原发性胆汁性胆管炎血脂异常分布特点

目的了解原发性胆汁性胆管炎(PBC)患者血脂异常特点,分析其分布与单纯血脂异常患者的差异及临床意义。方法对2010—2016年在北京协和医院住院及门诊就诊的PBC并血脂异常者100例(PBC组)及同期体检中心年龄和性别匹配的单纯血脂异常者83例(对照组)的临床资料进行回顾性分析,评估两组患者血脂异常分布特点的差异及其临床意义。结果PBC组患者的血脂异常以高胆固醇(TC)血症为主,对照组患者以高低密度脂蛋白(LDL-C)血症为主。临床分类分析发现,PBC组单纯TC和单纯三酰甘油(TG)均明显高于对照组(TC:14%vs. 5%;TG:19%vs. 8%),差异均有统计学意义(P=0. 046、0. 042),PBC组混合型高脂血症比例明显低于对照组(57%vs. 77%),差异有统计学意义(P=0. 004)。PBC组患者血浆TG水平明显高于对照组[(2. 36±2. 13) mmol/L vs.(1. 57±0. 75) mmol/L],PBC组患者HDL-C水平明显高于对照组[(1. 64±0. 75) mmol/L vs.(1. 31±0. 38) mmol/L],差异均有统计学意义(均P=0. 001)],PBC组患者LDL-C水平明显低于对照组[(3. 27±1. 22) mmol/L vs.(3. 61±0. 69) mmol/L],差异有统计学意义(P=0. 033)。结论 PBC血脂异常与单纯血脂异常患者血脂分布类型不同,其中临床分类差别更为明显,PBC血脂异常者较单纯血脂异常者更易出现高TC血症,且前者TG、HDL-C水平较后者高,LDL-C水平较后者低。     

抗纤维肌动蛋白抗体阴性的自身免疫性肝炎Ⅰ型患者临床特征分析

目的探讨抗纤维肌动蛋白抗体(AFA)阴性的自身免疫性肝炎(AIH)I型患者的临床特点。方法收集194例AIH-I型患者临床资料,按照检测结果将患者分为AFA阳性组124例和AFA阴性组70例,另外收集197例健康献血者作为对照组。采用ELSIA法检测AIH-I型患者AFA、抗肝肾微粒体I型抗体(LKM-1)、抗可溶性肝抗原/胰抗原抗体(SLA/LP)、抗肝细胞溶质抗原I型抗体(LC-1),间接免疫荧光法检测抗核抗体(ANA)、抗平滑肌抗体(ASMA)。对AIH-I型患者作肝脏病理组织学检查和生化检测。统计学处理采用t检验、秩和检验和χ2检验。结果 AIH-I型患者中AFA阴性与阳性的男女人数和年龄比较差异无统计学意义(P0.05),自身抗体ANA、ASMA、LKM-1、SLA/LP和LC-1检出率差异也无统计学意义(P0.05),但AFA阴性比阳性患者的急性发病人数百分率高(34.29%比12.90%,P0.01),血清ALT高[(146.32±20.87)U/L比(128.26±38.09)U/L,P=0.008]、AST高[(124.55±23.54)U/L比(97.62±45.26)U/L,P=0.004]、胆红素高[(42.57±14.17)μmol/L比(29.73±10.17)μmol/L,P=0.001]、免疫球蛋白G低[(18.42±5.11)g/L比(26.36±6.92)g/L,P0.01]。肝组织病理检测可见AFA阴性比阳性患者的浆细胞浸润率高(35.71%比21.77%,P=0.03)、中央肝小叶3区坏死率高(41.43%比11.29%,P0.01)。结论AIH-I型患者中AFA阴性比阳性患者的急性发病率高,血胆红素、ALT和AST升高,免疫球蛋白G降低,肝组织浆细胞浸润率、肝小叶3区坏死率升高。     

