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Cai Yong,2,* Zhengxin Wang,1,* Xing Zhang,3 Xiaomin Shi,1 Zhijia Ni,1 Hong Fu,1 Guoshan Ding,1 Zhiren Fu,1 Hao Yin1,3 1Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Transplantation, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China; 3Department of Surgery, University of Chicago, Chicago, IL, USA *These authors contributed equally to this article Abstract: Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1), locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77±32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%±7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%±5.29% and 43.49%±9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients. Keywords: MCP-1, electrospinning, islet transplantation, diabetes

Background: Polydatin, a glucoside of resveratrol, has shown protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism., Methods: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages., Results: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1β, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway., Conclusions: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ ²=9.99, P <0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ ²=4.85 and 5.58, both P <0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ ²=9.65 and 7.82,both P <0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.

Pediatric acute liver failure (PALF) is a rare and life-threatening clinical syndrome for which drug-induced liver injury is a cause. Lamotrigine (LTG) is generally a safe and effective antiseizure medication, and PALF related to LTG has rarely been reported. Here, we describe two cases of PALF associated with LTG in children with epilepsy. In both patients, LTG was used in combination with valproic acid at an initial dose exceeding the recommended dose, which increased the risk of adverse reactions. In addition, single nucleotide polymorphisms of genes associated with the pharmacokinetics and pharmacodynamics of LTG were selected for pharmacogenomic testing. However, the results revealed that genotypes of the patients had variable effects on the serum concentration and therapeutic responsiveness of LTG and therefore did not explain the clinical manifestations well. The findings of this case report caution clinicians to be aware of the risk of liver failure when using antiseizure medication in polytherapy, especially LTG in combination with valproic acid. When administered to children, the recommended dosage of LTG should be strictly followed. Further pharmacogenomic studies are needed to help improve the efficacy and safety of epilepsy treatment in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

Previous study showed that senescent hepatocytes from aged liver could be rejuvenated after repopulated in the young recipient liver. The proliferative capacity of hepatocytes was restored with the senescence reversal. However, it is unknown whether metabolic and homeostatic function of aged liver, as well as age-dependent liver steatosis could be rejuvenated or alleviated. Here, we found that senescent hepatocytes from aged liver were rejuvenated after exposing to young blood. An autonomous proliferation of senescent hepatocytes which resulting in ploidy reversal might be the underlying mechanism of senescent reversal. After performing 2/3 partial hepatectomy (2/3PHx) in young blood exposed old liver, delayed DNA synthesis of senescent hepatocytes was rescued and the number of BrdU positive hepatocytes was restored from 4.39±2.30% to 17.85±3.21%, similarly to that in the young mice at 36 hours post 2/3PHx. Moreover, Cyclin A2 and Cyclin E1 overexpression of hepatocytes in aged liver facilitating the G1/S phase transition was contributed to enhance liver regeneration. Furthermore, lipid droplet spread widely in the elderly human liver and old mouse liver, but this aged-associated liver steatosis was alleviated as senescence reversal. Collectively, our study provides new thoughts for effectively preventing age-related liver diseases., Competing Interests: Conflict of interest The authors have no conflict of interest to disclose., (copyright: © 2021 Liu et al.)

Purpose: Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer., Methods: The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1., Results: SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated β-galactosidase (SA-β-Gal) activity but lower proliferative capacity., Conclusion: Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment., Competing Interests: The authors declare no conflicts of interest., (© 2021 Wang et al.)

Introduction: Most of the immunosuppressive drugs are used for the treatment of autoimmune disease, allergic diseases, and transplant rejection, but toxicity is the major obstacle for the potent drugs in the wide use of these immunosuppressive drugs. Daphnetin, a Chinese herbal product, has been reported that daphnetin possesses antimicrobial, anticoagulation, antimalarial, anticancer, and antioxidant activity. In a previous study, we found that daphnetin exhibited a potential immunosuppressive effect on LPS-induced B lymphocyte cells in vitro , therefore, in this research, we investigated the immunosuppressive effects of daphnetin in BALB/c mice use OVA as a prototype antigen., Methods: Sixty BALB/c mice were divided into six groups. The emulsion (100 μL containing 100 μg OVA) was injected subcutaneously with OVA + CFA into the shaved backs of the BALB/c mice on day 1, and a boosting injection was administered in OVA + IFA 2 weeks later. Beginning on the day of immunization, the immunized mice were administered intraperitoneally with daphnetin at a dose of 5, 10, and 20 mg/kg in saline solution for 28 consecutive days. We measured the effect of daphnetin on OVA-specific antibody, cytokine production, and Splenocyte proliferation in vivo ., Results: The results revealed that daphnetin significantly suppressed serum immunoglobulin G levels (IgG), and the OVA-specific IgG subclasses IgG1 and IgG2b, daphnetin was also significantly decreased the Th1 and Th2 cytokine productions, inhibited the splenocytes proliferation rate in vivo ., Conclusions: It proved that daphnetin could suppress humoral response activity on OVA-sensitized mice, suggesting a potential role on daphnetin as a new immunosuppressive drug.

