PCT联合CRP在恶性血液病感染中的临床应用价值

目的探讨血清降钙素原(PCT)联合C-反应蛋白(CRP)在恶性血液病感染患者中的早期诊断价值。方法对108例血液科恶性血液病感染患者(一般感染组75例、败血症组33例)和50例健康体检者(对照组),采用荧光定量法检测血清PCT,免疫比浊法检测血清CRP。结果对照组PCT和CRP值分别为(0.03±0.009)ng/mL和(6.23±1.577)mg/L;一般感染组PCT和CRP值分别为(0.61±1.346)ng/mL和(17.55±19.917)mg/L;败血症组PCT和CRP值分别为(6.11±9.600)ng/mL和(82.43±43.217)mg/L,与对照组相比,差异具有统计学意义(P<0.01)。PCT的特异度和敏感度分别为92.45%、99.05%,CRP的特异度和敏感度分别为52.05%、85.88%。结论 PCT和CRP联合检测可为恶性血液病感染患者早期诊断提供更准确依据,有助于指导抗生素的使用。     

溃疡性结肠炎患者血清白细胞介素8和肿瘤坏死因子-α的水平和意义

目的 探讨白细胞介素8（IL-8）和肿瘤坏死因子-α（TNF-α）在溃疡性结肠炎（UC）发病中的作用及临床意义.方法 采用酶联免疫吸附法（ELISA）测定47例活动期UC患者（其中轻度15例、中度18例和重度14例）,21例缓解期UC患者及20例健康对照组的血清IL-8和TNF-α水平.结果 活动期UC患者血清IL-8和TNF-α水平分别为（58.3±11.6）、（62.1±10.8）ng/L,显著高于缓解期UC患者和健康对照组（均P＜0.05）,缓解期UC患者IL-8和TNF-α水平显著高于健康对照组（均P＜0.05）.重度活动期UC血清IL-8和TNF-α水平高于中度和轻度活动期UC,中度活动期UC血清IL-8和TNF-α水平高于轻度活动期UC,组间比较均差异有统计学意义（P＜0.05）.结论 IL-8和TNF-α参与了UC的炎性过程,检测血浆IL-8和TNF-α可作为判断UC患者病变严重程度和活动性的重要指标.     

溃疡性结肠炎患者血清降钙素原检测分析

目的:探讨检测血清降钙素原(PCT)水平在溃疡性结肠炎(UC)的临床意义。方法:采用ELISA法检测64例UC活动期患者和35例缓解期患者外周血PCT水平及血中性粒细胞计数。结果:UC活动期患者血中性粒细胞计数及PCT水平显著高于正常对照组(P<0.05),PCT水平在活动期也显著高于缓解期(P<0.05),PCT水平随活动期病情严重程度的加重而升高。结论:血清PCT水平可能作为评价UC患者病情活动及严重程度的辅助指标。     

急性胰腺炎患者白细胞介素18和白细胞介素15的变化意义

目的探讨白细胞介素18(IL-18)和白细胞介素15(IL-15)在急性胰腺炎(AP)发病机制中的作用。方法采用酶联免疫吸附法(ELISA)检测19例轻型急性胰腺炎(MAP)患者和7例重症急性胰腺炎(SAP)患者血清IL-18和IL-15的浓度,分析它们之间的相关性。结果血清IL-18和IL-15的表达在SAP组明显高于MAP组,两组中存在显著差异[IL-18(78.32±15.45)ng/L vs(28.21±13.18)ng/L,P<0.01;IL-15(42.17±19.15)ng/L vs(5.88±2.01)ng/L,P<0.01]。血清IL-15和IL-18在MAP组及SAP组均呈显著正相关(P<0.01)。结论血清IL-18和IL-15参与了急性胰腺炎的炎症反应过程,可能是预测急性胰腺炎严重程度的指标。     