自身免疫性肝炎与原发性胆汁性胆管炎重叠综合征患者的临床病理学特征分析

目的对自身免疫性肝炎(AIH)-原发性胆汁性胆管炎(PBC)重叠综合征患者的血清学指标、自身抗体及肝脏组织病理学表现进行记录,并分析这些患者的临床病理学特征。方法选取2016年6月至2019年6月我科临床确诊的自身免疫性肝病(AILD)患者78例,其中AIH患者32例(AIH组),PBC患者24例(PBC组),AIH-PBC重叠综合征患者22例(AIH-PBC组)。对于计量资料以(■±s)表示,组间比较采用t检验分析;计数资料以百分比表示,组间比较采用卡方检验。结果 AIH-PBC组[(412.4±226.4)U/L]患者ALP明显高于AIH组[(108.2±68.1)U/L],(P0.05);AIHPBC组[(430.5±152.8)U/L]患者GGT明显高于AIH组[(118.7±65.2)U/L](P0.05);AIH-PBC组[(5.2±1.7)g/L]患者IgM明显高于AIH组[(2.5±0.8)g/L](P0.05);AIH-PBC组[(182.6±68.1)U/L]中患者ALT明显高于PBC组[(98.7±45.7)U/L](P0.05);AIH-PBC组[(174.9±70.2)U/L]中患者AST明显高于PBC组[(104.6±52.4)U/L](P0.05);AIH-PBC组[(19.5±6.6)g/L]中患者IgG明显高于PBC组[(15.2±1.9)g/L](P0.05)。AIHPBC组中患者(72.7%)AMA表达明显高于AIH组(0%)(P0.05);AIH-PBC组中患者(100%)AMA M2表达明显高于AIH组(0%)(P0.05);AIH-PBC组中患者(72.7%)SMA表达明显高于PBC组(16.7%)(P0.05);AIH-PBC组中患者(90.9%)ANA表达明显高于PBC组(12.5%)(P0.05)。结论 AIH-PBC组患者血清学指标、自身抗体及肝组织穿刺病理学表现兼具AIH及PBC疾病的特点,而血清生化指标、自身抗体检测水平的差异可以作为鉴别AIH-PBC重叠综合征的依据。     

原发性胆汁性肝硬化患者外周血Th9细胞表达水平及其与肝功能和Mayo评分的相关性

目的探讨原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者外周血Th9细胞表达水平及其与肝功能指标和Mayo评分的相关性。方法纳入2017年1月至2019年1月深圳市宝安区石岩人民医院收治的50例PBC患者为PBC组。另选取同期于本院接受诊治的50例免疫系统异常患者作为对照组。采用流式细胞术检测外周血Th9细胞表达水平。采用日立全自动生化检测仪检测两组患者生物化学指标,包括碱性磷酸酶(alkaline phosphatase,ALP)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、γ-谷氨酰转肽酶(γ-glutamine transpeptidase,γ-GT)、总胆红素(total bilirubin,TBil)、白蛋白(albumin,ALB)和凝血酶原时间(prothrombin time,PT)并计算Mayo评分。采用间接免疫荧光法检测抗线粒体抗体的表达。水肿积分由2～3名有经验的医师通过患者症状进行双盲评价。采用实时荧光定量聚合酶链式反应检测外周血单个核细胞中嘌呤盒-1(purine-rich box 1,PU-1)和转化生长因子-β(transforming growth factor-β,TGF-β)m RNA相对表达量。采用Pearson相关性分析PBC患者外周血Th9细胞表达水平与肝功能指标和Mayo评分的相关性。结果 PBC组患者PT [(13.42±1.34)s vs(7.05±1.01)s]、ALP [(391.42±182.39)U/L vs(63.29±20.71)U/L]、AST [(147.20±60.28)U/L vs(19.04±7.23)U/L]、ALT [(166.19±80.34)U/L vs(24.12±10.38)U/L]、γ-GT [(442.08±124.47)U/L vs(28.10±13.82)U/L]、TBil [(140.58±20.75)μmol/L vs(12.84±3.99)μmol/L]、抗线粒体抗体阳性占比[25/50(50.00%)vs14/50(28.00%)]、水肿积分[(0.54±0.04)分vs(0.15±0.01)分]、肝脏形态缩小人数占比[6/50(12.00%)vs 0/50(0.00%)]、肝实质回声中结节增生表现人数占比[5/50(10.00%)vs 0/50(0.00%)]、肝内胆管壁增强人数占比[26/50(52.00%)vs 1/50(2.00%)]及肝实质回声中颗粒表现人数占比[34/50(68.00%)vs 2/50(4.00%)]均显著高于对照组,ALB水平[(31.29±7.45)g/L vs(45.12±1.88)g/L]显著低于对照组(P均0.05)。PBC组患者外周血Th9细胞亚群占比为(1.68±0.32)%,显著高于对照组的(0.19±0.04)%,PBC组患者Mayo评分为(6.45±1.17)分,显著高于对照组的(2.10±0.48)分,差异均有统计学意义(t=32.670、24.323,P 0.001)。Pearson相关性分析表明,PBC患者外周血Th9细胞表达水平与AST、ALT、γ-GT、TBil及Mayo评分均呈正相关(r均 0,P均0.05)。PBC组PU-1和TGF-βm RNA表达量均显著高于对照组(5.87±1.03 vs 1.34±0.47;4.33±0.78 vs 1.38±0.51),差异有统计学意义(t值分别为28.293、22.383,P均0.001)。结论 PBC患者外周血Th9细胞表达水平显著升高,且与肝功能指标和Mayo评分呈正相关。Th9细胞表达水平可能反映了患者病情的严重程度。     

