进行性家族性肝内胆汁淤积症3型

进行性家族性肝内胆汁淤积症3型(progressive familial intrahepatic cholestasis type 3,PFIC3)是一种常染色体隐性遗传性疾病,由编码多药耐药蛋白3(multidrug resistance protein 3,MDR3)的AB CB4(ATP-bindingcassette,sub-family B,member 4)基因突变引起~([1]).PFIC3临床上可表现为反复瘙痒、黄疸、白陶土样便、肝脾肿大及胃肠道出血等,常在成年前进展为肝硬化和肝衰竭~([1-3]).PFIC3是进行性家族性肝内胆汁淤积症的一种亚型,与进行性家族性肝内胆汁淤积症1型和2型的主要区别在于血清γ-谷氨酰转肽酶(GGT)升高及肝组织病理表现为明显的小胆管增生~([4]).     

ATP8B1缺陷病

进行性家族性肝内胆汁淤积症( progressive familial intrahepatie cholestasis,PFIC)是一组常染色体隐性遗传病,以肝内胆汁淤积为主要表现,通常在婴儿或儿童期起病,最终进展至肝功能衰竭.根据致病基因不同,PFIC主要分为3型,即PFIC1、PFIC2、PFIC3.其中PFIC1由ATP8B1基因突变引起,以持续性肝内胆汁淤积、黄疸伴瘙痒为特征,通常在1岁之前发病,随着病情的进展,最终发展为肝纤维化、肝硬化和肝功能衰竭.此外,ATP8B1基因突变还可导致良性再发型肝内胆汁淤积症(benign recurrent intrahepatic cholestasis,BRIC)1型和妊娠期肝内胆汁淤积1型(intrahepatic cholestasis of pregnancy,ICP)1型.因此,PFIC1、BRIC1及ICP1共同构成了ATP8B1缺陷病的临床疾病谱.     

原发性硬化性胆管炎28例临床特征及疗效回顾分析

目的分析原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)的临床特征及诊治经验,以提高对该病的认识。方法对我院2000年1月-2010年12月收治确诊的28例PSC患者的临床特征、生化、免疫学、组织学及治疗等资料进行回顾性分析。结果 28例PSC患者中男21例(75%),女性7(25%),中位诊断年龄52岁(4～69岁);临床表现主要为黄疸(89.3%,25/28)、纳差(32.1%,9/28)、皮肤瘙痒(25.0%,7/28)、肝区疼痛(25.0%,7/28);实验室检查表现为总胆红素水平升高(89.3%,25/28);均以结合胆红素升高为主,肝酶升高(89.3%,25/28),包括谷丙转氨酶、谷草转氨酶、碱性磷酸酶及γ-谷氨酰转肽酶,但均以轻度升高为主;20例(90.9%,20/22)患者经胆管造影检查得到确诊,主要表现为肝内外胆管变细、粗细不均和/或走行僵直,其中经内镜逆行胰胆管造影(ERCP)确诊11例(100%,11/11)、经磁共振胰胆管造影(MRCP)确诊6例(85.7%,6/7)、经皮肝穿刺胆管造影(PTC)确诊2例(66.7%,2/3),经T管造影确诊1例(100%,1/1);其余8例(100%,8/8)患者经肝穿刺活检病理组织学检查确诊,主要表现为汇管区胆管周围炎症及纤维组织增生;25例患者经药物治疗后,13例(52%,13/25)生化指标有不同程度好转,3例经手术治疗的患者1例(33.3%,1/3)好转。结论 PSC发病机制未明,好发于男性,黄疸为主要症状,主要表现为肝酶和胆红素轻度升高,确诊应首选胆道造影检查,目前尚无特效治疗药物。     

原发性胆汁性肝硬化瘙痒及乏力机制的研究进展

原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)是一种肝脏特异的慢性自身免疫性疾病.该病女性易患,以胆汁淤积、酶系升高为特征表现,病理以肝内小胆管非化脓性进行性破坏为特征,长期持续性肝内胆汁淤积可最终导致肝纤维化及肝硬化.     

