胰岛素样生长因子、瘦素与胎儿生长受限的相关性研究

目的探讨胰岛素样生长因子一1(Insulin-like growth factor-1,IGF-1)、瘦素与胎儿生长发育的关系,分析小于胎龄儿及宫内发育迟缓儿的原因。方法血清及脐血瘦素水平测定采用放射免疫法(RIA),血清及脐血IGF-1水平测定采用免疫放射法(IRMA),比较两组孕妇血清及脐血中IGF-1、瘦素水平。结果 FGR组孕妇血清瘦素为(24.56±2.37)ng/L,IGF-1为(136.45±10.46)ng/L;脐血瘦素为(5.68±0.34)ng/L,IGF-1为(66.37±3.42)ng/L,与对照组[(25.01±1.96)ng/L]比较两组孕妇血清瘦素比较无统计学意义(P>0.05)。FGR组脐血瘦素水平明显低于对照组[(9.25±1.22)ng/L],差异有统计学意义(P<0.05)。FGR组血清及脐血IGF-I水平低于对照组,两组比较有统计学意义(P<0.01)。结论瘦素与IGF一1在胎儿宫内生长和发育过程中起重要的调节作用,可评价胎儿的生长发育及营养状态。     

孕妇血清中可溶性endoglin水平与特发性胎儿生长受限的关系

目的 探讨血压正常孕妇血清中可溶性Eng水平与特发性胎儿生长受限（FGR）发生的相关性.方法 收集我院2008年11月至2009年11月分娩FGR的孕妇13例为FGR组,选择同期住院分娩的健康孕妇15例为对照组,采用酶联免疫吸附试验检测2组孕妇血清中可溶性Eng水平,分析血清中可溶性Eng水平与FGR发生的相关性并将血清中可溶性Eng水平与胎儿出生体质量作直线回归分析.结果 FGR组孕妇血清中可溶性Eng的水平为（20.0±4.0）μg/L,高于对照组的（4.46±1.71）μg/L,2组比较,差异有统计学意义（t=13.7,P＜0.05）;FGR组孕妇血清中可溶性Eng水平与胎儿出生体质量有负相关关系（r=-0.79,P＜0.05）,而对照组无明显相关性（r=0.07,P＞0.05）.结论 孕妇血清中可溶性Eng水平升高可能与FGR的发生有独立的相关性,并与胎儿出生体质量呈负相关关系.     

晚期妊娠糖尿病血清总蛋白、视黄醇结合蛋白 4水平与胎儿生长受限的相关性分析

目的 探究总蛋白(TP)、视黄醇结合蛋白4(RBP4)在晚期妊娠糖尿病(GDM)病人血清中水平与胎儿生长受限(FGR)的关系.方法 选取2017年3月至2019年10月海南医学院第一附属医院确诊的142例晚期GDM病人进行研究,其中发生FGR的40例为FGR组,新生儿出生体质量正常的102例为正常体质量组.分析比较两组临床资料;检测并比较两组孕妇血清TP水平;以酶联免疫吸附法(ELISA)检测两组孕妇血清RBP4水平;采用受试者特征工作曲线(ROC)评价血清TP、RBP4水平对FGR的诊断价值;logistic回归分析晚期GDM病人发生FGR的影响因素.结果 FGR组孕妇血清空腹血糖(FBG)、空腹胰岛素(FINS)、稳定型评价胰岛素抵抗指数(HOMA-IR)、RBP4水平均明显高于正常体质量组[(5.35±1.48)比(4.22±1.27)mmol/L,(81.52±39.67)比(72.87±33.54)pmmol/L,(18.16±5.53)比(12.42±4.46),(40.47±9.23)比(26.95±6.12)mg/L](P<0.05),血清TP水平明显低于正常体质量组[(52.56±7.15)比(68.98±9.53)g/L](P<0.05);血清TP、RBP4水平对FGR诊断的曲线下面积(AUC)分别为0.872、0.823,截断值分别为63.99 g/L、30.44 mg/L,此时相应灵敏度分别为86.7％、72.4％,对应特异度分别为75.5％、77.5％,血清TP、RBP4联合诊断FGR的AUC为0.921,其灵敏度、特异度分别为75.5％、94.1％;FBG、HOMA-IR、RBP4是影响晚期GDM发生FGR的危险因素(P<0.05),TP是影响晚期GDM发生FGR的保护因素(P<0.05).结论 晚期GDM病人血清TP、RBP4水平与FGR密切相关,两者水平有助于预测晚期GDM病人发生FGR.     

