Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acute cellular rejection (ACR) remains a major concern after liver transplantation. Predicting and monitoring acute rejection by non-invasive methods are very important for guiding the use of immunosuppressive drugs. Many studies have shown that exosomes and their contents are potential biomarkers for various liver diseases. Here, we identify and validate the role of exosomes and galectin-9 in ACR after liver transplantation. Exosomes were isolated from three sets of paired patients, with and without ACR, and the proteins within the exosomes were isolated and identified. Candidate proteins were then validated using a tissue microarray containing resected liver samples from 73 ACR and 63 non-rejection patients. Finally, protein expression and clinical manifestations were included in Kaplan-Meier survival and Cox regression analyses. Circulating exosomes were isolated from ACR and non-rejection patients and characterized using transmission electron microscopy and western blotting for CD63/CD81. Western blotting experiments revealed higher levels of galectin-9 protein in circulating exosomes from ACR recipients. Immunohistochemical analysis of the tissue microarray showed that the expression of galectin-9 in resected liver was significantly higher in the ACR group than in the non-rejection group (P<0.05). Higher levels of galectin-9 expression in resected livers were associated with poorer prognosis (P<0.05). Exosome-derived galectin-9 may be a novel predictor of rejection and prognosis after liver transplantation.

Advances in predicting the prognosis of hepatocellular carcinoma recipients after liver transplantation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide. Liver transplantation (LT) is known as a curative and therapeutic modality. However, the survival rates of recipients after LT are still not good enough because of tumor recurrence. To improve the survival rates of recipients after LT, identifying predictive factors for prognosis after LT and establishing a model assessing prognosis are very important to HCC patients. There has recently been a lot of clinical and basic research on recurrence and prognosis after LT. Progress has been made, especially in selection criteria for LT recipients and risk factors for predicting prognosis after LT. Hangzhou criteria, in line with China's high current incidence rate of primary liver, are first proposed by Chinese scholars of LT, and are accepted world-wide, and make an important contribution to the development of LT.

Mechanism of ablation with nanosecond pulsed electric field / 浙江大学学报·医学版

Nanosecond pulsed electric field ablation has been widely applied in clinical cancer treatment, while its molecular mechanism is still unclear. Researchers have revealed that nanosecond pulsed electric field generates nanopores in plasma membrane, leading to a rapid influx of Ca²⁺; it has specific effect on intracellular organelle membranes, resulting in endoplasmic reticulum injuries and mitochondrial membrane potential changes. In addition, it may also change cellular morphology through damage of cytoskeleton. This article reviews the recent research advances on the molecular mechanism of cell membrane and organelle changes induced by nanosecond pulsed electric field ablation.

Out-of-hospital cardiopulmonary resuscitation needs the ventilation / 浙江大学学报·医学版

Cardiopulmonary resuscitation (CPR) is series of rescue measures for saving cardiac arrest patients. Early initiation and good quality of CPR is crucial for increasing chance of survival from out-of-hospital cardiac arrest. In recent years, the CPR guidelines have changed a lot, especially in basic life support. The guideline now pays more attention on chest compression and less to ventilation. CPR with chest compression only and without mouth-to-mouth ventilation is more popular. In this article, we outline the development and recent researches of CPR. As depriving oxygen from a collapsed patient for 6 min may result in poor outcome, the average time for ambulance transport is longer (about 10 to 16 min) in China, which makes rescuers easy to feel fatigue, chest compression only CPR is not suitable in China. Though non-professional rescuers have difficulty to perform mouth-to-mouth ventilation, they generally show a willingness to do so. To strengthen public standard CPR training including mouth-to-mouth ventilation and chest compression, is most important to promote CPR in China.