原发性胆汁性肝硬化瘙痒及乏力机制的研究进展

原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)是一种肝脏特异的慢性自身免疫性疾病.该病女性易患,以胆汁淤积、酶系升高为特征表现,病理以肝内小胆管非化脓性进行性破坏为特征,长期持续性肝内胆汁淤积可最终导致肝纤维化及肝硬化.     

一组不明原因的肝损害患者肝组织病理学诊断研究*

目的 探讨在B超引导下肝穿刺活检术诊断不明原因的肝损伤(LIUO)的价值。方法 回顾性分析我院诊治的71例LIUO患者的临床资料,所有患者接受肝穿刺活检,进行全面的血清学、病毒学和影像学检查。结果 在71例患者中,53例(76.4%)表现为不明原因的血清转氨酶升高,6例(8.5%)为不明原因的血清胆红素升高,8例(11.3%)为不明原因的肝硬化,2例(2.8%)为不明原因的门脉高压,2例(2.8%)为胆管扩张;结合临床资料,组织病理学检查诊断13例(18.3%)为自身免疫性肝病,其中8例为原发性胆汁性胆管炎,2例为自身免疫性肝炎,2例为重叠综合征,1例为IgG4相关性胆管炎;18例(25.4%)为非酒精性脂肪性肝病,其中14例为非酒精性脂肪性肝炎;17例(23.9%)为药物性肝损伤;4例(5.6%)为化学性肝损害伤;2例(2.8%)为酒精性脂肪肝;2例为Gilbert综合征,1例诊断为Dubin-Johnson综合征,1例诊断为Caroli病,1例为特发性门脉高压,1例为糖原累积症相关性肝硬化,有1例非噬肝病毒感染,1例为肝内胆管病变,仍有9例(12.7%)肝损害无明显特异性,仅表现为非特异性反应性肝炎。结论 结合临床资料,肝穿刺活检组织病理学检查能够帮助临床医生提供大部分LIUO患者的病因学诊断。     

原发性胆汁性肝硬化与干燥综合征四例分析

目的探讨原发性胆汁性肝硬化(PBC)与干燥综合征(SS)的关系,提高临床医师对PBC的诊治水平。方法分析4例PBC或SS患者肝损害的临床病理表现、治疗和转归,并复习有关文献。结果3例PBC患者抗线粒体抗体M2阳性,生化检查及肝穿刺病理检查均提示胆汁淤积性肝损害,其中2例IgM升高。此3例均同时伴有口干燥症和眼干燥症,2例更符合2002年修订的干燥综合征国际分类标准,熊去氧胆酸治疗有效;而第4例单纯干燥综合征患者表现为非胆汁淤积性肝损害,以IgG升高为主,免疫抑制剂治疗有效。结论PBC肝损害以胆汁淤积为主,抗线粒体抗体M2阳性对PBC诊断有较高特异性,熊去氧胆酸为治疗首选;PBC常伴发SS,二者密切关联又有明显不同。     

进行性家族性肝内胆汁淤积症的研究现状

进行性家族性肝内胆汁淤积症(PFIC)是一组罕见的异质性常染色体隐性遗传性疾病,发病率约为1/50 000~1/100 000。依据编码肝细胞膜转运蛋白基因的不同,可将PFIC分为三型。PFIC-1、PFIC-2和PFIC-3分别是ATP8B1、ABCB11和ABCB4基因突变所致。PFIC-1和PFIC-2血清GGT活性正常,而PFIC-3血清GGT活性升高。PFIC以严重肝内胆汁淤积为主要特征,在婴儿或者儿童期发病,进展迅速,通常在儿童或者青春期进展为终末期肝病。诊断主要靠临床症状、生化学检测、肝脏影像学、肝脏病理学及基因检测等。熊去氧胆酸是所有类型PFIC患者的初始治疗药物,外科胆汁分流术能减轻部分PFIC-1或PFIC-2患者瘙痒症状,延缓病情进展,但对大多数患者肝移植是唯一有效的治疗措施。     

