自身免疫性肝病的回顾性研究

目的 提高对自身免疫性肝病的认识,以利于早期诊断、早期治疗.方法 回顾性对81例自身免疫性肝病患者进行诊断,比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(OS)的临床、血液化学及病理特点.结果 81例患者中,女性占91.4%;总体误诊率为45.7%,OS漏诊率为96.7%,初始诊断为肝硬化者60.5%(49/81),其中37%(30/81)为失代偿期肝硬化.AIH组18.2%(6/33)以急性肝功能衰竭发病,明显高于PBC、OS组,3组患者症状、体征基本一致,AIH、OS组患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及抗核抗体(ANA)阳性率明显高于PBC组(Z=6.411,P=0.041;Z=7.980,P=0.019;X2=11.951,P=0.003),PBC、OS组患者血清门冬氨酸氨基转移酶(GGT)、碱性磷酸酶(ALP)、总胆固醇、载脂蛋白B水平及抗线粒体抗体(AMA)阳性率明显高于AIH组(Z=37.327,P=0.000;Z=12.929,P=0.002;Z=16.722,P=0.000;Z=6.695,P=0.035;X2=31.219,P=0.000).结论 自身免疫性肝病误诊率高.AIH、OS患者氨基转移酶升高明显,ANA阳性率高,PBC、OS患者GGT、ALP升高明显,血脂代谢障碍,AMA阳性率高.     

自身免疫性肝病临床病理特征分析28例

目的:探讨并比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(AIH-PBC CS)的临床、生化、影象学以及组织学特征.方法:收集在我院自身免疫性肝病住院患者28例,其中v型AIH 13例、PBC 6例和AIH-PBCOS9例,回顾性分析患者临床资料.结果:AIH-PBC OS患者血清谷草转氨酶(AST)和γ-球蛋白(GLO)水平(分别为和)均明显高于AIH和PBC患者(132.67±35.05 vs 81.15±39.26,55.17±24.38;44.33±8.92 vs 34.23±9.89,33.17±6.79,均P＜0.05),而碱性磷酸酶(ALP)和γ-谷氨酰转肽酶(GGT)水平明显高于AIH患者(218.11±107.79 vs 106.85±91.57;280.33±133.51 vs 82.07±36.67,均P＜0.05),低于PBC患者(245.83±88.60,315.67±160.01,均P＜0.05).AIH-PBC OS和PBC患者的IgM水平均明显高于AIH患者(793.00±528.57 vs127.33±30.14;538.50±349.43 vs 127.33±30.14,均P＜0.05),而AIH-PBC OS患者的IgG水平明显高于PBC患者(2036.00±457.03 vs1121.25±313.8,P＜0.05).AIH-PBC OS患者界面性肝炎和破坏性胆管炎的发生率分别为88.9%和66.7%.腹部BUS提示三者常伴有脾大和腹腔淋巴结肿大.结论:AIH和PBC是典型的分别选择性损伤肝细胞及肝内小胆管的自身免疫性肝病,AIH-PBC OS同时具有AIH和PBC的临床病理学特征,与PBC相比,AIH-PBC OS更倾向于AIH.     