微小RNA-146a 靶向调控Krüppel 样转录因子7对强直性脊柱炎T 细胞炎症反应及自噬的影响

目的探讨微小RNA-146a(miR-146a)是否通过靶向调控Krüppel样转录因子7(KLF7)的表达而影响强直性脊柱炎病人T细胞炎症反应及自噬。方法采用实时荧光定量聚合酶链反应(qRT-PCR)检测强直性脊柱炎病人T细胞与健康人T细胞中miR-146a的表达量;分别将anti-miR-NC、anti-miR-146a、pcDNA3.1、pcDNA3.1-KLF7转染至强直性脊柱炎病人T细胞;采用酶联免疫吸附法(ELISA)检测白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、白细胞介素-23(IL-23)的水平;双荧光素酶报告实验验证miR-146a与KLF7的靶向结合关系;蛋白质印迹法(Western blotting)检测KLF7、自噬相关基因5(ATG5)、Beclin-1的表达量。结果与健康人T细胞比较,强直性脊柱炎病人T细胞中miR-146a的表达量升高［(1.00±0.08)比(2.74±0.13),t=53.54,P<0.05］;与anti-miR-NC组比较,anti-miR-146a组IL-6［(823.17±14.10)ng/L比(372.31±11.03)ng/L］、IL-17［(901.00±16.29)ng/L比(428.39±12.34)ng/L、IL-23［(886.38±15.11)ng/L 比(401.61±11.75)ng/L］的水平降低(t=43.62,40.06,43.87,P<0.05),ATG5［(0.33±0.03)比(0.79±0.07)］、Beclin-1［(0.42±0.04)比(0.91±0.08)］蛋白水平升高(t=10.46,9.49,P<0.05);双荧光素酶报告实验证实miR-146a可靶向结合KLF7;转染pcDNA3.1-KLF7可明显降低IL-6［(823.17±14.10)ng/L比(477.37±12.01)ng/L］、IL-17［(901.00±16.29)ng/L比(558.67±13.16)ng/L］、IL-23［(886.38±15.11)ng/L比(531.69±12.75)ng/L］的水平(t=32.34,28.31,31.07,P<0.05),提高ATG5［(0.32±0.03)比(0.60±0.06)］、Beclin-1［(0.44±0.04)比(0.78±0.07)］的表达水平(t=7.23,7.30,P=0.002)。结论抑制miR-146a表达可通过靶向KLF7而抑制强直性脊柱炎病人T细胞炎症反应及促进细胞自噬。     

溃疡性结肠炎患者血清 IL-1β和 IL-18的表达及临床意义

目的：检测溃疡性结肠炎（ulcerative colitis,UC）患者血清白介素-1β（IL-1β）和白介素（IL-18）的变化,探讨其在 UC 发生发展过程中的作用。方法活动期 UC 患者42例,缓解期 UC 患者20例和正常对照组10例。采用酶联免疫吸附法（ELISA 法）检测 IL-1β和 IL-18的含量,评价含量与 UC 患者病情轻重程度之间的关系。结果活动期 UC 组患者血清 IL-1β和 IL-18含量显著高于缓解期 UC 组患者和对照组（P ＜0．05）,缓解期 UC 组患者与对照组比较,血清 IL-1β和 IL-18含量明显升高（P ＞0．05）;血清 IL-1β和 IL-18含量活动期 UC 重型组高于中型和轻型组,与病情病情轻重程度均呈正相关（r 值分别为0．623和0．588,P ＜0．01）。结论活动期 UC 患者血清 IL-1β和 IL-18含量显著升高,其可作为病情活动性、严重性及疗效评价的参考指标。     

溃疡性结肠炎患者血浆P选择素水平及血小板计数的变化及其临床意义

目的 探讨溃疡性结肠炎(UC)患者血浆P选择素(P-sel)水平及血小板计数的变化及其临床意义.方法 采用酶联免疫分析方法检测45例UC患者和20例同期健康体检者血浆P-sel水平,采用血细胞记数仪测定血小板计数.结果 随着病情的加重,UC患者血浆P-sel水平和血小板计数逐渐升高,差异有统计学意义(P<0.01).同时,UC活动期血浆P-sel水平[(31.9±6.9)μg/L]明显高于对照组[(15.6±4.8)μg/L]和UC缓解期[(22.1±5.5)μg/L](P<0.01);UC缓解期明显高于对照组(P<0.05).UC活动期血小板计数[(230.8±75.9)×109/L]明显高于对照组[(163.1±47.8)×109/L](P<0.01),明显高于UC缓解期[(167.3±49.5)×109/L](P<0.01);UC缓解期与对照组比较,差异无统计学意义(P>0.05).结论 P-sel与UC的发病和病情进展密切相关,临床联合检测UC患者血浆P-sel水平及血小板计数,对病情的判断及其疗效的评估有一定参考价值.     

可溶性肿瘤坏死因子样凋亡弱诱导因子在斑秃病人血清及皮损中的表达及临床意义

目的检测可溶性肿瘤坏死因子样凋亡弱诱导因子( sTWEAK)在斑秃病人血清及皮损中的表达水平,并探讨其在斑秃发病过程中的作用及临床意义。方法以 2017年 10月至 2018年 11月在首都医科大学附属北京友谊医院确诊并治疗的斑秃病人 70例为斑秃组,依据病情分为轻症组( 44例)、重症组( 26例)。同期该院因色素痣或皮肤良性肿瘤进行头皮手术的人群 65例作为对照组。比较各组 sTWEAK及相关细胞因子白细胞介素( IL)-4、IL-12、γ干扰素( IFN-γ)蛋白及 mRNA表达水平;采用 Pearson法分析两指标间相关性。多元线性回归分析各指标与 sTWEAK或脱发严重度工具( SALT)评分的关系。结果斑秃组血清及皮损中 sTWEAK表达水平［(196.73±32.48)ng/L,(2.35±0.62)ng/L］高于对照组［(121.75±19.62)ng/L,(1.49±0.45)ng/L］(P<0.05)。斑秃组血清及皮损中细胞因子 IL-12、IFN-γ表达水平高于对照组( P<0.05)IL-4表达水平比较差异无统计学意义( P>0.05)。斑秃病人血清及皮损中 sTWEAK表达水平与 IL-12及 IFN-γ呈正相关,与 IL-4,表达水平无明显相关性。轻症组血清及皮损中 sTWEAK［(173.25±26.84)ng/L,(2.04±0.57)ng/L］IL-12及 IFN-γ表达水平低于重症组［(236.47±42.02)ng/L,(2.87±0.70)ng/L］(P<0.05);轻症组、重症组血清及皮损中 IL-4表达差异无统计学意义( P>0.05);斑秃病人血清、皮损处 sTWEAK、 IL-12、IFN-γ与 SALT评分均呈正相关(P<0.05)。多元线性回归分析显示, IL-12、IFN-γ与血清和皮损处 sTWEAK呈显著正相关;血清及皮损处 sTWEAK、IL-12、IFN-γ与 SALT评分存在正相关性(P<0.05)。结论斑秃病人血清及皮损中 sTWEAK表达水平增水平、加,与 IL-12及 IFN-γ呈正相关, sTWEAK、IL-12及 IFN-γ均与斑秃病情严重程度密切相关, sTWEAK可能参与斑秃炎症反应过程。     

