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A serum metabolomic analysis for diagnosis and biomarker discovery of primary biliary cirrhosis and autoimmune hepatitis

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Hepatobiliary & Pancreatic Diseases International 2015年第4期14卷 413-421页

作者： jiang-shan lian Wei Liu Shao-Rui Hao De-Ying Chen Yin-Yin Wang Jian-Le Yang Hong-Yu Jia Jian-Rong Huang Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Disease First Affiliated Hospital Zhejiang University School of Medicine Yantai City Hospital for Infectious Diseases

Because of the diversity of the dinical and laboratory manifestations, the diagnosis of autoimmune liver disease （AILD） remains a challenge in clinical practice. The value of metabolomics has been studied in the diagnosis of many diseases. The present study aimed to determine whether the metabolic profiles, based on ultraperformance liquid chromatography-mass spectrometry （UPLC-MS）, differed between autoimmune hepatitis （AIH） and primary biliary cir- rhosis （PBC）, to identify specific metabolomic markers, and to establish a model for the diagnosis of AIH and PBC. METHODS： Serum samples were collected from 20 patients with PBC, 19 patients with AIH, and 25 healthy individuals. UPLC-MS data of the samples were analyzed using principal component analysis, partial least squares discrimination analysis and or- thogonal partial least squares discrimination analysis. RESULTS： The partial least squares discrimination analysis model （R2y=0.991, Q2=0.943） was established between the AIH and PBC groups and exhibited both sensitivity and speci- ficity of 100%. Five groups of biomarkers were identified, in- eluding bile acids, free fatty acids, phosphatidylcholines, lyso- lecithins and sphingomyelin. Bile acids significantly increased in the AIH and PBC groups compared with the healthy con- trol group. The other biomarkers decreased in the AIH andPBC groups compared with those in the healthy control group. In addition, the biomarkers were downregulated in the AIH group compared with the PBC group. CONCLUSIONS： The biomarkers identified revealed the pathophysiological changes in AILD and helped to discrimi- nate between AIH and PBC. The predictability of this method suggests its potential application in the diagnosis of AILD.

关键词： autoimmune liver disease biomarkers metabolomics autoimmune hepatitis primary biliary cirrhosis overlap syndrome

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Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues： A Prospective Study

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Chinese Medical Journal 2017年第8期130卷 914-919页

作者： Jing Zhou Yue-Ying Liu jiang-shan lian Li-Fang Pan Jian-Le Yang Jian-Rong Huang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital College of Medicine Zhejiang University Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou Zhejiang 310003 China Department of Infectious Disease The First People's Hospital of Yongkang Jinhua Zhejiang 321300 China

Background： Tenofovir disoproxil （TDF） is a promising salvage therapy for patients with chronic hepatitis B （CHB） who failed regimens of other nucleoside analogues （NAs）. In this study, we aimed to investigate the clinical efficacy and safety ofTDF monotherapy in Chinese CHB patients with genotypic resistance. Methods： A total of 33 CHB patients who had tailed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients＇ demographic data （age, sex, history of hepatitis B virus [HBV] therapy）, laboratory testing results （hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay）, clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 （baseline） and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation. Results： With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability （r = 0.39, P = 0.030）. AET levels were normal in 30 of 33 patients （91%）. HBeAg negative conversion occurred in 7 of 25 patients （28%）, among whom HBeAg seroconversion （12%） and H BeAg seroclearance （16%） occurred. The time of complete virological response was significantly affected by the number of resistance loci （r = 0.36, P = 0.040）. Concerning safety, the study found that no adverse events were observed during the 48 weeks. Conclusion： TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

关键词： Drug Resistance Hepatitis B Tenofovir Therapy Safety

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胸腰段脊柱脊髓损伤患者的急诊分级护理

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中华护理杂志 2007年第2期42卷 136-138页

作者：单江莲北京市顺义区医院急诊科 101300

急性胸腰段脊柱脊髓损伤病情复杂,常为复合伤,依据“急性胸腰椎损伤急诊分型”提出分级护理的方法,即抓住“生命—神经功能—脊柱稳定性—功能康复”这条主线,将急性胸腰段脊柱脊髓损伤患者分为有严重合并伤、有神经症状、有神经损伤倾... 详细信息

急性胸腰段脊柱脊髓损伤病情复杂,常为复合伤,依据“急性胸腰椎损伤急诊分型”提出分级护理的方法,即抓住“生命—神经功能—脊柱稳定性—功能康复”这条主线,将急性胸腰段脊柱脊髓损伤患者分为有严重合并伤、有神经症状、有神经损伤倾向和单纯稳定性4型,针对不同类型患者的特点进行分级护理。结果96例患者在急诊无一例死亡,无一例因检查搬动而加重神经的损伤,为脊柱脊髓损伤的后续治疗创造了良好条件。

关键词：脊柱骨折急诊处理护理胸腰段脊柱脊髓损伤患者

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De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

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World Journal of Gastroenterology 2013年第37期19卷 6278-6283页

作者： jiang-shan lian Lin-Yan Zeng Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang liang Yu Jian-Hua Hu Ying-Feng Lu Ling Zheng Lan-Juan Li Yi-Da Yang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the FirstAffiliated HospitalZhejiang University School of Medicine

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver ***:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this *** patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two *** for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 *** measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 ***:Forty-five patients in each group were observed for 96 *** significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were *** B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was *** the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week *** increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both *** cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,***:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.

