李兰娟
从事传染病医疗科研,对病毒性肝炎尤其人工肝支持系统治疗重型肝炎,肠道微生态学研究等方面有甚深造诣
个性化签名
- 姓名:李兰娟
- 目前身份:
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学术头衔:
博士生导师
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学科领域:
内科学
- 研究兴趣:从事传染病医疗科研,对病毒性肝炎尤其人工肝支持系统治疗重型肝炎,肠道微生态学研究等方面有甚深造诣
李兰娟,女,浙江大学医学院附属第一医院教授、主任医师、博士生导师。卫生部传染病重点实验室主任,国家传染病重点学科、211建设学科学术带头人。从事传染病医疗、教学和科研工作30余年,对病毒性肝炎尤其人工肝支持系统治疗重型肝炎,肠道微生态学研究等方面有甚深造诣,为我国人工肝开拓者。为攻克重型肝炎病死率高达80%的国际性难题,李兰娟教授自1986年起历经15余年的艰苦攻关,创建了一整套独特有效的人工肝支持系统(ALSS)治疗重型肝炎,取得重大突破。ALSS研究成果获1998年国家科技进步二等奖,1997年浙江省科技进步一等奖,2003年吴孟超肝胆外科医学二等奖。此外,她还毫无保留地在全国推广该技术,迄今已举办了七期国家级ALSS成果推广应用继续医学教育班,主办了第一、第二届国际暨全国人工肝会议,并担任大会主席。并把十几年积累的人工肝经验总结起来,主编出版了我国第一部《人工肝脏》专著。人工肝推广应用研究获2002年中国高校科技二等奖。为了更好交流提高我国人工肝水平,她积极筹备成立了人工肝学组,现任中华医学会传染病与寄生虫病学会副主任委员,首届人工肝学组组长,全国人工肝培训基地主任,国际血液净化学会(ISFA)理事,主持制定了全国人工肝治疗指南,使我国人工肝临床应用更加标准化和规范化。李兰娟教授主持的人工肝研究得到了国家“十五”攻关项目、国家“863”攻关项目、国家自然科学基金资助。近年她率课题组应用新兴的生命学科――微生态学的理论和方法对慢性重型肝炎病人的肠道微生态变化进行了系列研究,首次发现慢重肝病人肠道微生态有显著的变化,提出并论证双歧杆菌与肠杆菌科细菌数量对数值之比(B/E)可以作为肠道微生物定植抗力指标的新观点;临床证实了使用肠道微生态调节剂可以降低慢性肝炎患者血内毒素水平。该成果获2001年浙江省科学技术进步一等奖。主编出版了我国首部《感染微生态学》著作。“器官移植术后微生态失衡与CGD的关系及干预研究”得到国家“973”资助。李兰娟教授还担任了中国医师协会副会长,中华预防医学会微生态学分会副主任委员,浙江省传染病与寄生虫病学分会主任委员,浙江省预防医学会微生态学专业委员会主任委员,《感染病杂志》主编,《中华传染病杂志》副主编。主编出版了教育部规划教材《传染病学》。
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【期刊论文】Treatment of hepatic failure with artificial liver support system
李兰娟, LI Lanjuan, YANG Qian, HUANG Jianrong, XU Xiaowei, CHEN Yuemei, CHEN Yagang, MA Weihang, CHEN Zhi and FU Suzhen
Chinese Medieal Journal 2001; 114 (9): 941-945,-0001,():
-1年11月30日
Objective To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. Methods 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i. e., early, middle and end stages). Results 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. Conclusion ALSS is a reliable therapy for advanced lliver diseases and treatment at early or middle stages is appropriate.
