AIM:To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential.METHODS:Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. Fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin (HE) staining.RESULTS:ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype (with expression of CD29 and CD90 and no expression of CD11b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. Fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC- and BMSC-transplanted mice. There was no significant difference between the two MSC groups.CONCLUSION:ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.

Question: A 58-year-old woman was admitted with multiple episodes of melena. The patient had a history of surgery for colon cancer 7 years ago and underwent radiofrequency ablation for metastatic liver cancer 4 year ago. She was treated in another hospital for massive hematemesis and a transient loss of consciousness and was relieved after blood transfusion and proton pump inhibitor administration 5 days ago. Physical examination showed an anemic appearance. Laboratory tests revealed a low level of hemoglobin (73 g/L). An emergency gastroscopy in our department revealed a bleeding gastric ulcer, blood-like fluid effusion in stomach lumen (Figure A). What is the most likely cause of upper gastrointestinal (GI) bleeding in this patient? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Abdominal enhanced computed tomography (CT) scanning revealed multiple metastatic tumors in the liver (Figure B, black arrows) and the body and tail of pancreas (Figure B, white arrow). Importantly, invasion of stomach wall by the neighboring pancreatic tumors led to the formation of a gastric fistula, through which the contrast media was leaking into stomach lumen. CT angiography and vascular reconstruction further confirmed tumor erosion of the splenic artery and the formation of splenic artery pseudoaneurysm (SAPA) as well as tumor–gastric fistula (Figure C, D). Digital subtraction angiography also demonstrated extravasation of contrast media from SAPA through the fistula (Figure E). The patient was treated by splenic artery embolization. Postoperative angiography revealed complete blockade of the SAPA (Figure F). An enhanced CT examination on the following day showed no sign of active bleeding. The patient recovered uneventfully and was discharged without any symptoms over a 6-month follow-up period. Splenic artery aneurysms are the most common visceral artery aneurysms and are broadly classified as true aneurysms and pseudoaneurysms.1Illuminati G. LaMuraglia G. Nigri G. Surgical repair of an aberrant splenic artery aneurysm: report of a case.Ann Vasc Surg. 2007; 21: 216-218Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Causes of SAPA include pancreatitis (52%), abdominal trauma (29%), iatrogenic and postoperative causes (3%), and peptic ulcer (2%).2Wang J. Wang B. Chen D.F. An unusual cause of recurrent massive upper gastrointestinal bleeding.Gastroenterology. 2012; 143: 542Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Metastatic pancreatic tumor is rare, accounting for only 2% of all pancreatic tumors.3Lee C.W. Wu R.C. Hsu J.T. et al.Isolated pancreatic metastasis from rectal cancer: a case report and review of literature.World J Surg Oncol. 2010; 8: 26Crossref Scopus (15) Google Scholar To the best of our knowledge, SAPA caused by metastatic pancreatic tumor has not yet been reported. In the present case, the complicated patient history and endoscopic findings make the diagnosis difficult. In this scenario, enhanced CT examination and vascular reconstruction are beneficial for the diagnosis of SAPA. Superselective splenic artery embolization represents an effective approach to treat these patients with high surgical risk.

Patients with cirrhosis used to be associated with frequent use of blood components because of their complex disorder of hemostasis and bleeding complications. Recent findings have indicated that patients with cirrhosis have a state of "rebalanced" or even procoagulant hemostasis and have questioned the prophylactic use of plasma. To evaluate the current status of plasma use in patients with cirrhosis, we conducted a retrospective survey in 11 tertiary-care hospitals in China from September 1 to October 31, 2013. All patients admitted with cirrhosis during the study period were included in the study. The survey collected information including patients' diagnostic and demographic data, clinical course including bleeding complications and invasive procedures, laboratory results, and plasma transfusion data. Among 1595 patients with cirrhosis admitted to the 11 hospitals, 236 (14.8%) patients received 1 or more plasma transfusions during the study period. The number of plasma transfusions is defined as the number of transfusion orders. A total of 1037 plasma transfusions were administered to these patients, with a mean of 4.4 transfusions per transfused patient, ranging from 1 to 22 transfusions per transfused patient. Most plasma transfusions (760/1037; 73.3%) were given to patients without bleeding, for treatment of coagulopathy either without planned invasive procedures (70.4%) or before invasive procedures (2.9%). The median dose of plasma transfusion was 3.8 mL/kg. The rate of plasma transfusion of participating hospitals varied from 53% to 31.8%. It is encouraging to see that in one teaching hospital, 85.7% plasma transfusions were given to patients with bleeding indication, showing a promising sign in appropriate transfusion. Prophylaxis or empirical plasma transfusion is still a common problem in managing patients with liver cirrhosis. Wide variations are found in plasma transfusion practice among hospitals. Effective measures to control and reduce empirical correction of abnormal coagulation tests through transfusing plasma should be strengthened urgently. (C) 2017 Published by Elsevier Inc.

