药物性肝损伤与原发性胆汁性肝硬化的临床特征比较

目的探讨并比较分析药物性肝损伤(DILI)与原发性胆汁性肝硬化(PBC)的临床特征。方法选取中国医科大学附属盛京医院2005年1月~(-2)013年12月确诊的116例PBC及124例DILI患者,比较2组患者的临床特征、实验室检查指标及肝组织病理学检查结果。计量资料组间比较采用t检验或Nemenyi秩和检验,计数资料组间比较采用χ~2检验。结果 2组发病年龄和性别组成差异有统计学意义(P值均0.05)。2组血清学指标(除白蛋白)、免疫学指标Ig G、Ig M和Ig A、自身抗体阳性率(除抗平滑肌抗体)的差异均有统计学意义(P值均0.05)。PBC组织学表现主要为肝细胞水肿样变性(30例),胆管周围炎性细胞浸润(29例),小胆管不典型增生(28例)等;DILI组织学表现主要为肝细胞脂肪变性(15例),肝细胞点状坏死脱失(14例)等。结论 DILI和PBC在实验室检查、病理学检查等方面存在差异,对临床鉴别诊断工作有一定的指导意义。     

原发性胆汁性胆管炎超声表现及与实验室指标的相关性研究

目的探讨原发性胆汁性胆管炎(primary biliary cholangitis,PBC)的超声表现,分析不同病理分期的生化、免疫指标的差异。方法回顾性分析病理确诊的75例PBC患者的超声表现、病理资料及临床实验室检查结果,总结不同病理分期超声表现,分析PBC患者的病理分期与肝功能、免疫学指标的相关性。结果不同病理分期的PBC患者超声表现不同:Ⅰ期患者超声表现正常或回声稍增粗,Ⅱ期患者超声表现为回声增粗及呈条索样改变,Ⅲ、Ⅳ期患者超声表现多呈条索及结节样改变,且部分患者可出现门静脉周围的低回声区。对实验室检查与纤维化病理分期的分析显示,ALT、ALP水平在4期之间差异有统计学意义(P均0.05),两两比较发现Ⅲ期ALT、ALP水平大于Ⅰ、Ⅱ期,其余各期之间差异无统计学意义(P均0.05);Ig G水平在4期患者之间差异有统计学意义(P0.05),两两比较发现Ⅳ期水平大于Ⅰ期,其余各期之间差异无统计学意义(P均0.05)。结论超声在PBC各病理分期的特征性影像学改变结合生化免疫指标,可对PBC提供客观的无创诊断依据,并与PBC的病理纤维化程度具有相关性。     

外周血GLDH、GLDH/ALT水平对原发性胆汁性胆管炎患者疾病分期的诊断价值

目的 探讨谷氨酸脱氢酶(GLDH)、GLDH/ALT比值对原发性胆汁性胆管炎(PBC)分期的诊断效能。方法 选取已明确病理分期的PBC患者212例，检测其外周血中GLDH水平，并计算FIB-4、APRI、AAR、RPR等一系列无创性血清学指标。通过Spearman分析各指标与PBC分期的相关性，绘制受试者工作特征曲线评价其诊断效能。结果 Ⅰ/Ⅱ期患者，GLDH及GLDH/ALT水平差异无统计学意义(P>0.05);Ⅱ/Ⅲ期及Ⅲ/Ⅳ期患者，GLDH及GLDH/ALT水平差异均有统计学意义(P<0.05); PBC病理分期与ALT(r=0.006,P=0.152)、GGT(r=-0.036,P=0.182)、GPRI (r=0.340,P=0.055)无明显相关性；与TBil(r=0.401,P=0.009)、DBil(r=0.403,P=0.007)、AST(r=0.217,P=0.019)、RDW(r=0.422,P<0.01)、FIB-4(r=0.774,P<0.01)、APRI(r=0.620,P<0.001)、AAR(r=0.359,P<0.0...     

原发性胆汁性肝硬化93例临床及病理特点分析

目的总结原发性胆汁性肝硬化（PBC）患者的临床及病理学特点,以加深对该病的认识,指导临床诊疗。方法回顾性分析93例经肝活组织穿刺病理检查确诊为PBC患者的临床表现、生化指标、免疫学指标、病理学特点以及不同病理分期与生化指标相关性。结果93例患者临床症状中以乏力、皮肤瘙痒、黄疸最为常见。PBC患者均有不同程度肝功能异常,以ALP、GGT升高最为多见,异常比例分别为94．6％、95．7％。69．9％患者血清AMA和（或）AMA—M2亚型阳性,64．5％患者ANA阳性。93例肝脏病理学检查,符合I期为25例,Ⅱ期37例,Ⅲ期21例,Ⅳ期10例。病理分期与TBil、TBA呈正相关,与CHE呈负相关（P〈0．05）。结论诊断PBC应重视病理学检查,对病情及预后判断可参考TBil、TBA、CHE等指标,也应综合分析其临床症状、生化指标、自身抗体检测及组织学检查等。     

