高脯氨酸血症1例报告

目的探讨高脯氨酸血症的临床及基因突变特点。方法回顾分析1例I型高脯氨酸血症患儿的临床资料,并复习相关文献。结果患儿,男,7岁半,因行走不稳伴反复抽搐、行为异常就诊。血氨基酸及酯酰肉碱谱检测提示脯氨酸升高(2 951.52μmol/L),尿有机酸分析提示3-羟基丙酸、3-甲基巴豆酰甘氨酸、巴豆酰甘氨酸浓度增高。基因测序示PRODH存在c. 1073 CT、c. 857 CT两处杂合突变,经基因功能预测具有致病性,患儿确诊为高脯氨酸血症I型。结论对于不明原因发育落后伴癫痫发作、精神行为异常,且血脯氨酸水平升高者应高度怀疑高脯氨酸血症,尽早行基因检测确诊。     

调补肺肾方对慢性阻塞性肺疾病合并气管支气管软化症患者肺功能和生活质量的影响

目的:探讨调补肺肾方对慢性阻塞性肺疾病合并气管支气管患者肺功能和生活质量的影响。方法:分析我科从2016年3月～2017年12月诊治的60例慢阻肺合并气管支气管软化症患者临床资料。根据入院先后及是否采用中医治疗分为对照组和观察组,2组各30例。对照组采用单纯西医对症治疗组,包括:轻度软化症患者常规给予沙美特罗替卡松(50/250 ug)2吸bid,或布地奈德福莫特罗(160/4.5 ug)2吸bid,或联合噻托溴铵(18 ug)1吸qd;中度患者在常规治疗基础上给予无创呼吸机辅助通气(模式BiPAP或CPAP),重度患者酌情给予气道支架植入,肺部感染患者给予抗感染治疗。观察组在对照组基础上加用中医调补肺肾方水煎剂,1剂/d, 3次/d。统计分析2组患者治疗前后肺功能、C反应蛋白(CRP, C-reactive Protein)、降钙素原(PCT, Procalcitonin)、改良英国医学研究学会呼吸困难指数(mMRC, Modified British Medical Research Council)、慢阻肺评估测试(CAT, Chronic Obstructive Pulmonary Disease Assessment Test)变化。结果:研究显示,与基线值比较,对照组与观察组都能改善患者肺功能FEV1值,降低CRP及PCT,改善呼吸困难指数及CAT评分,差异有统计学意义;但在改善FEV1/FVC、RV/TLC、DLCO、PO_2及PCO_2方面无统计学差异。组间比较显示,观察组较对照组能更好改善患者PO_2、mMRC及CAT评分,能进一步改善患者生活质量,差异有统计学意义,但2组在改善肺功能FEV1、FEV1/FVC、RV/TLC、DLCO及PCO2上无统计学意义。结论:调补肺肾方治疗慢阻肺合并气管支气管软化症疗效肯定,值得进一步研究。     

Enhanced antitumor efficacy by combination treatment with a human umbilical vein endothelial cell vaccine and a tumor cell lysate-based vaccine

Angiogenesis inhibitors combined with other anticancer drugs have been shown to inhibit tumor growth in animal models and some of them were recently used in clinical trials. In the present study, a whole hepatocellular carcinoma cell lysate based vaccine with diphtheria toxin (DT) and two tandem repeats of microbial HSP70 peptide epitope 407-426 (2 mHSP70407-426, M₂) as adjuvant, which was called HDM, was combined with a whole human umbilical vein endothelial cell (HUVEC) vaccine to develop a combination treatment regimen. This combination treatment regimen was named HUVEC-HDM, which was supposed to enhance its antitumor efficiency. HUVEC-HDM was administrated subcutaneously in both prophylactic and therapeutic procedures. Compared to either single vaccine, HUVEC-HDM induced a more significant inhibition on the growth and metastasis of H22 hepatocellular carcinoma in mice and prolonged the survival of tumor-bearing mice. Besides, HUVEC-HDM immunization elicited strong humoral and cellular immune responses targeting tumor cell as well as tumor angiogenesis, which could be responsible for the enhanced antitumor effect. Moreover, histochemistry analysis showed that HUVEC-HDM induced large areas of continuous necrosis within tumors, correlating well with the extent of tumor inhibition. These results not only highlight the superiority of the combined HUVEC-HDM treatment regimen, but also support the translation of such approaches into the clinic for the treatment of patients with hepatocellular carcinoma.     

