极速实时荧光聚合酶链反应与常规方法对新型布尼亚病毒检测的评价

目的探讨极速实时荧光聚合酶链反应(polymerase chain reaction,PCR)、实时荧光PCR、酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)和胶体金免疫层析法(gold immunochromatography assay,GICA)4种方法检测新型布尼亚病毒的特异度和灵敏度,为发热伴血小板减少综合征的早期诊断提供依据。方法采集2017年6月1日至9月30日山东大学附属济南市传染病医院86例临床诊断为发热伴血小板减少综合征患者的血清样本,分别应用极速实时荧光PCR、实时荧光PCR、ELISA和GICA 4种方法进行检测。统计学分析采用χ^2检验。结果86份患者血清标本中,极速实时荧光PCR、实时荧光PCR、IgM-ELISA、IgG-ELISA、IgM-GICA、IgG-GICA的新型布尼亚病毒阳性分别为82份(95.34%)、79份(91.86%)、41份(47.67%)、8份(9.3%)、19份(22.09%)和3份(3.49%)。极速实时荧光PCR特异度为100%,灵敏度达到1×103拷贝/mL,3次重复扩增试验显示其Ct值变异系数均<2%。在发热伴血小板减少综合征进展的1期、2期、3期病程中,极速实时荧光PCR的阳性检出率为41份(97.62%)、34份(94.44%)、7份(87.50%),实时荧光PCR的阳性检出率为39份(92.86%)、33份(91.67%)、7份(87.50%),在1期和2期两个病程,极速实时荧光PCR阳性检出率略高;IgM-ELISA阳性检出率从1期(28.57%)到3期(87.50%)显著增高,2期、3期与1期相比,差异均有统计学意义(χ^2=8.347、7.561,均P<0.01);IgM-GICA的阳性检出率从1期(14.29%)到2期(33.33%)也有增高,差异有统计学意义(χ^2=3.962,P<0.05),但与其他方法相比,其检出率偏低。1期,实时荧光PCR阳性检出率显著高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=33.740、55.080、49.010、64.340,均P<0.01)。2期,实时荧光PCR的阳性检出率高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=7.700、46.720、23.700、50.630,均P<0.01)。3期,极速实时荧光PCR、实时荧光PCR和IgM-ELISA表现出同样高的阳性检出率,远高于IgG-ELISA和GICA(IgM和IgG)。实时荧光PCR阳性检出率和IgG-ELISA、IgM-GICA、IgG-GICA之间差异均有统计学意义(均χ^2=6.250,P<0.05)。结论极速实时荧光PCR在新型布尼亚病毒的早期检测中有更高的灵敏度和特异度,且重复性好、稳定度高,与传统实时荧光PCR相比大大缩短了扩增时间,对发热伴血小板减少综合征的早期快速诊断具有重要价值。     

The effect of ICSI in infertility couples with non-male factor: a systematic review and meta-analysis

PurposeWe performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes.MethodsThe literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate.ResultsFour RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83–1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66–1.64), implantation rate (RR = 1.12, 95% CI: 0.67–1.86), and live birth rate (RR = 1.17, 95% CI: 0.43–3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03–1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01–1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77–0.94), implantation rate (RR = 0.78, 95% CI: 0.65–0.95), and live birth rate (RR = 0.86, 95% CI: 0.79–0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93–1.04).ConclusionICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01970-9) contains supplementary material, which is available to authorized users.     