PBC患者血清学指标与肝组织活检病理分期的关系及进展期PBC危险因素的Logistic回归分析

目的探讨原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者血清学指标与肝组织活检病理分期的相关性,并分析进展期PBC的相关危险因素,指导临床诊治及监测疾病进展。方法收集2013年1月至2018年4月昆明医科大学第二附属医院消化内科确诊PBC并行肝穿活检分期的87例患者的临床资料,按病理分期分为Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期,同时收集所有患者同期的生化、血细胞分析、凝血功能、免疫球蛋白、抗核抗体(ANA)及抗线粒体抗体(AMA)等指标,回顾性分析血清学指标与肝组织活检病理分期的关系及进展期PBC危险因素。结果 87例PBC患者以女性为主(81.61%),发病中位年龄为49.16岁,该研究中所统计的血清学指标在PBC病理Ⅰ期、Ⅱ期组间差异均无统计学意义(P0.05),其中白蛋白(ALB)、球蛋白(GLO)、白球比(A/G)、前白蛋白(PAB)、血小板(PLT)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、胆汁酸(TBA)、总胆红素(TB)、胆碱酯酶(CHE)、IgG、IgA、IgM仅部分在不同病理分期组间差异有统计学意义(P0.05),ANA、抗线粒体抗体M2(AMA-M2)在不同病理分期组间差异无统计学意义(P0.05)。多因素Logistic回归分析结果显示,A/G、TB、IgM是PBC病理分期进展的独立危险因素。结论虽然血清学指标对PBC的诊断具有重要意义,对评估早期及进展期肝组织病变有一定指导价值,但血清学指标对PBC不同肝组织活检病理分期的鉴别仍缺乏特异性及敏感性,A/G、TB、IgM是PBC进展期的危险因素,肝组织活检目前仍是明确PBC病理分期的可靠方法。     

原发性胆汁性胆管炎发生肝硬化失代偿危险因素评估病例对照研究

目的:探讨原发性胆汁性胆管炎(PBC)患者发生肝硬化失代偿的相关危险因素。方法:回顾性分析2008年8月至2019年12月首都医科大学附属北京地坛医院864例PBC患者病历资料，按纳入及排除标准收集到PBC肝硬化代偿期组(n=246)和肝硬化失代偿期组(n=183)两组患者。纳入两组患者入组时年龄、性别、ALT、AST、TBil、Glo、Alb、GGT及ALP水平、血脂水平、免疫球蛋白水平、INR、APRI、FIB-4、NLR等指标并进行分析。计量资料符合正态分布的组间比较采用独立样本t检验；非正态分布则采用Mann-Whitney U检验。计数资料组间比较采用卡方检验。用二元logistic回归模型进行单因素和多因素分析，计算相关因素危险比及95%置信区间。结果:与PBC肝硬化代偿期患者相比，PBC肝硬化失代偿期患者WBC、NE#、LY#、MO#、RBC、HGB、PLT、ALT、AST、Che、Alb、GGT、ALP、TC、TG、PTA水平均偏低(P<0.05);PBC肝硬化失代偿期患者NLR、TBil、DBil、TBA、PT、INR、TT、CREA、IgA、IgM、ARPI评...     

血清补体C3对原发性胆汁性胆管炎相关肝纤维化分期的诊断价值

目的 探讨血清补体C3水平对原发性胆汁性胆管炎（PBC）肝纤维化分期的诊断价值。方法 收集2012年1月—2022年10月在天津市第二人民医院就诊并行肝穿刺活检的108例PBC患者临床资料。依据Scheuer评分系统评估肝纤维化程度（S0～4），其中≥S2定义为显著肝纤维化，≥S3定义为进展期肝纤维化，S4定义为肝硬化。符合正态分布的计量资料两组间比较采用独立样本t检验，多组间比较采用单因素方差分析。不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H秩和检验。计数资料组间比较采用χ2检验或Fisher精确检验。通过受试者工作特征曲线下面积（AUC）评估补体C3对PBC患者肝纤维化的诊断效能。采用Spearman相关分析评估补体C3与肝纤维化分期的相关性。结果 本研究108例PBC患者中女性87例（80.6%），自身抗体阳性102例（94.4%）。肝纤维化分期S0期5例（4.6%）,S1期41例（38.0%）,S2期23例（21.3%）,S3期25例（23.1%）、S4期14例（13.0%）。补体C3在不同肝纤维化分期患...     

