文拉法辛缓释片与匹维溴铵治疗无明显情绪障碍腹泻型肠易激综合征的初步研究

背景：目前对选择性5-羟色胺再摄取抑制剂（SSRIs）可用于治疗伴抑郁或焦虑状态的肠易激综合征（IBS）已基本达成共识,但关于SSRIs治疗无明显情绪障碍IBS的研究相对较少。目的：评价5-羟色胺去甲肾上腺素再摄取抑制剂文拉法辛缓释片与匹维溴铵对无明显情绪障碍、长期反复发作腹泻型IBS（IBS—D）的治疗作用。方法：本临床研究协作组前期关于文拉法辛缓释片与匹维溴铵治疗IBS．D的随机对照多中心研究中,376例患者完成观察。23例经汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）评价为无明显抑郁、焦虑状态者中,对照组7例（口服匹维溴铵8周）,试验组16例（口服文拉法辛缓释片与匹维溴铵8周）。比较两组患者的症状评分和HAMD、HAMA评分以及总有效率。结果：服药1周后起,试验组腹痛、腹泻评分和症状总评分均显著低于对照组（P〈0．05）;服药4周后起,试验组HAMD、HAMA评分亦显著低于对照组（P〈0．05）。试验组总体症状改善的总有效率显著高于对照组（87．5％对28．6％,P〈0．05）。结论：文拉法辛缓释片与匹维溴铵可改善无明显情绪障碍IBS-D患者的核心症状和不良情绪因子,疗效明显优于单用匹维溴铵。     

便秘型肠易激综合征肛门直肠动力学的临床研究

便秘型肠易激综合征 (constipation predominantIBS ,IBS C)表现为伴有腹痛或腹部不适的便秘 ,便后腹部不适缓解。我们检测了IBS C的肛门直肠动力学改变 ,以探讨便秘的发生与肛门直肠动力学异常间的关系表 1　两组肛门直肠压力比较 (mmHg)分组直肠静息压肛门内括约肌静息压肛门外括约肌静息压肛门直肠屏障压IBS C 6.0 0± 1.73 88.3 3± 15 .17 3 2 .5 0± 8.0 482 .61± 15 .2 2 对照组 7.5 0± 3 .75 78.2 5± 2 9.2 0 3 6.75± 9.0 0 67.5 0± 2 2 .5 0　　注 :与对照组比较 : P <0 .0 5表 2　两组随意动作时肛门直肠压力比较 (m…     

匹维溴铵、双歧三联活菌和氟西汀合用治疗难治性肠易激综合征疗效观察

目的　研究匹维溴铵、双歧三联活菌和氟西汀合用治疗难治性肠易激综合征 (IBS) (便秘型 )的临床疗效。方法　对 62例难治性IBS(便秘型 )患者予以匹维溴铵 5 0mg ,每日 3次 ,双歧三联活菌 2 0 ,每日 2次 ,氟西汀10mg ,每日 1次 ,共 8周 ,治疗完成后连续随访 12周。结果　 62例中 5 8例完成了随访 ( 93 5 4% )。腹痛、腹胀缓解率为 79 3 1% ,便秘完全缓解 17例 ( 2 9 3 1% ) ,部分缓解 3 2例 ( 5 5 91% ) ,不缓解 9例 ( 15 5 1% )。心理障碍完全缓解 2 2例 ( 3 7 93 % ) ,部分缓解 3 0例 ( 5 1 72 % ) ,不缓解 6例 ( 10 3 4% )。结论　匹维溴铵、双歧三联活菌和氟西汀合用治疗难治性IBS(便秘型 )有一定疗效     

匹维溴铵治疗腹泻型肠易激综合征的临床观察

目的 观察匹维溴铵对腹泻型肠易综合征(IBS)的治疗效果.方法 95例腹泻型肠易激综合征患者接受匹维溴铵治疗2周,观察患者治疗前后腹痛、腹胀、腹泻、大便形态、生活质量改善以及药物副反应.结果 接受匹维溴铵治疗2周后,腹泻型lBS患者腹痛、腹胀和腹泻症状评分均较治疗前显著降低(P＜0.05),大便性状评分较治疗前下降(P＜0.05),生活质量评分较治疗前提高(P＜0.05).但在停药结束后4周上述指标评分较治疗前无明显差异(P＞0.05).结论 匹维溴铵可有效缓解腹泻型lBS患者的临床症状,但治疗疗程值得进一步研究.     