脐血流在胎儿生长受限中的应用

目的探讨胎儿生长受限(FGR)脐血流变化规律及其对围生儿预后的影响。方法 98例FGR组和100例正常孕妇组,进行脐动脉血流速度测定(脐动脉阻力指标S/D)。结果 FGR胎儿脐血流S/D增高率、围生儿预后不良发生率明显高于正常孕妇组(P<0.05)。结论对并发FGR孕妇常规进行胎儿脐血流阻力检测,早期干预,改善FGR围生儿预后。     

低分子肝素治疗胎儿生长受限的疗效

目的 观察低分子肝素治疗胎儿生长受限(FGR)的临床效果.方法 FGR孕妇52例分为治疗组和对照组,每组26例.治疗组在一般治疗基础上给予低分子肝素,对照组在一般治疗基础上给予低分子右旋糖酐加复方丹参注射液.比较两组治疗前后胎儿生长和脐血流变化情况,同时监测各项凝血指标,并记录新生儿出生情况及胎盘重量.结果 治疗组孕妇宫高和腹围增长高于对照组[(0.8±0.5) cm vs.(0.5±0.6) cm和(2.5±1.8) cm vs.(1.1±0.8)cm] (P＜0.05),胎儿双顶径、股骨长、头围及腹围的增长均明显高于对照组(P＜0.05);治疗组脐动脉收缩期最大血流速度与舒张末期血流速度比值(S/D)、搏动指数(PI)、阻力指数(RI)均明显低于对照组(P＜0.05);治疗组新生儿胎龄、出生体重、身长及胎盘重量均明显高于对照组(P＜0.05).两组孕妇治疗前后血小板(Plt)、血红蛋白(Hb)、凝血酶原时间(PT)、部分凝血活酶时间(APTT)差异均无统计学意义(P＞0.05).结论 低分子肝素治疗胎儿生长受限安全有效.     

Correlation between angiopietion-2 and Endoglin and fetal growth restriction

目的 探讨促血管生成素2(Ang-2)和Endoglin(Eng)在孕妇血清中的水平和在胎盘组织中的表达与胎儿生长受限( FGR)发病的关系.方法 选取剖宫产分娩的FGR孕妇30例作为FGR组,同期剖宫产分娩的正常足月孕妇30例作为对照组.采用ELISA测定孕妇血清中Ang-2、可溶性Endoglin(sEng)的水平;采用SP检测胎盘组织中Ang-2、Eng的表达.结果 (1)FGR组血清Ang-2为(8.86±0.43) ng/ml,显著低于对照组的(19.31±0.25) ng/ml(P＜0.01);FGR组sEng为(4.63±0.09) ng/ml,显著高于对照组的(2.77±0.09) ng/ml(P＜0.01).FGR组胎盘组织Ang-2的表达为118.17±1.59,显著低于对照组的151.64±1.64(P＜0.01);FGR组胎盘组织Eng的表达为106.04±1.12,显著高于对照组的92.64±1.26(P＜0.01).(2)FGR组胎盘组织中Ang-2的表达与孕妇血清Ang-2水平呈正相关(r=0.93,P＜0.01);FGR组胎盘组织中Eng的表达与孕妇血清中sEng水平呈正相关(r=0.88,P＜0.01);FGR组胎盘组织中Ang-2的表达与Eng的表达无相关性;FGR组孕妇血清Ang-2水平与sEng水平无相关性.结论 血清Ang-2水平和胎盘组织中表达显著降低,血清sEng和胎盘组织Eng表达水平显著升高可能参与了FGR的发病过程.     

妊娠期高血压综合征患者甲胎蛋白水平及其对围生儿预后的影响

目的 探讨妊娠期高血压综合征(PIH)患者血清甲胎蛋白(AFP)水平及其对围生儿预后的影响,为临床预测PIH及围生儿预后提供依据.方法 采用放射免疫法测定118例PIH孕妇(PIH组)和160例正常孕妇(对照组)的血清AFP水平,并随访至分娩,分析PIH患者血清AFP水平与妊娠结局及围生儿预后的相关性.结果 PIH组血清AFP水平为(209.88±34.18)μg/L明显高于对照组的(177.58±32.67)μg/L,差异有统计学意义(P<0.05);重度亚组血清AFP水平高于轻度、中度亚组孕妇及对照组,差异均有统计学意义(P<0.05).PIH组中AFP水平≥250μg/L足月小样儿发生率、孕妇新生儿出生1min Apgar评分≤7分者百分率及围生儿病死率均高于<250μg/L者,差异均有统计学意义(P＜0.05).结论 孕妇血清AFP水平可作为判断PIH病情轻重及判断围生儿预后的指标.     

