溴隐亭不同给药方案治疗高泌乳素血症女性性腺激素促排卵临床研究

目的:研究溴隐亭不同给药方案在治疗高泌乳素血症(HPRL)女性不育症中的临床疗效,关注其对女性促性腺激素诱导排卵的影响。方法:本研究共纳入60例就诊于我院的确诊为高泌乳素血症不孕不育患者,随机分为两组。分为研究组与对照组:研究组采取先口服溴隐亭调整血清泌乳素水平至正常后予以促性腺激素诱导排卵;对照组采取促性腺激素与溴隐亭同步治疗方案。结果:观察两组患者的促排卵周期数、平均用药天数、雌二醇水平及妊娠率,两组治疗前后的血清泌乳素都显著改善(P0.05);但是两组之间相比,采取溴隐亭药物治疗后诱导排卵的研究组在促排卵、雌二醇水平和妊娠率方面具有显著优势(P0.05)。结论:采用溴隐亭治疗高泌乳素血症患者,调整至正常后再使用促卵泡激素药物促排卵治疗不孕不育具为较优的治疗方案。     

中药当归枸杞子汤调节高泌乳素血症临床观察

目的通过连续动态监测泌乳素血液浓度,评价当归枸杞子汤对高泌乳素血症的调节作用。方法选择我院2012年5月~2013年5月门诊收治的高泌乳素血症患者130例,随机分为对照组30例,采用溴隐亭治疗;观察组100例,给予中药当归枸杞子汤治疗。连续动态监测血清泌乳素浓度,评价两组疗效。结果两组患者疗效比较无显著统计学意义(P0.05)。两组治疗后血清泌乳素均显著下降,与治疗前比较差异有统计学意义(P0.05);而两组治疗后比较差异无统计学意义(P0.05)。不良反应发生率比较,对照组显著高于观察组(P0.05)。结论中药当归枸杞子汤治疗高泌乳素血症安全、有效,且价格低廉,用法简单,有显著的临床推广应用价值。     

血清泌乳素水平对泌乳素瘤患者的临床价值研究

目的:分析术前血清泌乳素水平对泌乳素瘤患者的临床价值。方法:选择2011年1月至2016年12月于青岛大学附属医院行垂体腺瘤切除术且术前测得泌乳素(prolactin,PRL)水平、术后行病理免疫组化染色的垂体腺瘤164例,通过Spearman相关分析PRL水平与肿瘤大小的相关性,通过Kappa值判断PRL水平与病理诊断的一致性。采用ROC曲线获得PRL水平最佳临床诊断临界值。结果:(1)164例垂体瘤患者中,病理诊断单激素PRL瘤25例,主要表现为男性性功能低下及头痛、头晕,女性月经紊乱、闭经、泌乳;(2)术前PRL水平与年龄、性别无显著相关性(P均0.05),与肿瘤大小呈中度正相关(r=0.530,P0.05);(3)以正常范围上限值(23.3 ng/m L)为基线,分别以PRL23.3 ng/mL(1倍)、46.6 ng/m L(2倍)、69.9 ng/ml(3倍)、100 ng/mL、150 ng/m L、200 ng/mL为诊断标准,与病理免疫组化的一致性分析显示PRL69.9ng/m L作为诊断标准时符合率和Kappa系数最高,分别为82.3%和0.533;(4)以病理免疫组化作为诊断金标准作泌乳素瘤ROC曲线,以血清PRL为69.785 ng/m L作为诊断标准时,曲线下面积最大,此时符合率和Kappa系数分别为82.3%和0.553,灵敏度49.1%,特异度98.3%。结论:泌乳素瘤血清学诊断与病理免疫组化诊断一致性较高,血清PRL水平69.9 ng/mL(3倍于正常上限值)是诊断泌乳素瘤的最佳参考值。     

