细胞因子对白血病抑制因子和IL-6在骨髓基质细胞表达的调节

目的 :研究白细胞介素 1(IL 1)、TNF α、白细胞介素 4 (IL 4 )对骨髓基质细胞白血病抑制因子 (LIF)和白细胞介素 6 (IL 6 )表达的调节。方法 :用酶联免疫吸附试验 (ELISA)测定各细胞因子作用下的LIF与IL 6水平 ,用逆转录 聚合酶链反应 (PT PCR)测定各细胞因子作用下的LIF与IL 6转逆子水平。结果 :在IL 1、TNF α作用下LIF与IL 6水平明显升高 (P <0 .0 5 ) ,IL 4作用下IL 6水平明显升高 (P <0 .0 5 ) ,而LIF水平却明显降低 (P <0 .0 5 )。结论 :IL 1、TNF α有上调骨髓基质细胞LIF与IL 6表达 ,IL 4能上调骨髓基质细胞IL 6表达 ,却下调LIF的表达。     

儿童急性淋巴细胞白血病患者T淋巴细胞免疫功能的研究

目的 :研究儿童急性淋巴细胞白血病 (ALL)患者初治时和完全缓解 (CR)后外周血T淋巴细胞亚群及其分泌细胞因子的能力。方法 :采集B淋巴细胞系ALL儿童初治时、CR后的外周血 ,分离出其中的单个核细胞 (MNC)。用单克隆抗体在流式细胞仪上测定CD3、CD4、CD8以及IL 2受体CD2 5的含量 ;通过T淋巴细胞内细胞因子IFN γ和TNF α的测定 ,在单个细胞水平上分析T淋巴细胞功能的变化。结果 :①初治时 ,患者的CD4 /CD8为 (1.10± 0 .79) ,较健康儿童 (2 .74± 1.2 1)明显降低 (P <0 .0 1) ,CD4、CD8产生细胞因子IFN γ和TNF α的能力均低于正常对照 (P <0 .0 5 )。②CR后 ,CD4 /CD8为 2 .5 4± 1.39,比初治时明显提高 (P <0 .0 5 ) ,CD4、CD8产生细胞因子的能力增强 ,但与正常对照组相比 ,各项数值仍低。③初治患者的CD4 + CD2 5 + T淋巴细胞为 (0 .76± 0 .5 6 ) ,明显低于CR组 (2 0 .4± 5 .1) (P <0 .0 1)和对照组 (16 .3± 6 .3) (P <0 .0 1)。这表明 ,免疫损害在白血病的发病过程中起重要作用的细胞因子的产生和CD2 5都趋于正常。结论 :T淋巴细胞的免疫功能与儿童白血病的预后关系密切 ,促进患者免疫功能的恢复对本病的治疗非常重要     

黄芪对病毒性心肌炎心脏细胞因子mRNA表达的影响

目的 :研究黄芪治疗病毒性心肌炎 (VMC)对心脏组织白细胞介素 2 (IL 2 )mRNA、肿瘤坏死因子 α(TNF α)mRNA及白细胞介素 10 (IL 10 )mRNA表达的影响 ,探讨其治疗VMC的免疫调节作用机制。方法 :6 0只小鼠随机分成 4组 ,其中黄芪治疗组以黄芪口服液灌胃 ,0 .2ml/次 ,2次 /d ,共 10d。采用半定量RT PCR方法检测所有存活小鼠心脏组织中细胞因子mRNA表达情况。结果 :与病毒对照组比较 ,应用黄芪治疗后 ,VMC小鼠心脏组织中IL 2mRNA与TNF αmRNA表达下降 (P <0 .0 5 ) ,而IL 10mRNA表达则升高 (P <0 .0 5 )。结论 :黄芪通过改变细胞因子在心脏组织的表达而发挥其治疗VMC的有益的免疫调节作用。     