Background: Blood transfusions are commonly used to treat variceal bleeding in cirrhotic patients. However, massive transfusions can worsen portal hypertension and increase mortality in these patients. Minimizing blood usage is rarely considered when treating cirrhotic patients with variceal bleeding. Thus, we performed a systematic review to assess the effect of different variceal bleeding management strategies on reducing the blood transfusion volume in cirrhotic patients. Methods: PubMed, Embase (from inception to August 2014), and the Cochrane Library (2014, Issue 8) were searched for eligible randomized controlled trials (RCTs). Data were extracted and assessed for quality by two independent reviewers. The primary outcome of interest was the blood volume requirement. Results: We identified thirty-three RCTs including 3129 patients related to management of acute variceal bleeding. There was a large variation in the treatment interventions used to treat acute variceal bleeding, including endoscopic therapy, shunt therapy, pharmacological therapy and combined therapies. Approximately 58% (19/33) of the studies reported a significant difference among the different interventions in the number of units transfused per patient. Endoscopic plus pharmacological therapies tended to have the smallest required blood volume (1.9 units) compared with other interventions. Conclusions: There are many varied interventions for treating acute variceal bleeding in cirrhotic patients. For patient blood management in variceal bleeding, the combinatorial approach of endoscopic and pharmacological therapies can promptly control acute variceal bleeding prior to transfusion and reduce the subsequent blood transfusion requirements in cirrhotic patients. Appropriately designed RCTs that assess the effect of specific interventions on reducing blood transfusion requirements are urgently needed.

Background: The dysbiosis of intestinal microbiota plays an important role in the development of gut-derived infections, making it a potential therapeutic target against multiple organ dysfunction syndrome (MODS) after sepsis. However, the effectiveness of fecal microbiota transplantation (FMT) in treating this disease has been rarely investigated.Methods: Two male patients, a 65-year-old and an 84-year-old, were initially diagnosed with cerebellar hemorrhage and cerebral infarction, respectively, after admission. During the course of hospitalization, both patients developed MODS, septic shock, and severe watery diarrhea. Demographic and clinical data were collected. Intestinal dysbiosis was confirmed by 16S rDNA-based molecular analysis of microbiota composition in fecal samples from the two patients. The two patients each received a single nasogastric infusion of sterile-filtered, pathogen-free feces from a healthy donor. Fecal samples were collected every two days post infusion to monitor changes in microbiota composition in response to treatment.Results: Following FMT, MODS and severe diarrhea were alleviated in both patients. Their stool output and body temperature markedly declined and normalized. Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in both patients. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria that was associated with a decrease in the patients' fecal output and in the levels of plasma inflammation markers.Conclusions: The outcome of treating two patients with FMT indicates that restoration of the intestinal microbiota barrier can alleviate the infection and modulate the immune response. These findings warrant further investigation of FMT as a putative new therapy for treating microbiota-related diseases such as MODS.

We aim to assess the role and degree of contrast washout in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). Fifty-six histopathology-confirmed ICC nodules and 184 HCC nodules were included in this study. The nodules' washout degree on CEUS at 1, 2 and 3 min was semi-quantitatively and qualitatively assessed using gray-scale video signal intensity. Semi-quantitative assessment showed that the washout degree of ICCs at 1, 2 and 3 min were significantly lower than those of HCCs (p < 0.001) and similar results were found in the same size range subgroups. There were no significant differences in the washout degree of ICCs between patients with chronic hepatitis and those without. The areas under receiver operating characteristic curves, using the nodules' washout degree at 1, 2 and 3 min to differentiate ICC from HCC, were 0.957, 0.979 and 0.982, respectively. The qualitative assessment showed the washout of ICCs was more rapid and obvious than that of HCCs. At 3 min, moderate and marked washout were observed in all ICCs, but in only 12.5% HCCs (p < 0.001). In conclusion, ICCs displayed much higher degree of contrast washout than HCCs on CEUS, which allowed for differentiation from HCCs.