支气管肺泡灌洗液肿瘤标志物检查诊断肺鳞状细胞癌价值分析

目的:探讨支气管肺泡灌洗液(BALF)及血清中鳞状细胞癌相关抗原(SCC)、可溶性细胞角蛋白19片段(CYFRA 21-1)、癌胚抗原(CEA)浓度对肺鳞状细胞癌的诊断、TNM分期及预后的临床意义。方法:选择经组织病理学和(或)细胞学确诊的40例肺鳞状细胞癌患者作为观察组,40例肺部炎性病变患者作为对照组,采用日本Pentax EPS 3500型电子支气管镜,经气管镜收集BALF,应用酶联免疫吸附法测定两组患者BALF及血清中SCC浓度,应用化学发光法测定两组患者BALF及血清中CYFRA21-1及CEA的浓度。结果:(1)观察组BALF中SCC[(49.6±15.4)vs.(2.1±0.8)μg/L,P=0.000]、CYFRA 21-1[(245.6±95.5)vs.(2.0±0.9)μg/L,P=0.000]、CEA[(15.6±5.5)vs.(3.6±1.4)μg/L,P=0.000],血清中SCC[(13.1±6.0)vs.(1.8±0.7)μg/L,P=0.000]、CYFRA 21-1[(20.4±10.3)vs.(1.9±0.9)μg/L,P=0.000]、CEA[(5.7±2.2)vs.(3.2±1.2)μg/L,P=0.000]均高于对照组,差异有统计学意义(P<0.01)。(2)观察组BALF中SCC[(49.6±15.4)vs.(13.1±6.0)μg/L,P=0.000]、CYFRA 21-1[(245.6±95.5)vs.(20.4±10.3)μg/L,P=0.000]、CEA[(15.6±5.5)vs.(5.7±2.2)μg/L,P=0.000]均高于血清,差异有统计学意义(P<0.01)。(3)观察组Ⅲ~Ⅳ期BALF中SCC[(63.8±10.4)vs.(41.9±11.9)μg/L,P=0.000]、CYFRA 21-1[(328.3±61.0)vs.(201.1±80.0)μg/L,P=0.000]、CEA[(20.5±4.0)vs.(12.9±4.2)μg/L,P=0.000]均高于Ⅰ~Ⅱ期,差异有统计学意义(P<0.01)。结论:BALF中SCC、CYFRA 21-1及CEA的检测对肺鳞状细胞癌的早期诊断有较好的临床价值,同时对临床分期、监测病情、判断预后也有一定临床价值,值得在临床上推广应用。     

