可溶性细胞间粘附分子-1及其在肝病中的意义

细胞间粘附分子-1(intercellular adhesion molecule-1，ICAM-1)与组织器官炎症、免疫损伤及移植器官排斥反应的发生关系密切。细胞表面ICAM-1表达量的增加，在病毒性肝炎、自身免疫性肝炎等多种肝疾病中已有报道，并认为肝细胞ICAM-1表达强度与肝组织炎症损伤程度密切相关。ICAM-1与其它膜受体一样，也能以脱落或循环的形式     

骨髓源性肝细胞的研究进展

经典发育生物学认为,成体干细胞的分化能力有限,并具有器官特异性,主要用于维持细胞功能的稳态[1],一般不能分化为其他细胞类型.但在1997年,Eglitis等[2]用亚致死剂量放射性核素照射雌性小鼠,破坏其骨髓系统,然后将雄性小鼠的骨髓干细胞移植给雌鼠,结果发现这些细胞在受体内重新分化为神经胶质细胞,表明骨髓干细胞在一定条件下可以跨胚层分化成其他类型的细胞,这种现象被称为横向分化(transdifferentiation).近5年来,有关骨髓干细胞横向分化为肝细胞的研究已成为国际上干细胞研究的热点之一,这些研究发现了骨髓干细胞的新特性,有学者乐观地认为将来可以移植患者自身骨髓干细胞治疗急、慢性肝衰竭.     

肝卵圆细胞分化调控机制的研究进展

卵圆细胞是肝脏的干细胞，具备多向分化潜能，体内外实验证实其可以分化为肝细胞、胆管细胞、胰腺及肠型上皮细胞。在胚胎发育过程中，肝脏干细胞以肝细胞的形式存在，而在成年哺乳动物的肝组织中则以卵圆细胞的形式存在。对卵圆细胞分化调控机制的研究在基础理论和临床应用等方面均有重要意义，一方面，卯圆细胞可能参与肝脏损伤的修复与重建，研究其分化机制有助于阐明肝脏的发育机制；另一方面，卵圆细胞可分化为具有功能的成熟肝细胞，将为肝细胞移植和生物型人工肝提供重要的细胞来源，可能缓解供体肝脏严重缺乏的矛盾。但卵圆细胞的分化过程和机制非常复杂，分化异常可能导致肝细胞癌的发生。     

病毒性肝炎：总论

胚胎干细胞分化为肝细胞的研究进展（综述）——周庆军等（浙江杭州浙江大学生命科学学院310012）：《生物工程学报》，2005，21（2）：171-176[目前，细胞移植作为终末期肝病的辅助治疗方法，移植的细胞必须满足在受体肝脏中存活、增殖并可分化为成熟肝细胞两个重要条件，但目前应用的肝细胞来源有限。其功能随着培养时间的延长而逐渐下降等问题限制了这一治疗策略的广泛开展。     

肝干细胞移植治疗重症肝病

原位肝移植仍然是目前治疗重症肝病最有效的措施.但是,它存在的三大缺陷阻碍着其更广泛应用:(1)供肝缺乏;(2)供体肝与受体存在免疫排斥反应,肝移植术后需长期应用免疫抑制剂,使患者免疫力下降,易患各种疾病;(3)器官移植费用昂贵,对国家、社会、个人都是一种沉重的经济负担.干细胞是一类具有自我复制功能和多分化潜能的早期未分化细胞,通过控制条件可以使其分化为肝细胞,达到修复损伤组织,恢复部分肝脏功能的目的.自体肝干细胞移植治疗重症肝病是安全和有效的,但其长期疗效仍需要观察.     

肝干细胞研究进展

由于供体器官来源缺乏 ,肝移植治疗肝脏终末期疾病的应用受到限制。于是人们设计出了生物人工肝、肝细胞移植作为肝移植的辅助或替代疗法 ,用来治疗某些肝脏代谢性疾病 ,促进急性肝功能衰竭的肝再生 ,或者在患者得到合适供体肝脏之前提供肝功能支持。对于肝细胞移植及生物人工肝 ,原代肝细胞是患者理想供体 ,但其来源同样缺乏。此外 ,原代肝细胞体外培养或体内移植后的增殖及其功能保持情况不甚理想。研究指出发育的胚胎以及成年体内的某些细胞具有肝干细胞的特性 ,能在一定的条件下增殖并分化成为肝细胞或胆管细胞。这些发现具有重要的临床…     

胰腺干细胞的研究进展

胰岛移植是治疗糖尿病的一个热点 ,但供体的缺乏和存在免疫排斥反应限制了其应用。胰腺干细胞能定向分化成胰岛细胞 ,这为胰岛移植提供新的材料来源[1 3 ] 。胰腺干细胞能向外分泌腺组织定向诱导 ,对于急、慢性胰腺炎的发生、发展及治疗的研究有重要作用 ;并能修复胰腺外伤导致的胰腺功能不全。研究表明 ,胰腺干细胞对胰腺癌的发生、发展、调控和治疗具有重要的研究价值。一、干细胞概述1.干细胞的概念 :干细胞是一类具有自我更新与增殖分化能力的细胞 ,能产生出与自己完全相同的子细胞 ,同时还能分化为祖细胞[4] ;在特定条件下 ,它可以分化…     

骨髓间充质干细胞生物学特性及其在肝病应用中的进展

骨髓间充质干细胞（BM-MSCs）是肝细胞移植的重要来源之一，已成为肝细胞移植领域中继胚胎干细胞之后又一个“明星”细胞。作者通过计算机检索中国期刊网和Pubmed等数据库有关文献，归纳了BM—MSCs的免疫表型、异质性、增殖能力、分化潜能、归巢现象及体内外分化为肝样细胞的研究现状，对其在肝病中的应用前景和存在问题做初步探讨。     

骨髓干细胞治疗肝病的研究进展

骨髓干细胞是一类具有自我增殖和分化潜能的细胞,主要包括造血干细胞和间充质干细胞。体外通过生长因子,体内利用特定的微环境均可诱导骨髓干细胞分化为肝前体细胞和成熟肝细胞,并明显改善肝功能。其有望成为肝细胞移植或生物人工肝支持系统的新型种子细胞。此文就骨髓干细胞分化为肝样细胞及其临床治疗肝病的研究进展作一综述。     

肝脏干细胞移植

难治性肝病的治疗一直是全球性难题，原位肝移植是治疗终末期肝病的最佳选择，但由于供体器官紧缺，许多病人在等待肝移植时死亡，同时移植后并发症如免疫排斥反应等因素也限制了其应用。肝细胞移植治疗难治性肝病虽取得了一定的疗效，但由于肝细胞在体外不能大量繁殖且传代后不能保持其原有特性而难以推广应用。相比之下，肝脏干细胞具有长时间持续增生的能力，能在体外扩增达到临床所需的细胞数量，     

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.     

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.     

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.