Establishment of prediction model for spontaneous rupture of primary liver cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a prediction model for spontaneous rupture of primary liver cancer.</p><p><b>METHODS</b>The clinical data of 77 patients with spontaneous rupture of primary liver cancer and 95 primary liver cancer patients without spontaneous rupture were collected and compared. The risk factors of spontaneous rupture of primary liver cancer were analyzed with multivariate logistic regression.</p><p><b>RESULTS</b>Multivariate logistic regression analysis revealed that moderate or severe ascites, liver cirrhosis, protrusion of tumor from the liver surface, tumor size ≥ 5 cm were independent risk factors of spontaneous rupture of primary liver cancer. The area under the receiver operating characteristic curve of the established model for spontaneous rupture was 0.862 (P<0.05).</p><p><b>CONCLUSION</b>The established model base on the severity of ascites, liver cirrhosis, protrusion of tumor and large tumor size can effectively estimate the risk of spontaneous rupture of primary liver cancer.</p>

Association of microvascular invasion with recurrence and prognosis of patients with small hepatocellular carcinoma undergoing liver transplantation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the risk factors for recurrence in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).</p><p><b>METHODS</b>One hundred and fifteen small HCC patients, who met Milan criteria (single<5 cm or showing up to three nodules, each of them<3 cm without major vascular invasion or distant metastasis) and underwent LT in our hospital from January 2007 to November 2013, were enrolled in the study. The risk factors for recurrence were analyzed by Cox regression and the influence of the Milan criteria and microvascular invasion (MVI) on the disease-free survival (DFS) and recurrence of patients were assessed with survival analysis and ROC method.</p><p><b>RESULTS</b>Ninety-eight out of 115 small HCC patients were included for analysis, the 1-,3-, 5-year overall survival of patients was 91.8%, 80.6%, 79.6% and DFS was 87.8%, 74.5%, 73.5%, respectively. Survival analysis identified that MVI, macro-vascular invasion, exceeding the Milan criteria and pre-transplant down-staging treatment were related to tumor recurrence (P<0.05). Multivariate Cox regression analysis showed that MVI and exceeding the Milan criteria were two independent prognostic indicators for early recurrence of small HCC after LT. The 1-,3-,5-year DFS for 69 patients without MVI and 29 patients with MVI were 92.8%, 85.5%, 85.5% and 75.9%, 55.2%, 48.3%, respectively (P<0.01). The 1-,3-,5-year DFS for 84 patients meeting the Milan criteria and 14 exceeding the Milan criteria were 91.7%, 83.3%, 79.8% and 64.3%, 42.9%, 42.9%, respectively (P<0.01).</p><p><b>CONCLUSION</b>For early HCC patients undergoing LT, the presence of MVI would predict tumor recurrence and can be an indicator for the adjuvant treatment or other salvage treatments.</p>

Risk factors of biliary complications after liver transplantation from donation after cardiac death / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To analyze the risk factors for biliary complications of liver transplantation from donation after cardiac death (DCD).</p><p><b>METHODS</b>Clinical data of 109 patients undergoing liver transplantation from DCD in First Affiliated Hospital of Zhejiang University School of Medicine from October 2010 to October 2013 were studied retrospectively. The risk factors of biliary complications following DCD liver transplantation were analyzed.</p><p><b>RESULTS</b>Twenty-four (22%) patients developed biliary complications after DCD liver transplantation. Univariate analysis showed that biliary complications were associated with warm ischemia time (P<0.001) and length of ICU stay (P=0.013), but not associated with ABO blood types match (P>0.05). Administration of inotropic agents and fatty liver increased the trend of biliary complications. Multivariate analysis demonstrated that warm ischemia time and length of ICU stay were independent risk factors for predicting biliary complications.</p><p><b>CONCLUSION</b>Warm ischemia time and days of ICU stay are independent risk factors for predicting biliary complications after DCD liver transplantation.</p>

Risk factors of persistent thrombocytopenia after adult liver transplantation and prophylactic measures / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the risk factors associated with persistent thrombocytopenia after liver transplantation (LT), and to explore effective measures for prevention.</p><p><b>METHODS</b>One hundred and twenty-eight adult patients, who received liver transplantation in our hospital between January 2009 and June 2012 and met the inclusive criteria, were enrolled in the study. The clinical data were retrospectively analyzed, including pre-LT spleen volume, main portal vein size, coronary vein size, platelet and white blood cell levels, total bilirubin level and model of end stage liver disease score. The risk factors associated with persistent thrombocytopenia after LT were evaluated by logistic regression analysis. The effect of simultaneous splenic artery coarctation for high risk patients was evaluated with χ2 test.</p><p><b>RESULTS</b>Logistic regression analysis showed that per-LT spleen volume larger than 500 ml (P = 0.012, OR=2.789, 95%CI: 1.249-6.227) and portal vein size beyond 15 mm (P = 0.017, OR = 3.124, 95%CI: 1.230-7.933) were independent risk factors for persistent thrombocytopenia after LT. The incidence rate of persistent thrombocytopenia after LT in patients with or without simultaneous splenic artery coarctation were 16.7% (1/6) and 66.7% (32/48), respectively(P < 0.05).</p><p><b>CONCLUSION</b>Spleen volume larger than 500 ml and portal vein size beyond 15 mm are risk factors for persistent thrombocytopenia after LT. Simultaneous splenic artery coarctation may reduce the occurrence of persistent thrombocytopenia after LT.</p>

