肿瘤浸润性树突状细胞在口腔部鳞状细胞癌组织中的表达及价值

目的探讨口腔部鳞状细胞癌病人癌组织中肿瘤浸润性树突状细胞的表达及其价值。方法选择 2017年 6月至 2018年 6月河北省儿童医院收治的 50例口腔部鳞状细胞癌病人作为观察组,选取 50例同时期来该院进行治疗的口腔良性肿物病人作为本次研究的对照组。取两组病人的肿物组织标本进行免疫组织化学染色法分析肿瘤浸润性树突状细胞密度,采用流式细胞仪计数肿瘤浸润性树突状细胞的人主要组织相容性复合体 Ⅱ类(MHC?Ⅱ)阳性细胞比例和白细胞抗原 54(CD54)阳性细胞比例。结果观察组肿瘤肿瘤淋巴结转移分类(TNM)分期为 Ⅲ期的肿瘤浸润性树突状细胞密度、 MHC?Ⅱ阳性肿瘤浸润性树突状细胞比例及 CD54阳性肿瘤浸润性树突状细胞比例均明显低于 Ⅰ/Ⅱ期［(7.61±1.43)比(8.65±1.42),P=0.014;(5.31±1.80)%比(7.46±1.95)%,P=0.000;(6.62±2.11)比(8.21±1.86)%,P=0.008］;肿瘤组织的最大直径 ≥5 cm的肿瘤浸润性树突状细胞密度、 MHC?Ⅱ阳性肿瘤浸润性树突状细胞比例及 CD54阳性肿瘤浸润性树突状细胞比例均明显低于肿瘤组织直径＜ 5 cm的病人［(7.14±1.85)比(9.07±2.11)P=0.001;(5.42±1.84)比(7.73±1.85),P=0.000;(6.34±2.06)比(8.47±1.91),P=0.000］;观察组比均差异无统计学意义(P＞0.05);观察组肿瘤浸润性树突状细胞密度明显低于对照组肿瘤分化程度不同的病人上述指标相,［(8.27±2.11)比(9.68±2.38)P=0.002］MHC?Ⅱ阳性肿瘤浸润性树突状细胞比例明显低于对照组［(6.67±2.20)比(9.79±2.58), P=0.000］,CD54阳性肿瘤浸润,性树突状细,胞比例明显低于对照组［(7.46±2.31)比(9.83±2.54)P=0.000］。结论口腔部鳞状细胞癌病人癌组织内肿瘤浸润性树突状细胞的密度下降、 MHC?Ⅱ阳性及 CD54阳性的细胞比例降,低,且随着 TNM分期及肿瘤直径的增大,肿瘤浸润性树突状细胞的表达水平更低。     

免疫型肠内营养对食管癌患者术后免疫功能和生活质量的影响

目的 探讨免疫型肠内营养对食管癌患者术后免疫功能和生活质量的影响.方法 自2014年1月至2016年1月,前瞻性收集中国医科大学附属盛京医院收治的食管癌患者80例;食管癌术后,按照完全随机数字表法,将患者随机分为观察组和对照组,每组各40例,观察组采用免疫性肠内营养进行营养支持,对照组采用普通肠内营养进行肠内营养支持.主要观察指标为白蛋白、C反应蛋白、住院时间、T细胞亚群和生活质量.结果 两组患者术后第1天CD4+T细胞和CD8+T细胞比例均差异无统计学意义[(25.85±2.21)%比(25.08±2.09)%,P=0.111和(29.18±3.44)%比(28.75±3.41)%,P=0.576].与对照组比较,观察组患者术后第7天和第14天CD4+T细胞比例显著增高[(27.74±2.65)%比(25.29±2.74)%,P<0.001和(27.95±2.71)%比(25.52±2.47)%,P<0.001];第7天和第14天CD8+T细胞比例显著增高[(30.85±2.79)%比(28.44±2.69)%,P<0.001和(30.91±3.79)%比(29.07±3.64)%,P=0.030].两组患者术后第1天和第14天白蛋白均差异无统计学意义(P>0.05).两组患者术前C反应蛋白差异无统计学意义[(18.58±5.39)mg·L-1比(19.12±6.24)mg·L-1,P=0.617].与对照组比较,观察组患者术后第14天外周血中C反应蛋白显著降低[(7.37±2.85)mg·L-1比(11.57±4.85)mg·L-1,P<0.001];健康相关的生存质量评分显著增高[(79.57±8.57)分比(74.38±7.12)分,P=0.035];住院时间显著缩短[(21.73±3.26)d比(24.38±4.28)d,P=0.002].结论 免疫型肠内营养有助于提高食管癌术后患者免疫功能,改善患者生活质量.     

