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Reducing reactive oxygen species (ROS) production has proven an effective way for alleviating oxidative stress during ischemia-reperfusion injury (IRI). Moreover, inhibition of Rac1 could reduce ROS production and prevent oxidative stress injury. Previous studies have suggested a positive interactivation feedback loop between Rac1 and hypoxia-inducible factor (HIF)-1α, the latter being up-regulated early during ischemia. The positive inter-activation between Rac1 and HIF-1α would aggravate ROS production, thereby promoting IRI. This study was designed to verify the effects of Rac1 inhibition on hepatic IRI both at animal and cellular levels and to explore the interaction between Rac1 and HIF-1α during hepatic IRI.C57B/6 mice and AML-12 cells were used for the construction of hepatic IRI animal and cell models. Rac1 inhibition was achieved by NSC23766 (a specific Rac1 inhibitor). Lentiviral vectors were used for Rac1 knockdown. At designated time points, serum and liver tissues were collected from the mice and treated cells were collected for further analysis.NSC23766 treatment significantly alleviated the hepatic IRI in mice, manifesting as lower vacuolation score and less apoptosis cells, lower ROS and serum/liver alanine aminotransferase/aspartate aminotransferase levels, and fewer activated inflammatory cells. IRI of AML-12 was also alleviated by 50 µM NSC23766 or Rac1-knockdown, manifesting as reduced cell apoptosis, less extensive interruption of mitochondrial membrane potential, down-regulation of apoptosis, and effects on DNA damage-related proteins. Interestingly, Rac1 knockdown also down-regulated the expression level of HIF-1α.Our study supports a protective effect of Rac1 inhibition on hepatic IRI. Aside from the classic topics of reducing ROS production and oxidative stress, our study showed an interaction between Rac1 and HIF-1α signaling during hepatic IRI.

The Ig superfamily member V-domain Ig-containing suppressor of T-cell activation (VISTA) is a negative regulator with broad-spectrum activities and has reported that blockade of VISTA or combination with other negative checkpoint receptors sufficiently break tumor tolerance. However, it remains unclear whether VISTA could induce allogeneic T-cell hyporesponsiveness and inhibit allograft rejection. Here we found VISTA treatment significantly inhibited lymphocyte proliferation and activation in allogeneic MLR assay through impairing SYK-VAV pathway. Interestingly, though neither VISTA protein nor VISTA-Fc fusion protein administration exerted satisfactory immunosuppressive effect on allograft survival due to their short half-life in circulation, this problem was solved by conjugating VISTA protein on liposome by biotin-streptavidin system, which markedly prolonged its circulating half-life to 60 h. With islet transplant model, administration of VISTA-conjugated liposome could markedly prolong allograft survival by inhibition of SYK-VAV pathway, thus maintained the normal blood glucose level of recipients during treatment period. The results indicate VISTA is a promising therapeutic target to treat allograft rejection of islet transplantation.

4095 Background: HCC is a leading cause of cancer-related morbidity and mortality worldwide, of which glypican 3 is a highly specific marker. GPC3-directed CAR-T had shown promising safety but limited efficacy in the treatment of HCC. We developed an armored GPC3-directed CAR-T G3-CAR-ori2 by inserting of a novel and proprietary Ori2 element following the 4-1BB and CD3ζ domains in a second-generation CAR-T. Pre-clinical studies showed a significantly higher memory stem cell ratio and dramatically improved proliferation and persistence, compared with traditional CAR-T, thus offering prolonged efficacy in vitro and in vivo and potentiality leading to improved activity in the clinical setting (ChiCTR1900028121). Methods: This is an open-label, dose-escalation study of G3-CAR-ori2 cell HCC patients in two centers. Eligible patients were aged 18-70 years with histologically confirmed GPC3+ HCC, Child-Pugh score A or B, ECOG≤1, relapsed or refractory to standard therapies. Patients were pre-conditioned with fludarabine (25̃30 mg/m2) and cyclophosphamide (200̃300 mg/m2) daily for 3 days. G3-CAR-Ori2 was administered as a single infusion via intrahepatic or intravenous route with a total dose of 0.9 to 3x10e8 CAR-T. The objective was to assess the safety, preliminary efficacy, persistence and cytokine profiling of G3-CAR-ori2. Adverse events were graded using the Common Terminology Criteria for Adverse Events (version 5.0). Tumor responses were evaluated per RECIST (version 1.1). CAR-T cell expansion and persistence were measured by qPCR and flow cytometry. Results: As of Jan 21, 2021, 10 patients had received single infusion, in which 6 received G3-CAR-ori2 via intravenous route and 4 via intrahepatic route. 7 patients received the highest dose level of 3x10e8. 9 patients reached at least 1 month of follow-up and tolerated the treatment well with no dose-limiting toxicity. All patients experienced transient grade 4 decrease in lymphocyte count resulted from the lymphodepletion regimen. Cytokine release syndrome (CRS) was observed in 8 patients, in which 6 at grade 1 or 2 and 2 at grade 4 notably infused with 3 x10e8 both via intravenous route and reversed within 7 days by administering high-dose steroids and tocilizumab. Other grade 4 hematologic toxicities include thrombocytopenia (2/9) and neutropenia (1/9). No neurotoxicity was observed. Two subjects were not evaluable due to early withdrawal from the trial. Among the 7 evaluable subjects, the best responses achieved are 3 PR, 2 SD, 2 PD. The duration of remission of one patient with PR is more than 4 months, follow up is ongoing. CAR-T gene detected by q-PCR provide preliminary indication that G3-CAR-ori2 is able to expand and persist well in the clinical setting. Conclusions: These initial data provide evidence that G3-CAR-ori2 is safe and holds promising antitumor potential, and supports its continuing development in the treatment of r/r GPC3+HCC. Clinical trial information: ChiCTR1900028121.