Objectives Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. Some reports have shown that NAFLD may cause multisystem damage, but its influence on male reproductive function has rarely been studied. Aim To evaluate the influence of NAFLD on sperm quality and reproductive hormones in Chinese men. Materials and methods A total of 102 NAFLD men and 94 healthy men without fatty liver (control) were enrolled in this study. All participants underwent a physical examination, and were subjected to lifestyle questionnaires and abdominal ultrasound examination. The semen quality (volume, concentration, motility, and morphology) and serum hormonal levels (testosterone, estradiol, follicle-stimulating hormone, inhibin B, sex hormone-binding globulin, and luteinizing hormone) were examined and compared between the two groups. Results The levels of serum testosterone and sex hormone-binding globulin were significantly lower in the NAFLD patients compared with the control group. Sperm concentration (P=0.04), sperm count (P=0.01), and total motility (P=0.03) in the NAFLD patients were significantly decreased compared with the control group. However, no significant differences were observed in semen volume and morphology. Multivariate analysis showed that sperm concentration, sperm count, and motility were significantly associated with NAFLD and abstinence (P<0.05 or P<0.001). Conclusion These results suggest that NAFLD could significantly affect sperm quality and reproductive hormones.

Background and aims: Serum inflammatory biomarkers are closely associated with the risk of cardiovascular disease. However, the major source of these biomarkers is not yet determined. Therefore, we aimed to assess whether simple steatosis or visceral adiposity was a more relevant predictor for serum inflammatory biomarkers.Methods: A double approach was used: i) clinical: 50 patients with biopsy-proven simple steatosis, 50 non-simple steatosis overweight patients, and 50 controls were explored for their serum biomarkers (high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 activity, tumor necrosis factor alpha, and fibrinogen levels) and for visceral adiposity (measured by computed tomography); ii) experimental: using a rat simple steatosis model the effect of omentectomy on inflammatory biomarkers was investigated.Results: Serum inflammatory biomarkers were significantly higher in the simple steatosis group than in the overweight group. Using multivariate analysis, simple steatosis, visceral adiposity index and visceral adiposity were independently associated with inflammatory biomarkers. In particular, serum inflammatory biomarkers increased with the severity of liver histology (p < 0.05), but no with visceral adipose tissue increase. In rats with simple steatosis, the omentectomy treatment was not associated with a decrease of serum inflammatory biomarkers in rats with simple steatosis.Conclusions: Clinical and experimental data both indicate that simple steatosis may be more associated with inflammatory biomarkers than omental adipose tissue. (C) 2013 Elsevier Masson SAS. All rights reserved.

ObjectivesHematocrit levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) and related to hypoxia and hyperlipidemia.AimThis study was conducted to investigate the association between elevated hematocrit and liver histology in patients with NAFLD.Patients and methodsWe examined 215 consecutive adults with biopsy-proven NAFLD (108 with steatosis alone, 107 with nonalcoholic steatohepatitis) and 110 controls. The stage of fibrosis was measured using a four-point scale. All underwent anthropometric and metabolic profiling. Hematocrit and related hematologic variables such as blood viscosity and red blood cell count were also measured.ResultsNAFLD morbidity was found to be positively correlated with hematocrit levels. After adjusting for age, smoking, diabetes, BMI, homeostasis model assessment of insulin resistance, triglycerides, and obstructive sleep apnea, patients with hematocrit levels in the highest quartile were seen to have had an odds ratio of 3.05 (95% confidence interval 2.12-4.36, P=0.015) for NAFLD in males. Hematocrit levels increased significantly (P<0.001) in steatosis (42.44.6%) compared with control groups (38.2 +/- 4.2%), and in nonalcoholic steatohepatitis (45.1 +/- 5.2%) compared with steatosis patients. On multivariate analysis, hematocrit levels were found to be strongly and independently associated with fibrosis (=0.205, P=0.030). Moreover, hematocrit levels increased with the severity of hepatic fibrosis (P<0.05).ConclusionOur results indicate that hematocrit levels are significantly increased and independently associated with fibrosis in NAFLD patients. Therefore, hematocrit levels may have potential interest as a clinical marker of NAFLD severity.

