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Expression of HLA-G in patients with hepatocellular carcinoma

Hepatobiliary & Pancreatic Diseases International 2011年第2期10卷 158-163页

作者： Yan Wang,Zhou Ye,Xue-Qin Meng and Shu-Sen ZhengDivision of Hepatobiliary and Pancreatic Surgery key laboratory of Combined Multi-organ transplantation,Ministry of Public Health and key laboratory of organ transplantation zhejiang province, First Affiliated Hospital,zhejiang University School of Medicine,Hangzhou 310003,China Division of Hepatobiliary and Pancreatic Surgery key laboratory of Combined Multi-organ transplantation Ministry of Public Health and key laboratory of organ transplantation zhejiang province First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Human leukocyte antigen G(HLA-G)is a non-classical major histocompatibility complex class I molecule that has multiple immune regulatory functions including the induction of immune *** detection of HLA-G expression might serve as a clinical marker in the prediction of clinical outcomes for certain types of ***, we investigated whether or not HLA-G is also expressed in patients with hepatocellular carcinoma(HCC),and whether the expression has clinical value. METHODS:Serum levels of secreted HLA-G(sHLA-G)were measured by ELISA in 36 patients with HCC,25 patients with liver cirrhosis(LC)and 25 healthy *** expression of HLA-G in liver tissue was further studied using Western blotting in 36 patients with HCC and 25 with *** correlations between HLA-G status and various clinicopathological parameters including survival were analyzed. RESULTS:The ELISA assay showed that the serum levels of sHLA-G in the HCC,LC and healthy groups were 132.6± 31.4,63.5±22.1,and 47.0±15.5 U/ml,*** of variance was used for inter-group comparison and differences were found between the HCC group and the other two groups (both P<0.01),while no difference was found between the LC group and the healthy group(P=0.112).HLA-G protein expression in liver tissue was found in 66.7%(24/36)of the primary sites of HCC,but not in benign lesions(LC). Further,the HLA-G expression in tumors had no significant correlation with the parameters of age,gender,histological grade and alpha-fetoprotein ***,patients with HLA-G-positive tumors had a shorter postoperative survival time than those with HLA-G-negative tumors(P=0.014).Also, univariate analysis showed that HLA-G was an independent prognostic ***:Our results indicated that the expression of HLA-G was a characteristic feature of HCC and patients with positive expression of HLA-G in malignant liver tissue had a poor prognosis.

关键词： human leukocyte antigen G hepatocellular carcinoma prognosis

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Risk factors and incidence of acute pyogenic cholangitis

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Hepatobiliary & Pancreatic Diseases International 2012年第6期11卷 650-654页

作者： Yun-Sheng Qin, Qi-Yong Li, Fu-Chun Yang , Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery key laboratory of Combined Multi-organ transplantation, Ministry of Public Health key laboratory of organ transplantation zhejiang province, First Affiliated Hospital, zhejiang University School of Medicine, Hangzhou 310003, China Division of Hepatobiliary and Pancreatic Surgery key laboratory of Combined Multi-organ transplantation Ministry of Public Health and key laboratory of organ transplantation zhejiang province First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis. METHODS: We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC. RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%) Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariateanalysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC. CONCLUSIONS: This study demonstrates that advanced age, hypotension,

关键词： acute cholangitis suppurative endoscopic retrograde cholangiopancreatography

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Evaluation of hepatitis B viral replication and proteomic analysis of HepG2.2.15 cell line after knockdown of HBx

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Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 295-302页