严重高甘油三酯血症小鼠血液流变学的异常分析

目的:本研究旨在检测两种严重高甘油三酯血症(HTG)小鼠的血液流变学,建立具有异常血液流变学特点的HTG小鼠模型,以应用于进一步的相关机制研究。方法:采用ApoC3转基因与GPIHBP1基因敲除的HTG小鼠及野生型小鼠,所用小鼠均为C57BL/6J背景下8周龄雄性小鼠,通过生物物理法检测和比较其血浆粘度、红细胞渗透脆性、变形性与电泳率。结果:与野生小鼠相比,ApoC3转基因与GPIHBP1基因敲除的HTG小鼠血浆甘油三酯含量明显升高(P0.05),红细胞渗透脆性显著增加(P0.05),变形指数与电泳率明显降低(P0.05),血浆粘度显著升高(P0.05),但血细胞计数等血常规指标均未见显著差异(P0.05)。结论:Apo C3tg与GPIHBP1KO小鼠血液流变学发生异常改变,可能作为探讨HTG血液流变学异常和动脉粥样硬化心血管疾病病理机制的动物模型。     

高胆红素血症新生儿肠道菌群特点与苯巴比妥治疗效果的相关性

摘要 目的：探讨与分析高胆红素血症新生儿肠道菌群特点与苯巴比妥治疗效果的相关性。方法：选择2020年6月到2022年6月在本院诊治的565例高胆红素血症新生儿作为研究对象,所有患儿都给予苯巴比妥治疗,检测新生儿肠道菌群与血清α-谷胱甘肽-s-转移酶（α-GST）、肌酸激酶同工酶（CK-MB）、胆红素含量,判定患儿的治疗效果并进行相关性分析。结果：565例患儿治疗7 d后,有效490例（有效组）,有效率为86.7 %。有效组的血清胆红素、经皮胆红素含量都明显低于无效组（P<0.05）。有效组的血清α-GST、CK-MB含量都明显低于无效组（P<0.05）。有效组的肠球菌属、埃希氏菌属、链球菌属相对丰度均低于无效组,拟杆菌属相对丰度明显高于无效组（P<0.05）。在565例患儿中,Spearsman分析显示苯巴比妥治疗效果有效与肠球菌属、埃希氏菌属、链球菌属、拟杆菌属相对丰度都呈现相关性（P<0.05）。结论：苯巴比妥治疗新生儿高胆红素血症的效果有待提高,通过胆红素、α-GST、CK-MB、肠道菌群检测能有效判定患儿的治疗效果,同时肠道菌群与治疗效果存在相关性。     

高尿酸血症与肾脏疾病关系的研究进展

高尿酸血症(HUA)是血尿酸(UA)增高的一种疾病,也是常见的机体代谢紊乱,临床上大多数HUA患者无明显的症状。由于经济水平提高和生活方式的改变,其发病率有增高趋势,且男性高于女性。HUA多发于中老年人群,严重影响其生活质量,因此中老年人群HUA已经成为普遍关注的健康问题。近年来研究发现HUA是痛风的主要病因之一,并且血尿酸(UA)水平可导致肾功能减退。已有多项研究表明HUA与肾脏疾病的发生发展密切相关,HUA是Ig A肾病、糖尿病肾病、急性肾损伤等肾脏疾病的独立危险因素,本文主要从HUA的流行病学、危险因素、发病机制及其与肾脏疾病关系这几个方面展开综述。     