原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征患者的临床特征分析

背景:自身免疫性肝病相互之间以及与肝外自身免疫性疾病的重叠增加了诊断难度,深刻认识其临床特征至关重要。目的:分析原发性胆汁性肝硬化-自身免疫性肝炎(PBC-AIH)重叠综合征患者的临床特征,探讨合并肝外自身免疫性疾病对PBC-AIH重叠综合征的影响。方法:回顾性分析81例PBC-AIH重叠综合征患者的一般情况、临床表现、生物化学指标、免疫学指标、肝组织学表现、影像学特点以及肝外自身免疫性疾病发生情况。根据是否合并肝外自身免疫性疾病将患者分为合并组和非合并组,比较两组的临床特征。结果:81例PBC-AIH重叠综合征患者的男女比例为1∶9.1,平均发病年龄为(58.1±9.9)岁。53.1%的患者存在临床症状,其中黄疸和皮肤瘙痒占18.5%。血清ALT、AST、ALP、GGT、TBil、Glo水平均升高,多数患者血清Ig G、Ig M水平升高。ANA阳性率、AMA和(或)AMA-M2阳性率、SMA阳性率、gp210和(或)sp100阳性率分别为100%、90.1%、1.2%、11.1%。门管区淋巴浆细胞浸润、界面性肝炎为主要的组织病理学特征,同时具有PBC和AIH病理表现者占50.6%。影像学证实28例(34.6%)患者肝硬化,76例(93.8%)腹腔淋巴结肿大。23例(28.4%)PBC-AIH患者合并肝外自身免疫性疾病,主要为干燥综合征和自身免疫性甲状腺疾病,合并组GGT水平显著低于非合并组(P=0.001),其余临床特征组间差异无统计学意义。结论:深入认识PBC-AIH重叠综合征临床特征的同时筛查合并的肝外自身免疫性疾病至关重要,尤其是干燥综合征和自身免疫性甲状腺疾病。     

抗线粒体抗体阴性原发性胆汁性肝硬化患者的临床及病理学特点

目的 分析抗线粒体抗体(AMA)阴性的原发性胆汁性肝硬化(PBC)患者临床及病理学特点.方法 对208例PBC患者的临床及病理学资料进行分析,并将AMA阴性PBC患者与典型PBC和自身免疫性肝炎(AIH)患者进行比较.非正态连续变量的比较使用Mann Whitney U检验,分类资料构成比的比较使用Chi-Square检验.结果 208例PBC患者中,AMA阴性者30例,占14.4%.AMA/AMA-M2阳性PBC和AMA阴性PBC患者在一般情况,临床表现、体征、肝功能(ALT、AST,碱性磷酸酶、γ-谷氨酰转移酶和总胆红素)和肝组织学表现上的差异均无统计学意义(P值均>0.05).AMA/AMA-M2阳性PBC组患者γ-球蛋白、IgG、IgM和IgA明显升高,中位数(P25,P75)分别为8.6(6.6,10.9)g/L,16.8(13.7,19.4)g/L、3.6(2.7,5.4)g/L和2.9(2.2,3.8)g/L,与AMA阴性组[分别为7.1(5.6,7.9)g/L、14.1(11.3,17.6)g/L、2.7(1.9,4.5)g/L和2.1(1.5,3.4)g/L]相比,差异有统计学意义(Z值分别为-2.088、-2.177、-2.372和-2.764,P值均<0.05);两组间总胆固醇差异无统计学意义(P>0.05).AMA阴性PBC患者中,29例(96.7%)呈抗核抗体(ANA)阳性,其中胞质颗粒型14例(48.3%)、核膜型8例(27.6%)、着丝点型6例(20.7%)、均质型1例(3.4%).与AIH患者比较,AMA阴性PBC患者以胆汁淤积表现为主,碱性磷酸酶、γ-谷氨酰转移酶、IgM和胆固醇水平均较AIH组明显升高(P值均<0.05),而血清AST,IgG和IgA水平低于AIH患者(P值均<0.05).结论 在以胆汁淤积表现为主,IgM和胆固醇水平升高、ANA为非均质型为主要表现的患者中,AMA虽阴性仍需考虑PBC的可能.

Abstract：

Objective To explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA). Methods Two hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases. Results 30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P> 0.05). The γ -globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively). Conclusion In cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemcial and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.     