Objective To investigate the risk factors of cardiovascular disease in patients with nonalcoholic fatty liver disease (NAFLD). Methods Forty-eight patients with NAFLD and forty-three healthy persons were in-cluded in this study. The NAFLD was diagnosed by computed tomography. Ultrasound was taken for intimal medi-al thickness (IMT)and carotid atherosclerotic plaque examination. The clinical and biochemical features,endothelial function and coronary atherosclerotic plaque examination were also analyzed. Results The levels of sICM-1,ET-1 and baPWV in NAFLD group(185.1±36.2)ng/ml,(104.8±19.3)pg/ml and(15.5±2.3)cm/s were higher than those (85.4±17.3)ng/ml,(67.5±12.1)pg/ml and (13.6±2.4)cm/s,(P<0.05),while the FMD level (8.1±2.4)%was lower than that (13.2±3.5%),(P<0.05)in the healthy persons;In addition,the IMT (1.31±0.35)mmand the prevalence of patches in carotid(31.3%)and in coronary artery(35.4%)in patients with NAFLD increased than in healthy per-sons (0.76±0.18)mm,9.3% and 11.6%,(P<0.05). Conclusion NAFLD is closely associated with cardiovascular disease. The patients with NAFLD might have vascular endothelial dysfunction,and they might be checked-up for early evaluation of vascular atherosclerosis.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with reduced levels of testosterone, which may affect fertility. Herein, we investigated whether NAFLD impairs the reproductive function of male rats. Male Sprague-Dawley rats were fed a high fat diet (HFD) until they developed NAFLD. N-3 polyunsaturated fatty acid (PUFA) was then given for 4 weeks to prevent hepatic steatosis. Testes weight and serum and testicular testosterone were significantly lower in rats with NAFLD compared with healthy controls. Testicular pathological changes in NAFLD rats included markedly reduced sperm number and motility, and the number of apoptotic spermatogenic cells was higher, which was consistent with a reduction in the number of tetraploid cells. Breeding experiments indicated that paternal NAFLD affected neither the sperm morphology nor the development of fetuses and offspring, but did prolong the days required for insemination. However, administration of N-3 PUFA alleviated the impairment of reproductive function. These results suggest that NAFLD impairs reproductive function in male rats by decreasing testicular testosterone synthesis, and N-3 PUFA treatment may have a beneficial therapeutic effect.

Non-alcoholic fatty liver disease (NAFLD) related to insulin resistance (IR) is a growing global health concern. Recent studies have indicated that metformin could improve IR and may be beneficial in the treatment of NAFLD. This study aimed to assess the beneficial or harmful effects of metformin in NAFLD. We searched Medline and four other databases during April 2012. Selection criteria were randomized clinical trials comparing metformin with placebo or other interventions for treating NAFLD patients. The primary outcome was histological response. The secondary outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model assessment of IR (HOMA-IR), body mass index (BMI) and adverse events. Dichotomous data were reported as odds ratio (OR), while continuous data were calculated as the mean difference (MD), both with 95% confidence intervals (CI). Random and fixed effects meta-analyses were performed. Nine studies were included, involving 417 participants, and conducted for a time period ranging from 4 to 12 months. In the treated participants, improvements were observed in ALT (MD, -8.12 U/l; P=0.03), AST (MD, -4.52 U/l; P=0.04), HOMA-IR (MD, -0.61; P=0.005) and BMI (MD, -0.82 kg/m(2); P=0.04), but not in histological response: steatosis (P=0.66), inflammation (P=0.91), hepatocellular ballooning (P=0.25) and fibrosis (P=0.90). Sub-analysis of non-alcoholic fatty steatohepatitis showed that metformin failed to improve any pooled outcome. Adverse events were poorly reported. Current information indicates that metformin improves liver function, HOMA-IR and BMI to some extent, but not histological response in NAFLD patients. This finding could serve as a stimulus for future studies investigating issues such as dose-responsiveness, safety and patient tolerance to metformin therapy.

