首发抑郁症患者血清同型半胱氨酸水平及其与 P300的关系

目的：研究首发抑郁症患者的血清同型半胱氨酸（ Hcy）水平与事件相关电位（ ERP） P300之间的关系。方法选取117例首发抑郁症患者（病例组）及110例健康志愿者（健康对照组）,采用酶联免疫法测定两组的血清Hcy水平,采用深圳Brain Master脑诱发电位系统完成视觉P300的测定。结果病例组血清Hcy水平为（14．0±9．8）μmol/L,高于健康对照组的（10．5±7．5）μmol/L（t＝-3．087,P＜0．05）。病例组N1、N2潜伏期为（91．4±18．6）ms、（235．4±30．5）ms,较健康对照组的（88．6±13．0）ms、（204．3±20．3）ms延长（t＝1.305,8．990,均P＜0．01）,病例组P3潜伏期为（359．5±30．0）ms,较健康对照组（327．2±41．8）ms延长（t＝6.685,P＜0．05）。病例组靶P3、非靶P2波幅为（4．1±2．0）μV、（4．2±1．9）μV,显著低于健康对照组的（6．8±3.8）μV、（6．6±3．6）μV（ t＝-6．694,-6．485,均P＜0．01）。 HHcy病例组P2潜伏期为（194．4±13．6）ms,较非HHcy病例组的（163．1±21．8）ms延长（t＝8．486,P＜0．01）,HHcy病例组P3潜伏期为（357．0±24．5）ms,较非HHcy病例组的（337．1±45．5）ms延长（t＝2．645,P＜0．05）。 HHcy病例组靶P3、非靶P2波幅为（5．4±1．5）μV、（5．2±1．2）μV,显著低于非HHcy病例组的（5．8±3．8）μV、（5．4±3．2）μV（t＝-0．745,-0．208,均P＜0．01）。结论首发抑郁症患者血清Hcy水平升高,且P300潜伏期延长、波幅降低,Hcy代谢失衡与抑郁症患者的认知功能损害相关。     

青年脑梗死患者血清同型半胱氨酸和尿酸水平与颈动脉粥样硬化斑块稳定性的关系探讨

目的：探讨青年脑梗死患者血清同型半胱氨酸（ Hcy）和尿酸（ UA）水平与颈动脉粥样硬化斑块稳定性的关系。方法150例青年脑梗死患者行颈动脉超声检查,依据结果分为无斑块组37例、稳定斑块组52例和不稳定斑块组61例,测定三组血清Hcy和UA水平,并进行分析比较。结果稳定斑块组Hcy和UA水平分别为（15．92±2．52）μmol/L 和（294．85±25．52）μmol/L,均高于无斑块组（ t ＝7．33、6．89,均P＜0.05）;不稳定斑块组Hcy和UA水平分别为（23．17±3．82）μmol/L和（388．57±26．61）μmol/L,均显著高于无斑块组和稳定斑块组（t＝9．82、10．02、6．90、7．12,均P＜0．05）。结论颈动脉斑块的形成及其稳定性与Hcy和UA水平具有密切相关性。     

血清同型半胱氨酸及高敏C反应蛋白与冠心病相关性分析

目的：探讨血清同型半胱氨酸（ Hcy ）、高敏 C 反应蛋白（ hs-CRP ）与冠心病的相关性。方法测定111例冠心病患者组（冠心病组）及77例健康志愿者（健康对照组） Hcy、hs-CRP水平,分析其与冠心病的关系。应用循环酶法检测Hcy,应用免疫比浊法检测hs-CRP。冠心病组患者根据病情不同分为稳定型心绞痛（ SAP）组、不稳定型心绞痛（ UAP）组、急性心肌梗死（ AMI）组,分析各亚组Hcy、hs-CRP水平差异性。结果冠心病组患者血清Hcy、hs-CRP水平明显高于健康对照组[（21±9）μmol/L比（9±6）μmol/L,（15．1±1．4）mg/L比（1．0±0．9）mg/L]（P＜0．05）。冠心病各亚组比较：AMI组患者血清Hcy、hs-CRP水平明显高于SAP组及UAP组[（24±8）μmol/L比（16±5）、（19±6）μmol/L,（23．7±5．9）mg/L比（4．0±3．0）、（15．4±3．2）mg/L]（P＜0．05）。 UAP组患者血清Hcy水平、血清hs-CRP水平明显高于SAP组[（19±6）μmol/L 比（16±5）μmol/L,（15．4±3．2） mg/L 比（4．0±3．0） mg/L]（P ＜0．05）。结论血清Hcy及hs-CRP水平与冠心病病情相一致,检测血清Hcy及hs-CRP水平可以判断冠心病病情,对于指导治疗有积极的意义。     

