左卡尼汀治疗心功能正常的维持性血液透析患者左心室肥厚的疗效观察

目的：探讨左卡尼汀治疗心功能正常的维持性血液透析患者左心室肥厚的效果。方法选取133例心功能正常的维持性血液透析左心室肥厚患者,按临床用药不同分为左卡尼汀组75例和常规治疗组58例。比较两组左心室舒张末期内径（ LVDd）、左心室射血分数（ LVEF）、左室重量指数（ LVMI）、E/A值。结果左卡尼汀组LVMI、LVDd[（122．6±21．3） g/m^2、（45．3±2．2） mm]较治疗前[（142．5±19．2） g/m^2、（50.3±4．2）mm]显著下降（t＝6．34、5．92,均P＜0．05）,且显著低于常规治疗组[（135．3±19．3） g/m^2、（48．1±3．8）mm]（t＝4．31、4．62,均P＜0．05）;E/A、LVEF较治疗前[（44．3±3．2）、（0．62±0．11）]显著升高（t＝5．78、5．56,均P＜0．05）,且显著高于常规治疗组[（48．1±3．8）、（0．76±0．15）]（t＝4．92、4．11,均P＜0．05）。结论对心功能正常的维持性血液透析患者,左卡尼汀能明显改善心脏功能,逆转患者左心室的肥大。     

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。     

卡维地洛对尿毒症心肌病心力衰竭患者心肾功能的影响

目的观察卡维地洛对尿毒症心肌病患者心、肾功能及心脏结构的影响。方法100例患者随机分为两组，每组50例。一组予以常规治疗（对照组），另一组加用卡维地洛（治疗组）。观察SV、EF、CO、LVEDD、IVST、LVPWT、LVM、LVMI、BUN、Scr、Ccr的变化。结果两组SV、EF、CO、LVEDD、IVST、LVPWT、LVM、LVMI均有所改善（P〈0．01）或（P〈0．001）。治疗组改善高于对照组（P〈0．05），Ccr有增加趋势（P〉0．05），BUN、Scr有下降趋势（P〉0．05）。结论卡维地洛能改善尿毒症心肌病患者的心功能及结构，对肾功能也有改善趋势。     

缺血性心脏病患者血浆基质金属蛋白酶2和基质金属蛋白酶9与心脏重塑关系

目的探测缺血性心脏病（IHD）患者血浆基质金属蛋白酶2（MMP-2）、MMP-9活性水平与心脏重塑指标左心室质量指数（LVMI）之间的关系。方法选取2007年5月至2010年9月北京安贞医院住院的IHD患者254例,根据LVMI不同分为心脏重塑组（128例）和非心脏重塑组（126例）。对照组为214例门诊健康体检心脏功能正常的健康人。利用明胶酶谱方法测定各组受试者血浆MMP．2、MMP-9的活性水平,分析两者与心脏重塑指标的关系。结果心脏重塑组患者血浆MMP-2、MMP-9的活性高于对照组和非心脏重塑组[MMP-2：（13．0±2．9）m2／（g·L^-1）比（8．9±2．3）、（10．9±2．9）m2／（g·L^-1）;MMP-9：（2．6±1．0）m2／（g·L^-1）比（1．4±0．4）、（2．1±0．7）m2／（g·L^-1）,均P〈0．05],非心脏重塑组患者的MMP-2、MMP-9活性水平高于对照组（P〈0．05）。血浆MMP-2、MMP-9活性水平与LVMI明显相关（r=0．464、0．516,均P〈0．05）。结论MMP-2、MMP-9在IHD患者心脏重塑的发生和发展过程中起着一定作用,有可能用来预测IHD患者发生心脏重塑的进展及预后。     