肿瘤患者外周血树突状细胞亚群的变化及意义

目的 探讨肿瘤患者外周血树突状细胞亚群的变化及临床意义.方法 采用流式细胞术检测23例肿瘤患者和19例健康人外周血CD11c 、CD123 的树突状细胞亚群和淋巴细胞的数量.结果 正常对照组外周血CD11c DC占白细胞比例为0.19%±0.08%,绝对数为(9.3±3.9)× 106个/L;CD12 3 DC点白细胞比例为0.1 5%±0.07%,绝对数为(7.5±3.5)× 106个/L.肿瘤患者组外周血CD123 DC占白细胞比例为0.09%±0.06%,绝对数为(4.7±3.1)×106个/L;CD123 DC占白细胞比例为0.10%±0.06%,绝对数为(5.3±3.2)× 106个/L.与正常对照组比较,肿瘤患者CD11cDC比例和绝对数显著下降(P＜0.05);而CD123 DC比例和绝对数下降无显著性差异.另外,与正常对照组比较,肿瘤患者外周血T、Th、Ts、NK细胞数增均减低(P＜0.05);B细胞绝对数无显著差异.结论 肿瘤患者外周血CD1c DC数量下降,伴随T、Th、T s、NK细胞数降低,可能与肿瘤的发生发展有关.     

Influence of Raloxifene on VEGF, Ki-67 and CD34 Antigen Expression in Postmenopausal Women with Breast Carcinoma

目的:探讨雷洛昔芬对绝经期后乳腺癌血管内皮生长因子(VEGF)、Ki-67、CD34抗原表达的影响及其意义.方法:20例绝经期后乳腺浸润性导管癌(TNM分期Ⅱ期,雌激素受体阳性)女性口服雷洛昔芬60mg/d,连续用药21d后行乳腺癌改良根治术,术后采用免疫组化法检测治疗前后肿瘤组织VEGF、Ki-67、CD34抗原表达情况,对所得结果进行比较分析.结果:雷洛昔芬治疗前后VEGF表达阳性率分别为85％(17/20)和30％(6/20),差异有统计学意义(x2=12.38,P＜0.01).雷洛昔芬治疗前后Ki-67阳性细胞百分数分别为(19.36±1.66)％和(12.24±1.42)％,差异有统计学意义(t=2.86,P＜0.01).雷洛昔芬治疗前后CD-34抗原标记的肿瘤微血管数量分别为46.25±3.88和23.64±1.53,差异有统计学意义(t=2.93,P＜0.01).结论:雷洛昔芬可抑制绝经期后女性乳腺癌肿瘤细胞的增殖活性及肿瘤组织的微血管形成,这一作用可能是通过抑制肿瘤VEGF的表达实现的.     

肝癌患者癌组织及血清中CD163的表达水平及意义

目的 探究CD163在原发性肝癌患者癌组织及血清中的表达水平及其临床意义.方法 选取2013年9月至2016年9月于本院诊治的100例原发性肝癌患者为观察组研究对象,同期本院体检正常者50例为对照组研究对象,比较两组研究对象癌组织(正常肝组织)及血清中CD163的表达水平.结果 观察组CD163在癌组织中的表达水平显著高于对照组CD163在正常肝组织中的表达水平[(47.96±13.35) ng/ml比(20.50±6.57) ng/ml],差异具有统计学意义(t=13.721 0,P=0.000 0);观察组CD163在血清中的表达水平显著高于对照组[(2000.25±833.11) ng/ml比(307.76±140.18) ng/ml],差异具有统计学意义(t=14.241 5,P=0.000 0).结论 原发性肝癌患者癌组织及血清中CD163表达水平均显著升高,可为临床诊断肝癌提供重要参考.     