血清同型半胱氨酸、维生素B12、叶酸水平与老年性骨折的相关性分析

目的：探究血清同型半胱氨酸（ Hcy）、维生素B12、叶酸水平与老年性骨折的相关性。方法将160例老年性骨折患者作为观察组,在常规治疗基础上,进行维生素B12和叶酸的治疗,同期收集在该院体检中心进行体检的健康老年人130例作为对照组。检测2组Hcy、维生素B12、叶酸水平,并进行比较。比较观察组治疗前后Hcy水平,探讨血清Hcy水平与维生素B12水平、叶酸的相关性。结果观察组血清Hcy水平明显高于对照组,维生素B12、叶酸水平低于对照组,差异均有统计学意义（P＜0．05）;观察组入院时血清Hcy水平为（18．73±5．61）μmol／L高于治疗后的（11．21±4．20）μmol／L,差异有统计学意义（P＜0．05）。观察组老年性骨折患者的血清Hcy水平分别与维生素B12水平、叶酸水平呈负相关（r＝－0．3,－0．2,P均＜0．05）。结论老年性骨折患者Hcy水平明显升高,补充维生素B12、叶酸可降低血清Hcy水平,降低老年性骨折的发生率。     

2型糖尿病肾病患者血清同型半胱氨酸、叶酸及维生素B12水平的相互关系

目的探讨2型糖尿病肾病患者空腹血浆同型半胱氨酸（Hcy）、叶酸（FA）及维生素B12（VitB12）水平的相互关系及其影响因素。方法165例2型糖尿病患者根据尿微量白蛋白排泄率（UAER）分为尿微量白蛋白正常糖尿病组（A组）、早期。肾病组（B组）、临床肾病组（C组）,用酶联免疫吸附试验分别检测各组患者血浆Hey浓度,并同步应用发光免疫法测定血清FA、VitB12水平,与48例正常对照者（D组）进行比较。结果A组：UAERl（1．6±5．2）μg／min、HCY（14．8±3．6）μmol／L、FA（9．02±2．06）nmol／L、VitB12（552±162）pmol／L;B组UAER（82．9±45．8）μg／min、HCY（21．1±2．3）μmol／L、FA（7．85±2．45）nmol／L、VitB12（436±135）pmol／L;C组UAER（348．1±123．2）μg／min、HCY（32．3±2．5）μmol／L、FA（5．78±2．33）nmol／L、VitB12（292±92）pmol／L;D组UAER（10．9±5．3）μg／min、HCY（9．1±2．2）μmol／L、FA（10．39±2．93）nmol／L、VitB12（688±208）pmol／L。各组血Hey水平均明显高于正常对照组（P〈0．05）,C组又高于A组和B组（P〈0．05）,而FA、VitB12水平与对照组相比均显著降低（P〈0．05）,C组又低于A组和B组（P〈0．05）。Hey与UAER呈正相关（P〈0．01）,,与FA、VitB12呈负相关（P〈0。01）。结论定期测定糖尿病患者血浆Hcy、FA和VitB12有助于预测、判断2型糖尿病肾病的发展。     

血清同型半胱氨酸与小儿特发性癫痫的相关性研究

目的探讨血清同型半胱氨酸（Hcy）与小儿特发性癫痫的相关性。方法将81例小儿特发性癫痫患儿（研究组）的血清Hey水平与48例健康儿童（对照组）进行对比分析。结果研究组81例癫痫患儿的Hcy水平为7．6—22．0μmol／L,平均（15．91±2．38）μmol／L,而对照组48例健康儿童的Hcy水平为3—9μmol／L,平均（6．87±1．75）μmol／L。两组间差异有统计学意义（P〈0．05）。对照组小儿仅有6例Hcy水平高于15μmol／L,而研究组中有73例Hcy水平高于15μmol／L,差异有统计学意义（P〈0．05）。同时全身强直．阵挛性发作和简单或复杂性部分性发作两种癫痫之间的Hey水平差异无统计学意义（P〉0．05）。结论小儿特发性癫痫与高Hey血症存在显著关系,在对小儿特发性癫痫患临床治疗时,应密切监控患儿的血清Hcy水平,及时促进Hcy体内代谢。     