Application of transient elastography in early prognosis after liver transplantation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the application of transient elastography in early prognosis of patients after liver transplantation.</p><p><b>METHODS</b>Forty-three patients receiving orthotopic liver transplant in our hospital during December 2013 and March 2014 were included in this study. Liver stiffness measurement (LSM) was performed by FibroScan on day 1 (LSM-1) and day 7 (LSM-7) after transplantation. Patients were divided into higher LSM group (LSM>16 kPa) and lower LSM group (LSM<16 kPa). Clinical data and laboratory data were collected and the correlation of LSM with liver and renal function was analyzed.</p><p><b>RESULTS</b>The number of cases in higher LSM-1, lower LSM-7, higher LSM-7 and lower LSM-7 were 29, 11, 31 and 9, respectively. The cold ischemia time was corrected with LSM-7 (r=0.335, P=0.028), but not with LSM-1 (r=0.037, P=0.812); the length of ICU stay was positively correlated with LSM-1 (r=0.488, P=0.001), but not with LSM-7 (r=0.213, P=0.181). LSM was positively correlated with aspartate aminotransferase, bile acid and creatinine levels. The higher LSM-1 group had longer length of ICU and hospital stay than lower LSM-1 group did (9d vs 7d, P=0.013; 34d vs 23d, P=0.023); and the higher LSM-1 group had higher incidence rate of serious complications than lower LSM-1 group did (78.57% vs 27.59%, P=0.002).</p><p><b>CONCLUSION</b>The LSM correlates with the liver function and renal function of liver transplantation recipients, and may have value for assessing early prognosis.</p>

Efficacy of postoperative antiviral combined transcatheter arterial chemoembolization therapy in prevention of hepatitis B-related hepatocellular carcinoma recurrence / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative resection is the leading factor influencing the prognosis of the disease. Therefore, further improvement of long-term survival may depend on the prevention and treatment of the recurrent tumor. The aim of this research was to investigate the role of antiviral therapy and postoperative transcatheter arterial chemoembolization (TACE) in the prevention and treatment of hepatitis B-related HCC recurrence.</p><p><b>METHODS</b>One hundred and twenty patients who underwent curative resection of hepatitis B-related HCC between January 2005 and June 2008 at our hospital were enrolled. Patients were divided into four groups according to the post-operative adjuvant therapy they received, i.e., control, antiviral therapy group, TACE group, and combined group. The disease-free survival (DFS) and the 12-, 24-, 36-month cumulative recurrence rates were studied.</p><p><b>RESULTS</b>There was no significant difference between isolated postoperative antiviral therapy group and control in terms of disease-free survival (P = 0.283), while it was significantly higher in the TACE group compared to control (P = 0.019). In all patients, however, viral prophylactic therapy combined with/without TACE brought a favorable result compared to those only with/without TACE (P < 0.001). Similarly, no matter combined with or without antiviral treatment, postoperative TACE prolonged DFS (P = 0.015). Naturally, a combination of viral prophylactic therapy on the baseline TACE significantly benefited patients' postoperative DFS (P = 0.047) and vice verse (P = 0.002). The 24-month cumulative recurrence rates of combined group were significantly lower than that of isolated control group and antiviral therapy (P < 0.001 and P = 0.011 respectively). However, 36-month recurrence rate was significantly different in the control group compared to the TACE group and combined group (P = 0.040 and 0.002 respectively); same as the antiviral group compared to the combined group (P = 0.034).</p><p><b>CONCLUSIONS</b>Post-operative TACE prevents early recurrence while antiviral therapy prevents late recurrence of HCC. Combination of antiviral therapy and TACE are suggested for prevention in HCC patients with high risk of recurrence.</p>