抗氧化微量营养素对T1DM小鼠脾TNF-α表达的影响

目的 探讨联合抗氧化微量营养察(AM)对脾肿瘤坏死因子(TNF)-α吨表达的影响.方法 应用MLDS方法制备1型糖尿病(T1DM)小鼠模型,分别联合添加4种AM(Se+VE+V+Cr)和7种AM(Se+WE+V+Cr+VC+硫辛酸,烟酰胺)进行干预,利用流式细胞术和原位杂交方法观察小鼠外周血、脾淋巴细胞TNF-α表达的影响.结果 联合补充AM使T1DM小鼠血糖明显降低;T1DM小鼠外周血、脾淋巴细胞TNF-α表达明显高于正常对照组,AM4组和AM7组外周血、脾淋巴细胞TNF-α表达低于T1DM模型组小鼠;T1DM模型组TNF-αmRNA表达阳性信号比正常对照组强,而AM4组和AM7组阳性信号比T1DM模型组弱.结论 联合AM可下调T1DM模型小鼠脾、外周血淋巴细胞TNF-α表达,具有良好的拮抗糖尿病作用.     

趋化因子受体CCR5、CCR3在1型糖尿病患者中的表达

目的　研究Th1和Th2 细胞表面特征性的趋化因子受体CCR5、CCR3在 1型糖尿病发病机制中的作用。方法　对 15例新诊断的 1型糖尿病患者、10例 2型糖尿病患者以及 10例非糖尿病患者分离外周血单个核细胞 (PBMC)在体外培养 ,用流式细胞仪检测CD 4CCR5 及CD 4CCR3 淋巴细胞 ,并用酶联免疫吸附技术检测细胞培养上清中细胞因子IL 4、IFN γ的水平。结果　 1型糖尿病患者外周血中CD 4CCR5 淋巴细胞数显著高于 2型糖尿病患者和对照组 ,CD 4CCR3 显著低于其它两组 (均P <0 .0 5 )。 1型糖尿病患者和 2型糖尿病患者PBMC细胞上清液中的IFN γ水平高于对照组 (均P <0 .0 5 ) ,1型糖尿病患者IL 4水平低于其它两组 (P <0 .0 1)。结论　检测PBMC的CCR5、CCR3表达可以作为反映人类 1型糖尿病免疫活动的标志 ,从而为 1型DM的早期诊断和预防提供线索     

心力衰竭患者炎性与抗炎性细胞因子表达的平衡失调

目的 :了解炎性与抗炎性细胞因子在充血性心力衰竭 (CHF)过程中的变化及其临床意义。方法 :用双抗体夹心ELISA法测定 12 2例CHF患者及 30例健康人血浆中肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的浓度。结果 :①CHF患者血浆中TNF α水平明显高于对照者 (P <0 .0 5或 <0 .0 1) ,且随着心力衰竭程度的加重 ,TNF α水平呈进行性增高 ;CHF患者血浆IL 6及IL 10水平 ,心功能Ⅲ、Ⅳ级者明显高于对照者 (P <0 .0 5或 <0 .0 1) ,而心功能Ⅱ级者与对照者相比差异无显著性意义。②TNF α与IL 6 (r =0 .6 18,P <0 .0 1)、IL 10 (r =0 .5 6 6 ,P <0 .0 1)均呈正相关 ,但TNF α与IL 10的比率 (TNF α/IL 10 )也随着心功能的恶化而升高 ,IL 10的升高与TNF α的升高相比明显不足。结论 :细胞因子的变化与心力衰竭的严重程度密切相关 ,CHF患者血中炎性细胞因子明显升高的同时伴有抗炎性细胞因子升高的相对不足 ,炎性与抗炎性细胞因子之间的平衡失调可能参与了CHF的发生发展     