贵州省1例家族性高胆固醇血症家系基因突变筛查与评估

摘要 目的：探讨贵州省1例家族性高胆固醇血症（FH）家系基因突变筛查与评估结果。方法：参照荷兰脂质诊断网络（DLCN）指南诊断标准于2021年11月-2022年11月贵阳市某三甲医院选取1例临床诊断FH的患者进行研究,分析其家系系谱,采用C8000型全自动生化分析仪检测家系成员总胆固醇（TC）、甘油三酯（TG）、LDL-C、高密度脂蛋白胆固醇（HDL-C）水平;并采集家系临床相关数据,收集血清样本提取白细胞DNA进行全基因组外显子测序致病基因,筛选出4个FH相关基因[低密度脂蛋白受体（LDLR）、载脂蛋白B（ApoB）、西布曲明9a型（PCSK9）、LDLR衔接蛋白1（LDLRAP1）]的单核苷酸多态性（SNP）位点情况,采用Polyphen-2和SIFT软件对SNP位点进行致病性分析;同时回顾性分析双重滤过血浆置换(DFPP)吸附治疗期间的心血管疾病发生情况及治疗前后的载脂蛋白A（ApoA）、载脂蛋白E（ApoE）、载脂蛋白B（ApoB）、脂蛋白a（LPa）、TC、TG、HDL-C、LDL-C、游离脂肪酸（FFA）水平变化情况。结果：该家系Ⅰ-1成员血清LDL-C达8.16 mmol/L,Ⅱ-1成员血清LDL-C达7.0 mmol/L,Ⅱ-2成员血清LDL-C达3.45 mmol/L,按照DLCN标准,Ⅰ-1评7分,Ⅱ-1评6分,均提示患FH可能性大,达到FH临床诊断标准。利用Polyphen-2预测,该家系ApoB基因中rs676210、rs679899分别得分0.999、0.998,1个新位点c.10094A＞T得分为0.829,均提示可能致病,SIFT软件预测以上三个位点均有害。DFPP治疗后患者病情稳定,至今无心绞痛严重心血管事件发生。与吸附治疗前比较,吸附治疗后ApoA、ApoE、ApoB、LPa、TG、HDL-C、LDL-C、TC水平较低FFA水平较高,差异有统计学意义（P＜0.05）。结论：ApoB基因SNP位点突变很可能是该家系引起FH的主要原因,而DFPP治疗有利于调节FH患者血脂水平,进而降低心血管疾病的发生风险。     

血清cTnI、CK-MB及IGF-1在新生儿高胆红素血症中的变化及临床意义

摘要 目的：分析血清肌钙蛋白T( troponin T,cTnT)、肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)及胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)在新生儿高胆红素血症中变化及临床价值。方法：选择2015年1月至2019年12月我院新生儿科收治的80例新生儿高胆红素血症足月新生儿(观察组)以及80例非胆红素足月新生儿(对照组)为研究对象。收集住院资料,包括所有患儿的胎龄、日龄、出生体重、血清总胆红素（total bilirubin,TBIL）、CK-MB、cTnT、IGF-1、头颅核磁共振(skull magnetic resonance,MRI)、临床表现等及出院后随访资料。根据胆红素水平高低,将观察组分为轻度(33例)、中度组(27例)及重度组(20例),比较其：TBIL、IGF-1、CK-MB、cTnT水平。结果：各组新生儿TBIL、CK-MB、cTnT水平比较差异具有统计学意义(P＜0.05)。重度黄疸组TBIL、CK-MB、cTnT值分别高于轻度、中度黄疸组和对照组,IGF-1低于轻度、中度黄疸组和对照组(P＜0.05);中度黄疸组TBIL、CK-MB、cTnT高于轻度黄疸组和对照组,IGF-1低于轻度黄疸组和对照组(P＜0.05);轻度黄疸组TBIL、CK-MB、cTnT高于对照组,IGF-1低于对照组(P＜0.05)。血清cTnT与TBIL水平呈正相关(r=0.587,P＜0.05);血清CK-MB与TBIL水平无明显相关性(r=0.220,P＞0.05);血清IGF-1与TBIL水平呈负相关（r=-0.568,P＜0.05）。苍白球异常信号组患儿血清IGF-1值为(11.05±0.51) ng/mL,明显低于苍白球正常信号组(14.22±2.67) ng/mL(P＜0.05);苍白球异常信号组患儿血清TBIL水平为(347.62±33.01)μmol/L与苍白球正常信号组(341.75±35.14)μmol/L无明显差别(P＞0.05)。结论：检测血清cTnT和IGF-1水平分别有助于预测新生儿高胆红素血症心肌损伤和脑病的发生。     

