扶正消瘤颗粒对原发性肝癌血清中VEGF、HIF-1α表达的影响及临床意义＊

目的 探讨扶正消瘤颗粒对原发性肝癌血清中血管内皮生长因子（Vascular endothelial growth factor，VEGF）和缺氧诱导因子-1α（Hypoxia inducible factor-1α，HIF-1α）表达的影响及临床意义。方法 选择符合纳入标准的原发性肝癌患者66例，按1∶1随机分试验组和对照组。观察治疗过程中两组VEGF、HIF-1α水平的变化及对患者临床疗效指标的影响。结果 （1）在性别、年龄、合并乙型肝炎、Child-Pugh分级、AFP值、临床分期方面，试验组和对照组差异无统计学意义（P > 0.05）。（2）肝癌患者在治疗各时间节点的VEGF和HIF-1α表达水平呈线性正相关（r = 0.829，P < 0.001）。（3）VEGF浓度在经导管动脉化疗栓塞术（Transcatheter arterial chemoembolization，TACE）后3月降至术前水平（P > 0.05），HIF-1α在TACE后3月仍高于术前（P < 0.05）。（4）扶正消瘤颗粒可降低HIF-1α水平，下调VEGF的表达。（5）扶正消瘤颗粒可减少TACE序贯RFA治疗后的不良反应，提高患者的生活质量（P < 0.05）。（6）血清中VEGF水平与生活质量无明显相关性（P > 0.05，r = 0.251），HIF-1α水平与生活质量存在正相关性（P < 0.05，r = 0.450）。结论 扶正消瘤颗粒可明显改善TACE序贯RFA治疗后患者生活质量，降低HIF-1α水平，下调VEGF的表达，抑制肿瘤血管生成。     

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.     

腹腔镜"蘑菇状"剜除术治疗外生性肾血管平滑肌脂肪瘤的临床应用

目的对比研究腹腔镜下外生性肾血管平滑肌脂肪瘤"蘑菇状"剜除与标准肾部分切除术的安全性及有效性，为肾血管平滑肌脂肪瘤腹腔镜下"蘑菇状"剜除术术式的建立提供临床依据。 方法选取海南医学院第二附属医院与解放军总医院2018年1月至2019年5月期间，接受腹腔镜手术的肾血管平滑肌脂肪瘤患者53例，其中25例沿肿瘤假包膜行"蘑菇状"剜除术(A组)、28例行肾部分切除术(B组)。比较两组手术患者的肾动脉阻断时间、手术时间、术中出血量、术后24 h血红蛋白、术后eGFR(estimated glomerular filtration rate,估计肾小球率过滤)的变化、术后住院时间和术后肿瘤复发率。 结果53例手术无术中转开放，无死亡病例。肾动脉阻断时间：A组(11.9±2.2)min、B组(21.5±6.5) min(P<0.001)。手术时间：A组(87.9±24.8)min、B组(114.3±38.9) min(P<0.001)。术中出血量：A组20 ml(20～40)ml、B组50 ml(50～100)ml(P<0.001)。术后24 h血红蛋白变化：A组(7.4±4.3) g/L、B组(12.4±8.8) g/L(P＝0.013)。术后24 h eGFR变化：A组(6.2±7.2 )ml(min·1.73 m²)，B组(12.7±12.8)ml(min·1.73 m²)(P＝0.027)。术后6个月eGFR变化：A组(1.5±3.7)ml(min·1.73 m²)、B组(6.5±5.6)ml(min·1.73 m²)(P<0.001)。术后住院时间：A组4.0 d(3～4)d、B组4.5 d(3～6)d(P＝0.023)。术后随访两组术后肿瘤均无复发。 结论采用腹腔镜"蘑菇状"剜除术治疗外生性肾血管平滑肌脂肪瘤在肾动脉阻断时间、术中出血量、术后24 h血红蛋白、术后eGFR变化、术后住院时间等方面均优于传统肾部分切除术，两组术后肿瘤均无复发；该方法安全、有效，适于临床推广。     

AKR7A3在肺腺癌中异常表达及临床意义

目的:探讨醛-酮还原酶家族7成员A3（AKR7A3）在肺腺癌中的异常表达及与临床病理特征的关系，并探究其临床意义。方法:采用生物信息学数据库分析、免疫组化、Western Blot、Real-time PCR等方法对肺腺癌组织及不同细胞中AKR7A3的表达进行检测与分析。结果:Oncomine数据库分析结果显示，在肺腺癌中，AKR7A3的表达普遍高于正常肺组织，分别为正常肺组织的1.811倍（P=0.022）、1.356倍（P<0.01）、1.413倍（P=0.002）。Kaplan-Meier Plotter数据库分析结果显示，AKR7A3高表达的患者较低表达的患者生存时间缩短，差异具有统计学意义（P=0.003 7）。免疫组化染色显示肺腺癌组织中AKR7A3的表达较癌旁增高，在与临床病理特征的相关性分析中，发现其与肿瘤分化程度（P<0.01）、淋巴结转移情况（P=0.029）以及TNM分期（P<0.01）相关，且会造成患者生存时间缩短（P=0.031）。Cox多因素分析表明AKR7A3可能是影响肺腺癌患者预后的独立危险因素(P=0.012)。Western Blot及Real-time PCR实验提示不同肺腺癌细胞中AKR7A3蛋白及mRNA表达普遍增高。结论:AKR7A3在肺腺癌中表达增高，对预后有不良影响，有促进肿瘤发生发展的作用。     

Characterization of two pigeon paramyxovirus type 1 isolates in China

For over three decades, there has been a continuing panzootic caused by a virulent variant avian paramyxovirus type 1 strain, the so-called pigeon paramyxovirus type 1. It is found primarily in racing pigeons, but it has also spread to wild birds and poultry. In this study, two pigeon paramyxovirus type 1 strains, SD12 and BJ13, obtained from diseased pigeons in China, were characterized. Phylogenetic analysis based on complete sequences allowed characterization of both strains as genotype VI, class II. Further phylogenetic analysis of a 374-nucleotide section of the fusion gene showed that SD12 fell into lineage VIbii-d and BJ13 into VIbii-f. The deduced amino acid sequence of the cleavage site of the fusion protein confirmed that both isolates contained the virulent motif ¹¹²K/RRQKR↓F¹¹⁷ at the cleavage site. Nevertheless, the values of intracerebral pathogenicity indices showed the SD12 isolate to be a velogenic strain and BJ13 isolate to be a mesogenic strain. The SD12 isolate was further investigated via clinical observation, RNA detection, histopathology and viral serology in experimentally infected 3-week-old chickens. It showed a mild pathological phenotype in chickens, with viral replication restricted to a few tissues. The molecular mechanism for the SD12 isolate to have a virulent motif but low levels of virulence for chickens requires further study.