Calycosin is one of the main ingredients extracted from the Chinese medical herb, Radix astragali (RA). It has been shown to inhibit cell proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanism remains unclear. The effects of calycosin on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells, as well as its mechanism, were investigated in this study. Cell Counting Kit-8 assay results suggested that calycosin had anti-proliferation effects on HCC in dose- and time-dependent manners, and had less cytotoxicity in normal cells. Hoechst/PI double staining and flow cytometry results showed cellular morphological changes and apoptosis after treatment of HepG2 cells with calycosin. The western blot assay showed calycosin decreased the expression of Bcl-2 and increased the expression of Bax, caspase-3, and PARP. Calycosin induced the activation of MAPK, STAT3, NF-κB, apoptosis-related proteins, and induced cell cycle arrest in the G0/G1 phase by regulating AKT. In addition, calycosin reduced the expression of TGF-β1, SMAD2/3, SLUG, and vimentin. Furthermore, phosphorylation, apoptosis, and cell migration induced by calycosin were mediated by the production of reactive oxygen species. These events could be inhibited by pretreatment with N-acetyl-L-cysteine. Calycosin resisted HCC by activating ROS-mediated MAPK, STAT3, and NF-κB signaling pathways., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a widely studied inflammasome that plays a critical role in inflammatory responses. Many triggers, including microbial pathogens (ie, bacteria and viruses) and other signals (ie, reactive oxygen species, adenosine triphosphate, urate, silicon, and asbestos), can stimulate the NLRP3 inflammasome. Liver ischemia/reperfusion (I/R) injury is a common pathologic process during liver surgery and shock and can induce severe liver damage. Although its pathogenesis is still unclear, oxidative stress and overproduction of the inflammatory response are likely to contribute to I/R injury. The NLRP3 inflammasome is activated during the I/R process, resulting in further recruitment and activation of caspase-1. Activated caspase-1 cleaves the pro-forms of interleukin-1β and interleukin-18 and results in their maturation, triggering a proinflammatory cytokine cascade and causing liver damage. Bruton's tyrosine kinase is a critical molecule involved in diverse cellular pathways, such as proliferation, apoptosis, inflammation, and angiogenesis. Intrahepatic Bruton's tyrosine kinase is mainly expressed on Kupffer cells and sinusoidal endothelial cells, and the inflammasome is activated in Kupffer cells. Our study found that inhibition of Bruton's tyrosine kinase effectively attenuated liver I/R injury by suppressing activation of the NLRP3 inflammasome in Kupffer cells., (Copyright © 2019. Published by Elsevier Inc.)

Portal vein thrombosis (PVT) is currently not considered a contraindication for liver transplantation (LT), but diffuse or complicated PVT remains a major surgical challenge. Here, we review the prevalence, natural course and current grading systems of PVT and propose a tailored classification of PVT in the setting of LT. PVT in liver transplant recipients is classified into three types, corresponding to three portal reconstruction strategies: Anatomical, physiological and non-physiological. Type I PVT can be removed via low dissection of the portal vein (PV) or thrombectomy; porto-portal anastomosis is then performed with or without an interposed vascular graft. Physiological reconstruction used for type II PVT includes vascular interposition between mesenteric veins and PV, collateral-PV and splenic vein-PV anastomosis. Non-physiological reconstruction used for type III PVT includes cavoportal hemitransposition, renoportal anastomosis, portal vein arterialization and multivisceral transplantation. All portal reconstruction techniques were reviewed. This tailored classification system stratifies PVT patients by surgical complexity, risk of postoperative complications and long-term survival. We advocate using the tailored classification for PVT grading before LT, which will urge transplant surgeons to make a better preoperative planning and pay more attention to all potential strategies for portal reconstruction. Further verification in a large-sample cohort study is needed., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest. No financial support was provided., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Supramolecular aggregation-induced emission (AIE) has become a research hotspot in cell imaging. Herein, supramolecular assembly with AIE effect was constructed in two stages, where adamantane modified tetraphenylethene self-assembly emitted weak fluorescence, and then after adding β-cyclodextrin modified hyaluronic acid, the formed nanoparticles enhanced AIE fluorescence for targeted cancer cell imaging., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.

