周围型肝内胆管细胞癌超声造影与增强MRI的对比研究

目的 :比较周围型肝内胆管细胞癌的超声造影与增强磁共振成像(magnetic resonance imaging,MRI)的影像学特点,旨在提高影像学诊断的准确性。方法 :对51例经手术或穿刺病理证实为周围型肝内胆管细胞癌的患者的超声造影和增强MRI表现进行分析和比较。结果 :51例患者共有55个病灶。超声造影显示55个病灶在动脉期均有增强;门脉期有8个呈现为等回声,47个呈现为低回声;延迟期55个病灶均呈现低回声。增强MRI显示55个病灶在动脉期均有增强;门脉期和延迟期延迟强化的病灶有44个,11个病灶呈现为低回声。超声造影显示有42个(76.4%)病灶表现为周边环状增强,13个(23.6%)病灶表现为整体增强,增强过程中有40个(72.7%)病灶表现为"树枝样"向内延伸的增强方式;增强MRI显示40个(72.7%)病灶表现为周边环状强化,15个(27.3%)病灶表现为整体强化。超声造影的特征性表现为动脉期病灶周边环状增强,并呈"树枝样"向内延伸,达峰值时大多数病灶表现为不均匀增强;增强MRI的特征性表现为动脉期周边环状增强,而门脉期和延迟期表现为延迟强化。以"快进快出"、周边环状增强和(或)"树枝样"增强作为周围型肝内胆管细胞癌超声造影的特征,其出现率为70.9%(39/55);而以动脉期周边环状增强和延迟增强作为增强MRI的特征性表现,其出现率为69.1%(38/55)。超声造影与增强MRI的特征性影像出现率差异无统计学意义(P=1.000)。结论 :周围型肝内胆管细胞癌的超声造影和增强MRI均有特征性表现,具有较高的诊断价值。     

Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families

Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa‐specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM‐associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed‐effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow‐up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at RNASEL, hazard ratio (HR), 0.35, 95% CI, 0.18–0.66; p = 0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21–3.02; p = 0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23–0.90; p = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted.     

反义寡核苷酸对骨肉瘤细胞MTA1基因表达及侵袭性影响的研究

目的:合成人肿瘤转移相关基因(MTAl)的反义脱氧寡核苷酸,观察其转染后对人骨肉瘤MG-63细胞系中MTA1表达及骨肉瘤侵袭性的影响.方法:免疫细胞染色观察人工合成正义、反义及无意义MTA1基因片段转染人骨肉瘤细胞MG-63后,人肿瘤转移相关基因的表达;RT-PCR和蛋白质印迹法检测MTA1基因mRNA和蛋白质表达水平的变化;Boyden小室体外侵袭实验检测转染前后细胞侵袭力的变化.结果:反义寡核苷酸处理骨肉瘤细胞后,MTA1 mRNA的表达下降(吸光度之比为25.09±0.21),与正义链组、无意义链组和空白对照组(35.19±0.17、33.20±0.23和37.17±0.18)相比差异有统计学意义,P<0.05.Boy-den小室体外侵袭实验检测显示,反义寡核苷酸处理后骨肉瘤细胞的透膜能力明显下降.结论:MTA1同骨肉瘤的转移能力密切相关,反义寡核苷酸的转染可阻遏骨肉瘤细胞中MTA1的表达,并因此有可能限制骨肉瘤的侵袭和转移.     

Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues

We examined the promoter hypermethylation of tumor-suppressor genes RASSF1A and TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC) tissues (T tissues), and matched tumor-adjacent tissues outside 0.5 cm (P tissues) and outside 1.0 cm (Z tissues) to evaluate the role of promoter hypermethylation of RASSF1A and TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR) for RASSF1A and TSLC1 and quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, and Z tissues (n = 28) as well as chronic nasopharyngitis tissues (n = 8). Hypermethylated RASSF1A was frequently detected in the T (82%) and P tissues (75%), but less frequently in Z tissues (46%). he average quantities of EBV DNA (copies/microg DNA) in matched T, P, and Z tissues were 673,000, 90,000, and 7000. The differences of promoter hypermethylation of RASSF1A and EBV viral load among T, P, and Z tissues were statistically significant, with more frequent methylation and higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A and high EBV load might be important events in NPC pathogenesis, and they may be useful molecular diagnostic markers for this cancer.     