作者： Hai-Yang Xie,Jun Cheng,Chun-Yang Xing,Jin-Jin Wang,Rong Su,Xu-Yong Wei,Lin Zhou and Shu-Sen Zheng Author Affiliations:key laboratory of Combined Multi-organ transplantation,Ministry of Public Health key laboratory of organ transplantation zhejiang province and Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery,First Affiliated Hospital,zhejiang University School of Medicine,Hangzhou 310003,China key laboratory of Combined Multi-organ transplantation Ministry of Public Health key laboratory of organ transplantation zhejiang province and Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Hepatitis B virus (HBV) is one of the major pathogens of human liver *** have shown that HBV X protein (HBx) plays an important role in promoting viral gene expression and *** this study we performed a global proteomic profiling to identify the downstream functional proteins of HBx,thereby detecting the mechanisms of action of HBx on virion ***:HBx in the HepG2.2.15 cell line was knocked down by the transfection of small interfering RNA (siRNA).The replication level of HBV was evaluated by microparticle enzyme immunoassay analysis of HBsAg and HBeAg in the culture supernatant,and real-time quantitative PCR analysis of HBV ***-dimensional electrophoresis combined with MALDI-TOF/TOF was performed to analyze the changes in protein expression profile after treatment with HBx ***:Knockdown of HBx disturbed HBV replication in *** target siRNA significantly inhibited the expression of HBsAg,HBeAg and the replication of HBV *** significantly changed proteins (7 upregulated and 5 downregulated) were successfully identified by MALDI-TOF/TOF using proteomics differential expression analysis after the knockdown of *** these identified proteins,HSP70 was validated by Western ***:The results of the study indicated the positive effect of HBx on HBV replication,and a group of downstream target proteins of HBx may be responsible for this effect.

关键词： hepatitis B virus HBx replication proteomics

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Ischemic preconditioning enhances hepatocyte proliferation in the early phase after ischemia under hemi-hepatectomy in rats

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 521-526页

作者： Li-Ming Jin, Shui-Fang Jin, Yuan-Xing Liu, Lin Zhou, Hai-Yang Xie, Sheng Yan, Xiao Xu , Shu-Sen Zheng Department of General Surgery and Intensive Care Unit, First Affiliated Hospital, zhejiang Chinese Medical University, Hangzhou 310006, China key laboratory of Combined Multi-organ transplantation, Ministry of Public Health, key laboratory of organ transplantation, zhejiang province, and Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, zhejiang University School of Medicine, Hangzhou 310003, China [a] Department of General Surgery First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China [b] Intensive Care Unit First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 Hangzhou China [c] key laboratory of Combined Multi-organ transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Ischemia/reperfusion (I/R) injury is an important barrier to liver surgery and transplantation because it impairs remnant liver/reduced-size-graft regeneration. Ischemic preconditioning (IPC), as an effective measure to overcome I/R injury, has been shown to enhance the regenerative capacity of hepatocytes. However, investigations have always focused on regeneration in the late phase after reperfusion. This study aimed to investigate whether IPC enhances hepatocyte proliferation in the early phase after reperfusion and possible underlying mechanisms. METHODS: A total of 90 rats were divided into three groups: hemi-hepatectomy alone (PHx group), 60 minutes of ischemia plus hemi-hepatectomy (I/R group), and a cycle of 10 minutes of alternating I/R prior to 60 minutes of ischemia plus hemi-hepatectomy (IPC group). Each group was divided into five subgroups sacrificed after 0.5, 2, 6, 12 or 24 hours (n=6/ subgroup). Subsequently, serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured; caspase-3 and proliferating cell nuclear antigen (PCNA) proteins were also determined by Western blotting. Furthermore, PCNA was detected by immunohistochemistry to identify the expression ***: Serum ALT and AST levels after 2-24 hours of reperfusion in the PHx and IPC groups were remarkably decreased compared to the I/R group, and the serum TNF-α was relatively lower. A significant increase of serum IL-6 levels was found in the PHx and IPC groups compared with the I/R group at each time point. Furthermore, PCNA expression was remarkably increased in the IPC group after 6-12 hours of reperfusion, and in the earlier 0.5 and 6 hours time points after reperfusion have shown the massive PCNA-positive hepatocytes. At the same time, the expression of liver p-JNK was higher in the IPC group in the early phase after reperfusion than that of the I/R group and its expre

关键词： reperfusion injury ischemic preconditioning hepatocytes proliferation hemi-hepatectomy

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Liver transplantation in Crigler-Najjar syndrome type I disease