The Influence of the Severity of Chronic Virus-Related Liver Disease on Propofol Requirements during Propofol-Remifentanil Anesthesia

PURPOSE: The purpose of this study was to investigate the influence of chronic virus-related liver disease severity on propofol requirements. MATERIALS AND METHODS: In this study, 48 male patients with chronic hepatitis B infection were divided into three groups according to Child-Turcotte-Pugh classification of liver function (groups A, B, and C with mild, moderate and severe liver disease, respectively). After intubation, propofol concentration was adjusted by +/-0.3 microg/mL increments to maintain bispectral index in the range of 40-60. Target propofol concentrations at anesthesia initiation, pre-intubation and pre-incision were recorded. RESULTS: The initial concentration used in group C was significantly lower than that used in group A or B (p<0.05), whereas no difference was observed between groups A and B. At pre-intubation, the actual required concentration of propofol increased significantly (3.2 microg/mL) in group A (p<0.05), which lead to significant differences between the groups (p<0.05). At pre-incision, the requirements for propofol decreased significantly in both groups A and B (3.0 microg/mL and 2.7 microg/mL, respectively) compared with those at pre-intubation (p<0.05), and were significantly different for all three groups (p<0.05), with group C demonstrating the lowest requirement (2.2 microg/mL). The required concentrations of propofol at pre-incision were similar to those at induction. CONCLUSION: In this study, propofol requirements administered by target-controlled infusion to maintain similar depths of hypnosis were shown to depend on the severity of chronic virus-related liver dysfunction. In other words, patients with the most severe liver dysfunction required the least amount of propofol.

Chylous pleural effusion caused by mediastinal angiomyolipomas / 中华医学杂志(英文版)

Classical angiomyolipomas are benign tumors composed of various tissues, including fat, abnormal blood vessels and smooth muscle cells. The present study reports a male patient affected by mediastinal angiomyolipomas with massive chylous pleural effusion. The tumors were characterized with histological and immunohistochemical methods.

Expression of the recepteur d'originenantais receptor tyrosine kinase in non-small cell lung cancer and its clinical significance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recepteur d'originenantais (RON) is a receptor tyrosine kinase (RTK) that belongs to the MET proto-oncogene family. The aim of this study was to investigate the expression of RON receptor tyrosine kinase in human non-small cell lung cancer (NSCLC) and its relationship with clinical pathology of NSCLC and prognosis.</p><p><b>METHODS</b>RON protein expression by immunohistochemistry (IHC) in 96 NSCLC specimens was evaluated and compared with the clinical pathology and prognosis, and 20 para-neoplastic tissues were included as controls. RON mRNA and protein expression in 25 fresh tissue samples of lung cancer and 10 normal lung tissues were also analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.</p><p><b>RESULTS</b>The rate of positive RON expression differed significantly between NSCLC tissues (55.2%, 53/96) and para-neoplastic tissues (5%, 1/20) (P < 0.001). RON protein expression was not found to be associated with gender or age. However, RON expression positively correlated with clinical TNM stage (P = 0.004), histological types (P = 0.001), lymph node metastasis (P = 0.012) and differentiation (P = 0.035). RT-PCR and Western blotting analysis also confirmed that the expression of RON mRNA and protein was significantly increased in the NSCLC tissues versus normal tissues. In addition, RON expression was associated with a poor prognosis for patients with NSCLC (P = 0.045).</p><p><b>CONCLUSIONS</b>The expression of RON protein and mRNA is significant in human NSCLC and low in para-neoplastic and normal tissues. Elevated RON expression may contribute to the occurrence, progression and metastasis of NSCLC, inferring that it could be useful as a new prognostic indicator for patients with NSCLC.</p>