// Yangyang Zhan 1, * , NanXin Zheng 2, * , Fei Teng 2, * , Leilei Bao 1, 3 , Fang Liu 2 , Mingjian Zhang 1 , Meng Guo 1, 2 , Wenyuan Guo 2 , Guoshan Ding 2 and Quanxing Wang 1 1 Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China 2 Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China 3 Department of Pharmacy, No. 411 Hospital of PLA, Shanghai 200080, China * These authors have contributed equally to this work Correspondence to: Quanxing Wang, email: wangqx@immunol.org Guoshan Ding, email: dingguoshanmail@163.com Keywords: miRNA, hepatocellular carcinoma, miR-199a/b-5p, metastasis, ROCK1 Received: January 20, 2017 Accepted: April 26, 2017 Published: May 22, 2017 ABSTRACT In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients. miR-199a/b-5p overexpression in HCC cell lines inhibited cell proliferation, migration and invasion, both in vitro and in vivo . In addition, miR199-a/b-5p post-transcriptionally suppressed Rho-associated coiled-coil kinase 1 (ROCK1). This in turn led to inhibition of ROCK1/MLC and PI3K/Akt signaling, which is necessary for HCC proliferation and metastasis. These results indicate that miR-199a/b acts as tumor suppressors in HCC and represent promising therapeutic targets.

Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients.

// Fei Teng 1, * , Meng Guo 1, * , Fang Liu 1, * , Ce Wang 2 , Jiayong Dong 1 , Lei Zhang 1 , You Zou 1 , Rui Chen 1 , Keyan Sun 1 , Hong Fu 1 , Zhiren Fu 1 , Wenyuan Guo 1 , Guoshan Ding 1 1 Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China 2 Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China * These authors have contributed equally to this work Correspondence to: Guoshan Ding, email: dingguoshanmail@163.com Wenyuan Guo, email: gwyuan7502@aliyun.com Keywords: HCC, liver cancer, SLC12A1, cancer outlier profile analysis, Bumetanide Received: October 02, 2015 Accepted: July 06, 2016 Published: July 18, 2016 ABSTRACT A central aim in cancer research is to identify genes with altered expression patterns in tumor specimens and their potential role in tumorigenesis. Most types of tumors, including hepatocellular carcinoma (HCC), are heterogeneous in terms of genotype and phenotype. Thus, traditional analytical methods like the t-test fail to identify all oncogenes from expression profiles. In this study, we performed a meta-Cancer Outlier Profile Analysis (meta-COPA) across six microarray datasets for HCC from the GEO database. We found that gene SLC12A1 was overexpressed in the Hep3B cell line, compared with five other HCC cell lines and L02 cells. We also found that the upregulation of SLC12A1 was mediated by histone methylation within its promoter region, and that SLC12A1 is a positive regulator of the WNK1/ERK5 pathway. Consistent with in vitro results, treatment with the SLC12A1 antagonist Bumetanide delayed tumor formation and reduced Hep3B cell tumor size in mouse xenografts. In summary, our research reveals a novel subset of HCCs that are sensitive to SLC12A1 antagonist treatment, thereby offering a new strategy for precision HCC treatment.