幽门螺杆菌相关胃炎中TNF-α和IL-1β分泌的原位研究

目的 :原位检测幽门螺杆菌 (Hp)感染时胃黏膜活检标本中肿瘤坏死因子 α(TNF α)和白介素 1 β(IL 1 β)的产生情况。方法 ;采集 1 3例Hp阴性受检者和 32例Hp阳性受检者的胃黏膜活检标本 ,通过放免法、免疫组织化学法观察并比较两组胃黏膜活检标本中细胞因子TNF α和IL 1 β的产生。结果 :胃黏膜活检标本中TNF α和IL 1 β的分泌在Hp阳性组显著高于Hp阴性组 (P <0 .0 1 ) ,但其分泌与胃黏膜的病理分型似无显著相关性 (P >0 .0 5)。TNF α和IL 1 β的组织表达在Hp阳性组也显著高于Hp阴性组 (P <0 .0 5)。结论 :Hp感染可以使局部细胞因子TNF α和IL 1 β产生增加 ,可能在Hp相关胃炎中起致病作用     

幽门螺杆菌相关胃炎中细胞因子分泌与Fas抗原的原位关系研究

目的　原位检测幽门螺杆菌 (Hp)感染时胃粘膜活检标本中肿瘤坏死因子 α(TNF α)和白细胞介素 1β(IL 1β)的产生及Fas抗原的表达 ,并分析它们之间的关系。 方法　采集 13例Hp阴性受检者和 3 2例Hp阳性受检者的胃粘膜活检标本 ,通过放免法、免疫组化法观察并比较两组胃粘膜活检标本中TNF α和IL 1β的产生及Fas抗原的表达。 结果　胃粘膜活检标本中TNF α和IL 1β的分泌在Hp阳性组显著高于Hp阴性组 (P <0 .0 1) ,但与胃粘膜的病理分型无显著相关性 (P >0 .0 5 ) ;Hp阳性组的胃粘膜组织切片中TNF α、IL 1β和Fas抗原表达显著高于Hp阴性组 ;Hp阳性组中TNF α和IL 1β产生与胃粘膜Fas抗原的表达呈显著正相关 (P <0 .0 5 )。 结论　通过原位检测发现Hp感染可以使局部细胞因子TNF α和IL 1β产生增加 ,造成局部的炎症微环境 ,从而上调Fas抗原表达 ,导致胃粘膜损伤     

乌梢蛇水解液对炎性和抗炎性细胞因子的作用

目的　观察乌梢蛇水解液对胶原诱导的关节炎 (CIA)大鼠的炎性细胞因子和抗炎性细胞因子的作用。方法　将CIA大鼠随机分成对照组、低剂量组 (0 .5mg/kg)、中剂量组 (5mg/kg)和高剂量组 (15mg/kg) ,每天给予灌胃乌梢蛇水解液一次 ,共用 2 1d。疗程结束后处死动物分离血清 ,用ELISA方法测定血清中TNF α、IL 1β、IL 4和IL 10的水平。 结果　CIA大鼠外周血清中TNF α水平明显升高而IL 10水平低下 ,IL 1β和IL 4水平与正常大鼠无差异 ,中剂量和高剂量的乌梢蛇水解液能降低CIA大鼠血清TNF α水平和提高血清中IL 10水平 (P <0 .0 5 ) ,对IL 1β和IL 4水平无影响 (P >0 .0 5 )。结论　乌梢蛇水解液能下调CIA大鼠血清中TNF α水平 ,提高IL 10水平     

基因表达谱芯片分析日本血吸虫感染慢性期CD4+细胞的应答特征

目的　立足于全基因水平考察日本血吸虫慢性感染小鼠CD4+细胞的相关细胞因子的变化 ,探讨其与疾病的相关性。方法　采用高密度寡核苷酸芯片 (Affemetrix芯片 )结合三色流式细胞术 ,对日本血吸虫感染 13周的小鼠脾脏中的CD4+细胞进行基因转录及蛋白表达水平的分析 ,获得相关细胞因子的变化图谱。结果　日本血吸虫慢性感染小鼠CD4+细胞中IL 4的转录及蛋白表达水平均明显高于正常小鼠 (P <0 .0 5) ,尤其以可溶性虫卵抗原刺激后最为显著 (P <0 .0 1) ;感染小鼠IFN γ的转录及蛋白表达水平也有所增高 ,但不及IL 4的升高程度 ;IL 10、IL 1β、小诱导细胞因子(smallinduciblecytokine)等因日本血吸虫的感染而升高 ,但TGF β1呈下降趋势。结论　日本血吸虫慢性感染小鼠细胞因子分泌谱表现为Th1和Th2型细胞因子并存的格局 ,但以Th2应答为主。它们可能通过诱导产生相应的趋化因子共同参与疾病的病理改变     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.     