高度近视合并白内障患者术后人工晶状体位移对屈光度的影响

目的　探讨高度近视合并白内障患者行超声乳化摘出联合人工晶状体植入术后人工晶状体位移对屈光度的影响。方法　收集2017年6月至2018年1月在我院行白内障超声乳化摘出联合人工晶状体植入术的高度近视合并白内障患者21例27眼，记录术后1 d、1周、1个月的裸眼视力、最佳矫正视力及屈光度，使用IOL Master生物测量仪测量眼轴长度、晶状体厚度及角膜曲率，使用Tomey SS1000眼前节光学相干断层扫描（anterior segment optical coherence tomography，AS-OCT）测量有效晶状体位置，观察术后人工晶状体在囊袋内的位移，并分析其对术后屈光度的影响。结果　高度近视合并白内障患者术后1 d、1周、1个月屈光度分别为（-1.59±1.64）D、（-1.80±1.66）D、（-1.47±1.39）D，术后各时间点屈光度比较差异无统计学意义（F=0.295，P=0.746）。运用Spearman秩相关分析发现，术后屈光度变化与人工晶状体位移呈正相关（r=0.355，P=0.008），且术后1个月绝对屈光度误差与眼轴长度呈正相关（r=0.514，P=0.006），运用Pearson相关分析发现术后1个月绝对屈光度误差与术前角膜曲率及晶状体厚度均无相关性（均为P＞0.05）。结论　高度近视合并白内障患者术后人工晶状体位移是术后屈光度变化的主要影响因素。高度近视合并白内障手术患者眼轴越长术后绝对屈光误差越大。     

术前中性粒细胞与淋巴细胞比值在临床评估急性胆管炎伴胆总管结石患者病情中的价值

目的探讨术前中性粒细胞与淋巴细胞比值(NLR)对急性胆管炎伴胆总管结石患者手术预后评估的临床意义。 方法选取江苏大学附属武进人民医院普外科2016年1月至2019年6月收治的急性胆管炎伴胆总管结石行手术治疗的患者60例为研究对象进行回顾性研究，其中男性27例，女性33例；年龄46～88岁，平均(67.93±11.46)岁。术前NLR <5.435患者作为低NLR组(31例)，NLR≥5.435患者作为高NLR组(29例)。比较两组患者术前白细胞计数、C反应蛋白、谷草转氨酶、谷氨酰转肽酶水平；同时分析两组住院总天数、术后住院天数、住院总费用等。 结果低NLR组白细胞计数低于高NLR组[(6.28±1.66)×10⁹/L比(10.59±3.55)×10⁹/L，P<0.05 ]；低NLR组C反应蛋白水平低于高NLR组[(57.63±47.68)ug/mL比(81.38±38.25)ug/mL，P<0.05 ]；低NLR组谷草转氨酶水平低于高NRL组[(96.17±71.25)U/L比(281.90±438.30)U/L，P<0.05]；低NLR组谷氨酰转肽酶水平均低于高NLR组[(297.57±255.97)U/L比(509.70±462.06)U/L，P<0.05]，差异有统计学意义(P<0. 05)。低NLR组住院总天数[(13.34±4.55)d比(15.49±3.94)d，P<0.05]、术后住院天数[(10.07±2.80)d比(11.6±3.41)d，P<0.05]及住院总费用[(26 984.78±4 316.30)元比(30 875.35＝±4 305.50)元，P<0.05]等均低于高NLR组，差异有统计学意义(P<0. 05)。 结论急性胆管炎伴胆管结石患者外周血NLR值与其炎症感染程度呈正相关，临床上可将NLR作为对其病情及手术预后进行评估的指标。     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