促血管生成素2和Endoglin与胎儿生长受限的相关性

目的探讨促血管生成素2(Ang-2)和Endoglin(Eng)在孕妇血清中的水平和在胎盘组织中的表达与胎儿生长受限(FGR)发病的关系。方法选取剖宫产分娩的FGR孕妇30例作为FGR组,同期剖宫产分娩的正常足月孕妇30例作为对照组。采用ELISA测定孕妇血清中Ang-2、可溶性Endoglin(sEng)的水平;采用SP检测胎盘组织中Ang-2、Eng的表达。结果 (1)FGR组血清Ang-2为(8.86±0.43)ng/ml,显著低于对照组的(19.31±0.25)ng/ml(P<0.01);FGR组sEng为(4.63±0.09)ng/ml,显著高于对照组的(2.77±0.09)ng/ml(P<0.01)。FGR组胎盘组织Ang-2的表达为118.17±1.59,显著低于对照组的151.64±1.64(P<0.01);FGR组胎盘组织Eng的表达为106.04±1.12,显著高于对照组的92.64±1.26(P<0.01)。(2)FGR组胎盘组织中Ang-2的表达与孕妇血清Ang-2水平呈正相关(r=0.93,P<0.01);FGR组胎盘组织中Eng的表达与孕妇血清中sEng水平呈正相关(r=0.88,P<0.01);FGR组胎盘组织中Ang-2的表达与Eng的表达无相关性;FGR组孕妇血清Ang-2水平与sEng水平无相关性。结论血清Ang-2水平和胎盘组织中表达显著降低,血清sEng和胎盘组织Eng表达水平显著升高可能参与了FGR的发病过程。     

胎儿生长受限时孕妇血及脐血中Mg2＋水平与胎盘病理变化的关系研究

目的 研究胎儿生长受限（FGR）时孕妇血及脐血中Mg2＋水平与胎盘病理变化之间的关系,探讨FGR的发病机制.方法 选取本院2011年3月～2013年6月收治的妊娠合并FGR患者32例作为观察组,选取同时期正常孕妇32例作为对照组,利用自动生化分析仪对孕妇血、脐血中Mg＋水平进行分析,利用光镜对两组孕妇的胎盘和胎儿附属物进行观察.结果 观察组孕妇血与脐血中Mg2＋水平显著低于对照组,差异有统计学意义（P＜0.05）;胎盘病理变化发生率显著高于对照组,差异有统计学意义（P＜0.05）.结论 在FGR时孕妇血和脐血中Mg2＋水平显著降低,导致胎盘与胎儿之间的血液循环受到的阻力加大,向胎盘灌注的血流减少,导致缺氧缺血现象发生,致使胎盘病理变化显著增加.     

孕妇外周血、脐血中Ang-1、Ang-2的表达与胎儿生长受限的相关性研究

目的探讨孕妇外周血、新生儿脐血中促血管生成素-1（Ang-1）、促血管生成素-2（Ang-2）的表达及其与胎儿生长受限（FGR）发病的关系。方法选择2010年7月至2012年10月在潍坊市人民医院产科住院分娩的FGR孕妇30例作为实验组,正常妊娠妇女60例作为对照组。酶联免疫法（EusA）检测两组孕妇外周血、新生儿脐血中Ang-1、Ang=2的浓度。结果（1）FGR组孕妇血清中Ang-1水平高于对照组,Ang-2水平低于对照组,差异均有统计学意义（P〈0．05）。（2）FGR组新生儿脐血中Ang-1水平高于对照组,Ang-2水平低于对照组,差异均有统计学意义（P〈0．05）。（3）FGR孕妇外周血、新生儿脐血中Ang-1／Ang-2水平显著高于对照组,差异有统计学意义（P〈O．05）。（4）FGR组孕妇外周血、新生儿脐血中Ang_1／Ang-2与新生儿体重及胎盘重量呈负相关（P〈0．05）。结论孕妇外周血、脐血中Ang-1与Ang-2表达失调与FGR的发病密切相关。     

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.