血清外泌体 miR-155、miR-222表达对乳腺癌术后复发转移的预测价值

目的探究血清外泌体 miR-155、miR-222表达对乳腺癌术后复发转移的预测价值。方法选取 2016年 1月至 2017年 6月于南通市中医院收治的乳腺癌病人 72例作为乳腺癌组,同期选取确诊为乳腺纤维瘤病人 40例为对照组。根据乳腺癌病人术后是否发生复发转移分为复发转移组 27例和未复发转移组 45例。利用外泌体试剂盒提取血清中外泌体,采用荧光定量 PCR技术检测外泌体 miR-155、miR-222水平。采用受试者工作特征( ROC)曲线评价血清外泌体 miR-155、miR-222水平对乳腺癌病人术后复发转移的诊断价值。结果研究组血清外泌体 miR-155(1.46±0.62)、 miR-222(1.87±0.79)水平均明显高于对照组［( 0.98±0.03)、(1.02±0.02)］(均 P<0.05);复发转移组病人血清外泌体 miR-155(1.68±0.47)、 miR-222(2.13±0.53)水平均明显高于未复发转移组［(1.33±0.24)、(1.71±0.26)］(均 P<0.05);临床病理分析结果显示,乳腺癌病人血清外泌体 miR-155、miR-222表达与 TNM分期、淋巴结转移有关(均 P<0.05); ROC结果显示,血清外泌体 miR-155、miR-222预测乳腺癌病人术后复发转移的曲线下面积( AUC)分别为 0.82［95%CI:(0.71,0.87)］0.79［95%CI:(0.68,0.88)］,对应的灵敏度分别为 69.37%、59.26%,特异     

血清hs-CRP、CK-MB、cTnI在急性心肌梗塞早期诊断中的临床价值

目的探讨血清hs-CRP、CK-MB与cTnI在急性心肌梗塞(AMI)早期中的临床价值。方法对36例AMI胸痛发作在3￣4h患者,50例AMI胸痛发作4￣12h患者,采用定时免疫散射比浊法检测其血清hs-CRP,免疫抑制法测定血清CK-MB,化学发光法检测血清cTnI,并与40例健康对照作比较,探讨三者在AMI早期中的变化情况。结果AMI胸痛发作3￣4h组、4￣12h组hs-CRP含量分别为(7.42±3.27)mg/L、(25.26±18.15)mg/L,均明显高于对照组(0.84±0.73)mg/L(P<0.01);CK-MB含量AMI胸痛发作3￣4h组(25.4±14.6)U/L与4￣12h组(64.6±53.2)U/L均较对照组(5.6±3.4)U/L有显著性差异(P<0.05);而AMI胸痛发作3￣4h组cTnI含量(0.08±0.06)μg/L与对照组(0.06±0.04)μg/L无显著性差异(P>0.05),4￣12h组的cTnI含量(28.9±37.6)μg/L与其它两组比较均有显著性差异(P<0.05)。AMI患者胸痛发作4h内,以hs-CRP(91.7%)最敏感,CK-MB(55.6%)次之,阳性检出率均明显高于cTnI(25%);胸痛发作4￣12h,hs-CRP(100%)、CK-MB(92%)、cTnI(84%)均具有较高的阳性检出率。结论联合检测hs-CRP、CK-MB、cTnI对于AMI早期诊断具有很高的灵敏度与特异性,可将诊断与治疗提前到4h以内,并能作为AMI的预后监测及疗效观察的指标。     

心肌肌钙蛋白Ⅰ、超敏C-反应蛋白及血乳酸对病毒性心肌炎的诊断价值

目的 探讨心肌肌钙蛋白Ⅰ(cTnI)、超敏C-反应蛋白(hs-CRP)和血乳酸的动态变化在病毒性心肌炎(VMC)诊断中的意义.方法 回顾性分析急性病毒性心肌炎患者(VMC组,n=54)和急性上呼吸道感染(上感)患者(上感组,n =34)共88例,动态监测两组cTnI 、hs-CRP和血乳酸水平,并对比VMC轻症患者(n=39)与重症患者(n=15)的cTnI水平.结果 VMC组入院24h内所测得的cTnI水平[(0.59±0.10) ng/L]较上感组[(0.10±0.08)ng/L]明显升高(t=2.79,P＜0.05),其血乳酸(t=2.71,P＜0.05)及hs-CRP水平(t=2.48,P＜0.05)在不同时段也有升高的表现.结论 cTnI对诊断病毒性心肌炎有重要的意义,其水平高低与患者病情严重程度相关,hs-CRP及血乳酸与病毒性心肌炎的炎症损伤也有一定相关性.     