首次发病精神分裂症患者早期认知功能改变研究

目的:探讨首次发病精神分裂症患者早期认知功能损伤情况。方法:选取我院2015年1月~2016年1月收治的73例首次发病精神分裂症患者(研究组)和75例健康者(对照组)作为研究对象,采用神经心理测验工具评估两组对象认知功能并进行比较。结果:BVMT-R试验中研究组延迟回忆、回忆总数、3试、2试和1试得分均低于对照组,差异有统计学意义(P0.05)。HVLT-R试验中研究组延迟总数、3试和2试得分均低于对照组,差异有统计学意义(P0.05)。研究组沟槽钉板测验中利手与非利手耗时均高于对照组,连线测验中连线测验A、颜色连线1及2完成时间均高于对照组,差异均有统计学意义(P0.05)。PASAT测试中研究组尝试数和正确数均低于对照组,差异有统计学意义(P0.05)。WAIS-Ⅲ测试中研究组符合搜索错误数目高于对照组,而符号搜索正确数目、符号搜索总分及数字符号分数均低于对照组,差异有统计学意义(P0.05)。Stroop色词测验中研究组单词总数、颜色总数和色/词总数均低于对照组,差异有统计学意义(P0.05)。WMS-Ⅲ测验结果组间比较差异无统计学意义(P0.05)。结论:首次发病精神分裂症患者早期认知功能广泛损伤。     

允许性高碳酸血症在腹腔镜直肠癌手术中的应用及对循环的影响

目的:研究允许性高碳酸血症在腹腔镜直肠癌手术中的应用效果、最佳适宜范围及对患者循环功能的影响。方法:选取沧州市中心医院拟择期行腹腔镜直肠癌手术的患者90例,随机分为试验1组、2组和对照组3组,每组30例。试验1组血二氧化碳分压(partial pressure of carbon dioxide,PaCO_2)维持在56～65 mm Hg,试验2组PaCO_2维持在46～55 mm Hg,对照组PaCO_2维持在35～45 mm Hg。观察并比较三组患者气腹时间、机械通气时间、手术时间、拔管时间、苏醒时间,气腹前10 min(T_1)、气腹后1 h(T_2)、气腹后2 h(T_3)、放气后15 min(T_4)时间点的平均动脉压、心率、气道峰压,计算动态肺顺应性、氧合指数,记录皮下气肿、呕吐、烦躁及术后认知功能障碍等并发症的发生情况。结果:三组患者手术时间、气腹时间、机械通气时间、拔管时间和苏醒时间比较差异无统计学意义(P0.05)。与对照组相比,试验组T_2、T_3时心率(heart rate,HR)、血氧分压(partial pressure of oxygen,PaO_2)、肺动态顺应性(lung dynamic compliance,Cdyn)均明显升高,P_(max)明显下降(P0.05);与T_1相比,试验组T_2、T_3时HR、气道峰压(Pmax)、PaO_2均升高,Cdyn下降(P0.05);与试验2组比较,试验1组HR、P_(max)明显更低,PaO_2、Cdyn明显更高(P0.05),但三组氧合指数(oxy-genation Index,OI)比较差异无统计学意义(P0.05)。与对照组相比,试验组T_2、T_3时动脉血二氧化碳分压(partial pressure of car-bon dioxide,PaCO_2)、Qs/Qt均升高,氢离子浓度指数(hydrogen ion concentration,pH)、平均动脉压(mean arterial pressure,MAP)下降;与T_1相比,试验组T_2、T_3时PaCO_2、Qs/Qt均升高,pH、MAP下降;与试验2组比较,试验1组PaCO_2、PaCO_2明显更低,pH明显更高(P0.05),但三组MAP比较差异无统计学意义(P0.05)。手术开始30 min和1 h,试验组中心静脉压(central venous pressure,CVP)、心输出量(cardiac output,CO)以及心脏指数(cardiac index,CI)较对照组更低,而试验1组较试验2组明显更低(P0.05)。三组并发症的改善情况比较差异无统计学意义(x~2=0.1973,P=0.9954)。治疗后,试验组MMSE评分较治疗前明显降低,且试验组明显高于对照组,而试验1组又显著高于试验2组(P0.05)。结论:允许性高碳酸血症在长时间腹腔镜直肠癌手术中在保障氧合同时降低气道压改善肺的顺应性,可一定程度上减少术后认知功能障碍的发生,有一定的脑保护作用。     

Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment

A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at baseline, reduced levels of antioxidant enzymes were associated with increased plasma lipid peroxides and reduced membrane EPUFAs, particularly omega-3 fatty acids. Furthermore, these biochemical measures normalized after 6 months of antipsychotic treatment. Parallel-improved psychopathology indicated that membrane EPUFA status might be partly affected by oxidative damage, which together may contribute to the pathophysiology and thereby, psychopathology of schizophrenia. These data also support the augmentation of antipsychotic treatment by supplementation with a combination of antioxidants and omega-3 fatty acids.     

N-Methylanilide and N-methylbenzamide derivatives as phosphodiesterase 10A (PDE10A) inhibitors

PDE10A is a recently identified phosphodiesterase with a quite remarkable localization since the protein is abundant only in brain tissue. Based on this unique localization, research has focused extensively on using PDE10A modulators as a novel therapeutic approach for dysfunction in the basal ganglia circuit including Parkinson’s disease, Huntington’s disease, schizophrenia, addiction and obsessive compulsive disorder. Medicinal chemistry efforts identified the N-methyl-N-[4-(quinolin-2-ylmethoxy)-phenyl]-isonicotinamide (8) as a nanomolar PDE10A inhibitor. A subsequent Lead-optimization program identified analogous N-methylanilides and their corresponding N-methylbenzamides (29) as potent PDE10A inhibitors, concurrently some interesting and unexpected binding modes were identified.     

Effects of the putative antipsychotic alstonine on glutamate uptake in acute hippocampal slices

A dysfunctional glutamatergic system is thought to be central to the negative symptoms and cognitive deficits recognized as determinant to the poor quality of life of people with schizophrenia. Modulating glutamate uptake has, thus, been suggested as a novel target for antipsychotics. Alstonine is an indole alkaloid sharing with atypical antipsychotics the profile in animal models relevant to schizophrenia, though divergent in its mechanism of action. The aim of this study was to evaluate the effects of alstonine on glutamate uptake. Additionally, the effects on glutathione content and extracellular S100B levels were assessed. Acute hippocampal slices were incubated with haloperidol (10 μM), clozapine (10 and 100 μM) or alstonine (1–100 μM), alone or in combination with apomorphine (100 μM), and 5-HT₂ receptor antagonists (0.01 μM altanserin and 0.1 μM SB 242084). A reduction in glutamate uptake was observed with alstonine and clozapine, but not haloperidol. Apomorphine abolished the effect of clozapine, whereas 5-HT_2A and 5-HT_2C antagonists abolished the effects of alstonine. Increased levels of glutathione were observed only with alstonine, also the only compound that failed to decrease the release of S100B. This study shows that alstonine decreases glutamate uptake, which may be beneficial to the glutamatergic deficit observed in schizophrenia. Noteworthily, the decrease in glutamate uptake is compatible with the reversal of MK-801-induced social interaction and working memory deficits. An additional potential benefit of alstonine as an antipsychotic is its ability to increase glutathione, a key cellular antioxidant reported to be decreased in the brain of patients with schizophrenia. Adding to the characterization of the novel mechanism of action of alstonine, the lack of effect of apomorphine in alstonine-induced changes in glutamate uptake reinforces that D₂ receptors are not primarily implicated. Though clearly mediated by 5-HT_2A and 5-HT_2C serotonin receptors, the precise mechanisms that result in the effects of alstonine on glutamate uptake warrant elucidation.     

Are Striatal Dopamine D4 Receptors Increased in Schizophrenia?