Objective: Wuzhi (WZ) capsule contains an ethanol extract of Schisandra sphenanthera. The efficacy of WZ in treating non-alcoholic fatty liver disease (NAFLD) has not yet been elucidated. The present study assessed the effects of WZ on NAFLD. Material and methods: A C57BL/6 male mouse model of NAFLD was established by feeding the animals a methionine-choline-deficient (MCD) diet. Mice fed the basal diet were used as controls. Both groups were randomly administered WZ or vehicle by gavage for 5 weeks. Body weight change, liver/body weight ratio, metabolic parameters, and histological changes were assessed. Serum levels of IL-1β, IL-6, IL-10, and TNF-α were analysed by ELISA; mRNA expression of these genes in the liver was studied by real-time PCR. Western blotting was used to analyse the protein levels of PPAR-α, PPAR-γ, MCAD, LCAD, and p65 in the liver. Results: After 5 weeks of the MCD diet, the liver/body weight ratio of WZ mice was higher than that of control mice. Liver histology revealed significantly less steatosis, inflammation, and necrosis, which was confirmed by decreased intrahepatic triglycerides and serum ALT in WZ-treated mice. WZ also reduced the liver mRNA expression of IL-1β, IL-6, and TNF-α and the serum levels of IL-1β and IL-6. Sensitivity to steatohepatitis due to WZ administration correlated significantly with alterations in the expression of PPAR-α/γ, as well as the NF-κB signalling pathway. Conclusions: WZ plays a protective role against MCD-induced steatohepatitis. The underlying mechanism likely involves the upregulation of PPAR-α/γ and downregulation of the NF-κB signalling pathway. Based on its beneficial effects on the liver, WZ is a promising therapeutic for NAFLD patients.

SummaryIn hepatocellular carcinoma (HCC), biomarkers for prediction of prognosis and response to immunotherapy such as interferon-α (IFN-α) would be very useful in the clinic. We found that expression of retinoic acid-inducible gene-I (RIG-I), an IFN-stimulated gene, was significantly downregulated in human HCC tissues. Patients with low RIG-I expression had shorter survival and poorer response to IFN-α therapy, suggesting that RIG-I is a useful prognosis and IFN-α response predictor for HCC patients. Mechanistically, RIG-I enhances IFN-α response by amplifying IFN-α effector signaling via strengthening STAT1 activation. Furthermore, we found that RIG-I deficiency promotes HCC carcinogenesis and that hepatic RIG-I expression is lower in men than in women. RIG-I may therefore be a tumor suppressor in HCC and contribute to HCC gender disparity.

Dong J-Y, Yin H, Li R-D, Ding G-S, Fu Z-R, Wu Y-M, Wang Z-X. The relationship between adenosine triphosphate within CD4+ T lymphocytes and acute rejection after liver transplantation. Clin Transplant 2011: 25: E292–E296. © 2011 John Wiley & Sons A/S. Abstract: Background: There have been increasing interests in the relationship between CD4+ T lymphocytes and acute rejection (AR) in transplantation. In this study, we explore the role of CD4+ T lymphocytes after liver transplantation. Methods: From February to October 2009, 87 patients underwent liver transplantation. They were divided into the AR group and non-acute rejection (NAR) group, with 56 healthy individuals in the control group. Blood specimens were collected preoperatively and at one, two, and four wk postoperatively for all groups and also on the day when AR occurred and one wk after intravenous glucocorticoid therapy for the AR group. Adenosine triphosphate (ATP) levels were measured using the ImmuKnow™ test kits for immune cell functions. Results: After transplantation, the ATP levels within CD4+ T lymphocytes were significantly elevated in the two groups when compared with the preoperative levels. It peaked in the AR group and was significantly higher than that of the NAR group (p