不同组合人工肝支持系统治疗乙型肝炎病毒相关早、中期慢加急性肝衰竭患者的疗效及对炎症指标的影响

目的比较不同组合人工肝支持系统治疗乙型肝炎病毒相关早、中期慢加急性肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者的疗效及对炎症指标的影响。方法纳入2019年1月至2020年1月在成都市公共卫生临床医疗中心治疗的早、中期HBV-ACLF患者167例进行回顾性研究,根据治疗方案不同分为双重血浆分子吸附系统(double plasma molecular adsorption system,DPMAS)联合血浆置换(plasma exchange,PE)组(DPMAS+PE组,86例)和血浆胆红素吸附(plasma bilirubin adsorption,PBA)联合PE组(PBA+PE组,81例)。比较两组患者治疗前后丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBil)、凝血酶原时间(prothrombin time,PT)、凝血酶原活动度(prothrombin activity,PTA)、降钙素原(procalcitonin,PCT)、C反应蛋白(C reactive protein,CRP)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-10(interleukin-10,IL-10)等的差异,比较两组患者治疗效果的差异。结果治疗前两组患者的年龄、性别等基线资料差异无统计学意义(t=-0.928,P=0.355;χ²=0.242,P=0.623)。DPMAS+PE组和PBA+PE组患者治疗前ALT[(584.64±158.33)U/L vs(601.23±176.96)U/L]、AST[(489.90±136.31)U/L vs(507.57±141.09)U/L]、TBil[(327.92±97.01)μmol/L vs(307.19±103.83)μmol/L]、PT[(27.39±3.36)s vs(26.78±2.94)s]和PTA[(30.35±5.08)%vs(31.19±4.73)%]水平差异无统计学意义(P均>0.05)。治疗后,DPMAS+PE组患者ALT[(72.13±27.37)U/L vs(88.33±31.76)U/L]、AST[(52.45±20.46)U/L vs(67.90±24.15)U/L]和TBil[(59.71±25.27)μmol/L vs(72.87±29.63)μmol/L]水平显著低于PBA+PE组,差异有统计学意义(t=-3.420、-3.087、-2.993,P=0.001、0.003、0.003);PT[(17.97±3.53)s vs(18.30±3.41)s]和PTA[(65.85±21.20)%vs(61.59±18.67)%]水平差异无统计学意义(t=-0.425、0.955,P=0.672、0.343)。与治疗前相比,两组患者治疗后ALT、AST、TBil和PT水平均显著降低,PTA水平显著升高,差异有统计学意义(P均<0.001)。治疗前,两组患者PCT[(0.95±0.42)μg/L vs(0.88±0.40)μg/L]、CRP[(16.42±6.04)mg/L vs(15.15±5.94)mg/L]、TNF-α[(0.026±0.008)μg/L vs(0.027±0.009)μg/L]、IL-6[(79.59±8.15)ng/L vs(80.57±6.65)ng/L]和IL-10[(16.72±2.46)ng/L vs(17.26±2.12)ng/L]水平差异无统计学意义(P均>0.05)。治疗后,DPMAS+PE组患者PCT[(0.37±0.27)μg/L vs(0.58±0.25)μg/L]、CRP[(7.25±4.41)mg/L vs(9.70±5.57)mg/L]、TNF-α[(0.016±0.004)μg/L vs(0.020±0.005)μg/L]和IL-6[(54.23±9.03)ng/L vs(62.65±10.82)ng/L]水平均显著低于PBA+PE组,IL-10[(25.01±3.86)ng/L vs(22.56±3.51)ng/L]水平显著高于PBA+PE组,差异均有统计学意义(t=-3.574、-2.181、-3.258、-3.781、2.969,P均<0.05)。与治疗前相比,两组患者治疗后PCT、CRP、TNF-α、IL-6和IL-10均显著降低,差异有统计学意义(P均<0.001)。对于早期HBV-ACLF患者,DPMAS+PE组28 d好转率和12周存活率分别为90.6%(58/64)、90.6%(58/64),均显著高于PBA+PE组的75.8%(47/62)、75.8%(47/62),差异有统计学意义(χ²=4.979、4.979,P=0.026、0.026);对于中期HBV-ACLF患者,DPMAS+PE组和PBA+PE组28 d好转率[68.2%(15/22)vs 52.6%(10/19)]和12周[63.6%(14/22)vs 52.6%(10/19)]存活率差异无统计学意义(χ²=1.036、0.509,P=0.309、0.476)。结论与PBA+PE治疗相比,DPMAS+PE治疗有助于早、中期HBV-ACLF患者体内各种毒素和炎性介质的清除,可改善肝功能,提高早期HBV-ACLF患者的治疗效果。     