心脏肌钙蛋白I测定在病毒性心肌炎诊断中的意义

目的比较心肌肌钙蛋白I(cTnI)与常用急性病毒性心肌炎(VMC)诊断标致物的临床应用价值.方法同时检测50例病毒性心肌炎(VMC)患儿血清cTnI、CK、CK-MB、LDH和GOT水平并分别对各指标间的差异作对比分析.结果cTnI对急性病毒性心肌炎诊断敏感性和特异性高于CK、CK-MB、LDH和GOT.结论cTnI对于VMC的诊断具有较高的特异性,是一种心肌损伤的特异性标志物,具有较好的临床应用价值.     

BMSCs外泌体来源miR-133a对大鼠脊髓损伤修复的影响

目的 探讨骨髓间充质干细胞(BMSCs)外泌体来源miR-133a对大鼠脊髓损伤(SCI)修复的影响。方法 原代分离和培养BMSCs,测定BMSCs细胞表面标记物(CD90,CD45)表达;提取BMSCs外泌体,观察外泌体形态及外泌体标记分子(Alix、CD63)表达;建立SCI大鼠模型,随机将大鼠分为假手术组、SCI组、外泌体组、外泌体-抑制剂对照(NC)组、外泌体-miR-133a抑制剂组,28 d后,对各组大鼠进行BBB评分评估脊髓损伤程度;分离大鼠骨髓组织,检测该组织病理学变化、细胞凋亡状况;同时检测相关蛋白[胶质纤维酸性蛋白(GFAP)、神经元核抗原(NeuN)、炎性小体3(NLRP3)、半胱氨酸天冬氨酸酶(caspase)-1]及miR-133a表达水平。双荧光素酶实验验证miR-133a、NLRP3靶向关系。结果 BMSCs细胞中CD90、CD45表达率分别为98.07%、0.09%。外泌体呈球形,Alix、CD63呈阳性表达。与假手术组比较,SCI组BBB评分、NeuN、miR-133a表达显著降低,细胞凋亡率、GFAP、NLRP3、caspase-1表达显著增加(P&...     

不同检测指标在急性心肌梗死早期诊断中的应用价值

目的 探讨肌酸激酶同工酶(CK-MB)、超敏-C反应蛋白(hs-CRP)及心肌肌钙蛋白I(cTnI)检测对急性心肌梗死早期诊断的临床应用价值.方法 选择本院2011年6月至2015年6月收治的120例急性心肌梗死(AMI)患者,采用全自动生化分析仪对患者不同疾病时段的血清CK-MB、hs-CRP及cTnI进行检测,并与同期进行体检的100例健康者的血清指标进行比较.结果 AMI组患者CK-MB、hs-CRP及cTnI指标浓度显著高于健康体检组,组间比较差异均有统计学意义(P＜0.01).hs-CRP阳性出现时间最早,8～12小时hs-CRP检出率可达100.00％,cTnI阳性出现时间次之,12 ～ 24小时cTnI检出率可达100.00％,且检测窗口时间较长,CK-MB阳性出现最晚,在12～24小时内CK-MB检出率最高仅为90.83％.CK-MB、hs-CRP及cTnI指标对AMI的诊断灵敏度分别为85.00％、95.00％和90.83％,特异性分别为94.00％、89.00％和97.00％.结论 AMI患者疾病不同时间段进行CK-MB、hs-CRP及cTnI指标存在灵敏度及特异性的差异,但对于患者的具体情况,结合三种指标检测能够降低漏诊及误诊率,对心肌梗死的临床诊断、治疗及病情康复情况等均具有重要应用价值.     