肠易激综合征患者肠黏膜肥大细胞与神经纤维的关联

目的　探讨肠黏膜肥大细胞与神经纤维之间的关联及其与肠易激综合征 (IBS)发病的关系。方法　应用电镜和免疫组化双重染色技术 ,对 5 6例符合罗马Ⅱ标准的腹泻型IBS患者和 12例非IBS对照组患者末端回肠和直肠 乙状结肠交界部位肠黏膜内的肥大细胞与神经纤维的关联进行了检测。结果　IBS患者和对照组肠黏膜内多数肥大细胞与神经纤维紧邻。患者末端回肠、直肠 乙状结肠交界处黏膜内神经元特异性烯醇化酶 (NSE)、P物质、5 羟色胺 (5 HT)的表达明显高于对照组 (P <0 .0 5 ) ,肥大细胞周围NSE、P物质、降钙素基因相关肽 (CGRP)、5 HT的表达也明显增强。IBS患者末端回肠黏膜内肥大细胞的数目 (10 .98± 2 .96 )与对照组 (6 .0 5± 0 .5 1)相比明显增多 (P <0 .0 1)。IBS患者与对照组相比 ,末端回肠内NSE(6 .73± 1.0 2比 4 .2 5± 0 .5 0 )、P物质 (6 .84± 0 .85比 4 .2 8± 0 .4 0 )、CGRP(6 .73± 0 .82比 4 .33± 0 .5 4 )、5 HT(6 .72± 0 .81比 4 .0 0± 0 .6 3)阳性神经纤维紧邻的肥大细胞数目亦明显增多 (P <0 .0 1)。结论　IBS患者肠黏膜内肥大细胞数量的增多及其周围神经肽表达的增强表明 :免疫系统与肠神经丛之间通路的活化可能与IBS的发病有关。     

肠易激综合征患者饮冰水及直肠扩张脑诱发电位的研究

目的　通过记录并比较直肠扩张脑诱发电位 (CEP)的特征及饮冰水后CEP的改变 ,探讨肠易激综合征 (IBS)患者内脏高敏感性的发生机制 ,旨在进一步获得IBS感觉传入通路异常的客观依据。方法　根据罗马Ⅱ标准选择女性IBS患者 2 0例 ,其中腹泻型 10例 ,便秘型 6例 ,腹泻 便秘交替型4例 ,另设 12例女性健康志愿者为对照组 ,对其进行快速直肠气囊扩张 ,首先测出每例受试者感觉阈值 ,用该阈值空气体积作为刺激 (频率 1Hz,连续 10 0次 ,休息 10min ,重复 1次 ) ,启动并记录两组受试者CEP的变化。随后 ,每例受试者饮 4℃冰水 2 2 0ml,2 0min后重复上述步骤。结果　直肠节律性机械扩张引出可识别、复制的CEP。与健康对照者 [(87± 17)ms,(14 0± 2 3)ms ,(198± 31)ms]相比 ,IBS患者N1、P1、N2 潜伏期 [(6 9± 15 )ms,(12 1± 2 1)ms,(177± 2 4 )ms) ]明显缩短 (P <0 .0 5 ) ;腹泻型较便秘型IBS患者CEP潜伏期明显缩短 (P <0 .0 5 ) ;饮冰水后 ,IBS患者N1、P1、N2 潜伏期缩短 ,与饮冰水前相比差异有显著性 [分别为 (5 4± 16 )ms,(10 8± 2 0 )ms,(16 1± 2 4 )ms比 (6 9± 15 )ms,(12 1± 2 1)ms,(177± 2 4 )ms;P <0 .0 5 ],而健康对照组饮冰水后CEP无明显变化 ,两组CEP波幅无明显改变。结论　IBS患者经直肠节律性     