进行性家族性肝内胆汁淤积症研究进展

进行性家族性肝内胆汁淤积症(progressive familial intrahepatic cholestasis, PFIC)是一组常染色体隐性遗传病,以肝内胆汁淤积为主要表现,通常在婴儿或儿童期起病。根据致病基因不同,PFIC 可分为 6 型。这些患儿若得不到及时干预,多在儿童期发展为肝硬化和肝衰竭。因此早期诊断及干预十分重要。本文将对 PFIC 的发病机制、临床表现、诊断及治疗的研究进展作综述。     

107例胆汁淤积性肝病的临床特征分析

目的分析胆汁淤积性肝病的临床特征,为临床加强该病的诊疗提供参考。方法回顾性分析2015年1月-2017年12月收治于厦门大学附属成功医院并确诊为胆汁淤积性肝病的107例患者的临床资料。计量资料2组间比较采用t检验。结果多数患者出现不同程度全身乏力、食欲不振、恶心、腹胀、皮肤瘙痒及黄疸等临床症状。按胆汁淤积部位分为肝内胆汁淤积64例(59. 8%)和肝外胆管淤积43例(40. 2%)。按病因分为胆总管结石21例(19. 6%),胆管寄生虫1例(0. 9%),原发性硬化性胆管炎2例(1. 9%),原发性胆汁性肝硬化3例(2. 8%),肝癌8例(7. 5%),胆管癌5例(4. 7%),胰腺癌4例(3. 7%),胰腺炎12例(11. 2%),病毒性肝炎28例(26. 2%),药物性肝损伤11例(10. 3%),酒精性肝炎6例(5. 6%),非酒精性脂肪性肝病4例(3. 7%),自身免疫性肝炎2例(1. 9%)。合并基础病患者的肝功能(ALT、AST、GGT、ALP、胆汁酸和TBil)明显差于单纯性胆汁淤积性肝病患者(t值分别为-3. 44,-2. 99,-2. 42,-4. 39,-3. 34,-2. 49,P值均0. 05)。大多数患者经保肝、降酶、退黄等治疗后患者恢复良好。肿瘤患者预后不佳。结论胆汁淤积性肝病病因众多,临床特征无特异性,应引起足够重视。     

Control of intraabdominal hemorrhage and shock: a comparison of fluid resuscitation, MAST, and balloon occlusion

Our study examined the efficacy of four treatment modalities in controlling hemorrhage and achieving hemodynamic stabilization in hemorrhagic shock: intravenous fluid replacement (IV); military antishock trousers used concomitantly with fluids (MAST); balloon occlusion at the level of the diaphragm with concomitant fluid replacement (balloon); and a combination of MAST inflation, balloon occlusion, and fluid resuscitation (MAST and balloon). Twenty-eight mongrel dogs were anesthetized, and the spleen was exposed and completely crushed. The abdomen was closed, and treatment was initiated and continued for four hours or until the dog died. For all conditions the hematocrit dropped during the course of the experiment; balloon occlusion was effective at slowing this drop (P less than .0001), but MAST had no statistically significant effect. Animals with balloons bled more slowly into the abdominal cavity than did animals in the other two groups (P less than .0001). MAST also were effective at slowing the bleeding (P less than .05). Of the balloon and the MAST and balloon dogs, all except one survived the entire four hours; this difference between balloon and nonballoon dogs is significant (P = .002). MAST did not have a statistically significant effect on survival. Perfusion pressure (PP) declined during the course of the experiment, and the balloon was effective at slowing this decline (P less than .0001); none of the other comparisons was statistically significant.     