Question: A 50-year-old man presented with acute onset of massive hematemesis and a transient loss of consciousness. He denied acid reflux, or abdominal pain or distension. His past history revealed bleeding duodenal ulcer diagnosed by endoscopy 1 year ago. Although treated with esomeprazole continuously, he suffered from recurrent hematemesis 4 times during the last year. Physical examination showed unstable vital signs with hypotension (92/70 mmHg) and tachycardia (heart rate, 106 bpm). The patient was treated conservatively with fluid infusion and esomeprazole. After 2 episodes of melena, there were no signs of massive rebleeding. Gastroscopy was performed and blood-like fluid effusion in the duodenal bulb was detected (Figure A). After washing with normal saline, a deep ulcer-like lesion with a diameter about 0.2 cm was revealed on noninflamed duodenal mucosa (Figure B). Both cross-sectional (Figure C) and coronal (Figure D) imaging of contrast-enhanced computed tomography (CT) showed a large hematoma between the duodenal bulb and pancreas in the artery phase. What is the most likely cause of upper GI bleeding in this patient? Look on page 872 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. CT angiography revealed that splenic artery coursed a pseudoaneurysm (Figure E, F). The splenic artery pseudoaneurysm (SAPA) was further disclosed by volume rendering reformatted coronal (Figure G) and left oblique sagittal images (Figure H). The patient underwent splenectomy and gastrojejunal Roux-en-Y anastomosis. Surgical findings showed a SAPA–duodenal bulb fistula that was temporarily embolized by thrombus. Postoperatively, the patient recovered uneventfully and was discharged on day 18 after admission. Gastrointestinal bleeding from SAPA is unusual but potentially lethal.1Pasha S.F. Gloviczki P. Stanson A.W. et al.Splanchnic artery aneurysms.Mayo Clin Proc. 2007; 82: 472-479Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar To date, only about 160 cases of SAPA have been reported.2Tessier D.J. Stone W.M. Fowl R.J. et al.Clinical features and management of splenic artery pseudoaneurysm: case series and cumulative review of literature.J Vasc Surg. 2003; 38: 969-974Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar Causes of SAPA include pancreatitis (52%), trauma (29%), iatrogenic and postoperative causes (3%), and rarely peptic ulcer (gastric ulcer; 2%).2Tessier D.J. Stone W.M. Fowl R.J. et al.Clinical features and management of splenic artery pseudoaneurysm: case series and cumulative review of literature.J Vasc Surg. 2003; 38: 969-974Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar To the best of our knowledge, duodenal ulcer erosion of a SAPA has yet to be reported. SAPA rupture is life threatening. A common site of hemorrhage is the pancreatic duct, with some into peritoneal cavity, stomach, or even into colon.2Tessier D.J. Stone W.M. Fowl R.J. et al.Clinical features and management of splenic artery pseudoaneurysm: case series and cumulative review of literature.J Vasc Surg. 2003; 38: 969-974Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar, 3Sweetser S.R. Wong Kee Song L.M. An unusual cause of hematochezia.Gastroenterology. 2009; 137: 1895Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar However, SAPA fistulizing to duodenal bulb is extremely rare, which makes accurate diagnosis difficult. In the present case, the unusual patient history and endoscopic findings preclude pharmaceutical and endoscopic approach for diagnosis and hemostasis. In this situation, imaging techniques, especially CT angiography and 3-dimensional rendering, are beneficial for survey of the bleeding vessels. Surgical intervention or endovascular therapy is recommended to repair the bleeding pseudoaneurysm. Jun Wang and Bin Wang contributed equally to this work.

目的:肝细胞生成素(HPO)特异性刺激肝细胞增生的信号转导存在特异性核受体信号转导途径.方法:利用125I标记的HPO,通过受体结合和特异性竞争抑制实验及Scatchard分析原代培养大鼠肝细胞和肝癌细胞核抽提物中核受体.结果:原代培养大鼠肝细胞和肝癌细胞核抽提物中存在核受体,核受体数量分别为1.7×109/g、和5.0×109/g,平衡解离常数(Kd)分别为35 pmol及1 2 pmol,且存在数量上和亲和力的差异,此结合不能被EGF、生长激素和甲状腺激素所竞争抑制.HepG2细胞放射自显影显示HPO核受体的存在.结论:HPO促肝细胞增生作用可以通过肝细胞核受体介导.