肠易激综合征病人肠道气体定量分析

目的　通过X线腹部平片对肠道气体进行定量测试 ,分析肠道气体容量与肠易激综合征(IBS)的关系。方法　 4 8例根据罗马Ⅱ标准诊断的IBS病人和 2 5例正常对照的X线腹部平片经数字化转换后输入电脑 ,肠道气体量在电脑显示为象素值 ,经体格标准化后 ,以气体容量积分 (GVS)表达。以对照GVS的 x± 2s为正常值 ,分析GVS与IBS型别的关系。结果　正常对照GVS为 0 .0 5 5±0 .0 12 ,离散系数为 2 1.8% ;便秘型IBS均值 (0 .0 76± 0 .0 2 7,t =3.5 99,P <0 .0 1)与正常人比较显著增高 ,4 4 .4 %的个体GVS大于正常值 ,余在正常范围 ;腹泻型IBS均值 (0 .0 4 8± 0 .0 32 ,t =1.4 76 ,P >0 .0 5 )与正常人比较差异无显著性 ,但离散系数高达 6 6 .7% ,4 2 .9%的病人GVS降低 ,14 .3%增高。结论　IBS病人肠道气体容量存在明显改变 ,并与型别有关 ;便秘型以增多为主 ,腹泻型以减少为主。     

西沙必利对便秘型肠易激综合征患者小肠传递时间的影响

目的　探讨西沙必利对便秘型肠易激综合征 (IBS)患者小肠传递时间 (SBTT)的影响。方法　应用乳果糖氢气呼吸试验方法 (HBT)检测 18例便秘型IBS患者应用西沙必利前后SBTT的变化。结果　便秘型IBS患者和正常人 (对照组 )的SBTT分别为 ( 10 9.5± 2 5 .4)min和( 83.8± 2 2 .5 )min (P <0 .0 1) ,应用西沙必利后 ,患者的SBTT缩短为 ( 86 .6± 2 7.9)min (P <0 .0 1) ,与对照组比较 ,差异无显著性 (P >0 .0 5 )。结论　西沙必利有明显的促胃肠动力作用 ,可用于便秘型IBS的治疗。     

匹维溴胺单用及联用黛力新治疗肠易激综合征的疗效观察

目的 观察匹维溴胺及匹维溴胺联用黛力新对肠易激综合征患者治疗的效果。方法 按罗马Ⅱ标准选择126例IBS随机分为两组,每组63例。仅予匹维溴胺治疗者为单剂组,同时予匹维溴胺和黛力新治疗者为联用组。单剂组口服匹维溴胺50mg,tid;联用组患者在单剂组的用药基础上加用黛力新,每日2片。结果 治疗2周后,单剂组和联用组的症状学评分均显著降低(P<0.05),联用组在便秘、腹痛、腹胀三项症状的改善上显著优于单用组(各为:0.52±0.20比1.63±0.16;0.74±0.20比1.42±0.20;0.69±0.11比1.37±0.44;P<0.05)。结论 匹维溴胺能够有效缓解IBS患者的症状;对于以便秘、腹痛、腹胀为主的IBS患者,加用黛力新可以得到更好的疗效。     