超敏C反应蛋白、心脏型脂肪酸结合蛋白、肌酸激酶同工酶、肌红蛋白及肌钙蛋白联合检测对急性心肌梗死的诊断价值

目的 探讨超敏C反应蛋白(hs-CRP)、心脏型脂肪酸结合蛋白(H-FABP)、肌酸激酶同工酶(CK-MB)、肌红蛋白(MYO)及肌钙蛋白I(cTnI)联合检测对急性心肌梗死(AMI)诊断价值.方法 选择临床诊断为AMI患者46例(AMI组)和健康体检正常者96例(对照组),检测两组hs-CRP、H-FABP、CK-MB、MYO、cTnI水平,并观察比较AMI组在入院2、4、6h时各项观察指标变化情况.结果 AMI组患者入院2h时血清中hs-CRP、H-FABP、CK-MB、MYO、cTnI等水平明显高于对照组(t=46.0,均P＜0.01),AMI组在入院4h时各项观察指标明显高于入院2h时(t=46.0,均P＜0.01),入院6h时明显高于4h时(t=46.0,均P＜0.01);且hs-CRP、H-FABP、CK-MB、MYO、cTnI联合检测时,对AMI诊断的灵敏度为98.9％、特异性100％、阳性预测值100％.结论 hs-CRP、H-FABP、CK-MB、MYO、cTnI联合检测对AMI的诊断有重要临床价值.     

CK-MB、cTnI和hs-crp联合检测对儿童病毒性心肌炎诊断价值

目的探讨肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）和超敏C反应蛋白（hs-CRP）对儿童病毒性心肌炎的诊断价值。方法 42例病毒性心肌炎患儿作为观察组,42例健康儿童作为对照组,测定两组儿童的血清CK-MB,cTnI和hs-CRP。结果观察组患儿血清CK-MB,cTnI和hs-CRP均明显高于对照组（P〈0.01）。观察组患儿CK-MB,cTnI,hs-CRP联合检测的灵敏性胃89.6%,特异性为94.6%,准确性胃92.7%,准确性明显高于单纯检测CK-MB、cTnI、hs-CRP（P〈0.05）。结论联合检测CK-MB、cTnI和hs-crp可以更准确的诊断儿童病毒性心肌炎。     

探讨心肌酶及其比值与肌钙蛋白的测定对儿童病毒性心肌炎的诊断

目的初步了解本地区儿童心肌酶的正常范围,探讨其比值及肌钙蛋白I(cTnI)对儿童病毒性心肌炎(VMC)的诊断价值。方法采用日立7080全自动生化分析仪来测定肌酸激酶(CK)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)、α羟丁酸(αHBDH)并计算出CK-MB/CK、αHBDH/LDH;CK采用酶耦联测定法,αHBDH采用连续监测法,LDH采用连续监测法(LDHL),CK-MB采用免疫抑制法;cTnI采用固相层析免疫分析法测定。结果本地区100例健康儿童心肌酶水平均高于健康成人(P<0.01),但不同组的CK-MB/CK<2%的占85%以上,αHBDH/LDH在0.6~0.8之间占87%以上。50名健康儿童运动后的心肌酶普遍高出儿童正常范围,但其比值并未升高。已确诊的66例儿童病毒性心肌炎患者的心肌酶异常的有55例(占84%),CK-MB/CK>6%的有41例,αHBDH/LDH>0.8的有39例,cTnI结果阳性的有46例,比值和cTnI的结果经配对检验,存在一致性关联。结论不能用成人的标准来判断儿童心肌酶异常与否,儿童心肌酶单项升高不能作为VMC的诊断依据;CK-MB/CK>6%、αHBDH/LDH>0.8以及cTnI结果阳性对诊断VMC有极大的临床价值。     

病毒性心肌炎患儿心型脂肪酸结合蛋白的变化及意义

目的:探讨病毒性心肌炎(VMC)患儿血清心型脂肪酸结合蛋白(h-FABP)的变化,进一步确定其临床应用价值.方法:对58例病毒性心肌炎惠儿和36例健康对照组儿童检测血清h-FABP、心肌肌钙蛋白Ⅰ(cTnI)和肌酸激酶同工酶(CK-MB),并进行相关性分析和不同心功能级别VMC患儿h-FABP比较.结果:病毒性心肌炎患儿血清h-FABP、cTnI和CK-MB水平较健康对照组明显升高(P均<0.01),治疗后较治疗前明显下降(P<0.01).h-FABP与cTnI、CK-MB水平呈显著正相关(r=0.754,0.683,P<0.01).心功能分级不同,h-FABP水平不同,心功能愈差,h-FABP水平愈高,差异有统计学意义(P<0.05).结论:血清h-FABP水平可作为病毒性心肌炎诊断及判断心功能及预后的指标.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.