A Call to Action to Enhance Filovirus Disease Outbreak Preparedness and Response

The frequency and magnitude of recognized and declared filovirus-disease outbreaks have increased in recent years, while pathogenic filoviruses are potentially ubiquitous throughout sub-Saharan Africa. Meanwhile, the efficiency and effectiveness of filovirus-disease outbreak preparedness and response efforts are currently limited by inherent challenges and persistent shortcomings. This paper delineates some of these challenges and shortcomings and provides a proposal for enhancing future filovirus-disease outbreak preparedness and response. The proposal serves as a call for prompt action by the organizations that comprise filovirus-disease outbreak response teams, namely, Ministries of Health of outbreak-prone countries, the World Health Organization, Médecins Sans Frontières, the Centers for Disease Control and Prevention—Atlanta, and others.     

Interplay between interferon-mediated innate immunity and porcine reproductive and respiratory syndrome virus

Innate immunity is the first line of defense against viral infection, and in turn, viruses have evolved to evade host immune surveillance. As a result, viruses may persist in host and develop chronic infections. Type I interferons (IFN-α/β) are among the most potent antiviral cytokines triggered by viral infections. Porcine reproductive and respiratory syndrome (PRRS) is a disease of pigs that is characterized by negligible induction of type I IFNs and viral persistence for an extended period. For IFN production, RIG-I/MDA5 and JAK-STAT pathways are two major signaling pathways, and recent studies indicate that PRRS virus is armed to modulate type I IFN responses during infection. This review describes the viral strategies for modulation of type I IFN responses. At least three non-structural proteins (Nsp1, Nsp2, and Nsp11) and a structural protein (N nucleocapsid protein) have been identified and characterized to play roles in the IFN suppression and NF-κB pathways. Nsp's are early proteins while N is a late protein, suggesting that additional signaling pathways may be involved in addition to the IFN pathway. The understanding of molecular bases for virus-mediated modulation of host innate immune signaling will help us design new generation vaccines and control PRRS.     

Disease Pandemics and Major Epidemics Arising From New Encounters between Indigenous Viruses and Introduced Crops

Virus disease pandemics and epidemics that occur in the world’s staple food crops pose a major threat to global food security, especially in developing countries with tropical or subtropical climates. Moreover, this threat is escalating rapidly due to increasing difficulties in controlling virus diseases as climate change accelerates and the need to feed the burgeoning global population escalates. One of the main causes of these pandemics and epidemics is the introduction to a new continent of food crops domesticated elsewhere, and their subsequent invasion by damaging virus diseases they never encountered before. This review focusses on providing historical and up-to-date information about pandemics and major epidemics initiated by spillover of indigenous viruses from infected alternative hosts into introduced crops. This spillover requires new encounters at the managed and natural vegetation interface. The principal virus disease pandemic examples described are two (cassava mosaic, cassava brown streak) that threaten food security in sub-Saharan Africa (SSA), and one (tomato yellow leaf curl) doing so globally. A further example describes a virus disease pandemic threatening a major plantation crop producing a vital food export for West Africa (cacao swollen shoot). Also described are two examples of major virus disease epidemics that threaten SSA’s food security (rice yellow mottle, groundnut rosette). In addition, brief accounts are provided of two major maize virus disease epidemics (maize streak in SSA, maize rough dwarf in Mediterranean and Middle Eastern regions), a major rice disease epidemic (rice hoja blanca in the Americas), and damaging tomato tospovirus and begomovirus disease epidemics of tomato that impair food security in different world regions. For each pandemic or major epidemic, the factors involved in driving its initial emergence, and its subsequent increase in importance and geographical distribution, are explained. Finally, clarification is provided over what needs to be done globally to achieve effective management of severe virus disease pandemics and epidemics initiated by spillover events.     

Barrett's Esophagus: Where Do We Stand?

Barrett''s esophagus (BE) is a precursor for esophageal adenocarcinoma, which has an increased incidence rate over the last few decades. Its importance stems from the poor five-year survival of esophageal adenocarcinoma and current data that suggest a survival benefit when surveillance programs are implemented. In this review, we will cover the pathophysiology and natural history of BE and the different endoscopic findings. The prevalence of BE in different geographic areas and the incidence of high-grade dysplasia and adenocarcinoma in this patient population is reviewed. Recent recommendation for screening and surveillance of BE has been covered in this review as well as the efficacy of nonconventional imaging modalities and endoscopic ablation therapies.     