Objective: There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of Trametes robinophila Murr (Huaier granule) to address this unmet need., Design and Results: A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively., Conclusions: This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group., Trial Registration: NCT01770431; Post-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Atmospheric particulates, especially PM2.5, not only damage the respiratory system, but also play important roles in pulmonary immunity. China is influenced by atmospheric diffusion conditions, industrial manufacturers, and heating and discharging. PM2.5 levels in the air rise substantially in the winter, which is also a period of flu high-incidence. Although an epidemiological link exists between PM2.5 and flu, we do not understand how long-term PM2.5 inhalation affects pulmonary immunity and the influenza virus response. Our study has prepared an in vivo PM2.5 mouse pharyngeal wall drop-in model and has found that PM2.5 exposure leads to mouse inflammatory injuries and furthers influenza A infection. Our results suggest that short-term exposure to PM2.5 significantly enhances the survival rate of influenza A-contaminated mice, while long-term PM2.5 inhalation lowers the capacity of pulmonary macrophages to secrete IL-6 and IFN-β. A disorder in the pulmonary innate defense system results in increased death rates following influenza infection. On a macromolecular level, this mechamism involves Kdm6a down-regulation after long-term exposure to PM 2.5 and a resultant increase in H3K4 and H3K9 methylation in IL-6 and IFN-β promoter regions. In summary, PM2.5 causes injuries of lung tissue cells and downregulates immune defense mechanisms in the lung., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To determine the effects of curing mode of one-step and two-step universal adhesives on the micro-tensile bond strength (μTBS) of different dual-cure resin cements to dentin., Methods: One-step universal adhesive Single Bond Universal (SBU), and two-step universal adhesive OptiBond Versa (VSA) were chosen as the subjects, one-step self-etching adhesive OptiBond All in One (AIO) and two-step self-etching adhesive Clearfil SE Bond (SEB) were control groups, and two dual-cure resin cements RelyX Ultimate (RLX) and Nexus 3 Universal (NX3) were used in this study. In this study, 80 extracted human molars were selected and the dentin surface was exposed using diamond saw. The teeth were divided into 16 groups according to the adhesives (AIO, SBU, SEB, VSA), cure modes of adhesives (light cure, non-light cure) and resin cements (RLX, NX3). The adhesives were applied on the dentin surface following the instruction and whether light cured or not, then the resin cements were applied on the adhesives with 1 mm thickness and light cured (650 mW/cm(2) for 20 s. A resin was built up (5 mm) on the cements and light cured layer by layer. After water storage for 24 h, the specimens were cut into resin-cement-dentin strips with a cross sectional area of 1 mm×1 mm and the μTBS was measured., Results: Regarding one-step universal adhesive (SBU) light cured, the μTBS with RLX [(35.45±7.04) MPa] or NX3 [(26.84±10.39) MPa] were higher than SBU non-light cured with RLX [(17.93±8.93) MPa)] or NX3 [(10.07±5.89) MPa, P<0.001]. Compared with AIO, light-cured SBU combined with RLX presented higher μTBS than AIO group [(35.45±7.04) MPa vs. (24.86±8.42) MPa, P<0.05]. When SBU was not lighted, the μTBS was lower than AIO [(17.93±8.93) MPa vs. (22.28±7.57) MPa, P<0.05]. For two-step universal adhesive (VSA) and control adhesive (SEB), curing mode did not affect the μTBS when used with either RLX or NX3 (25.98-32.24 MPa, P>0.05)., Conclusion: Curing mode of one-step universal adhesive may affect the μTBS between dual-cure resin cements and dentin, while for two-step universal adhesive, the curing mode and the type of resin cements did not influence the μTBS.

Objective: To establish a non-invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters., Methods: In this prospective study, contrast-enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients., Results: The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross-sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 × SVD (mm) + 0.231 × SV/body mass index (× 10(4) cm(5) /kg) + 3.44 × aspartate aminotransferase-to-platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867-1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients' actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856-1.000)]., Conclusions: The MRI-based formula has great potential for detecting portal hypertension. As a non-invasive measurement, it may be clinically accepted for the replacement of invasive modalities after further refinement., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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 < 0.001). Multivariate analysis identified that IBL > 4 L (P < 0.001; hazard ratio [HR] = 2.32, 95 % confidence interval [CI] = 1.60-3.36) was an independent risk factor for post-LT HCC recurrence, as well as age < 60 years, exceeding Milan criteria, α-fetoprotein levels > 400 ng/mL, and micro- and macrovascular invasion. IBL > 4 L (P < 0.001; HR = 2.45, 95 % CI = 1.64-3.66) was also independently associated with early (within 1 year) recurrence after LT. Furthermore, a significant correlation between IBL > 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.