肠易激综合征患者脑部痛觉功能区域的变化

目的应用血氧水平依赖性功能性磁共振(BOLD fMRI)技术研究肠易激综合征(irritablebowelsyndrome ,IBS)患者颅内痛觉功能区的变化及临床意义并比较与正常人的差异。方法2 0 0 2年1月～2 0 0 4年2月期间,参照罗马II诊断标准纳入67例肠易激综合征患者和10例正常志愿者,其中腹泻型肠易激综合征44例,男19例,女2 5例。年龄3 4～73岁,平均年龄5 3 0 7±8 44岁。便秘型肠易激综合征2 3例,其中男12例,女11例,年龄2 1～74岁,平均年龄46 2 2±14 64岁。直肠注气试验记录感觉阈值和感觉评分;功能性磁共振(fMRI)分析直肠扩张3 0ml、60ml、90ml和12 0ml时颅内痛觉功能区扣带前皮质(ACC)、脑岛皮质(IC)、额前皮质(PFC)及丘脑(THAL)的激活面积和强度。结果腹泻型IBS患者排便急迫和疼痛阈值显著低于便秘型患者和正常志愿者(P <0 0 5 ) ;腹泻型IBS患者在直肠注气90ml和12 0ml时视觉模拟评分(VAS)显著高于正常志愿者(P <0 0 5 ) ;便秘型IBS患者直肠扩张12 0ml时额前皮质、右侧丘脑兴奋面积较正常对照组显著增高(P <0 0 5 ) ,腹泻型IBS患者直肠扩张12 0ml时右侧脑岛皮质、额前皮质和右侧丘脑的兴奋面积较正常对照组显著增高(P <0 0 5 ) ;所有IBS患者直肠扩张90ml时脑岛皮质、直肠扩张12 0ml时脑岛皮质、额前皮质和丘脑     

妊娠时间与肺结核复发的相关性研究及诊治对策

目的 分析肺结核史患者妊娠时间和肺结核复发间相关性.方法 选取我院收治的有肺结核史的妊娠妇女576例作为研究对象,对其妊娠前肺结核治疗、治愈后妊娠时间、妊娠后复发肺结核等进行分析,总结有肺结核史育龄女性的妊娠时间和肺结核复发之间的关系.结果 肺结核治愈后不同时间段妊娠者的结核复发率比较,差异具有显著性（P＜0.05）,停药后间隔时间越久妊娠,肺结核复发的几率越小.结论 加强孕期痰菌检查,及早发现复发肺结核,提高母婴安全.     

我国骨关节结核诊治的回顾与展望

骨关节结核是危害人们健康的严重感染性疾病,近95％由他处结核病继发而来.罹患骨关节结核疾病后几乎均将致残,严重影响人们的健康、工作和生活.建国以来在党和国家的关心和支持下,骨关节结核的诊治水平取得了长足进步.时至今日,由于多种原因,学科发展和被重视程度受到一定的制约,同整个医疗行业的发展不相适应.回顾过去,展望未来,我们需要重新审视骨关节结核的诊治方法,努力推进骨关节结核诊疗技术的科学发展.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44~(MAPK), p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44~(MAPK), p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44~(MAPK) and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between P42/44~(MAPK) and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Raf/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44~(MAPK), c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

Overweight and Obesity and Progression of ADPKD

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Effects of sex and time of day on metabolism and excretion of corticosterone in urine and feces of mice

Non-invasive techniques to monitor stress hormones in small animals like mice offer several advantages and are highly demanded in laboratory as well as in field research. Since knowledge about the species-specific metabolism and excretion of glucocorticoids is essential to develop such a technique, we conducted radiometabolism studies in mice (Mus musculus f. domesticus, strain C57BL/6J). Each mouse was injected intraperitoneally with 740 kBq of 3H-labelled corticosterone and all voided urine and fecal samples were collected for five days. In a first experiment 16 animals (eight of each sex) received the injection at 9 a.m., while eight mice (four of each sex) were injected at 9 p.m. in a second experiment. In both experiments radioactive metabolites were recovered predominantly in the feces, although males excreted significantly higher proportions via the feces (about 73%) than females (about 53%). Peak radioactivity in the urine was detected within about 2h after injection, while in the feces peak concentrations were observed later (depending on the time of injection: about 10h postinjection in experiment 1 and about 4h postinjection in experiment 2, thus proving an effect of the time of day). The number and relative abundance of fecal [3H]corticosterone metabolites was determined by high performance liquid chromatography (HPLC). The HPLC separations revealed that corticosterone was extensively metabolized mainly to more polar substances. Regarding the types of metabolites formed, significant differences were found between males and females, but not between the experiments. Additionally, the immunoreactivity of these metabolites was assessed by screening the HPLC fractions with four enzyme immunoassays (EIA). However, only a newly established EIA for 5alpha-pregnane-3beta,11beta,21-triol-20-one (measuring corticosterone metabolites with a 5alpha-3beta,11beta-diol structure) detected several peaks of radioactive metabolites with high intensity in both sexes, while the other EIAs showed only minor immunoreactivity. Thus, our study for the first time provides substantial information about metabolism and excretion of corticosterone in urine and feces of mice and is the first demonstrating a significant impact of the animals' sex and the time of day. Based on these data it should be possible to monitor adrenocortical activity non-invasively in this species by measuring fecal corticosterone metabolites with the newly developed EIA. Since mice are extensively used in research world-wide, this could open new perspectives in various fields from ecology to behavioral endocrinology.     