MDM2/MDMX双靶点抑制蛋白在p53突变型乳腺癌中的作用及机制

目的:明确MDM2/MDMX双靶点抑制蛋白在p53突变型乳腺癌中的抗肿瘤作用及可能机制。方法:采用MTT比色法检测细胞增殖、流式细胞仪测定细胞周期和Annexin V/FITC-PI双染法检测细胞凋亡，明确MDM2/MDMX抑制蛋白对mt-p53乳腺癌的抗肿瘤活性。应用Western Blot检测MDM2、MDMX、p53、p21、PUMA和bax蛋白在mt-p53乳腺癌细胞中的表达水平，初步探讨抑制蛋白抗mt-p53乳腺癌的可能机制。结果:MDM2/MDMX抑制蛋白抑制mt-p53乳腺癌细胞24 h、48 h细胞增殖显著优于Nutlin-3α（P均＜0.05）。MDM2/MDMX抑制蛋白干预mt-p53乳腺癌细胞株24 h和48 h后G0/G1期的细胞比例明显高于Nutlin-3α（P<0.05）。抑制蛋白诱导mt-p53乳腺癌细胞24 h和48 h凋亡比例为（15.97±1.48）%和(17.80±2.21)%(MDA-MB-231细胞)；(11.09±2.45)%和(10.44±2.90)%(BT-474细胞)。mt-p53乳腺癌细胞中，抑制蛋白干预组MDM2和MDMX蛋白表达明显降低，p53蛋白则未见明显变化；PUMA、p21和bax蛋白表达则显著增加。结论:MDM2/MDMX抑制蛋白可抑制mt-p53乳腺癌细胞增殖，阻滞周期于G0/G1期和诱导细胞凋亡。抑制蛋白可抑制MDM2和MDMX蛋白的表达，但未能激活p53蛋白表达，以p53非依赖途径上调p21，bax和PUMA蛋白表达发挥抗乳腺癌活性。     

Prognostic factors for the survival of patients with papillary renal cell carcinoma after surgical management

To examine the possible prognostic factors in patients with type 1 and type 2 papillary renal cell carcinoma (pRCC) after surgical management and to identify the independent predictive factors of the prognosis. From 2010 to 2017, 1405 patients underwent surgery for renal cell carcinoma, of whom 114 had type 1 or type 2 pRCC and follow-up data were available for 88 patients. Clinicopathological and prognostic parameters were compared between type 1 and type 2 pRCC. Possible prognostic factors were retrospectively analyzed by univariate and multivariate analyses with Cox regression. The study included 63 males and 25 females with a mean age of 54.27 ± 12.91. 53 patients were diagnosed by regular physical examination and others presented with hematuria or lumbago. 53 (60.2%) underwent radical nephrectomy and 35 (39.8%) underwent nephron sparing surgery. After a mean follow-up of 46.08 ± 22.65 months, 16 patients died of pRCC metastasis and the 5-year disease-specific survival was 79.3%. The comparison of the 39 (44.3%) type 1 and 49 (55.7%) type 2 pRCCs revealed that type 2 pRCC had significantly higher grade and worse prognosis. Univariate analysis showed that symptomatic diagnosis, type, grade, and tumor stage were prognostic factors. Multivariate analysis identified that type and tumor stage were independent factors of the prognosis. Pathological type and tumor stage could serve as independent factors for the prognosis of patients with pRCC.     

Distinguishing craniomorphometric characteristics and severity in metopic synostosis patients

The decision about which metopic synostosis patients should undergo surgery remains controversial. Multiple measures for radiographic severity have been developed in order to determine the optimal criteria for treatment. The aim of this study was to perform an extensive craniomorphometric analysis of patients who underwent surgery for metopic synostosis to validate and compare the various severity scales developed for this non-syndromic craniosynostosis. A comparative morphometric analysis was performed using computed tomography scans of preoperative metopic synostosis patients (n = 167) and normal controls (n = 44). Measurements included previous and newly developed metopic severity indices. Volumetric and area analyses were used to determine the degree of anterior cranial area and potential volume restrictions. Of the severity indices measured, the frontal angle, endocranial bifrontal angle (EBF), adjusted EBF (aEBF), anterior cranial fossa angle, horizontal cone angle, and bitemporal/biparietal distance ratio were significantly different in the metopic subjects relative to controls overall. However, metopic index, orbital rim angle, foramen ovale distance, and cranial volume exhibited no significant difference from controls. Only the frontal angle and aEBF correlated with the changes in anterior cranial dimensions observed in metopic synostosis. In conclusion, the frontal angle and aEBF provide the most accurate measures of severity in metopic synostosis.