Abstract: The density of dopamine D₂-like receptors was determined using [³H]emonapride binding in putamen tissue taken postmortem from schizophrenic subjects and matched controls. A 72% increase in number of these receptors was identified in the schizophrenics, although three patients not receiving antipsychotic drug treatment before death exhibited receptor densities in the control range. Displacement of 1 n M [³H]emonapride binding by raclopride was used to define the contribution of the D₄ subtype of dopamine receptors to total [³H]emonapride binding. No evidence was obtained for the presence of D₄ receptors in putamen tissue from either control or schizophrenic subjects, indicating that the increase in D₂-like receptor density in schizophrenia is due not to an increase in number of D₄ sites in the disease, but to an up-regulation of D₂ or D₃ receptors probably induced by chronic treatment with antipsychotic drugs.     

Haloperidol and atypical antipsychotics share a same action of decreasing P75(NTR) mRNA levels in PC12 cells

P75(NTR) is a common neurotrophin receptor which binds all neurotrophins with similar affinities and has been shown to be capable of mediating programmed cell death. In this study, we investigated effects of the antipsychotic drugs (APDs) haloperidol, clozapine, quetiapine, and risperidone on p75(NTR) mRNA levels in PC12 cells. Haloperidol is a prototype of typical APDs, and the other three drugs are atypical APDs, which are effective in reducing negative symptoms and cognitive deficits of schizophrenia, cause less side effects, and are more tolerable compared to haloperidol. PC12 cells were cultured with various concentrations of haloperidol, clozapine, quetiapine, or risperidone, in their media. After culture for 48h, the cell viabilities and p75(NTR) mRNA levels were measured. It was shown that both haloperidol and the atypical APDs used in this study deceased p75(NTR) mRNA levels in PC12 cells in a dose dependent manner, while not affecting cell viabilities. In further experiments, doses that produced significant/greatest effects were chosen and provided in the culture media for various periods. Decreases in p75(NTR) mRNA levels were observed in cultures treated for 12h with quetiapine, 24h with clozapine or risperidone, or for 48h with haloperidol. These results suggest that both haloperidol and atypical APDs have the same action of decreasing p75(NTR) mRNA levels in PC12 cells. Although the underlying molecular mechanism of this action remains to be elucidated, this finding is particularly relevant given the neurodevelopmental deficits associated with schizophrenia and important roles of p75(NTR) in mediating cell death.     

Differential Effects of Locally Administered Clozapine and Haloperidol on Dopamine Efflux in the Rat Prefrontal Cortex and Caudate-Putamen

Abstract: Previous research has shown that systemically administered antipsychotic drugs enhance dopamine release from the nigrostriatal and mesocortical dopamine pathways. However, the degree of enhancement differs as a function of the drug used (atypical versus typical antipsychotic) and the dopamine pathway examined. The present studies examined whether these differences result from differential actions of these drugs on dopamine terminal regions. Clozapine or haloperidol was infused locally into the caudate-putamen or prefrontal cortex through reverse microdialysis. Although both drugs increased extracellular dopamine levels, clozapine produced greater effects than haloperidol in the prefrontal cortex, whereas haloperidol produced greater effects in the caudate-putamen. These results suggest that neurochemical differences within dopamine terminal regions may explain the differential actions of antipsychotic drugs on striatal and cortical dopamine release.     

Effects of metachlopromide-induced hyperprolactinemia on serum testosterone and its response to hCG in adult male common marmosets (Callithrix jacchus)

Intramuscular administration of metachlopromide (2.5, 10, and 25 mg) induced increase in serum prolactin levels. Following 10 and 25 mg dose levels, prolactin levels were elevated at least for 8 hr. Single administration of metachlopromide failed to affect the nocturnal rise in circulating levels of testosterone. Daily treatment of metachlopromide (10 mg) for 30 days suppressed the nocturnal elevation of testosterone on day 28 of treatment. However, the hCG-stimulated testosterone production on day 30 was unaffected. The results of the present study demonstrate that metachlopromide-induced hyperprolactinemia in adult male common marmosets affects the hypothalamo-pituitary axis without any effect on testicular response to hCG.