Downregulation of endothelin-1 by somatostatin improves liver function of recipients undergoing adult-to-adult living donor liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The aim of this study was to investigate the possible effect of somatostatin on the liver function of recipients undergoing living donor liver transplantation.</p><p><b>METHODS</b>Forty recipients were randomized into group A (n = 20) and group B (n = 20). Recipients in group A received no somatostatin whereas somatostatin was administrated for recipients in group B perioperatively. Liver function, the plasma concentration of endothelin-1 and nitric oxide, the intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2 hours after declamping of the portal vein were compared between the two groups.</p><p><b>RESULTS</b>Compared to group A, alanine transaminase values in group B were significantly reduced at 2 hours after portal vein declamping, at the end of the operation and postoperation day 1 (P < 0.05), whereas aspartate aminotransferase values in group B decreased at 30 minutes after portal vein clamping, at 2 hours after portal vein declamping and at the end of the operation (P < 0.05). Total bilirubin values in group B were reduced significantly at 2 hours after portal vein declamping and at the end of the operation when compared to group A (P < 0.05). Intragraft expression of endothelin-1 was significantly downregulated at 2 hours after declamping of the portal vein accompanied with a reduction of plasma concentration of endothelin-1 in the peripheral blood (P < 0.05).</p><p><b>CONCLUSIONS</b>Somatostatin had a protective effect on liver function during the early phase after declamping of portal vein for recipients undergoing living donor liver transplantation, and the possible mechanism might be partially attributed to the downregulation of endothelin-1.</p>

Coagulase-negative staphylococcus and enterococcus as predominant pathogens in liver transplant recipients with Gram-positive coccal bacteremia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT.</p><p><b>METHODS</b>A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients.</p><p><b>RESULTS</b>In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month. The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates), methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades II - IV (P = 0.013, OR: 16.253, 95%CI: 1.822 - 144.995), pre-LT use of empirical antibiotics (P = 0.018, OR: 1.029, 95%CI: 1.002 - 1.057), post-LT urinary tract infections (P < 0.001, OR: 20.340, 95%CI: 4.135 - 100.048) and abdominal infection (P = 0.004, OR: 2.820, 95%CI: 1.122 - 10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli.</p><p><b>CONCLUSIONS</b>Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.</p>

Clinical significance of heterozygosity loss at Mfn2 gene in hepatocellular carcinoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the loss of heterozygosity (LOH) at mitofusin-2 (Mfn2) gene in hepatocellular carcinoma (HCC) and its clinicopathological significance.</p><p><b>METHODS</b>Four high polymorphic microsatellite markers flanking Mfn2 were selected for LOH analysis in 29 cases of HCC.</p><p><b>RESULT</b>The frequencies of LOH on D1S2667, D1S2740, D1S434 and D1S228 were 21%, 23%, 21% and 22%, respectively. LOH at Mfn2 was closely correlated with tumor size, age, capsule, differentiation and t HBV infection (P<0.05), not with gender, thrombosis, cirrhosis and serum AFP levels (P>0.05).</p><p><b>CONCLUSION</b>LOH at Mfn2 gene in HCC is associated with the clinicopathological features of patients.</p>

Application of Ligasure vessel sealing instrument in laparoscopic hepatectomy for liver cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the indication and effect of the application of Ligasure vessel sealing instrument in laparoscopic hepatectomy for liver cancer.</p><p><b>METHODS</b>Eleven patients with liver cancer undergoing laparoscopic hepatectomy were analyzed for the tumor size and location, operation time, volume of intraoperative bleeding, postoperative hospital stay and short-term clinical outcomes.</p><p><b>RESULTS</b>All the operations were performed successfully in the 11 cases. All the tumors were less than 7 cm in diameter, locating at the segments II, III, V, VI and VII. The mean operation time was 91 min (80-126 min), and the intraoperative blood loss averaged 82 ml (20-200 ml). The average postoperative hospital stay of the patients was 8 days (7-9 days). No complications were observed in these cases.</p><p><b>CONCLUSION</b>Ligasure vessel sealing instrument in laparoscopic hepatectomy is applicable in cases of perimeter liver cancer. This instrument can decrease the operation time, reduce the intraoperative blood loss and postoperative hospital stay with good safety and minimal invasiveness.</p>