110例原发性胆汁性胆管炎的临床特点

目的探讨原发性胆汁性胆管炎患者的临床特点,提高对该病的认识。方法分析110例PBC患者的一般资料、临床表现、生化检查、自身抗体、免疫学及肝组织病理检查资料。结果 110例PBC患者中男性13例,女性97例,确诊时的平均年龄(57.54±12.17)岁。110例患者最常见的症状为乏力(71.82%,79/110),其次为黄疸(40.00%,44/110)、腹水(34.55%,38/110);并发原发性腹膜炎1例(0.91%,1/110)。13例合并干燥综合征(13.73%)、5例合并系统性红斑狼疮、4例合并病毒性肝炎标志物阳性。生化结果表现为总胆红素[(48.20±56.16)μmol/L]及结合胆红素[(28.20±46.89)μmol/L]升高,血清碱性磷酸酶[(224.34±159.55)IU/L]及γ-谷氨酰转肽酶[(142.04±231.70)IU/L](t=4.166,P=0.000)均显著升高,ALT水平无明显升高[(60.30±156.07)IU/L]、AST水平升高[(70.62±127.88)IU/L]。胆固醇水平升高[(5.70±0.99)mmol/L],患者的血清免疫学检查结果显示,IgM[(6.00±4.15)g/L,t=5.446,P=0.000)]、IgG[(18.84±6.12)g/L,t=3.417,P=0.001]水平升高、IgA[(3.15±2.31)g/L,t=1.709,P=0.09]轻度升高。IgM[(3.15±2.31)g/L]水平升高,Ro-52阳性54例(49.09%),PM-Scl阳性52例(47.27%),AMA或AMA-M2阳性81例(73.63%),3E(BP0)阳性16例(14.55%),gp210阳性8例(7.27%),SP100阳性17例(15.45%),ANA阳性84例(76.36%)。30例肝穿刺患者的病理学检查结果显示,病变符合Ⅰ、Ⅱ期者20例,Ⅲ期7例,Ⅳ期3例。抗AMA-M2和抗3E(BPO)的阳性率比其他抗体高。结论原发性胆汁性胆管炎在中国并不少见,多见于女性,最常见的临床表现是乏力,血清碱性磷酸酶(ALP)和γ-谷氨酰转肽酶升高和特异性抗体[线粒体抗体和(或)线粒体抗体M2亚型]可用于诊断PBC,ANA、Ro-52、gp210、3E(BP0)、Sp100、PM-Scl对诊断线粒体抗体和(或)线粒体抗体M2亚型阴性的PBC有一定的价值,肝活检病理检查可用于进一步确诊该病和组织学分期。     

抗着丝点抗体阳性原发性干燥综合征的临床特点

目的 通过分析抗着丝点抗体(ACA)阳性原发性干燥综合征(pSS)患者的临床特点,提高对本病的诊治水平.方法 回顾性分析北京协和医院风湿免疫科收治的60例ACA阳性pSS患者(ACA阳性组)的临床资料,并与同期收治的139例ACA阴性pSS者(ACA阴性组)相比较.结果 (1)ACA阳性组发病年龄晚于ACA阴性组[(48±11)岁比(41±12)岁,P=0.000],而2组在性别构成、口干、眼干、唇腺活检阳性率差异元统计学意义.(2)肝脏受累是ACA阳性组患者最常见的腺外脏器损害,其发生率远高于ACA阴性组(68.3%比37.0%,P=0.000),而肾脏受累(13.3%比30.9%,P=0.009)、神经系统受累(1.7%比11.5%,P=0.025)、高γ球蛋白血症的发生率(20.8%比45.7%,P=0.002)均低于ACA阴性组.(3)2组抗核抗体阳性率无差异,但ACA阳性组以散点型免疫荧光表型最为常见(占61.7%).与ACA阴性组相比,ACA阳性组中抗SSA抗体、抗SSB抗体、抗U1 RNP抗体的阳性率减低(P＜0.05),而抗线粒体抗体及其M2亚型的阳性率增高(P＜0.05).(4)ACA阳性组死亡5例,其中3例死于胃食管静脉曲张破裂出血.结论 对ACA阳性pSS者应警惕肝脏受累.由于ACA阳性pSS在发病年龄、腺外器官受累、免疫指标、自身抗体谱及预后方面均不同于经典pSS,故可能是pSS的一种独特亚型.     