关键词： Chronic hepatitis B Decompensated liver cirrhosis Lamivudine Adefovir dipivoxil Combination therapy Entecavir

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Hepatitis B surface antigen levels during natural history of chronic hepatitis B: A Chinese perspective study

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World Journal of Gastroenterology 2014年第27期20卷 9178-9184页

作者： Lin-Yan Zeng jiang-shan lian Jian-Yang Chen Hong-Yu Jia Yi-Min Zhang Dai-Rong Xiang liang Yu Jian-Hua Hu Ying-Feng Lu Lin Zheng Lan-Juan Li Yi-Da Yang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital of Zhejiang University School of Medicine

AIM: To determine the baseline hepatitis B surface antigen (HBsAg) levels during the different phases of chronic hepatitis B (CHB) patients in China.

关键词： Hepatitis B surface antigen quantification Chronic hepatitis B Natural history Perspective

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Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B

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World Journal of Gastroenterology 2015年第12期21卷 3657-3662页

作者： Hong-Yu Jia Feng Ding Jian-Yang Chen jiang-shan lian Yi-Min Zhang Lin-Yan Zeng Dai-Rong Xiang liang Yu Jian-Hua Hu Guo-Dong Yu Huan Cai Ying-Feng Lu Lin Zheng Lan-Juan Li Yi-Da Yang Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Disease First Affiliated Hospital of Zhejiang University School of Medicine

AIM: To evaluate urine β2-microglobulin(β2-M), retinol-binding protein(RBP) excretion, and renal impairment with adefovir dipivoxil(ADV) for chronic hepatitis B. METHODS: We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy(n = 90) or ADV plus lamivudine combination therapy(n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate(e GFR) at the initiation of antiviral therapy and every 6 mo for a period of five years. RESULTS: Urine β2-M abnormalities were observed in patients during the first(n = 3), second(n = 7), third(n = 11), fourth(n = 16), and fifth(n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first(n = 2), second(n = 8), third(n = 12), fourth(n = 15), and fifth(n = 22) year of ADV treatment. e GFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in e GFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and e GFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment. CONCLUSION: Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.

关键词： Adefovir dipivoxil Entecavir Retinol binding prote

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简析春秋时期秦国官制的特点

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咸阳师范学院学报 2007年第5期22卷 1-3页

作者：江连山绥化学院历史系黑龙江绥化152061

春秋时期秦国因建国较晚,又僻居西戎之地,故其官制很不完备。本文简析了这套官制的特点,指出了这套官制存在的进步性及其历史作用。

关键词：春秋秦国官制特点原始性开放性进步性

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西汉官制历史地位评述(二)

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绥化学院学报 2011年第1期31卷 52-55页

作者：江连山绥化学院黑龙江绥化152061

西汉由弱到强,又由盛转衰,寻找其变化原因多种,其中一最重要原因是其官制设置与变化的合理与否,自古以来,许多人称赞汉唐盛世,进而赞美西汉官制的总体合理;当然亦有不少人,甚至当时人也指出其官制的局部不合理和弊端。文章亦就西汉官制... 详细信息

西汉由弱到强,又由盛转衰,寻找其变化原因多种,其中一最重要原因是其官制设置与变化的合理与否,自古以来,许多人称赞汉唐盛世,进而赞美西汉官制的总体合理;当然亦有不少人,甚至当时人也指出其官制的局部不合理和弊端。文章亦就西汉官制所处时期及六次改革观察,大略陈述、评论其合理的地方、合理的时候,不合理的地方、不合理的时候,以及坏乱地步;略说西汉官制在当时的积极及消极作用,对后世的影响。

关键词：西汉官制改革合理不合理作用影响

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“參川尉印”及封泥归属猜想

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咸阳师范学院学报 2010年第5期25卷 8-11页

作者：江连山绥化学院历史系黑龙江绥化152061

"參川尉印"封泥,《封泥考略》、《秦封泥集》、《新出土秦代封泥印集》等皆认定为秦封泥。根据文献、考古实物以及秦和汉初的用字习惯,将其只定为嬴秦之物似乎不妥,其归属还有另一种可能,即为项羽所封河南王申阳之属官的印迹遗物。

关键词： “參川尉印”封泥三川郡參川郡归属

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西汉前期避皇帝之名并不严格

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咸阳师范学院学报 2009年第1期24卷 13-16页

作者：江连山绥化学院历史系黑龙江绥化152061

中国古代从西周始实行一种回避君主、尊长之名的制度。秦朝建立皇帝制度后,此制度形成定制。此后,逐渐完善到严格、严厉化。近代以来一些学者、史家便以是或否避讳某代君主名作为判定地下发掘带字实物所属时代的极重要因素,如对秦国、... 详细信息

中国古代从西周始实行一种回避君主、尊长之名的制度。秦朝建立皇帝制度后,此制度形成定制。此后,逐渐完善到严格、严厉化。近代以来一些学者、史家便以是或否避讳某代君主名作为判定地下发掘带字实物所属时代的极重要因素,如对秦国、秦朝、西汉初、前期物品的断定。其实,诸多考古资料证明秦国到西汉前期避君主名并不严格,因此,不应该以是与否回避某君主之名,作为判定某地下发掘实物是与不是哪时代物品的标志。

关键词：避讳西汉前期刘邦属邦不严格

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