转移率高,预后较差。网膜弓淋巴结转移是横结肠癌病人预后的独立影响因素。     

腹腔镜直肠癌前切除术肠系膜下动脉不同结扎平面对患者预后的影响

目的分析腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面对患者预后的影响。 方法选取2007年6月至2014年6月间青岛市市立医院收治的行腹腔镜直肠癌前切除术136例患者为研究对象，根据肠系膜下动脉不同的结扎平面，分为保留左结肠动脉的低位结扎组（LL组）76例和不保留左结肠动脉的高位结扎组（HL组）60例。比较两组患者围手术期指标，随访并评价两组的预后。 结果两组手术时间、术中出血量、术后肛门排气时间、淋巴结清扫总数和第253组淋巴结清扫个数差异无统计学意义（t=6.109、4.339、8.386、0.233、0.198，P=0.318、0.416、0.512、0.821、0.669）；LL组术后吻合口瘘的发生率明显低于HL组（χ²=5.186，P=0.029）。HL组术后3、5年总体生存率分别为80.00%和73.33%，LL组分别为77.63%和72.37%，两组比较差异无统计学意义（χ²=1.536、2.156，P=0.863、0.698）。 结论腹腔镜直肠癌前切除术中肠系膜下动脉不同结扎平面可获得相近的淋巴结清扫效果，保留左结肠动脉的低位结扎平面术后吻合口瘘的发生率更低，其他围手术期指标没有差异，联合第三站中央淋巴结清扫值得应用推广。