Germline mutations in the VHL gene associated with 3 different renal lesions in a Chinese von Hippel-Lindau disease family

Von Hippel–Lindau (VHL) disease is a rare autosomal dominant inherited cancer syndrome that is characterized by hemangioblastomas in the central nervous system and retina, renal cell carcinoma and cysts, pancreatic tumors and cysts, and pheochromocytoma. The underlying gene in this disease is the VHL tumor suppressor gene. We characterized a family with 2 affected siblings. The brother and sister displayed VHL type 2B and type 2A features, respectively. Renal lesions in the brother exhibited 3 different phenotypes, including simple renal cysts, multilocular cystic renal cell carcinoma and clear cell renal cell carcinoma. The phenotypes of the 3 concurrent renal lesions were first reported in this study. Mutation detection of the VHL gene revealed 2 recurrent mutations, namely c.256C>T (p.P86S) and c.340 + 5G > C. The former was predicted to be deleterious and to destabilize the hydrophobic core and lead to VHL dysfunction; however, the latter was predicted to be a benign variant. Our findings provided new data for the genotype-phenotype of VHL diseases and elucidated the pathogenic mechanism with in silico analysis.     

小儿外科手术中行丙泊酚靶控加单次硬膜的效果探究

目的探究在小儿外科手术中行丙泊酚靶控加单次硬膜的效果。方法选取2012年9月-2014年1月来本院接受手术治疗的80例患儿作为研究对象，随机等分为研究组和对照组，分别为单次硬膜外加丙泊酚靶控和氯胺酮麻醉，比较不同时间段的两组患者血压、心率及血氧饱和度及肢体乱动、肌松程度等指标。结果对照组开始手术和结束手术时的血压、心率与进手术时前相比均显著升高（P〈0．05），而研究组的血压则无明显变化，但同时刻比较对照组则较低，差异有统计学意义（P〈0．05）；研究组心率在开始手术和结束手术时与进手术时前相比明显降低（P〈0．05），与对照组同时点相比也降低不少（P〈0．05）；研究组肢动较少，苏醒时间缩短，差别有统计学意义（P〈0．05）。结论在小儿外科手术中行丙泊酚靶控加单次硬膜对小儿呼吸、循环影响不大，并且有效果好、苏醒快、安全的特点。     

Identification of PTPN22, ST6GAL1 and JAZF1 as psoriasis risk genes demonstrates shared pathogenesis between psoriasis and diabetes

The biological connections between psoriasis and diabetes have been suggested by epidemiological, immunological and genetic studies. To identify additional shared susceptibility loci and investigate shared pathogenesis between these two diseases, we genotyped 89 reported diabetes susceptibility loci in 4456 psoriasis cases and 6027 controls of Chinese population using the MassARRAY system from Sequenom. We discovered three significant associations at rs6679677 on 1p13.2 (P=6.15×10^?5, OR=5.07), rs16861329 on 3q27.3 (P=2.02×10^?4, OR=0.87) and rs849135 on 7p15.1 (P=6.59×10^?9, OR=1.78), which suggested PTPN22, ST6GAL1 and JAZF1 as novel susceptibility genes for psoriasis in Chinese population. Our findings implicated the involvement of T‐cell receptor signalling pathway in the pathogenesis of psoriasis and further confirmed the shared genetic susceptibility between psoriasis and diabetes.