artificial liver
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【期刊论文】The status of drug resistance and ampC gene expression in Enterobacter cloacae
李兰娟, ZHOU Zhihui, LI Lanjuan, YU Yunsong and MA Yilin
Chinese Medical Jounal 2003; 116 (8): 1244-1247,-0001,():
-1年11月30日
Objective To inve stigate the status of the drugre sistance and the ampC gene expre ssion of Enterobacter cloacae1 Methods Disk diffusion test swere made for detecting the susceptibility of antimicrobial agents against Enterobacter cloacae1 AmpC gene was amplified by polymera se chain reaction (PCR) and verified by DNA sequencing1 AmpC gene expression was analyzed according to antimicrobial agent sensitive phenotype. Results The sensitivity rates of 144 strains to imipenam, cefepime and cefoperazone/sulbactam were 98161%, 65197% and 63189%, respectively. The sensitivity rates of 144 strains to other antimicrobial agent swere lower. Among the 144 strains 120 were found to be po sitive by PCR for ampC. The PCR product showed high homology to the GenBank ampC sequence1 Stably derepre ssed strains, hyperinducible strains and unexpre ssing or lower level expre ssing strains accounted for 3010% (36/120), 3715% (45/120), and 3215% (39/120), re spectively1 Fifty-six out of 120 strains (46167%) also produced extended spectrumβ-lactama se s (ESBLs). The hyperinducible strains were highly sensitive to all the antimicrobial agents except amoxicillin/ clavulanic acid and cefuroxime, while the stably derepre ssed strains were only sensitive to imipenam and cefepime1 However, sensitivity to cefepime decrea sed if the strains also produced ESBLs. Co nclusions The durg re sistant status of Enterobacter cloacae is severe1 Clearing out the expre ssive status of ampC gene will be helpful in selection of antimicrobial agents in the treatment of clinical infection.
Enterobacter cloacae
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李兰娟, L.J. LI, Z. J. SHEN*, Y.L. LU and S.Z. FU
BJU International (2001), 88, 536-539,-0001,():
-1年11月30日
Objective To clarify the value of endotoxin concentrations in expressed prostatic secretions (EPS) in the diagnosis and classification of chronic prostatitis. Patients, subjects and methods The study included 88 consecutive patients with chronic prostatitis and 15 controls with no urological disease. The diagnosis and classification were based on a history, symptoms, a digital rectal examination of the prostate, and a white blood cell count in the EPS. Endotoxin concentrations in the EPS or urine were measured using a colorimetric assay and standard microbiological methods used to identify bacterial growth. Results In men with chronic prostatitis caused by Gramnegative or combined Gram-negative and -positive bacteria, the endotoxin levels in urine collected immediately after prostatic massage were significantly greater (P<0.01) than in a midstream urine sample, and the concentration in the EPS was significantly higher (P<0.05) than that in the control group. The same was true of patients with chronic prostatitis and Gram-positive bacteria isolated from the EPS or urine after massage. In patients with chronic pelvic pain syndrome (grade IIIA) the endotoxin level in the urine after massage was also significantly higher (P<0.05) than that of the midstream sample, but there was no significant difference between the concentration in these samples in patients with grade IIIB, and no significant difference between the endotoxin concentration of the EPS in patients with grade IIIB and that in controls. Conclusion Endotoxin concentrations are increased in the EPS or urine (after prostatic massage) of men with bacterial chronic prostatitis or chronic pelvic pain syndrome grade IIIA. The current routine examinations (including bacterial culture and routine examination of EPS or urine) before diagnosis and classifition of chronic prostatitis are insuficient to describe the cause and pathogenesis of this condition. The endotoxin concentration of the EPS or urine after massage may provide a supplementary tool to identify the cause of chronic prostatitis.
prostatitis,, endotoxin,, expressed prostatic secretions
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【期刊论文】Study of severe hepatitis treated with a hybrid artificial liver support system
李兰娟, Y. QIAN, L. LANJUAN, H. JIANRONG, L. JUN, C. HONGCUI, F. SUZHEN, Y. XIA , Y. SHUHONG
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-1年11月30日
Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 109 porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.