降钙素原和淀粉样蛋白A在重型肝炎自发性 细菌性腹膜炎中的诊断价值

目的 探讨降钙素原(procalcitonin, PCT)和淀粉样蛋白A在重型肝炎自发性细菌性腹膜炎(spontaneous bacterial peritonitis, SBP)中的诊断价值。方法 自2014年1月至2016年1月,前瞻性收集内蒙古医科大学附属医院收治的重型肝炎124例,根据是否发生SBP分为SBP组(n=48)和非SBP组(n=76),比较两组PCT、淀粉样蛋白A、C反应蛋白、白细胞和白介素6(Interleukin-6, IL-6)水平,并分析PCT、淀粉样蛋白A、C反应蛋白、白细胞和IL-6在诊断重型肝炎病人SBP中的价值。结果与非SBP组比较,SBP组PCT显著升高[(0.78±0.54)比(0.19±0.11)] ng/mL, P=0.000;淀粉样蛋白A显著升高[(23.58±9.58) 比(12.57±8.82)]mg/L, P=0.000;C反应蛋白显著升高[(8.68±2.48)比(5.49±1.82)] mg/L, P=0.000;白细胞显著升高[(9.26±3.29) 比(7.65±2.84)]×10⁹/L, P=0.000;IL-6显著升高[(89.58±38.58)比(39.58±18.58)] pg/mL, P=0.000。PCT、淀粉样蛋白A、C反应蛋白、白细胞和IL-6在诊断重型肝炎SBP中的ROC曲线下面积分别为0.875(95%CI:0.816~0.934)、0.898(95%CI:0.840~0.957)、0.695(95%CI:0.598~0.793)、0.709(95%CI:0.617~0.801)和0.876(95%CI:0.812~0.940),差异有统计学意义(P=0.000)。与存活病人比较,死亡病人入院时PCT显著升高[(1.05±0.51) 比(0.70±0.48)] ng/mL, P=0.042。结论 PCT和淀粉样蛋白A在诊断重型肝炎SBP中均具有较强的应用价值,PCT升高可能与SBP预后不良有关。     

血清白介素-6、血管内皮细胞黏附分子1、E-选择素在慢性阻塞性肺疾病合并侵袭性肺曲霉病中的表达及意义

目的探究慢性阻塞性肺疾病(COPD)合并侵袭性肺曲霉病(IPA)病人血清白介素-6(IL-6)、血管内皮细胞黏附分子1(VCAM-1)、E-选择素(E-Selectin)表达水平及与半乳甘露聚糖(GM)值的相关性。方法选取2017年1月至2019年1月河南省胸科医院收治的COPD病人136例,根据其是否合并IPA分为COPD合并IPA组47例,COPD未合并IPA组89例。采用酶联免疫吸附(ELISA)法检测血清中IL-6、VCAM-1、E-Selectin水平及GM抗原。采用Pearson法分析COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平与GM值相关性;采用logistic回归模型分析COPD合并IPA发生的影响因素;采用受试者工作特征曲线(ROC)分析血清IL-6、VCAM-1、E-Selectin水平及GM值对COPD合并IPA的诊断价值。结果COPD合并IPA组病人血清IL-6［(59.57±16.43)ng/L比(6.31±2.05)ng/L］、VCAM-1［(716.93±232.09)μg/L比(364.28±156.41)μg/L］、E-Selectin表达水平［(76.52±24.05)μg/L 比(41.34±15.36)μg/L］及GM 值［(0.92±0.19)比(0.37±0.15)］均明显高于COPD 未合并IPA 组(P<0.05)。COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平与GM值均呈正相关(P<0.05)。血清IL-6、VCAM-1、E-Selectin、GM值高水平均是COPD合并IPA发生的危险因素(P<0.05)。血清E-Selectin表达水平对COPD合并IPA发生诊断的曲线下面积、灵敏度、特异度均为最高。结论COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平明显升高,与GM值均呈正相关,可能作为生物标志物,用于评估COPD合并IPA发生。     

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.