乙型肝炎病毒相关肝细胞癌患者并发上消化道出血的影响因素

目的分析乙型肝炎病毒(hepatitis B virus,HBV)相关肝细胞癌患者并发上消化道出血的影响因素。方法选取2014年1月至2017年12月于深圳市第三人民医院确诊的135例HBV相关肝细胞癌患者进行回顾性分析,根据患者是否发生上消化道出血分为出血组(45例)和对照组(90例),比较两组患者的临床特征和转归。具体指标包括年龄、性别、是否抗病毒治疗、HBV DNA、血小板(blood platelet,PLT)、白蛋白(albumin,ALB)、凝血酶原时间(prothrombin time,PT)、脾脏厚度、门静脉癌栓、食管胃底静脉曲张、红色征、门脉高压性胃病、腹水、腹膜炎、肝性脑病和肝肾综合征。采用Logistic多因素回归分析HBV相关肝细胞癌并发上消化道出血的影响因素。结果出血组与对照组患者HBV DNA阳性率(77.8%vs 66.7%)和PLT计数(中位数:147.87×10~9/L vs 148.51×10~9/L)差异无统计学意义(χ~2=1.776,P=0.183;U=2009.500,P=0.942)。出血组患者ALB水平显著低于对照组[(31.47±6.64)g/L vs(36.24±7.04)g/L],PT显著长于对照组(中位数:17.85 s vs 16.91 s),脾脏厚度较对照组增厚[(47.98±10.93)mm vs(43.71±11.45)mm],差异均有统计学意义(t=-3.787,P 0.001;U=221.500,P 0.001;t=2.072,P=0.040)。出血组患者门静脉癌栓(73.3%vs 40.0%)、食管胃底静脉曲张(71.1%vs 46.7%)、红色征阳性(42.2%vs 6.7%)、门脉高压性胃病(48.9%vs 12.2%)、腹水(77.8%vs 44.4%)、腹膜炎(55.6%vs 22.2%)、肝性脑病(17.8%vs 3.3%)和肝肾综合征(17.8%vs2.2%)发生率均显著高于对照组,差异有统计学意义(P均0.05)。Logistic多因素回归分析表明,ALB(OR=0.912,95%CI:0.852～0.977,P=0.008)、红色征(OR=8.551,95%CI:2.808～26.036,P 0.001)、门静脉癌栓(OR=4.368,95%CI:1.761～10.834,P=0.001)、腹膜炎(OR=4.135,95%CI:1.877～9.10~9,P 0.001)和肝性脑病(OR=5.466,95%CI:1.282～23.313,P=0.022)是HBV相关肝细胞癌并发上消化道出血的独立影响因素,其中ALB为保护性因素,红色征为最主要的独立危险因素。出血组患者病死率显著高于对照组(51.5%vs 11.1%),差异有统计学意义(χ~2=25.989,P 0.001)。出血组中病死者和生存者ALB水平差异无统计学意义[(31.11±5.73)g/L vs(31.84±7.59)g/L;t=-0.366,P=0.716],对照组中病死者和生存者ALB水平差异也无统计学意义(中位数:32.56 g/L vs 36.70 g/L;U=256.500,P=0.065)。出血组和对照组患者仅合并红色征(0%vs 0%)、门静脉癌栓(3.0%vs 11.1%)、腹膜炎(8.0%vs 5.0%)及肝性脑病(12.5%vs 0%)的病死率差异无统计学意义(P均 0.05)。结论红色征、门静脉癌栓、腹膜炎和肝性脑病是HBV相关肝细胞癌并发上消化道出血的独立危险因素,ALB为保护性因素。临床工作中应尽早采取干预措施减少上消化道出血的发生,降低病死率,提高生存率。     