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 545-548页

作者： Zhen-Hua Tu, De-Sheng Shang, Jin-Cai Jiang, Wu Zhang, Min Zhang, Wei-Lin Wang, Hai-Yan Lou,Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, zhejiang University School of Medicine, key laboratory of Combined Multi-organ transplantation, Ministry of Public Health & key laboratory of organ transplantation of zhejiang province Department of Radiology,First Affiliated Hospital,zhejiang University School of Medicine, Hangzhou 310003, China [a] Division of Hepatobiliary and Pancreatic Surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Key Laboratory of Combined Multi-Organ Transplantation Ministry of Public Health & Key Laboratory of Organ Transplantation of Zhejiang Province Hangzhou 310003 Hangzhou China [b] Department of Radiology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 Hangzhou China

BACKGROUND: Crigler-Najjar syndrome type I (CNS I) is a very rare autosomal recessive inherited disease that liver transplantation can properly deal with. METHODS: We present one case of an 18-month-old child with CNS I diagnosed by clinical findings and genetic detecting LTx was performed 5 days after kernicterus broke out and neurological symptoms were successfully reversed. RESULT: Magnetic resonance imaging and magnetic resonance spectroscopy showed encouraging results that brain pathology had a trend to return to normal in 1-year follow-up, combined with electroencephalogram and motor development estimate studies. CONCLUSIONS: Liver transplantation can cure CNS I with reversible neurological symptoms to some extent in time Magnetic resonance spectroscopy may be a future option of predicting brain conditions and selecting suitable patients with CNS I for transplantation.

关键词： Crigler-Najjar liver transplantation inborn error of metabolism magnetic resonance imaging hyperbilirubinemia

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Effects of suppressing glucose transporter-1 by an antisense oligodeoxynucleotide on the growth of human hepatocellular carcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2011年第1期10卷 72-77页

作者： Tian-Qi Liu,Jun Fan,Lin Zhou and Shu-Sen Zheng key laboratory of Combined Multi-organ Trans-plantation,Ministry of Public Health key laboratory of organ Trans-plantation,zhejiang province and Division of Hepatobiliary and Pancreatic Surgery,Department of Surgery State key laboratory for Diagnosis and Treatment of Infectious Disease,First Affiliated Hospital,zhejiang University School of Medicine,Hangzhou 310003,China Department of Hepatobiliary Surgery,the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021,China [a] key laboratory of Combined Multi-organ transplantation Ministry of Public Health key laboratory of organ transplantation Zhejiang Province and Division of Hepatobiliary and Pancreatic Surgery Department of Surgery Zhejiang University School of Medicine Hangzhou 310003 China [b] State key laboratory for Diagnosis and Treatment of Infectious Disease First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China [c] Department of Hepatobiliary Surgery the People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021 China

BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect *** study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell *** were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose ***:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 *** Glut-1 gene maybe a potential therapeutic target for HCC.

关键词： hepatocellular carcinoma HepG-2 cell glucose transporter-1 therapeutic target

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Genetic factors for individual administration of immunosuppressants in organ transplantation

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Hepatobiliary & Pancreatic Diseases International 2006年第3期5卷 337-344页

作者： Song-Feng Yu, Li-Hua Wu and Shu-Sen Zheng key laboratory of Combined Multi-organ transplantation, Ministry of Public Health, the First Affiliated Hospital, zhejiang University School of Medicine, Hangzhou 310003, China key laboratory of Combined Multi-organ transplantation Ministry of Public Health the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs. DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation. RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors. CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

关键词： cytochrome P4503A P-glycoprotein pharmacogenetics individual administration

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Evaluation of hepatitis B virus replication and proteomic analysis of HepG2.2.15 cell line after cyclosporine A treatment

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Acta Pharmacologica Sinica 2007年第7期28卷 975-984页

