三例眼皮肤白化病患者TYR和P基因的突变分析

目的 分析眼皮肤白化病(oculocutaneom albinism,OCA)患者酪氨酸酶(tyrosinase,TYR)基因和P基因的基因突变.方法 应用聚合酶链反应(polymerase chain reaction ,PCR)和变性高效液相色谱(de-naturing high-perfomanee liquia chromatography,DHPLC)技术对3例患者的眼皮肤白化病Ⅰ、Ⅱ型相关基因(TYR和P基因)的外显子进行突变检测,并对DHPLC检出的突变样本进行测序和限制性内切酶分析以验证该突变.针对未见报道的新突变,筛查100名表型正常的无关个体,排除多态的可能.结果 在3例患者中检测出两种P基因突变,未检测到TYR基因突变.其中,患者1的P基因第13外显子发生杂合突变T450M;患者2的P基因发生两个杂合突变,分别是第13外显子T450M和第23外显子G775R;患者3的P基因第23外显子发生杂合突变G775R.P基因第13外显子限制性内切酶分析显示,患者1、2均出现杂合突变T450M导致的Oli I酶切位点部分消失,100名表型正常的无关个体未检出该突变;经检索,T450M为一未见报道的新突变.结论 联合应用PCR、DHPLC、DNA测序和限制性内切酶分析的方法可有效的对白化病进行基因诊断.     

Association of E-cadherin, matrix metalloproteinases, and tissue inhibitors of metalloproteinases with the progression and metastasis of hepatocellular carcinoma.

Molecular markers can provide additional information to traditional histomorphological evaluation for the assessment of tumor progression and predicting the likelihood of invasion and metastasis in various types of malignancies. We studied the association of E-cadherin, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinase with the progression and metastasis of hepatocellular carcinoma. Tissue microarray including six normal livers, 14 cirrhotic livers, 39 macroregenerative nodules, 16 dysplastic nodules, 22 grade I hepatocellular carcinomas, 43 grade II hepatocellular carcinomas, seven grade III hepatocellular carcinomas, and 10 metastatic hepatocellular carcinomas were stained immunohistochemically with antibodies against MMPs -1, -2, -3, -7, -9, tissue inhibitors of metalloproteinase-1, -2, -3, and E-cadherin. The intensities of staining were scored manually by two pathologists and verified by the Chromavision Automated Cellular Imaging System. Compared with normal liver, cirrhotic liver had significantly lower E-cadherin and tissue inhibitors of metalloproteinase-1 but higher MMP-1 and -7, which suggest a more favorable environment for tumor invasion and metastasis. Grade I and grade II hepatocellular carcinomas demonstrated high E-cadherin and decreased MMP-3 and -9, which may explain the rarity of extrahepatic metastasis in low-grade hepatocellular carcinomas despite the high circulatory volume of the liver. The histological progression from dysplastic nodule to well-differentiated hepatocellular carcinoma and to less differentiated tumors was associated with a gradual decrease in tissue expression of E-cadherin, tissue inhibitors of metalloproteinase-2 and -3. Metastatic hepatocellular carcinomas showed significantly lower level of tissue inhibitors of metalloproteinase-1, -2, -3 but higher level of MMP-7. These data suggest that tissue expression of E-cadherin, certain MMPs, and tissue inhibitors of metalloproteinases could be useful markers to predict the progression and metastasis of hepatocellular carcinoma.     

Impact of anxiety,stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency

Background

Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).

Methods

This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.

Results

139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0–45) and 6 (min-max: 0–10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).

Conclusions

This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

     

国际典型综合类科技期刊公众传播特点及对我国综合类科技期刊公众传播能力建设的启示

【目的】 分析国际顶级综合类科技期刊公众传播模式及特点,为我国科技期刊公众传播能力建设提供建议。【方法】 以Altmetric Top 100入选论文数量最多的Nature、Science和PNAS三刊为研究对象,剖析其在公众传播产品、媒体传播体系和新闻媒体人才支撑等方面的模式和特征。对照分析我国最有影响力的综合类科技期刊《国家科学评论》和《科学通报》的公众传播特点。【结果】 以《国家科学评论》和《科学通报》为代表的我国综合类科技期刊的公众传播能力提升迅速,但仍存在新闻传媒人才短缺、期刊集约化程度不高、公众传播机制尚未建立等问题。【结论】 我国综合类科技期刊需要着力增强传媒人才培育、集约化品牌发展、公众传播机制建设,以促进我国科技期刊公众传播能力提升。     