肝癌患者外周血CD_4~+CD_(25)~+T细胞的检测意义及冷冻消融对其表达的影响

目的探讨肝癌患者外周血CD4+CD25+T细胞的变化意义及冷冻消融治疗对其表达的影响。方法采用流式细胞技术分别检测18例原发性肝癌患者外周血CD4+CD25+T细胞的变化,并与健康对照组比较。同时检测10例原发性肝癌患者冷冻消融术前和术后3个月外周血CD4+CD25+T细胞水平的变化。结果肝癌患者外周血CD4+CD25+T细胞占总CD4+T淋巴细胞百分比高于健康对照组[(15.1±1.6)%vs(7.3±1.2)%,t=15.56,P=0.000]。其升高与患者血清AFP浓度(t=2.16,P<0.05)、肿块大小(t=2.73,P<0.05)和临床分期(t=3.00,P<0.01)显著相关,而与患者性别(t=0.23,P>0.05)、年龄(t=1.61,P>0.05)和结节数量(t=1.00,P>0.05)无显著相关。冷冻消融治疗能使CD4+CD25+T细胞显著性降低[(14.5±1.6)%vs(11.3±1.4)%,t=4.37,P<0.01]。结论原发性肝癌患者外周血CD4+CD25+T细胞水平较高,检测外周血CD4+CD25+T细胞表达可作为肝癌患者荷瘤状况和疗效评估的方法之一。     

两种疝修补术治疗成年人腹股沟疝疗效比较

目的 比较平片法无张力疝修补术(Lichtenstein)与开放式前入路腹膜前疝修补术(OIHP)治疗成年人腹股沟疝的效果.方法 回顾分析Lichtenstein术111例(Lichtenstein组)和行OIHP术97例(OIHP组)的临床资料,比较两种疝修补术的临床疗效.结果 两组手术均成功.与Lichtenstein组相比,OIHP组手术费用高[(7 142±368)元与(5 524±325)元,t=33.673,P=0.000]、手术时间短[(45±8)min与(60±9)min,t=-12.725,P=0.000]、手术切口小[(4±1)cm与(7±1)cm,t=-21.584,P=0.000]、术后开始活动早[(6±1)h与(8±2)h,t=-9.290,P=0.000]、住院时间短[(3±1)d)与(4±1)d,t=16.552,P=0.000].两组术后疼痛、并发症、复发差异无统计学意义.结论 开放式前入路腹膜前疝修补术比平片法疗效更佳,两种手术方式均值得临床推广.     

甲状腺功能减退对妊娠妇女骨代谢及骨密度的影响

目的 探讨甲状腺功能减退(甲减)对妊娠妇女骨代谢及骨密度(BMD)的影响.方法 选取82例妊娠中期甲减患者作为甲减组,同期50例妊娠中期产检正常的妇女作为对照组.采用超声骨密度仪测定并比较跟骨部位的BMD值,同时检测并比较两组血钙(Ca)、血磷(P)、碱性磷酸酶(ALP)、总Ⅰ型前胶原氨基端延长肽(TPⅠNP)、Ⅰ型胶原羧基端肽 β特殊序列(CTX-β)等骨代谢指标,促甲状腺激素(TSH)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)等甲状腺功能指标.采用Pearson线性相关分析各指标之间的相关性.结果 甲减组跟骨BMD值较对照组显著降低[(1.08±0.16比0.96±0.15)g·cm-2],骨质疏松的发生率(6.0%比18.3%)则显著升高(t=4.347,P=0.000;χ2=3.985,P=0.046).与对照组比较,甲减组血清Ca[(2.22±0.14比2.54±0.16)mmol·L-1]、ALP[(63.92±10.32比69.53±11.24)U·L-1]明显降低,P[(1.43±0.23比1.18±0.17)mmol·L-1]、TPⅠNP[(56.32±12.52比47.06±11.86)μg·L-1]、CTX-β[(0.32±0.12比0.21±0.07)pg·L-1]明显升高(t=12.062,P=0.000;t=7.148,P=0.000;t=2.929,P=0.004;t=4.204,P=0.000;t=6.650,P=0.000).TSH与跟骨BMD值及Ca、ALP呈负相关(r=-0.58,-0.51,-0.45,P<0.05),与TPⅠNP、CTX-β呈正相关(r=0.48,0.44,P<0.05),FT3、FT4与跟骨BMD值、Ca、ALP呈正相关(r=0.43,0.40,0.41;0.51,0.44,0.48,P<0.05),与TPⅠNP、CTX-β呈负相关(r=-0.47,-0.50;-0.46,-0.51,P<0.05).结论 甲减可影响妊娠妇女骨代谢,降低骨密度,导致骨量丢失、骨折风险增加,临床上应加强对妊娠妇女的甲状腺功能筛查.     