卡培他滨用于52例蒽环类和紫杉类治疗失败的转移性乳腺癌

[目的]观察卡培他滨单药应用于蒽环类和紫杉类治疗失败的转移性乳腺癌的近期疗效和不良反应。[方法]对既往接受过蒽环类和紫杉类药物的转移性乳腺癌患者，口服卡培他滨14d，21d为1个周期，每例患者至少进行2个周期的治疗。观察近期疗效和不良反应。[结果]52例患者中无1例完全缓解，部分缓解率（PR）10例（19．2％），病情稳定（SD）26例（50．0％），病情进展（PD）16例（30．8％），临床获益率（CR＋PR＋SD）69．2％。常见的不良反应是手足综合征31例（59．6％），皮肤色素沉着21例（40．4％），恶心呕吐8例（15．4％），腹泻6例（11．5％），骨髓毒性和肝脏毒性较轻。[结论]单药卡培他滨治疗蒽环类和紫杉类失败的转移性乳腺癌仍有一定的疗效，患者耐受性良好。     

RFLP法检测IGF2和H19基因胚胎印迹缺失

目的探讨肾母细胞瘤的发生、发展与IGF2和H19基因胚胎印迹缺失（LOI）的关系。方法PCR－RFLP法检测6例肾母细胞瘤中IGF2和H19的等位基因表达。结果6例中3例存在IGF2基因的LOI，而H19基因的LOI仅为1例，并且，这两种基因的LOI均可在I期肿瘤内被检测到。结论提示肾母细胞瘤的发生与IGF2基因的LOI有密切关系；这种胚胎印迹紊乱可发生在肿瘤的早期。     

Effectiveness of novel,lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china

This study examined the efficacy of the OncoE6? Cervical Test, careHPV? and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ～10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ～10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV? on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6? test. The OncoE6? test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.     

补体组分1q和胱抑素C对狼疮性肾炎的实验室诊断

目的：探讨血清尿素（Urea）、肌酐（creatinine,Creat）、胱抑素C（cystatin C,CysC）、估算肾小球滤过率（estimated glomeru－lar filtration rate,eGFRCysC与c-aGFR）和补体组分1q（component 1q,C1q）检测在狼疮性肾炎（lupus nephritis,LN）诊断中的应用价值。方法：选取2017年3月至2017年12月在绵阳市中心医院就诊的系统性红斑狼疮（systemic lupus erythematous,SLE）患者共560例,其中未累及肾脏患者339例（SLE组）,LN活动期患者150例（LNA组）,LN非活动期患者71例 （LNI组）,另有360例健康个体作为对照（HC组）。测定血清Urea、Creat、Urea/Creat、CysC和C1q水平,并计算eGFRCysC与c-aGFR,以此评估这些指标对LN的诊断性能。结果：各观察指标在各组之间均有统计学差异（均P=0.000）。Spearman相关性分析显示,C1q与Creat（r=0.046,P=0.160）、Urea（r=0.011,P=0.748）、Urea/Creat（r=-0.011,P=0.743）无统计相关,与CysC（r=-0.183,P=0.000）、eGFRCysC（r=-0.183,P=0.000）和c-aGFR（r=-0.075,P=0.023）成负相关;CysC与Urea（r=0.309,P=0.000）和Creat（r=0.382,P=0.000）成正相关,与c-aGFR（r=-0.430,P=0.000）成负相关,与Urea/Creat（r=0.003,P=0.927）不相关。受试者工作特征曲线（receiver operating characteristic curve,ROC）分析显示,各观察指标单独对LN的诊断性能（area under curve,AUC）以eGFRCysC（0.891）CysC（0.890）为最大,其后依次为：C1q（0.804）、Urea（0.660）、Urea/Creat（0.630）、c-aGFR（0.547）和Creat（0.501）。C1q+CysC+c-aGFR联合检测即可达到最大诊断性能（AUC=0.962）,其敏感度为89.3%,特异度为93.1%,YI＝0.824。增加检测指标,不能改善诊断性能。结论：单独检测时,以CysC或eGFRCysC对LN的诊断性能最高,其次为C1q。联合检测以C1q +CysC+c-aGFR三项为最优,若出于经济考虑,C1q+CysC联合检测也可达到相近于最优的诊断性能。