原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征诊治进展

目的 原发性胆汁性胆管炎(PBC)是一种慢性自身免疫性肝内胆汁淤积性疾病,自身免疫性肝炎(AIH)是一种自身免疫反应介导的肝脏实质性炎症。该两种疾病共存于同一患者,称之为“原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征(PBC-AIH OS)”。PBC-AIH OS患病率低,较单纯PBC进展快、预后差。目前,其诊断标准的临床应用及治疗方案的选择仍有挑战性。本文对PBC-AIH OS的定义、流行病学、临床特征、诊断、治疗和预后的最新研究进展进行了综述,以期获得更深入的认识,为疾病的精准诊疗提供依据。     

原发性胆汁性肝硬化患者自身抗体测定的意义

目的:探讨自身抗体测定对诊断原发性胆汁性肝硬化(PBC)的临床意义.方法:PBC患者52例和非PBC患者202例,其中包括自身免疫性肝炎(AIH)41例,原发性硬化型胆管炎(PSC)18例,乙型肝炎(HBV)89例,丙型肝炎(HCV)54例以及健康体检者40例,采用间接免疫荧光法(IIF)检测抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA)、抗心肌抗体(HRA)、抗骨骼肌抗体(ASA)、抗胃壁细胞抗体(PCA)、抗双链DNA(ds-DNA)抗体、抗肝肾微粒体抗体(LKM)、抗可溶性肝抗原(SLA)抗体和抗中性粒细胞胞质抗体(ANCA)等自身抗体,ELISA法检测抗髓过氧化酶抗体(MPO),并对其结果进行回顾性分析.结果:PBC患者中AMA阳性例数最高为46例(88.5%),ANA阳性率为71.2%(37/52);非PBC患者中阳性例数则分别为20例(9.9%)和51例(25.2%),两组比较,有非常显著性意义(P<0.01).AMA、SMA抗体检测在PBC与AIH患者中,均有非常显著性意义(P<0.01).但两组之间的ANA阳性率无显著性意义(P>0.05).PSC患者18例ANA阳性6例,AMA阳性7例均低于PBC患者.HBV,HCV感染患者检测ANA阳性率分别只有9.0%和22.2%;AMA阳性率也只有7.9%和3.7%,与PBC患者比较均有显著性差异(P<0.01).PBC患者及对照组检测ds-DNA,ANCA,LKM,SLA和MPO抗体结果显示PBC患者检测最高的ANCA阳性率为26.9%(14/52),其次是MPO阳性率为25.0%(13/52),与AIH比较,均有非常显著性意义(P<0.01).结论:血清自身抗体的检测对诊断、治疗和阻止原发性胆汁性肝硬化的发展有着十分重要作用.对提高PBC同其他疾病鉴别诊断和治疗有着非常重要的意义.     

自身免疫性肝病109例的临床与病理特征分析

目的 分析比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)及AIH重叠综合征的临床特点、生化特征和组织学变化,以提高对自身免疫性肝病(AILD)的认识.方法 收集2004年1月-2008年6月肝穿刺病理学检查确诊的AILD患者共109例,其中AIH 27例、PBC 67例、PSC 4例、AIH-PSC重叠综合征1例和AIH-PBC重叠综合征10例,对患者的临床及实验室检查资料进行回顾性分析.结果 AILD患者多发于中年女性(73.3%,80/109),常见症状为黄疸、乏力、纳差和皮肤瘙痒.AIH患者的发病年龄高峰在50岁左右,肝功能检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常值,62.9%的患者(17/27)抗核抗体(ANA)阳性.肝组织病理变化以界面性肝炎为主(77.7%),在重度患者则出现重度界面件肝炎、桥样坏死等.PBC患者主要表现为碱性磷酸酶、γ-谷氨酰转肽酶和胆红素明显升高,伴免疫球蛋白M升高,74.6%的患者(50/67)线粒体抗体(AMA)和(或)AMA-M2亚型阳性.所有PBC患者行肝脏病理学检查,早期(Ⅰ、Ⅱ)占28.3%,晚期(Ⅲ、Ⅳ)占71.7%,肝组织病理变化以小胆管减少甚至消失为主(62.6 0A).AIH-PBC重叠综合征患者的临床表现和肝组织病理学具有AlH和PBC的双重特征,其中有3例患者同时检测到ANA和AMA/AMA-M2阳性.结论 AILD在中国人中并非少见,其诊断需综合临床表现、生化、免疫指标和组织学变化.     