碱性成纤维细胞生长因子与慢性乙型肝炎及肝纤维化临床检测指标的关系

目的观察碱性成纤维细胞生长因子(b-FGF)在不同肝纤维化分期(S)肝组织中表达的差异性及其与临床检测常用的肝功能指标、肝纤维化指标、HBV DNA复制水平以及肝硬化Child-Pugh分级之间的关系。方法选取122例HBV引起的慢性肝炎及肝硬化患者,空腹静脉血检测:(1)肝功能指标:ALT、TBil、Alb;(2)肝纤维化指标:透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、Ⅳ型胶原(CⅣ);(3)HBV DNA复制水平;(4)对临床诊断肝硬化患者计算其Child-Pugh评分。行肝脏穿刺活检术后,经病理作纤维化分期(S1～S4)。免疫组织化学法测定肝组织中b-FGF在不同病理分期的表达及定位特点,半定量分析法计算b-FGF值,观察b-FGF与肝功能指标、肝纤维化指标、HBV DNA水平以及肝硬化Child-Pugh分级之间的关系。结果 (1)肝纤维化S1～S4期肝组织中b-FGF的表达部位及水平不同;(2)肝纤维化S1～S4期肝细胞中b-FGF的表达与肝纤维化分期(S1～S4)呈显著正相关(r=0.542,P<0.01);(3)不同肝纤维化分期中b-FGF的表达差异与患者ALT、TBil及Alb进行比较,其差异无统计学意义(P>0.05),不同肝纤维化分期患者,进行HBV DNA检测,其差异无统计学意义(P>0.05);(4)不同肝纤维化分期中,b-FGF与血清纤维化指标HA、PCⅢ、LN、CⅣ之间呈正相关;(5)b-FGF的表达与临床Child-Pugh分级无明显相关性。结论 b-FGF的表达与肝脏纤维化程度、肝纤维化指标有正相关关系,与患者ALT、TBil、Alb、Child-Pugh评分、及HBV DNA水平无关。     

慢性乙型肝炎患儿HBV DNA载量与肝脏病理、肝功能、肝纤维化血清学指标的相关性分析

目的探讨慢性乙型肝炎(CHB)患儿HBV DNA载量与肝脏病理及肝功能、肝纤维化血清学指标的关系。方法收集2010年7月-2015年6月湖南省儿童医院肝病中心收治的确诊为CHB的患儿79例,根据患儿血清HBV DNA载量分为低载量组(103拷贝/mlHBV DNA载量≤105拷贝/ml,n=8)、中载量组(105拷贝/mlHBV DNA载量≤107拷贝/ml,n=54)和高载量组(107拷贝/mlHBV DNA载量,n=17),比较各组间肝脏病理变化程度及血清ALT、AST、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、透明质酸(HA)、Ⅳ型胶原CⅣ水平。计量资料组间比较采用Kruskal-Wallis秩和检验,相关性分析采用Kendall's tau-b等级相关检验。结果 3组肝脏病理炎症程度分级均以G1为主,分别占75%、74.1%、64.7%,高载量组G2比例上升(35.5%);3组肝组织纤维化分期均以S1为主,分别占75.0%、72.2%、70.6%,低载量组出现S4(12.5%)。HBV DNA载量与肝组织炎症分级和纤维化分期均无相关性(r值分别为0.069、-0.047,P值均0.05)。随着HBV DNA载量的增高,各组间血清ALT、AST水平逐渐增高,3组间ALT水平比较差异有统计学意义(χ2=5.37,P=0.048)。随着HBV DNA载量的增高,各组间血清HA、LN、PCⅢ和CⅣ水平则逐渐降低,3组间PCⅢ水平比较差异有统计学意义(χ2=6.26,P=0.044)。结论 CHB患儿HBV DNA载量与肝脏病理无显著相关性。临床综合分析HBV DNA载量及肝功能、肝纤维化血清学指标,结合肝活组织病理检查,才能更加客观、准确地评估CHB的病情。     

原发性胆汁性肝硬化患者肝组织Foxp3+和转化生长因子β1的表达及临床意义

目的 检测原发性胆汁性肝硬化(PBC)患者肝组织Foxp3+和转化生长因子(TGF)β1表达与肝组织病理的相关性.方法 采用免疫组织化学法检测29例PBC患者肝组织中Foxp3+和TGFβ1表达.同时选取20例正常肝组织作为正常对照组.结果 PBC患者肝组织Foxp3+表达量显著高于正常对照组,差异有统计学意义(P=0.000),且Ⅰ期/Ⅱ期PBC患者肝组织表达量与Ⅲ期/Ⅳ期,差异有统计学意义(P=0.002).PBC患者肝组织TGFβ1表达量显著高于正常对照组,差异有统计学意义(P=0.000),且Ⅰ期/Ⅱ期PBC患者肝组织表达量与Ⅲ期/Ⅳ期差异无统计学意义(P＞0.05).PBC患者肝组织Foxp3+和TGFβ1表达量之间存在显著正相关(r=0.765,P=0.000).结论 PBC患者肝组织中Foxp3+和TGFβ1表达与肝组织炎症活动度密切相关.     

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.