Dénervation rénale pour HTA réfractaire sans anesthésie générale : intérêt d’un protocole MEOPA Morphine. Expérience préliminaire

Renal denervation using the technique of radiofrequency is used only recently for the treatment of resistant hypertension. Normally, it is done under general anesthesia because the ablation point technique is painful. We suggest an alternative to general anesthesia comprising an association of morphin 0.1 mg/kg IV to MEOPA (gas combining oxygen and azot protoxyd) delivered through an oxygen mask. Our series includes 12 consecutive patients treated between October 2011 and June 2013, the first five patients (group 1) have received only an hydroxizin and morphin sedation. Every five have felt the ablation painful, in two cases bearable pain (EVA < 5), in three cases intense (EVA > 5) pain leading to increasing doses of morphin, (total dose of 0.25 mg/kg in two cases, 0.17 mg in one case). For the seven following patients, a protocol including hydroxyzin, morphin and MEOPA given through a mask has been set up. Only one patient has felt a mild pain (EVA 5) leading to an increasing dose of morphin (total dose 0.17 mg/kg). None of the six other patients has felt any pain during the procedure. The average dose of morphin is 0.17 mg/kg in group 1, 0.11 mg/kg in group 2. This is a preliminary study; if confirmed, it will allow a lot of hospitals without on-site possibilities of general anesthesia, to realize such procedures. Conclusion: regarding pain, the procedure of renal ablation was well tolerated for six among seven patients receiving the association MEOPA and IV morphin. In contrast, in the five patients treated only with IV morphin, we observed a less good tolerance to pain and the need to increase the doses of IV morphin.     

Scale‐up of TB and HIV programme collaborative activities in Zambia – a 10‐year review

Objective To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. Methods Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000–2010. Results The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti‐retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV‐infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co‐trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. Conclusions The scale‐up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti‐retroviral (ARV) rollout with improved treatment outcomes among TB patients co‐infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).     

C-MET在非小细胞肺癌对表皮生长因子受体酪氨酸激酶抑制剂耐药中的作用研究进展

以表皮生长因子受体(EGFR)为靶点的酪氨酸酶抑制剂(TKI)是近年来非小细胞肺癌(NSCLC)治疗的重大突破.但是随着临床的广泛应用,耐药成为新的难点.新近研究已发现对EGFRTKI的耐药产生主要涉及原癌基因C-MET的扩增突变.C-MET是原癌基因,是蛋白产物肝细胞生长因子/离散离子(HGF/SF)的受体,具有酪氨酸酶活性,C-MET基因扩增激活ErbB3-PI3K信号途径导致NSCLC对EGFR-TKI产生耐药,大量研究证实NSCLC患者对EGFR-TKI耐药约20％归因于C-MET基因扩增.     

Artificial intelligence in pancreaticobiliary endoscopy

Artificial intelligence (AI) applications in health care have exponentially increased in recent years, and a few of these are related to pancreatobiliary disorders. AI‐based methods were applied to extract information, in prognostication, to guide clinical treatment decisions and in pancreatobiliary endoscopy to characterize lesions. AI applications in endoscopy are expected to reduce inter‐operator variability, improve the accuracy of diagnosis, and assist in therapeutic decision‐making in real time. AI‐based literature must however be interpreted with caution given the limited external validation. A multidisciplinary approach combining clinical and imaging or endoscopy data will better utilize AI‐based technologies to further improve patient care.