H型高血压病人心率变异性与临床特征分析

目的 探讨H型高血压病人心率变异性与临床特征。方法 前瞻性收集四川省达州市中心医院2016年1月至2017年3月收治的高血压病人147例,根据病人入院时同型半胱氨酸水平,将病人分为观察组63例(H型高血压,同型半胱氨酸≥10 mmol/L)和对照组84例(同型半胱氨酸<10 mmol/L)。观察两组病人24 h心率变异性,同时分析心率变异性与病人靶器官功能损伤的相关性。结果 与对照组比较,观察组病人24 h全部窦性R-R间期标准差(SDNN)显著降低[(89.75±18.28)比(104.38±22.71) ms,P=0.000];每5分钟窦性R-R间期均值的标准差(SDANN)显著降低[(92.47±13.47)比(101.72±15.28) ms,P=0.000];24 h连续5 min窦性R-R间期标准差的均值(SDNN-Index)显著降低[(33.29±8.73)比(40.67±10.38) ms,P=0.000];所有临近窦性R-R间期差值的均方根(rMSSD)显著降低[(27.48±9.12)比(31.84±10.55) ms,P=0.010];所有相邻两个窦性R-R间期差值大于50 ms的心搏数占全部心搏数的百分比(PNN50)显著降低[(9.21±5.38)比(15.38±8.91)%,P=0.000];颈动脉内膜中膜厚度显著增加[(0.97±0.12)比(0.89±0.14)mm,P=0.000];左室质量指数显著增加[(132.48±21.48)比(122.48±22.72) g/m²,P=0.008]。SDNN、SDNN-Index和PNN50与颈动脉内膜中膜厚度显著负相关(P<0.05),SDNN、SDANN、SDNN-Index、rMSSD和PNN50与左室质量指数显著负相关(P<0.05)。结论 H型高血压病人心率变异性显著降低,与靶器官功能损害有关。     

表皮生长因子受体及血管内皮生长因子在非小细胞肺癌组织中的表达

目的 观察非小细胞肺癌(NSCLC)组织中表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)的表达情况以及与临床病理特征的关系.方法 采用免疫组化法检测124例NSCLC组织和15例远离肿块无癌细胞浸润的肺组织(距肿瘤病变＞5 cm)标本EGFR、VEGF的表达.结果 EGFR、VEGF在124例NSCLC标本中的阳性表达率分别为52.4％、66.1％,在15例远离肿块无癌细胞浸润的肺组织(距肿瘤病变＞5 cm)均无表达.Ⅲ期NSCLC组织的VEGF表达率为80.4％ (41/51),高于Ⅰ-Ⅱ期的56.2％ (41/73)(x2=4.24,P＜0.05);淋巴结阳性的NSCLC组织VEGF表达率为78.2％ (50/64),明显高于淋巴结阴性的53.3％(32/60)(x2=4.77,P＜0.05),VEGF和EGFR表达与病理类型、性别、年龄、肿瘤细胞分化等无关.EGFR与VEGF呈正相关关系(r=0.93,P＜0.05).结论 EGFR、VEGF在NSCLC组织中过表达;VEGF可能与TNM分期及淋巴结转移有关,EGFR与VEGF在NSCLC肿瘤血管形成过程中可能起协同作用.     

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.