整蛋白型肠内营养对老年肝硬化患者营养指标、NRS2002评分、肝功能及并发症的影响

目的探讨整蛋白型肠内营养对老年肝硬化患者营养指标、NRS2002评分、肝功能及并发症的影响。方法选取2015年3月至2019年3月文昌市人民医院收治的148例老年肝硬化患者为研究对象,采用随机数字表法分为观察组和对照组,每组74例。对照组进行常规饮食,观察组在常规饮食的基础上加用整蛋白型肠内营养剂,两组连续干预6个月。比较两组患者治疗前后体重指数(body mass indes,BMI)、白蛋白(albumin,ALB)、前白蛋白(prealbumin,PA)、凝血酶原活动度(prothrombin activity,PTA)、淋巴细胞计数(total lymohocyte count,TLC)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、总胆红素(total bilirubin,TBil)及凝血酶原时间(plasma prothrombin time,PT)的差异。采用NRS2002评分筛查两组患者营养风险。记录治疗期间消化道出血、肝肾综合征、肝性脑病及继发感染等并发症发生情况。结果治疗前,观察组和对照组患者BMI[(19.07±2.80)kg/m²vs(19.15±2.56)kg/m²]、ALB[(32.78±2.81)g/L vs(31.94±2.84)g/L]、PA[(98.06±18.84)mg/L vs(99.74±19.60)mg/L]、PTA[(54.82±19.54)%vs(53.79±18.68)%]及TLC[(1.21±0.92)×10⁹/L vs(1.23±1.02)×10⁹/L]水平差异无统计学意义(P均>0.05)。治疗后,观察组患者BMI[(22.14±2.52)kg/m²vs(20.97±2.37)kg/m²]、ALB[(36.25±2.66)g/L vs(34.89±2.88)g/L]、PA[(10⁹.17±17.64)mg/L vs(101.46±16.51)mg/L]及PTA[(66.30±20.30)%vs(56.14±19.28)%]水平显著高于对照组,差异有统计学意义(P均<0.05),TLC[(1.11±0.94)×10⁹/L vs(1.21±0.82)×10⁹/L]水平差异无统计学意义(t=0.690,P=0.491)。治疗前,两组患者存在营养不良风险的比例差异无统计学意义[2.70%(2/74)vs 5.41%(4/74);χ²=0.174,P=0.677],治疗后,观察组存在营养不良风险的比例显著低于对照组[40.54%(30/74)vs 94.59%(70/74);χ²=49.333、P<0.001]。治疗后,两组患者存在营养不良风险的比例均显著高于治疗前,差异有统计学意义(χ²=31.259、117.730,P均<0.001)。治疗前,观察组和对照组患者ALT[(77.15±20.54)U/L vs(69.58±19.97)U/L]、TBil[(50.70±15.25)μmol/L vs(49.26±12.60)μmol/L]及PT[(19.13±2.65)s vs(19.76±2.36)s]水平差异无统计学意义(P均>0.05)。治疗后,观察组ALT水平[(39.83±11.32)U/L vs(34.51±12.17)U/L]显著高于对照组,TBil[(22.95±8.53)μmol/L vs(33.85±11.93)μmol/L]和PT[(14.76±1.64)s vs(18.87±1.59)s]水平显著低于对照组,差异有统计学意义(P均<0.05)。两组患者治疗后ALT、TBil及PT水平均显著低于治疗前,差异有统计学意义(P均<0.05)。在治疗期间,观察组肝性脑病[4.05%(3/74)vs 18.92%(14/74)]和继发感染[8.11%(6/74)vs 25.68%(19/74)]的发生率显著低于对照组,差异有统计学意义(χ²=6.646、8.134,P=0.010、0.004);消化道出血[6.76%(5/74)vs 10.81%(8/74)]及肝肾综合征[2.70%(2/74)vs 6.76%(5/74)]发生率差异无统计学意义(P=0.384、0.245)。结论整蛋白型肠内营养可改善老年肝硬化患者营养不良及肝功能,降低其营养风险率,可有效预防并发症的发生,值得临床推广。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.