OBJECTIVE:  To investigate how hepatopoietin (HPO) and partial hepatectomy induce the expression of immediate early genes. METHODS:  mRNA expression related to liver regenera­tion was investigated within 1 h after a two-thirds partial hepatectomy by representational difference analysis and with the addition of HPO in a primary cultured hepatocyte system by reverse transcription polymerase chain reaction. RESULTS:  In the expressed sequence tag library, most of the genes identified were immediate early genes, and one Tec gene that might be associated with liver regeneration was found. Moreover, the Tec gene was rapidly induced after partial hepatectomy, with peak expression (7−10-fold) within 1−2 h after the operation as identified by northern blotting. Hepato­poietin was able to rapidly induce the expression of immediate early genes (e.g. c- fos , LRF -1, Tec ) in primary cultured rat hepatocytes. The c- fos and LRF -1 mRNA were also known to be induced during the early hours of liver regeneration, and increased after treatment of isolated hepatocytes with HPO. Addition of HPO resulted in rapid and transient induction of Tec mRNA with a peak at 0.5−2 h (3−5-fold), which might be one of the molecular mechanisms of the effect of HPO on the stimulation of hepatocyte proliferation. CONCLUSION:  Hepatopoietin and partial hepa­tectomy can rapidly induce the expression of the immediate early genes. Our results suggest that the Tec gene is an immediate early gene related to liver regeneration.

OBJECTIVE: To investigate how hepatopoietin (HPO) and partial hepatectomy induce the expression of immediate early genes.METHODS: mRNA expression related to liver regenera­tion was investigated within 1 h after a two‐thirds partial hepatectomy by representational difference analysis and with the addition of HPO in a primary cultured hepatocyte system by reverse transcription polymerase chain reaction.RESULTS: In the expressed sequence tag library, most of the genes identified were immediate early genes, and one Tec gene that might be associated with liver regeneration was found. Moreover, the Tec gene was rapidly induced after partial hepatectomy, with peak expression (7−10‐fold) within 1−2 h after the operation as identified by northern blotting. Hepato­poietin was able to rapidly induce the expression of immediate early genes (e.g. c‐fos, LRF‐1, Tec) in primary cultured rat hepatocytes. The c‐fos and LRF‐1 mRNA were also known to be induced during the early hours of liver regeneration, and increased after treatment of isolated hepatocytes with HPO. Addition of HPO resulted in rapid and transient induction of Tec mRNA with a peak at 0.5−2 h (3−5‐fold), which might be one of the molecular mechanisms of the effect of HPO on the stimulation of hepatocyte proliferation.CONCLUSION: Hepatopoietin and partial hepa­tectomy can rapidly induce the expression of the immediate early genes. Our results suggest that the Tec gene is an immediate early gene related to liver regeneration.

目的 肝部分切除术后肝细胞生成素 （HPO）迅速增加 ,该文观察人重组肝细胞生成素（rhHPO）和肝部分切除 （PH）迅速诱导瞬时早期反应基因表达情况。方法 将Wister大鼠分为PH组和对照组 ,每组 3只。利用表达性差异显示分析技术和序列分析 ,检测 2 /3PH后 1h及原代培养大鼠肝细胞体系的选择性基因表达。结果 EST库中的大部分为瞬时早期反应基因 ,发现一种新的可能与肝再生调控相关的Tec基因 ,Northern杂交证实 2 /3PH可迅速诱导Tec基因的表达 ,其表达高峰为术后 1～ 2h。HPO在原代培养大鼠肝细胞体系中可迅速诱导瞬时早期反应基因 （c fos、LRF 1和Tec等 ）表达。结论 HPO和PH可迅速诱导瞬时早期反应基因表达 ,首次报道Tec基因是一种与肝再生调控密切相关的早期反应基因。

OBJECTIVE To investigate the effect of recombinant human hepatopoietin (rhHPO) and partial hepatectomy on rapidly induced expression of immediate early gene. METHODS We investigated the different gene expression within 1 hour after 2/3 partial hepatectomy by representational difference analysis and in primary cultured hepatocytes system. RESULTS In the expressed sequence tag (EST) library, we identified that most of these genes were immediate early gene, and found one new gene PC3 that might be associated to liver regeneration in the EST library. Moreover, PC3 gene was rapidly induced after 2/3 partial hepatectomy and the expressing peak was within 1~2 hours after operation. HPO can rapidly induce the expression of these genes (c-fos, LRF-1, and PC3, etc.) in primarily cultured rat hepatocyte, which might be one of HPO molecular mechanism on stimulating hepatocyte proliferation. CONCLUSIONS rhHPO and partial hepatectomy can rapidly induce the expression of immediate early gene. PC3 gene is immediate early gene related to liver regeneration.