葛花、枳椇子及其配伍对小鼠急性酒精性胃黏膜损伤的保护作用及机制

目的 探讨葛花、枳椇子及其配伍对急性酒精性胃黏膜损伤的改善作用,为进一步开展葛花、枳椇子及其配伍防治酒精致多脏器损伤奠定基础。方法 采用多次灌胃给予56%红星二锅头白酒（15 mL·kg^-1）建立小鼠急性酒精性胃黏膜损伤模型,将120只ICR雄性小鼠随机分为空白组、模型组、奥美拉唑组（0.026 g·kg^-1）、葛花-枳椇子（配伍）高、中、低剂量组（29.2、14.6、7.3 g·kg^-1）、葛花组（19.5 g·kg^-1）、枳椇子组（19.5 g·kg^-1）共8个组,每组15只,动物适应性喂养1周后,按10 mL·kg^-1预给相应药物3 d,从第4天开始,给药1 h后按15 mL·kg^-1灌胃二锅头白酒,空白组给予相同体积去离子水,记录小鼠醉酒和醒酒时间,连续给药给酒3 d,末次给药1 h后摘眼球处死;气相色谱仪测定各组小鼠血清中乙醇体积分数,紫外-可见分光光度计检测各组小鼠胃黏膜中乙醇脱氢酶（ADH）活性;苏木素-伊红（HE）染色观察胃黏膜病理变化;酶联免疫吸附测定法（ELISA）检测各组小鼠血清中炎症因子含量;实时荧光定量聚合酶链式反应（Real-time PCR）检测核转录因子-κB（NF-κB）p65和NF-κB抑制蛋白α（IκBα）mRNA表达。结果 与正常组比较,模型组血清中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）含量升高（P<0.05）,胃黏膜组织NF-κB p65 mRNA表达升高（P<0.01）,IκBα mRNA表达降低（P<0.01）;与模型组比较,奥美拉唑组、配伍高、中剂量组、葛花组醉酒时间延长（P<0.05）,配伍高、中剂量组醒酒时间缩短（P<0.05）,配伍高剂量组血清中乙醇体积分数降低（P<0.05）,奥美拉唑组、配伍高、中剂量组胃黏膜中ADH活性升高（P<0.05）,配伍各剂量组、葛花组肉眼损伤评分降低（P<0.05）,奥美拉唑组、配伍各剂量组、葛花组病理损伤评分降低（P<0.01）,各给药组血清中IL-6表达降低（P<0.05）,奥美拉唑组、配伍各剂量组、枳椇子组血清中IL-1β表达降低（P<0.05）,配伍高、中剂量组血清中TNF-α表达降低（P<0.05）,各给药组胃黏膜组织NF-κB p65 mRNA表达降低（P<0.05）,奥美拉唑组、配伍各剂量组胃黏膜组织IκBα mRNA表达增加（P<0.05）;与高剂量组比较,配伍低剂量组与枳椇子组醉酒时间缩短（P<0.01）,葛花、枳椇子组醒酒时间延长（P<0.01）,配伍中、低剂量组、葛花组、枳椇子组血清中乙醇体积分数升高（P<0.05）,配伍中、低剂量组、枳椇子组肉眼损伤积分增加（P<0.05）,配伍中、低剂量组、葛花组、枳椇子组病理损伤积分增加（P<0.01）,配伍低剂量组、葛花组、枳椇子组血清中IL-1β含量升高（P<0.01）,葛花组与枳椇子组胃黏膜组织IκBα mRNA表达量降低（P<0.05）;与配伍中剂量组比较,枳椇子组醉酒时间缩短（P<0.05）,葛花组醒酒时间延长（P<0.05）,葛花组、枳椇子组病理损伤积分增加（P<0.01）,配伍低剂量组、葛花组、枳椇子组血清中IL-1β含量升高（P<0.05）;与配伍低剂量组比较,枳椇子组病理损伤积分增加（P<0.05）。结论 葛花、枳椇子及其配伍能起到对小鼠急性酒精性胃黏膜损伤的防治作用,可能与抑制胃黏膜NF-κB信号通路的表达有关,且配伍高剂量组药效最佳。     