自身免疫性肝病临床及免疫学特征

目的 分析自身免疫性肝病的临床特征和免疫学特点,以提高对该类疾病的认识和诊断水平.方法 对164例自身免疫性肝病患者的临床症状、体征及免疫学检查资料进行回顾性分析.结果 原发性硬化性胆管炎(PSC)多发于青年男性,自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(AIH-PBC)多发于中年女性;临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84%、78%、90%和67%,皮肤瘙痒的发生率分别为43%、56%、81%和60%.但AIH、PBC和PBC-AIH患者之间的年龄、性别、黄疸、皮肤瘙痒等症状无显著性差异(P均＞0.05).AIH首诊正确诊断率为8%(6/77),PSC为9%(1/11),PBC为13%(6/46).从发病到确诊PBC平均为38月,AIH为46月,PSC为31月,PBC-AIH重叠综合征确诊最难,平均需51月,常误诊为可能的AIH或单纯PBC.AIH、PBC、PSC和PBC-AIH肝外自身免疫性疾病的发生率分别为47%、11%、27%和24%,各自身免疫性肝病患者均有较高的自身抗体发生率.结论 自身免疫性肝病在临床上并不少见,患者常伴发肝外自身免疫性疾病及较高的自身抗体发生率;诊断需综合临床、生化、自身抗体和病理组织学等指标.     

原发性胆汁性肝硬化患者的免疫学特点分析

目的 分析原发性胆汁性肝硬化(PBC)出现的自身抗体等免疫学指标及其临床意义。 方法对3000例肝功能异常患者采用间接免疫荧光法检测抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)和抗肝肾微粒体抗体(抗-LKM)等,并对ANA和AMA亚型及抗可溶性肝抗原/肝胰抗原(抗-SLA/LP)、LKM-1和抗肝特异性胞浆抗原型1抗体(抗-LC-1)等肝脏疾病相关的自身抗体进行了检测。结果 3000例肝病患者中,PBC 52例占1.7％。PBC患者的AMA和AMA-M2抗体均为阳性,52例PBC中,94.0％呈AMA高滴度(≥1:320)阳性,79.0％M2>200 RU/L,78.0％ANA阳性。ANA的主要荧光模式为细胞核膜型、细胞核点型和着丝点型。少见的荧光模式有抗干燥综合征A/B(SS-A/SS-B)、细胞核均质型、核仁型及颗粒型等。PBC患者免疫球蛋白M、碱性磷酸酶和γ-谷氨酰转肽酶高于乙型肝炎肝硬化患者;其白细胞介素(IL)-6、IL-10、肿瘤坏死因子α和干扰素γ水平高于正常人。5例表现为自身免疫性肝病重叠综合征,其中2例抗-SLA/LP阳性,提示PBC与自身免疫性肝炎(AIH)3型的重叠;1例抗-LKM-1阳性,提示PBC与AIH 2型的重叠;2例ANA阳性,且肝活体组织检查证实存在AIH和PBC的病理改变,提示为PBC与AIH 1型的重叠综合征。 结论 PBC在我国肝病患者中约占1％~2％。临床已出现典型症状者一     