Effect of emodin in suppressing acute rejection following liver allograft transplantation in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of action of emodin for suppressing acute allograft rejection in a rat model of liver transplantation.</p><p><b>METHODS</b>Brown Norway (BW) recipient rats of orthotopic liver transplantation (OLT) were divided into three groups, Group A receiving isografting (with BW rats as donor), Group B receiving allografting (with Lewis rats as donor), Group C receiving allografting and emodin treatment (50 mg/kg daily). They were sacrificed on day 7 of post-transplantation, and their hepatic histology, plasma cytokine levels, and T-cell subset expression were detected.</p><p><b>RESULTS</b>Compared with those in Group A, rats: in Group B exhibited severe allograft rejection with a rejection activity index (RAI) of 7.67+/-0.98, extensive hepatocellular apoptosis with an apoptosis index (AI) of 35.83+/-2.32, and elevated plasma levels of interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), CD4(+) and CD4 CD4(+)/CD8(+) ratio. However, recipients in Group C showed a decrease in histological grade of rejection and hepatocellular apoptosis, as well as a decrease in plasma levels of IL-2, TNF-alpha, CD4(+) and CD4(+)/CD8(+) ratio, but elevated levels of IL-10 as compared with the allograft group.</p><p><b>CONCLUSION</b>Post-OLT acute rejection could be attenuated by emodin, its mechanism of action may be associated with protecting hepatocytes from apoptosis, polarizing the Th 1 paradigm to Th2, and inhibiting the proliferation of CD4(+) T cell in plasma.</p>

The study on the relationship between expression of B7-H1 on HBV transgenic mice and immune tolerance to HBV / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether there is an association between the expression of B7-H1 in HBV transgenic mice and the immune tolerance to HBV.</p><p><b>METHODS</b>T cells stimulatory capacity of DC was analyzed using mixed lymphocyte reaction. Expression of MHC-II, CD80, CD86, B7-H1 on DC was detected by Flow Cytometry. IL-2, IFNgamma, IL-10 production of T cells were determined by using ELISA. B7-H1 mRNA and protein expression in liver tissue were detected by RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>The ability of DC cells from HBV transgenic mice to stimulate T cell proliferation was significantly impaired compared with DC cells from control mice (t = 16.674, 19.674, 21.712, P less than 0.01). Expression of MHC-II, CD80 on DC was markedly decreased in transgenic mice (t = 7.910, 6.413, P less than 0.05). Meanwhile, the expression of CD86 and B7-H1 on DC cells in HBV transgenic mice were not significantly different from that in control mice. The levels of IL-2, IFNgamma, IL-10 in supernatant of T cells was significantly lower compared with controls (t = 18.712, 18.712 and 11.683, P less than 0.05). There was no significant difference in B7-H1 expression at mRNA and protein levels in liver tissue compared with controls.</p><p><b>CONCLUSIONS</b>Functional defect of DC, partly due to decreased expression of MHC-II, CD80, but not related to B7-H1 expression, is the cause for immune tolerance to HBV in HBV transgenic mice.</p>

Spectrum and risk factors for invasive candidiasis and non-Candida fungal infections after liver transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients. The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients. The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients.</p><p><b>METHODS</b>A retrospective analysis was made of recorded data on the epidemiology, risk factors, and mortality of invasive fungal infections in 352 liver transplant recipients.</p><p><b>RESULTS</b>Forty-two (11.9%) patients suffered from invasive fungal infection. Candida species infections (53.3%) were the most common, followed by Aspergillus species (40.0%). There were 21 patients with a superficial fungal infection. The median time to onset of first invasive fungal infection was 13 days, first invasive Candida infection 9 days, and first invasive Aspergillus infection 21 days. Fifteen deaths were related to invasive fungal infection, 10 to Aspergillus infection, and 5 to Candida infection. Invasive Candida species infections were associated with encephalopathy (P = 0.009) and postoperative bacterial infection (P = 0.0003) as demonstrated by multivariate analysis. Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy (P = 0.004), renal dysfunction (P = 0.005) and hemodialysis (P = 0.001).</p><p><b>CONCLUSIONS</b>The leading etiologic species of invasive fungal infections are Candida and Aspergillus, which frequently occur in the first posttransplant month. Encephalopathy and postoperative bacterial infection predispose to invasive Candida infection. Posttransplant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection. More studies are needed to determine the effect of prophylactic antifungal therapy in high risk patients.</p>