Wang Z-X, Song S-H, Teng F, Wang G-H, Guo W-Y, Shi X-M, Ma J, Wu Y-M, Ding G-S, Fu Z-R. A single-center retrospective analysis of liver transplantation on 255 patients with hepatocellular carcinoma. Clin Transplant 2010: 24: 752–757. © 2009 John Wiley & Sons A/S. Abstract: Background: Liver transplantation (LT) was advocated as a salvage treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). This study was designed to assess the eligibility of LT criteria for patients with HCC and to analyze the factors influencing the recurrence of HCC following LT, aiming to further improve the efficacy of LT for patients with HCC. Methods: Clinical data of 255 patients with HCC who underwent LT between December 2001 and December 2007 at Shanghai Changzheng Hospital, China were retrospectively analyzed. Results: Among these cases, 75 patients were within the Milan criteria and 180 were beyond it; 110 patients were within the University of California, San Francisco (UCSF) criteria, while 145 were beyond it. The difference in overall survival rates was not only significant between the patients within and beyond the Milan criteria but also between patients within and beyond the UCSF criteria. Tumor-node-metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre-operative alpha-fetoprotein (AFP) level were independent risk factors affecting the overall survival and post-operative recurrence-free survival rates of patients with HCC. Pathological staging and pre-operative local treatment of HCC had no obvious correlation with the post-operative recurrence-free survival rate. Conclusion: LT is an effective treatment modality for HCC. The UCSF criteria did not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the pre-operative AFP level are closely related to the recurrence of HCC following LT.

Ischemia/reperfusion (I/R) injury can be characterized as an inflammatory response including recruitment of inflammatory cells to a post-ischemic organ or tissue and a cascade of mediators. Sinomenine (SIN), a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum, has been used to treat various inflammatory diseases including rheumatism and arthritis. However, whether SIN can attenuate I/R injury has not previously been examined. Using a syngeneic orthotopic liver transplantation model in rats, we investigated the effect of SIN on hepatic I/R injury, in particular its effect on heme oxygenase-1 (HO-1) induction and its hepatocellular protective effect. To our knowledge, our results were the first to show that: (a) SIN pretreatment was able to induce HO-1 expression in donor livers in a dose dependent manner; (b) SIN pretreatment protected the liver graft from cold I/R injury; and (c) the protective effect of SIN was, at least in part, mediated by HO-1, as proved by the fact that inhibiting HO-1 activity with zinc protoporphyrin (ZnPP) reduced the protection. Thus, SIN deserves further exploration as a novel agent to attenuate I/R injury.

The aim of this study was to validate a criteria-specific long-term survival prediction model (MHCAT) in a large cohort of hepatocellular carcinoma (HCC) patients after liver transplantation (LT) in China. Independent risk factors in MHCAT were retrospectively analysed for HCC patients recorded in the China Liver Transplant Registry. Survival predictions for each patient were calculated using MHCAT scores and the Metroticket formula separately and the prediction efficacy of MHCAT and Metroticket was compared using the area under ROC curve (c-statistic). A total of 1371 LTs for HCC were analysed in the study, with a median follow-up of 22.2 months (IQR 6.1–72.4 months). The proportions meeting the Milan, UCSF, Fudan and Hangzhou criteria were 34.4%, 39.7%, 44.2% and 51.9%, respectively. The c-statistics for MHCAT predictions of 3- and 5-year survival rates of HCC recipients were 0.712–0.727 and 0.726–0.741, respectively. Among these patients, 1298 LTs for HCC were ultimately selected for the comparison analysis for prediction efficacy. The c-statistic of MHCAT for predictions of 3-year survival with reference to the Milan, UCSF and Fudan criteria was significantly increased compared with that for Metroticket (p

Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise, we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.

To the EditorPlatelets may affect tumor cell proliferation and angiogenesis by releasing several cytokines including platelet-derived growth factor and vascular endothelial growth factor, among oth...

It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.

To assess the effect of the drug combination of Schisandra sphenanthera extract (SchE) and Rapamycin (RAPA), 18 healthy subjects were given oral treatments of RAPA alone and with SchE. Pharmacokinetic investigations and indexes of hepatic and renal functions, as well as other indices of oral RAPA administration (2 mg), were performed both before and after the SchE treatment period. Whole-blood RAPA concentrations were determined by enzyme-linked immunosorbent assay. The research found that the mean whole-blood RAPA AUC0–∞, Cmax, and tmax increased almost 2-, 2.1-, and 1.3-fold, respectively, and CL/F (–38.0%) decreased almost 1.6-fold in these subjects when RAPA was administered with SchE compared with oral RAPA administered alone. The results of this study proved that SchE can increase the oral bioavailability of RAPA and will add important information to the interaction area between drugs and herbal products.

Background In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 °C University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT. Methods From June 2007 to January 2008, 11 adult LDLT patients received modifed right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 °C UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation. Results MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outfow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent. Conclusion The cadaveric venous allograft preserved in 4 °C UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outfow of the MHV.