原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征44例临床特点及疗效分析

目的 分析熊去氧胆酸(UDCA)联合免疫抑制剂治疗原发性胆汁性肝硬化-自身免疫性肝炎重叠综合征( PBC- AIH)的长期疗效及预后.方法 从2000年1月至2011年1月天津医科大学总医院确诊的387例自身免疫性肝病患者中筛选出44例PBC-AIH患者,回顾分析其临床资料、治疗方法及疗效.结果 44例PBC-AIH患者均有不同程度的血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBil)升高,84.09％ (37/44)的患者球蛋白(GLO)或免疫球蛋白G(IgG)水平升高.38.63％(17/44)的患者免疫球蛋白M(IgM)升高,97.73％(43/44)的患者抗核抗体(ANA)阳性,90.91％(40/44)的患者抗线粒体抗体(AMA)阳性,11.36％(5/44)的患者抗平滑肌抗体(SMA)阳性.病理学表现为界面性肝炎,不同程度的肝内小胆管损伤.使用UDCA联合免疫抑制剂治疗后,病情缓解率为61.36％(27/44),不完全应答率为29.55％(13/44),治疗失败率为9.09％(4/44).病情缓解患者中停药6例,复发率为5/6.至随访结束时,PBC-AIH患者ALT、AST、ALP、GGT、TBil水平均较治疗前明显下降,其中ALP、GGT、ALT、AST在治疗前6个月下降明显,ALP、GGT在随访结束时出现轻微上升趋势.随访中PBC-AIH患者病情进展率为29.55％(13/44),10年存活率为93.33％(28/30).结论 UDCA联合免疫抑制剂治疗PBC-AIH可明显改善患者生化指标,延缓患者病情进展,提高生存率,缓解率较高,但停药后复发率亦较高.     

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.     

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.     

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.     

陕西省新型结核病防治管理模式实施前后能力建设与诊治效果分析

目的 分析陕西省新型结核病防治管理模式实施前后结核病防治能力建设及诊治效果,为进一步完善我省结核病防控政策和措施提供参考。方法 本研究采用描述性研究,对全省10个地级市、108个县(区)结核病防治能力建设情况,以及患者发现、治疗管理等指标变化情况进行对比分析。能力建设情况以2014年和2017年数据作对比,分别来源于《陕西省“十二五”结核病防治规划》评估和2017年全省结核病防治工作联合大检查。患者发现、治疗管理指标来源于《结核病信息管理系统》,以实施前3年(2012—2014年)与实施后3年(2015—2017年)的数据作对比。运用SPSS 19.0处理数据,率和构成比的比较采用χ ²检验,以P<0.05为差异有统计学意义。 结果 2014年和2017年全省设有结核病定点医院的数量分别为20家和107家,2017年较2014年增加了87家。2014年全省共有结核病防治人员923名,其中疾病预防控制中心(CDC)656名,定点医院267名。2017年全省共有结核病防治人员1200名,其中CDC 403名,定点医院797名;与2014年相比,CDC人员减少了38.57%,定点医院人员增加了198.50%。2014年全省有3个地级市开展了分子生物学耐药检测,5.56%(6/108)的县(区)开展了分子生物学检测,12.04%(13/108)的县(区)开展了痰培养。2017年全省有8个地级市开展了分子生物学耐药检测,49.07%(53/108)的县(区)开展了分子生物学检测,55.56%(60/108)的县(区)开展了痰培养。新型防治模式实施前3年全省初诊查痰率为98.50%(329981/335014),发现肺结核患者63892例(其中结核性胸膜炎患者4089例),发现病原学阳性患者14087例,病原学阳性率为23.56%(14087/59803)。实施后3年全省初诊查痰率为95.00%(312503/328948),发现肺结核患者61583例(其中结核性胸膜炎5295例),病原学阳性患者10588例,病原学阳性率为18.81%(10588/56288)。新型防治模式实施前后初诊查痰率降低(χ ²=6484.178,P=0.000),病原学阳性率降低(χ ²=390.104,P=0.000)。实施前3年因症就诊发现肺结核患者占29.43%(18805/63892),转诊发现患者占43.90%(28047/63892)。实施后3年因症就诊发现肺结核患者占25.38%(15628/61583),转诊发现患者占57.79%(35586/61583)。转型后因症就诊发现患者的构成比下降(χ ²=259.002,P=0.000),转诊发现患者的构成比上升(χ ²=2419.762,P=0.000)。新模式实施前后3年非结核病防治机构报告患者总体到位率分别为93.18%(62177/66726)和89.96%(61323/68169),实施后总体到位率下降(χ ²=453.550,P=0.000)。新模式实施前后患者治疗成功率分别为95.04%(60464/63619)和94.97%(57872/60939),实施前后比较差异无统计学意义(χ ²=0.356,P=0.551)。 结论 我省新型结核病防治管理模式推进顺利,防治能力加强,但部分患者诊治及管理指标有所下滑,实施质量仍需提升。     

dsRNA-Dependent Protein Kinase PKR and its Role in Stress,Signaling and HCV Infection