高血压患者左心房内径变化的临床意义

目的探讨原发性高血压病左心房内径变化及临床意义。方法对照组20例．高血压病左心室心肌质量指数（LVMI）正常组35例，高血压病左心室肥厚（LVH）组30例。用超声心动图测量三组左心房内径（LAD）、室间隔厚度（IVST）、左心室后壁厚度（LVPWT）、左室射血分数（LVEF）、左室质量指数（LVMI）、左房室瓣E峰和A峰最大流速比值（E／A），测定静息心率（RHR）并进行对比分析。结果与对照组对比，高血压LVMI正常组LAD扩大较显著（P〈0．05），而IVST、LVPWT、LVMI、E／A、LVEF及RHR无显著变化（P〉0．05）。与对照组相比，高血压病LVH组b∞扩大更显著（P〈0．01），IVST、LVPWT、LVMI、E／A、LVEF及RHR均有显著改变（P〈0．05）。结论在高血压病早期IVST、LVPWT、LVM1、E／A、LVEF及RHR尚无明显异常时，已出现LAD扩大。提示LAD扩大是高血压病心脏受损的最早期表现，比左心室肥厚及E／A〈1更有临床意义。     

腹腔镜手术对子宫内膜异位症不孕患者血清多项指标的影响

目的：观察腹腔镜手术（ LPS ）对子宫内膜异位症（ EMS ）不孕患者血清基质金属蛋白酶－9（MMP－9）、金属蛋白酶抑制因子－1（TIMP－1）和白细胞介素－2（IL－2）、白细胞介素－10（IL－10）的影响。方法选择2012年8月至2013年8月接受手术的EMS患者80例,根据手术方式的不同分为观察组（接受LPS手术治疗）和对照组（接受开腹手术治疗）,每组各40例。观察两组治疗前后血清MMP－9、TIMP－1、MMP－9／TIMP－1和IL－2、IL－10、IL－2／IL－10的变化及术后6个月的受孕情况。结果观察组术后 MMP－9水平[（51．21±24．01）μg／L]比治疗前[（261．88±190．11）μg／L]明显下降,且观察组比对照组下降更明显;观察组TIMP－1水平[（45．88±11．02）μg／L]比对照组[（25．32±6．67）μg／L]明显上升（t＝4．846,P＜0．05）;观察组MMP－9／TIMP－1较对照组明显降低,差异有统计学意义（t＝3．636,P＜0．05）;两组治疗后IL－2、IL－10、IL－2／IL－10差异均有统计学意义（t＝4．228、4．415、3．396,均P＜0．05）;观察组受孕率65．0％、流产率7．7％,均优于对照组的30．0％、33．3％（χ^2＝9．825、4．060,均P＜0．05）。结论 LPS是一种治疗EMS的有效方法,可提高血清TIMP－1和IL－2水平,降低MMP9和IL－10水平;改善免疫指标,提高患者的生育能力。     

DWI 在肝脏占位性病变中的临床应用价值

目的：评价磁共振弥散加权成像（DWI）在肝脏占位性病变鉴别诊断中的价值。方法回顾性分析我院2014年4月至2015年1月临床发现的124例肝脏占位患者的临床资料,并对所有患者行DWI检查及对ADC值进行测量和计算。结果肝细胞癌与肝血管瘤的ADC分别为[（1．32±0．15）×10－3 mm2／s VS （1．79±0．28）×10－3 mm2／s , t＝7．882,P＜0．05];肝细胞癌与肝囊肿的ADC分别为[0．32±0．15）×10－3 mm2／s VS （3．42±0．58）×10－3 mm2／s ,t＝18．796,P＜0．05];肝细胞癌与肝转移瘤的 ADC 分别为[（1．32±0．15）×10－3 mm2／s VS （1．38±017）×10－3 mm2／s ,t＝1．725,P＝0．088]：肝细胞癌与肝转移瘤的瘤／肝ADC值分别为[（1．08±0．13）×10－3 mm2／s VS （0．52±0．17）×10－3 mm2／s ,t＝17．217,P＝0．000]。结论对肝脏占位性病变性DWI检查并对ADC值进行分析,能够显著提高M RI对占位性病变良恶性诊断的准确性,为临床鉴别肝脏占位性病变提供了一种新的诊断办法。     