Replication and Inhibitors of Enteroviruses and Parechoviruses

The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.     

Effect of phosphorylation of MAPK and Stat3 and expression of c-fas and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.     

心电图、心电向量图与冠状动脉造影结果对比分析

目的:通过分析心电图(Electrocardiogram,ECG)和心电向量图(Vectorcardiogram,VCG)的改变与冠脉造影（CAG）结果进行对比,探讨ECG、VCG在冠状动脉病变中的诊断价值。方法: 选择2008年1月~2009年12月临床拟诊断为冠心病患者108例,行常规ECG、VCG检查,并于1周内进行CAG,对检查结果依据各自的诊断标准进行判定,以CAG为标准诊断法,利用四格表法,计算相关评价真实性的指标并进行比较。结果: ①VCG检测的灵敏度、特异度、准确度显著高于ECG(P<0.05,P<0．01)。②ECG、VCG阳性率与冠脉病变支数组间比较:在单支病变、双支病变中,VCG阳性率明显高于ECG(P<0.05),左主干或三支病变无统计学意义;组内比较:ECG组左主干或三支病变组较单支病变、双支病变阳性率高(P<0.05,P<0.01);VCG组左主干或三支病变组较单支病变阳性率高(P<0.05);与双支病变阳性率比较无统计学意义;③ECG、VCG阳性率与冠脉病变程度组间比较:冠脉病变狭窄50%～69%的VCG阳性率明显高于ECG (P<0.05),其他两组阳性率比较无统计学意义;组内比较:ECG组冠脉病变狭窄≥90%较50%～69%、70%～89%的阳性率高(P<0.05,P<0.01); VCG组狭窄≥90%较50%～69%阳性率高（P<0.01),其他无统计学意义。结论: VCG对冠心病检测价值显著高于ECG。     

Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence

Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O(2)(.-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E(+)). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O(2)(.-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O(2)(.-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E(+). However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O(2)(.-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O(2)(.-). Analysis of the fluorescence characteristics of ethidium (E(+)) and 2-OH-E(+) strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O(2)(.-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable [corrected] for detecting intracellular O(2)(.-).     

大鼠骨髓间充质干细胞的分离培养和外源基因的导入

目的探讨绿色荧光蛋白基因转染骨髓间质干细胞的可行性。方法采用F icoll-PaqueTMP lus淋巴细胞分离液,根据细胞密度梯度原理,分离大鼠骨髓间充质干细胞(rM SC s)并进行体外原代培养和传代扩增,倒置相差显微镜观察细胞生长情况,免疫细胞化学法对其初步鉴定。流式细胞仪分析转染效率。结果原代和传代培养的细胞呈现梭形外观,具有较强的生长增殖能力;细胞均一表达CD44、CD54、CD106、CD29抗原。电穿孔法转染rM SC s转染率为32.8%±3%。结论采用比重为1.077 g/L的F icoll-PaqueTMP lus能分离获得大鼠骨髓间充质干细胞,经原代培养和传代培养能够迅速扩增。电穿孔法具有较高的介导外源基因表达于rM SC s的效率。