The Technology Transfer from Europe to China in the 17th–18th Centuries: Non-Invasive On-Site XRF and Raman Analyses of Chinese Qing Dynasty Enameled Masterpieces Made Using European Ingredients/Recipes

Two masterpieces of the Qing Dynasty (1644–1912 CE), one in gilded brass (incense burner) decorated with cloisonné enamels stylistically attributed to the end of the Kangxi Emperor’s reign, the other in gold (ewer offered by Napoleon III to the Empress as a birthday present), decorated with both cloisonné and painted enamels bearing the mark of the Qianlong Emperor, were non-invasively studied by optical microscopy, Raman microspectroscopy and X-ray microfluorescence spectroscopy (point measurements and mapping) implemented on-site with mobile instruments. The elemental compositions of the metal substrates and enamels are compared. XRF point measurements and mappings support the identification of the coloring phases and elements obtained by Raman microspectroscopy. Attention was paid to the white (opacifier), blue, yellow, green, and red areas. The demonstration of arsenic-based phases (e.g., lead arsenate apatite) in the blue areas of the ewer, free of manganese, proves the use of cobalt imported from Europe. The high level of potassium confirms the use of smalt as the cobalt source. On the other hand, the significant manganese level indicates the use of Asian cobalt ores for the enamels of the incense burner. The very limited use of the lead pyrochlore pigment (European Naples yellow recipes) in the yellow and soft green cloisonné enamels of the Kangxi incense burner, as well as the use of traditional Chinese recipes for other colors (white, turquoise, dark green, red), reinforces the pioneering character of this object in technical terms at the 17th–18th century turn. The low level of lead in the cloisonné enamels of the incense burner may also be related to the use of European recipes. On the contrary, the Qianlong ewer displays all the enameling techniques imported from Europe to obtain a painted decoration of exceptional quality with the use of complex lead pyrochlore pigments, with or without addition of zinc, as well as cassiterite opacifier.     

Formoterol Delivered via the Dry Powder Aerolizer® Inhaler Versus Albuterol MDI and Placebo in Mild-to-Moderate Asthma: A Randomized, Double-Blind, Double-Dummy Trial

The objectives of this study were to compare the efficacy and tolerability of twice-daily formoterol dry powder 12 µg and 24 µg (Foradil) delivered via Aerolizer inhaler with four times daily albuterol (salbutamol) 180 µg delivered via metered dose inhaler (MDI) and placebo. A total of 554 adolescents and adults (ages 12-75 years) with mild-to-moderate asthma were randomized to this 12-week, multicenter, double-blind, double-dummy, placebo-controlled, parallel-group study. Twelve-hour spirometry measurements were taken at weeks 0, 4, 8, and 12. A total of 484 patients completed the study (122, 116, 127, and 119 given formoterol 12 µg, formoterol 24 µg, albuterol, and placebo, respectively). For the primary efficacy variable, the forced expiratory volume in 1 second (FEV₁), both formoterol 12 µg and 24 µg were statistically superior to placebo at all time points on all test days (p ≤ 0.017) and to albuterol at most time points on all test days (p ≤ 0.001). The onset of improvement in FEV₁ was rapid, with 15% increase within 5 min in 57%, 71%, and 65% of formoterol 12 µg, formoterol 24 µg, and albuterol patients, respectively. Formoterol was also superior to placebo and albuterol in terms of secondary efficacy variables: FEV₁ area under the curve, percentage of predicted FEV₁, forced vital capacity and forced expiratory flow, asthma symptom scores, and peak expiratory flows. In conclusion, both formoterol doses were superior to placebo in all lung function measurements. Overall, compared with albuterol, both formoterol doses produced superior bronchodilation. Formoterol and albuterol were safe and well-tolerated.