急性心肌梗死患者血清基质金属蛋白酶-9和前胶原氨基末端肽水平变化

目的探讨急性心肌梗死患者血清基质金属蛋白酶-9（MMP-9）和Ⅲ型前胶原氨基末端肽（PII-INP）水平变化及其临床意义。方法检测76例心肌梗死患者（观察组）治疗前及治疗后血清MMP-9和PII—INP水平,并与选取的同期30例健康体检者相比较。结果观察组治疗前血清MMP-9（191．6±38．5）μg/L和PIIINP（8．9±1．8）μg／L水平明显高于对照组[（85．6±33．2）μg/L、（3．5±1．5）μg／L]（t=13．01、14．55,P〈0．05）;治疗后3d,7d、14d血清MMP-9[（170．2±30．2）μg／L、（123．6±32．7）μg／L、（90．2±30．2）μg／L]和PIIINP[（6．9±1．7）μg／L、（5．2±1．6）μg／L、（3．7±1．8）μg／L]水平逐渐降低与治疗前比较差异均有统计学意义（t=12．63、9．58、5．36、5．01、18．0、17．8,均P〈0．05）,至治疗后14d血清中MMP-9（90．2±30．2）μg/L和PIIINP（3．7±1．8）μg／L水平至正常,与对照组比较差异无统计学意义（t=0．69、0．54,均P〉0．05）。结论MMP-9和PIIINP为临床诊断和治疗急性心肌梗死有指导意义。     

急性冠脉综合征患者血清超敏C 反应蛋白基质金属蛋白酶-1和白细胞介素-10水平的变化

目的：探讨急性冠脉综合征（ACS）患者血清超敏C反应蛋白（hs-CRP）、基质金属蛋白酶-1（MMP-1）和IL-10水平的变化。方法选取ACS患者50例（治疗组）均予以阿司匹林、肝素、硝酸酯类、β-受体阻滞剂和血管紧张素转换酶抑制剂等药物治疗,时间为2周。另取同期在该院体检中心健康体检者50例作为对照组。观察并比较治疗前后两组血清hs-CRP、MMP-1和IL-10水平的变化。结果治疗组治疗前hs-CRP和MMP-1水平[（14．13±2．95）mg/L、（18．46±4．45）ng/L]明显高于对照组[（0．49±0．12）mg/L、（8．52±2．05）ng/L],血清IL-10水平[（14．17±2．92）μg/L]明显低于对照组[（29．16±7．02）μg/L]（t＝20.7、4.12、4．06,均P＜0．01）。治疗2周后,治疗组hs-CRP和MMP-1水平[（9．12±2．16） mg/L、（13．25±3.62）ng/L]均较治疗前明显下降,而血清IL-10水平[（23．25±3．12）μg/L]较治疗前明显上升（t＝3．09、3.02、3.31,P＜0．05或P＜0．01）。结论 ACS患者存在炎性反应及炎性细胞因子失衡,血清促炎性因子和抗炎性因子水平的变化可作为ACS患者治疗疗效随访和预后观察的敏感血清学指标。     

奥曲肽联合普萘洛尔对肝硬化上消化道出血患者血流动力学指标的影响

目的：探讨奥曲肽联合普萘洛尔治疗肝硬化上消化道出血的疗效及对血流动力学指标的影响。方法将88例肝硬化上消化道出血患者采用随机数字表分为两组,观察组联合应用奥曲肽与普萘洛尔,对照组仅采用奥曲肽;对比两组的治疗效果。结果观察组止血时间（13．25±3．67） h,显著短于对照组的（21．68±4．22）h（t＝4．843,P＜0．05）;观察组总有效率（93．18％）高于对照组（77．27％）（χ^2＝4．773,P＜0.05）。治疗后,观察组门静脉内径（9．94±1．83）mm,小于对照组的（11．73±1．78）mm（t＝4．626,P＜0．05）;观察组门静脉血流速度（14．67±3．11）cm／min,低于对照组的（18．23±3．03）cm／min（t＝4．781,P＜0．05）;观察组门静脉血流量（705．15±186．46）mL／min,少于对照组的（831．56±225．66）mL／min（t＝4．246,P＜0．05）。观察组治疗后心率（75．77±5．87）次／min、平均动脉压（101．53±9．44） mmHg,低于对照组的（96．73±6．22）次／min,（116．57±9．56）mmHg（t＝4．853,P＜0．05;t＝4．924,P＜0．05）。结论奥曲肽联合普奈洛尔能够降低肝硬化患者门静脉压力,提高上消化道出血的治疗效果。     

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.     

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.     

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.     

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。     

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.     

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.     

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.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

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.