Artificial liver,, Hybrid,, Severe hepatitis,, Hepatic failure
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【期刊论文】Severe acute respiratory syndrome-associated coronavirus genotype and its characterization
李兰娟, LI Lanjuan, WANG Zhigang, LU Yiyu, BAO Qiyu, CHEN Suhong, WU Nanping, CHENG Suyun, WENG Jingqing, ZHANG Yanjun, YAN Juying, MEI Lingling, WANG Xiaomeng, ZHU Hanping, YU Yingpu, ZHANG Minli, LI Minhong, YAO Jun, LU Qunying, YAO Pingping, BO Xiaochen, WO Jianer, WANG Shengqi and HU Songnian
Chinese Medical Journal 2003; 116 (9): 1288-1292,-0001,():
-1年11月30日
Objective To study the severe acute respiratory syndrome (SARS)-associated coronavirus genotype and its characteristics. Methods A SARS-associated coronavirus isolate named Z J0. was obtained from throat swab samples taken from a patient in Hangzhou, Zhejing province. The complete genome sequence of Z J0. consisted of 29 715 bp (GenBank accession: AY297028, version: gi: 30910859). Seventeen SARS-associated coronavirus genome sequences in GenBank were compared to analyze the common sequence variations and the probability of co-occurrence of multiple polymorphisms or mutations. Phylogenetic analysis of those sequences was done. Results By bioinformatics processing and analysis, the 5 loci nucleotides at Z J0. genome were found being T, T, G, T and T, respectively. Compared with other SARS-associated coronavirus genomes in the GenBank database, an A/G mutation was detected besides the other 4 mutation loci (C: G: C: C/T: T: T: T) involved in this genetic signature. Therefore a new definition was put forward according to the 5 mutation loci. SARS-associated coronavirus strains would be grouped into two genotypes (C: G: A: C: C/T: T: G: T: T), and abbreviated as SARS coronavirus C genotype and T genotype. On the basis of this new definition, the Z J0. isolate belongs to SARS-associated coronavirus T genotype, first discovered and reported in mainland China. Phylogenetic analysis of the spike protein aene fraaments of these SARS-associated coronavirus strains showed that the GZ0. isolate was phylogenetically distinct from other isolates, and compared with groups F1 and F2 of the T genotype, the isolates of B J01 and CUHK-Wl were more closely related to the GZ0. isolate. It was interesting to find that two (A/G and C/T) of the five mutation loci occurred in the spike protein gene, which caused changes of Asp to Gly and Thr to lie in the protein, respectively. Conclusion Attention should be paid to whether these genotype and mutation patterns are related to the virus's biological activities, epidemic characteristics and host clinical symptoms.
severe acute respiratory syndrome
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李兰娟, Lanjuan Li a, Jianer Woa, +, Junbing Shao a, Haihong Zhu a, Nanping Wua, Minwei Li a, Hangpin Yao a, Minjun Hua, Reinhard H. Dennin b
Journal of Clinical Virology 28(2003)239-244,-0001,():
-1年11月30日
Background: The etiologic agent of severe acute respiratory syndrome (SARS) is a recently identified, positive singlestranded RNA (ssRNA) coronavirus (SARS-CoV). Little is known about the dynamic changes of the viral replicative form in SARS cases. Objectives: Evaluate whether SARS-CoV can infect and replicate in peripheral blood mononuclear cells (PBMCs) of infected persons and reveal any dynamic changes to the virus during the course of the disease. Study design: Peripheral blood mononuclear cells collected from SARS cases infected by the same infectious source were tested for both negative-stranded RNA (minus-RNA, "replicative intermediates") and positivestranded RNA (genomic RNA) of SARS-CoV during the course of hospitalization by reverse transcription-polymerase chain reaction (RT-PCR). Results: SARS-CoV minus-RNA was detected in PBMCs from SARS patients. The viral replicative forms in PBMCs were detectable during a period of 6 days post-onset of the disease, while the plus-RNA were detectable for a longer period (8/12 days post-onset). Conclusions: SARS-coronavirus can infect and replicate within PBMCs of SARS patients, but viral replication in PBMCs seems subject to self-limitation.