作者： Hai-yang XIE,Wei-liang XIA,Chun-chao ZHANG,Li-ming WU,Hao-feng JI,Yu CHENG,Shu-sen ZHENG~2Department of Hepatobiliary Pancreatic Surgery,key laboratory of Multiple organ transplantation,Ministry of Public Health,key Labo-ratory of organ transplantation zhejiang province,First Affiliated Hospital,School of Medicine,zhejiang University,Hangzhou 310003,China Department of Hepatobiliary Pancreatic Surgery Key Laboratory of MultipleOrgan Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation ZhejiangProvince First Affiliated Hospital School of Medicine Zhejiang University

Aim:The effect of cyclosporine A (CsA) on hepatitis B virus (HBV) replicationwas investigated,and proteomics expression differentiation after CsA treatmentwas studied in order to provide clues to explore the effect of CsA on ***:Methyl thiazolyl tetrazolium (MTT) assay was used toevaluate the cytotoxicity of *** HBV replication level in the HBV genomicDNA transfected HepG2.2.15 cell line was determined by an ELISA analysis ofhepatitis B surface antigens (HBsAg) and Hepatitis B e antigens (HBeAg) inculture supernatant,while the intracellular HBV DNA replication level was ana-lyzed by slot blot ***-dimensional electrophoresis was used toinvestigate the alteration of protein expression in HepG2.2.15 after CsA treatmentin *** differentially-expressed proteins were identified by Matrix-assistedlaser desorption/ionization-time of flight mass spectrometry combined with anonline database ***:CsA was able to inhibit the expression of HBsAg,HBeAg,and HBV DNA replication in vitro in a dose-dependent *** analysis indicated that the expression of 17 proteins changed signifi-cantly in the CsA treatment group compared to the control *** of the 17proteins were identified,including the overexpression of eukaryotic translationinitiation factors (eIF) 3k,otubain 1,14.3.3 protein,eIF2-α,eIF5A,and thetyrosine 3/tryptophan 5-mono-oxygenase activation protein in CsA-treatedHepG2.2.15 *** downregulation of the ferritin light subunit,erythrocytecytosolic protein of 51 kDa (ECP-51),stathmin 1/oncoprotein,adeninephosphoribosyl-transferase,and the position of a tumor protein,translationally-controlled 1,was shifted,suggesting it had undergone ***:Our study identified the inhibitory effect of CsA onHBV replication,and found that a group of proteins may be responsible for thisinhibitory effect.

关键词： hepatitis B virus cyclosporine A replication proteomics

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Enteral supplementation with glycyl-glutamine improves intestinal barrier function after liver transplantation in rats

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Hepatobiliary & Pancreatic Diseases International 2011年第4期10卷 380-385页

作者： Jian-Wen Jiang,Zhi-Gang Ren,Lu-Yan Chen,Li Jiang,Hai-Yang Xie,Lin Zhou and Shu-Sen Zheng key laboratory of Combined Multi-organ transplantation,Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery,First Affiliated Hospital,zhejiang University School of Medicine,Hangzhou 310003,China key laboratory of Combined Multi-organ transplantation Ministry of Public Health Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier ***-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal *** study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive ***:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic *** recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day *** 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same *** 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 *** were harvested for sampling on postoperative day *** following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial ***:All recipients were alive after *** preoperative day 3,all parameters were similar in the two *** postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day ***,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial ***:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.

关键词： liver transplantation glycyl-glutamine bacterial translocation intestinal barrier function

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Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma

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Hepatobiliary & Pancreatic Diseases International 2011年第1期10卷 88-94页

作者： Cheng-Jiang Li,Hua-Li Zhou,Jun Li,Hong-Tian Yao,Rong Su and Wen-Peng Li Department of Endocrinology(Li CJ,Zhou HL and Li WP),Department of Pathology,and key laboratory of Multi-organ transplantation of Ministry of Public Health,First Affiliated Hospital,zhejiang University School of Medicine,Hangzhou 310003,China [a] Department of Endocrinology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China [b] Department of Pathology First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China [c] key laboratory of Multi-organ transplantation of Ministry of Public Health First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma *** content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s *** glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high *** and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

关键词： sulfonylurea receptor 1 multidrug resistance protein 1 ATP-binding cassette transporters insulinoma insulin secretion

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