新式阴道前、后壁联合修补术临床分析

目的探讨新式阴道前、后壁联合修补术治疗盆腔脏器脱垂(POP)的临床效果。方法选择2017年1月至2021年1月,于南京医科大学附属淮安第一医院接受手术治疗的120例POP患者为研究对象。根据采用的手术方式,将其分为研究组(n=60,采用新式阴道前、后壁联合修补术)及对照组(n=60,采用腹腔镜下全子宫双侧附件切除术+传统阴道前、后壁修补术)。采用独立样本t检验及χ^(2)检验,对2组患者一般临床资料,术中及术后情况进行统计学比较。本研究经南京医科大学附属淮安第一医院医学伦理委员会批准(审批文号:YX-P-2020-023-01)。所有患者知情同意并与之签署临床研究知情同意书。结果①2组POP患者年龄、人体质量指数(BMI)、产次、绝经者比例及POP脱垂程度比较,差异均无统计学意义(P>0.05)。②研究组POP患者手术时间、术中出血量、总住院时间、术后住院时间及住院费用分别为(88.0±30.6)min、(24.7±36.0)mL、(7.3±2.1)d、(4.6±1.4)d及(10727±1812)元,均短于或低于对照组的(118.0±33.4)min、(56.7±43.8)mL、(9.8±2.3)d、(6.4±1.6)d及(26318±3890)元,并且差异均有统计学意义(t=5.130、4.372、6.218、6.558、28.138,均为P<0.001)。2组POP患者术后3、6、12个月复发率构成比比较,差异无统计学意义(P>0.05)。结论新式阴道前、后壁联合修补术在不增加POP患者术后复发率的基础上,不仅能缩短手术时间、减少患者术中出血量,还可以缩短住院时间、减少住院费用,并且易于操作,适宜推广。     

前列腺素E1治疗老年慢性肺心病急性期的疗效观察

目的 :探讨前列腺素E1(PGE1)对老年慢性肺心病急性期的疗效。方法 :对 40例老年慢性肺心病急性期患者应用PGE110 0 μg·d-1静脉滴注 ,疗程 7d。于治疗前后同步检测患者血浆D -二聚体 (D -dimer) ,血清纤维蛋白降解产物 (FDP) ,动脉血氧分压 (PaO2 ) ,及动脉血二氧化碳分压 (PaCO2 )并观察症状体征变化 ,同时与对照组患者及 2 0例健康者进行比较。结果 :两组老年慢性肺心病急性期患者的D -二聚体和FDP显著高于健康组 (P <0 .0 1) ,治疗组病例治疗后D -二聚体及FDP较治疗前显著降低 (P <0 .0 1) ,症状体征显著改善 (P <0 .0 5～ 0 .0 1) ,对照组的D -二聚体 ,FDP及部分症状和体征 ,治疗前后比较差异有显著性 (P <0 .0 5～ 0 .0 1)。治疗后PaO2 两组均显著增高 (P <0 .0 1) ,组间比较无差别 (P >0 .0 5 )。治疗后PaCO2 两组均降低 ,但治疗组降低幅度更明显 (P <0 .0 1)。结论 :PGE1对老年慢性肺心病急性期确有良好疗效     

The effect of cardiovascular morbidity on clinical response provided by tadalafil in patients with erectile dysfunction

We aimed to investigate the association between erectile dysfunction and severity of cardiovascular morbidity and to assess clinical responses to tadalafil of patients in different cardiovascular risk groups. Between November 2019 and August 2020, a total of 258 male patients aged 45–70 years with ED were included. They were divided into three groups according to the Framingham risk score: low-risk (n: 86, 33.3%), intermediate-risk (n: 103, 39.9%) and high-risk (n: 69, 26.8%). At admission, all domains of the International Index of Erectile Function score were worse in high-risk group compared to other risk groups (p < .001). After a 12-week follow-up, a more significant improvement was observed in all domains of erectile function in all risk groups, but high-risk group had lower sexual scores (p < .001). The lowest rate for complete responsiveness to tadalafil was observed in the high-risk group (37.7%). The rate of failure in complete responsiveness was found to be 4.127 times greater with higher Framingham score and 3.102 times greater with higher erectile dysfunction severity at admission. Our preliminary findings show that more severe sexual disorders are observed in high-risk patients with cardiovascular morbidity. Individualised treatment may be important in high-risk group since they may benefit less from tadalafil, and failure in complete responsiveness can be more common in this group.