胃内容物潜血阳性患者血红蛋白与凝血指标关系分析

目的：探讨胃内容物潜血阳性患者血红蛋白（ Hb）的含量高低与其凝血指标检测结果的关系。方法选择379例胃内容物潜血阳性患者,分为男、女2组,根据男女Hb正常参考范围,将男性患者分为Hb≥120 g／L（ Hb正常组）及Hb＜120 g／L（贫血组）2组;将女性患者分为Hb≥110 g／L（Hb正常组）及Hb＜110 g／L（贫血组）2组;同时男女各设对照组。检测各组血浆凝血酶原时间（ PT）、活化部分凝血活酶时间（ APTT）及D-二聚体（ D-dimer）水平,分别观察上述三种检测指标在男女相应各组间有无差异。结果男女患者各组PT检测结果与对照组比较差异无统计学意义（ P ＞0．05）。 APTT及D-dimer检测结果为男性Hb 正常组[（29．1±3．4）s、（0．23±0．12）g／L]、贫血组[（28．1±2．9）s、（0．45±0．26）g／L]、正常对照组[（30．1±0．6）s、（0．26±0．09）g／L]。贫血组与Hb正常组（ t ＝2．04, P ＜0．05;t ＝3．55, P ＜0．05）及对照组（ t ＝2．23, P ＜0．05;t ＝3．29, P ＜0．05）比较,差异有统计学意义（ P＜0．05）,Hb 正常组与对照组差异无统计学意义（ P ＞0．05）。 APTT和D-dimer检测结果女性Hb正常组[（30．1± 3．4）s、（0．21±0．14）g／L]、贫血组[（29．1±2．8）s、（0．42±0．19）g／L]、对照组[（31．1±3．2）s、（0．22±0．15）g／L]。贫血组与Hb正常组（ t ＝1．99, P ＜0．05;t ＝3．01, P ＜0．05）及对照组（ t ＝2．03, P ＜0．05;t ＝2．83, P ＜0．05）比较,差异有统计学意义（ P ＜0．05）,Hb正常组与对照组比较差异无统计学意义（ P ＞0．05）。结论上消化道出血量较大的患者机体明显处于高凝状态,临床上应考虑给予对症治疗。     

孕妇血清同型半胱氨酸及胱抑素C与妊娠期高血压疾病相关性分析

目的：探讨孕妇血清同型半胱氨酸（Hcy）及胱抑素C（CysC）与妊娠期高血压疾病的相关性。方法选取妊娠期高血压疾病患者60例作为研究组,健康晚期孕妇60例作为健康组,非妊娠期健康女性60例为对照组,比较3组成员血清Hcy和Cys C水平。结果研究组血清Hcy、Cys C水平均高于对照组和健康组,差异有统计学意义（P＜0．05）,健康组孕妇Cys C水平高于对照组,差异有统计学意义（P＜0．05）;健康组血清Hcy水平与对照组比较差异无统计学意义（P＞0．05）。结论检测Hcy和Cys C水平对于预测妊娠期高血压疾病具有重要的临床价值。     

强化阿托伐他汀治疗对非 ST 段抬高型急性冠脉综合征患者同型半胱氨酸和 N 末端 B 型脑钠肽的影响

目的：探讨强化阿托伐他汀治疗对非ST段抬高型急性冠脉综合征患者同型半胱氨酸（ Hcy）和N末端B型脑钠肽（ NT－proBNP）的影响。方法120例非ST段抬高型急性冠脉综合征患者按数字表法随机分为观察组60例、对照组60例,观察组在常规治疗的基础上每晚加用阿托伐他汀40 mg治疗,对照组在常规治疗基础上每晚加用阿托伐他汀20 mg治疗。两组共治疗2个月,比较两组治疗前后血浆Hcy和NT－proBNP的变化。结果观察组、对照组治疗前Hcy分别为（25．5±8．6）μmol／L、（26．3±9．1）μmol／L,治疗后分别为（10．3±4．7）μmol／L、（16．9±7．1）μmol／L;观察组、对照组治疗前NT－proBNP分别为（374．7±39．2） ng／L、（359．6±36．1）ng／L,治疗后分别为（127．4±15．3）ng／L、（237．1±24．3）ng／L。两组治疗后血浆Hcy和NT－proBNP均比治疗前明显降低,治疗后观察组较对照组降低更明显（t＝6．004、29．591,均P＜0．05）。两组患者均未见因明显的肝酶及肌酶升高而导致停药情况的发生。结论强化阿托伐他汀治疗可以明显降低非ST段抬高型急性冠脉综合征患者血浆Hcy和NT－proBNP。     

拉贝洛尔联合甲基多巴治疗妊娠期高血压疾病对患者血清 Hcy及CysC 的影响

目的：观察拉贝洛尔联合甲基多巴对妊娠期高血压疾病患者血清同型半胱氨酸（ Hcy）及胱抑素C （ Cys C）水平的影响。方法将120例妊娠期高血压疾病患者随机分为研究组和对照组各60例。对照组给予硫酸镁治疗,研究组在对照组的基础上加用拉贝洛尔和甲基多巴。比较2组患者治疗前后血清Hcy及Cys C水平变化。结果治疗前2组患者血清Hcy、Cys C水平差异无统计学意义（P＞0．05）,治疗后2组血清Hcy、Cys C水平均有所下降,且研究组下降幅度大于对照组,差异均有统计学意义（P＜0．05）。结论在常规治疗的基础上运用拉贝洛尔及甲基多巴治疗妊娠期高血压疾病可显著降低血清Hcy、Cys C水平。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.