The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN)‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2α). As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2α kinase, its participation in the regulation of the NF-κB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV). PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2α-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.     

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.     

A comparison of stapled and handsewn anastomoses in patients undergoing resection for Dukes' B and C colorectal cancer

This study was to assess the effect of stapled colorectal anastomoses on local recurrence, disease-free survival, and survival following curative resection for Dukes' B and C adenocarcinoma. Data were derived from two randomized prospective trials of the National Surgical Adjuvant Breast and Bowel Project designed to evaluate the efficacy of adjuvant therapy in colorectal cancer. Of 1111 patients with colonic anastomoses, 255 were stapled mechanically. There were no significant differences in disease-free survival, survival, or local tumor recurrence among patients subjected to stapled or handsewn anastomoses. Of the 181 patients undergoing anterior resection for rectal cancer, 82 anastomoses were fashioned with staples. No significant disadvantage in disease-free survival, survival, or local recurrence could be attributed to use of the mechanical stapling devices. Twelve percent of patients undergoing stapled rectal anastomoses developed a local recurrence as a first sign of treatment failure compared with 19 percent for the handsewn group. No significant differences in the length of distal margins were detectable. The average time on study was 41 months. The use of stapled anastomoses for carcinoma of the colon or rectum is not associated with an adverse effect on long-term outcome. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, May 5 to 10, 1985. Supported by USPHS NIH-U10-34212 and an American Cancer Society Grant RC-13.     

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.     

Crohn's disease and growth deficiency in children and adolescents

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn’s disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using “pediatric inflammatory bowel disease”, “pediatric Crohn’s disease”, “linear growth”, “pubertal growth”, “bone health”, and “vitamin D” as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients’ growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a “top-down” approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients’ nutritional status.     

Prevalence and factors associated with hypertension among school children and adolescents in urban and semi‐urban areas in Cameroon

Few data to date exist on pediatric hypertension (PH) prevalence and risk factors in semi‐urban areas in Cameroon, and they are believed to be the same as urban areas. These data are needed to design targeted preventive strategies and contribute to reducing the burden of PH in Cameroon and countries with equivalent standards of care. The authors conducted a cross‐sectional study, from November, 2017 to June, 2018, in primary and secondary schools, from semi‐urban (Bamboutos, West Region) and urban (Mfoundi, Center Region) settings in Cameroon, including children and adolescent aged between 3 and 19 years, recruited on a stratified probability sampling. PH was defined according to the American Academy of Pediatrics 2017. Overall, 1001 and 842 participants were, respectively, included in urban and semi‐urban areas. The overall average age was 13.9 ± 4.03 years, and two‐thirds were girls. Overweight and obesity were more prevalent in urban area (overweight: 17.1%; obesity: 5.9%), compared to semi‐urban (overweight: 1.1% and obesity: 0.8%) (p < .001). The prevalence of hypertension was higher in urban (12%) than semi‐urban areas (8.6%) (p = .01). We have identified as factors associated with PH: age > 14 years (OR = 3.18 [1.6; 6.2]) and secondary level of education (OR = 2.5 [1.2; 5.5]) in urban areas; family history of hypertension (OR 1.93 [1.1; 3.4] in semi‐urban areas. PH prevalence is higher in urban than semi‐urban areas, and the associated factors are not the same. Policies to address hypertension in the pediatric population must be targeted and tailored to the different population profiles.