SUMMARY The full scale of human miRNome in specific cell or tissue, especially in cancers, remains to be determined. An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and hepatocellular carcinoma (HCC) was carried out in this study. We found nine miRNAs accounted for � 88.2% of the miRNome in human liver. The third most highly expressed miR-199a/b-3p is consistently decreased in HCC, and its decrement significantly correlates with poor survival of HCC patients. Moreover, miR-199a/b-3p can target tumorpromoting PAK4 to suppress HCC growth through inhibiting PAK4/Raf/MEK/ERK pathway both in vitro and in vivo. Our study provides miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases.

Recent studies have shown that Th17 cells, as a distinct lineage from Th1 and Th2 subsets, play an obligatory role in the pathogenesis of autoimmune diseases. It is well known that immunotherapy with Complete Freund's adjuvant (CFA) is effective in preventing from the onset of autoimmune diabetes in nonobese diabetic (NOD) mice. In the present study, we investigated whether CFA treatment restrained Th17 development and down-regulated Th17-related cytokine production in NOD mice. Th17-related cytokines (i.e. IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-6, TGF-beta) production in splenocytes was decreased dramatically on day 18 following CFA immunization. This effect was also observed at 10 and 20 week after adjuvant treatment. Injection of IL-17 into CFA-treated diabetes-free mice led to occurrence of overt diabetes, indicating that therapeutic effects of adjuvant treatment may be partially due to suppressing Th17 commitment. Interestingly, the main producer of IL-17 resided in a population of myeloid cells, which negatively expressed makers of neutrophil or macrophages. IL-23 stimulation did not alter the distribution of IL-17 in myeloid cells. Furthermore, this pattern of IL-17 expression was also present in Balb/c and C57BL/6 strains. These findings may have important implications for understanding of mechanisms underlying adjuvant treatment on autoimmune diseases.

To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT).Two hundred and twenty-three patients with HCC were followed for at least six years to identify independent risk factors for long-term survival after liver transplantation (LT). The criteria for HCC liver transplantation included the Milan, University of California San Francisco, Hangzhou and Shanghai Fudan criteria. The Cox regression model was used to build MHCAT specifying these criteria. A survival analysis was carried out for patients with high or low risk.The one-, three- and five-year cumulative survival of HCC patients after LT was 78.9%, 53.2% and 46.4%, respectively. Of the HCC patients, the proportion meeting the Hangzhou and Fudan criteria was significantly higher than the proportion meeting the Milan criteria (64.6% vs 39.5%, 52.0% vs 39.5%, P0.05). Moreover, the proportion meeting the Hangzhou criteria was also significantly higher than the proportion meeting other criteria (P0.01). Pre-operative alfa-fetoprotein level, intraoperative blood loss and retransplantation were common significant predictors of long-term survival in HCC patients with reference to the Milan, University of California San Francisco and Fudan criteria, whereas in MHCAT based on the Hangzhou criteria, total bilirubin, intraoperative blood loss and retransplantation were independent predictors. The c-statistic for MHCAT was 0.773-0.824, with no statistical difference among these four criteria. According to the MHCAT scoring system, patients with low risk showed a higher five-year survival than those with high risk (P0.001).MHCAT can effectively predict long-term survival for HCC patients, but needs to be verified by multi-center retrospective or randomized controlled trials.

Background Several studies have investigated the effect of intraoperative blood loss (IBL) on recurrence of tumors. However, the independent effect of IBL on oncological outcome after liver transplantation (LT) for hepatocellular carcinoma (HCC) is unclear. Methods A total of 479 patients who underwent LT for HCC from January 2001 to December 2012 at our institution were enrolled in this retrospective study. Kaplan–Meier and Cox regression methods were used to assess the recurrence rate, as well as its risk factors. Stratified analysis was performed to further examine the effect of IBL on HCC recurrence according to different characteristics of tumors. We also investigated the independent risk factors for excessive IBL using logistic regression analysis. Results The median follow-up was 28 months (range, 1–131 months). Kaplan–Meier analysis with the log-rank test according to IBL at per liter intervals showed that IBL > 4 L was significantly associated with a higher recurrence rate (P 4 L (P 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P 4 L and vascular invasion (P = 0.019) was found. IBL > 4 L was independently associated with HCC recurrence for patients with vascular invasion, but not for patients without vascular invasion. Finally, we found that the presence of ascites, model for end-stage liver disease score, and operation time were independent risk factors for IBL > 4 L. Conclusions Excessive IBL is an independent predictor of HCC recurrence after LT, especially in patients with vascular invasion.