Severe acute respiratory syndrome (, SARS), , SARS-coronavirus, Replicative negative-stranded RNA, Peripheral blood mononuclear cells (, PBMCs),
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李兰娟, LI Lanjuan, SHEN Zhoujun, WANG Hua, FU Suzheng and CHENG Guang
Chinese Medical Joumal 2001; 114 (5): 510-513,-0001,():
-1年11月30日
Objective To clarify the infection risks and the value of endotoxin determination in urine during extracurporeal shock wave lithotripsy (ESWL). Methocls According to the distribution and complications of upper urinary calculi, 164 patients were divided into five groups. Group A consisted of 48 patients with 1 to 4 renal calculi, which were or lees than 2c,m in diameter. Group B was composed of 24 patients with renal calculus larger than 2cm in diameter or one to multiple renal calculi. Group C was comlposed of 22 patients with. to 3 renal calculi accompanied by 1 to 2 ureteric calculi. Group D consisted of 51 patients with. to 3 ureteric calculi that were 0.5 to 1.2 cm in diameter, respectively. Group E included 19 patients with compricated renal calculus, such as casting and staghom renal calculus. Urine and blood samples of these patients were obtained before and after ESWL, respectively. Their urine samples ware proven sterile prior to treatment. All samples were cultured for bacteria and investigated for endotoxin concentration by the limulus lysate test. Results No significant difference in serum endotoxin was noted before and after ESWL. Blood bacterial cultures ware all negative in all patients after ESWL, similar to those before ESWL. Significant increases in urine endotoxin after ESWL compared with that before ESWL in patients of Groups B, C and E were observed, respectively (P<0.05), There was no significant difference in urine endotoxin after ESWL compared with that before ESWL in patients of Groups A and D. The positive incidences of urine bacterial culturewe significantly increased (P<0.05) in Groups B and C and very significantly increased (P<0.01) in Group E compared with those in Groups A and D. Conc lusions Urinary infection risk following ESWL was lower in patients with one to several renal calculi, which were less than 2 cm in diameter and did not interfere obviously with the urine flow or in patients with 1 to 3 ureterlc calculi that were 0.5 to 1.2 om in diameter. The risk was higher in those with complioeted calculi, such as casting, staghom renal calculus, renal calculus larger than 2 cm in diameter or renal calculi accompanied by ureterlc calculi. For patients with higher infection risk after ESWL, pr ophylactic antibiotics are necessary even if bacteriuria is not present before ESWL. Endotoxin determination in urine is a reliable, sensitive and simple method for the diagnosis of bacterial infection in patients undergoing ESWL.
extracorporeal shock wove lithotripsy
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【期刊论文】Effects of ursodeoxycholic acid on intrahepatic cholestasis in rats
李兰娟, LI Lanjuan, XU Xiaowei, LU Fangfang and ZHAO Nianfeng
Chinese Medical Joumal 2003; 116 (7): 1099-1103,-0001,():
-1年11月30日
Objective To investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism. Method Rats suffering from intrahepatic cholestasis were treated with UDCA. Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBL), direct bilirubin (DBL), γ-glutamyl transpeptidase (γ-GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na+ and TCH of bile were measured before and after treatment. In addition, the changes of liver tissue under microscrope were observed and recorded. Results Compared with the control group, serum ALT, ALP, TBIL, DBL, γ-GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na+ and TCH decreased significantly. Degeneration of hepatocytes, infiltration of inflamed cells and prolil'eration of small bile ducts in the treatment group were improved under microscope. Conclusion UDCA may have therapeutic effects on cholestatic hepatitis. The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation.
ursodeoxycholic acid
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【期刊论文】Changes in intestinal microflora in patients with chronic severe hepatitis
李兰娟, LI Lanjuan, WU Zhong Wen, MA Weihang, YU Yunsong and Chert Yagang
Chinese Medical Journal 2001; 114 (8): 869-872,-0001,():
-1年11月30日
Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease. Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one healthy volunteer as the control group. Fecal flora from all subjects were analyzed. Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alpha (TNF-a) and interleukin-1 beta (IL-1β) and liver function were assessed. Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significantly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P<0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were significantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and total bilirubin (TBiL) were significantly increased in the CSH group. The concentration of endotoxin positively correlated with levels of both TNF-α, IL-1β and TBiL (P<0.001, respectively). Levels of plasma endotoxin were positively correlated with the number of fecal enterobacteriaceae and negatively correlated with bifidobacterium (P<0.05, P<0.001, respectively). Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturbed and gut mircobiologicel colonization resistance was impaired. Changes in intestinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.
chronic severe hepatitis
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【期刊论文】Severe hepatitis treated with an artificial liver support system
李兰娟, Li Lanjuan, M.D.*, Yang Qian, M.D., Huang Jianrong, Xu Xiaowei, Chen Yuemei, Chen Yagang, Ma Weihang, Chen Zhi, Fu Suzhen
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-1年11月30日
We designed an artificial liver support system (ALSS) including plasma exchange, charcoal hemoperfusion, plasma bilirubin absorption, charcoal plasma perfusion, hemofiltration and hemodialysis. We chose different methods or their combinations according to the patients' conditions. We investigated the effect of ALSS in 154 patients with severe hepatitis, 72 patients survived. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e. early, middle and end stages). After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while BCAA/AAA ratio increased. Patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. Thus, we concluded that ALSS is a reliable therapy to advanced liver diseases and treatment in early or middle stages is appropriate.
Artificial liver Severe hepatitis Therapy
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