Galectin-9 (Gal-9), a member of the galectin family, has a variety of biologic activities. However, its role in allografts is not fully clarified yet. The relationship between interleukin-17 (IL-17) and Gal-9 and the role of Gal-9 in T(H)17-cell differentiation also remain unclear. We built a murine cardiac transplantation model, which we treated with Gal-9 and/or EX-527, a specific Sirtuin-1 inhibitor. Afterwards, flow-cytometric analysis and reverse-transcription polymerase chain reaction were used to detect the number of T(H)17 cells and the expression of key factors involved in the differentiation of T(H)17 cells; in addition, the survival times of cardiac transplanted mice in different groups were recorded. The levels of circulating T(H)17 cells were found to increase in the peripheral blood of mice that exhibited acute rejection (AR) after heart transplantation, which was determined to be correlated with the rejection grade. Gal-9 or EX-527 can inhibit the activation and differentiation of T(H)17 cells and effectively suppress T(H)17-cell-mediated AR. These data provide new evidence for the potential regulatory effects of Gal-9 in alloimmune responses in a murine model of heart transplantation, and suggest the combined use of galectin-9 and EX-527 may be a powerful method to induce tolerance of fully mismatched murine cardiac allografts., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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 < 0.05). In conclusion, MHCAT can effectively predict long-term survival for HCC recipients after LT.

Aim: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT)., Methods: 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., Results: 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%, P < 0.05). Moreover, the proportion meeting the Hangzhou criteria was also significantly higher than the proportion meeting other criteria (P < 0.01). 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 (P < 0.001)., Conclusion: MHCAT can effectively predict long-term survival for HCC patients, but needs to be verified by multi-center retrospective or randomized controlled trials.

Objective: Tacrolimus is a potent immunosuppressive agent mainly used for allogeneic solid organ transplantation. Although usage of tacrolimus led to a significant increase in short-term allograft survival, the long-term morbidity remains high. Endothelin-1 (ET-1) is reported to be associated with increased vascular resistance, CNI-induced nephrotoxicity and chronic rejection., Materials and Methods: In the present study, we first detected the serum and renal ET-1 level of rats treated by tacrolimus and found strong positive correlations were existed between the ET-1 level and the tacrolimus dosage and treated time. Furthermore, we studied the protective effect of ambrisentan in liver transplantation rats when co-administrated with tacrolimus. Healthy inbred male Wistar and Sprague-Dawley (SD) rats were used in this study. The post-operative general condition, transplantation survival time, hepatic aminotransferase, serum IFN-γ and level kidney injury biochemical index were recorded and compared to evaluate the immune response and outcomes in the recipient rats after liver transplantation., Results: Our results indicate that ambrisentan prevents the changes of ET-1 content in rats of non-operative treatment group and reduced the nephrotoxicity in the rats with liver transplantation. Rats from ambrisentan co-administration group exhibited good postoperative condition and prolonged survival., Conclusions: Ambrisentan reverted some effects induced by tacrolimus in the kidney and indicated a positive potential for therapeutic benefit.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A + 0.019C + 1.322R (simplified into T = 2A + 3C + 200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity = 80%, specificity = 79.9%,AUC = 92.3%) and 1939.5 (sensitivity = 93.9%, specificity = 77.6%, AUC = 88.6%), relatively (p < 0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients., (© 2013 John Wiley & Sons A/S.)

Hepatocellular carcinoma (HCC), the most common primary malignant tumor of the liver, often associated with the dysregulation of transcriptional pathways involved in cell growth and differentiation. The hematopoietically expressed homeobox protein (Hhex) is an important transcription factor throughout liver development and is essential to liver bud formation and hepatoblast differentiation. Here, we report a relationship between Hhex expression and HCC. First, adenovirus-mediated Hhex delivery into the hepatoma cell line, Hepa1-6, resulted in decreased expression of several proto-oncogenes (c-Jun and Bcl2), increased expression of some tumor suppressor genes (P53 and Rb), and enhanced expression of a cluster of hepatocytic and bile ductular markers. Second, Hhex expression significantly attenuated Hepa1-6 tumorigenicity in nude mice. Third, we report a correlation between Hhex expression and the differentiation state of human HCC. In 24 cases of clinical specimens, there was a significant difference in Hhex expression between poorly differentiated HCC and well-differentiated HCC (P < 0.001). Taken together, these results indicate that Hhex is a potential candidate molecular marker for HCC pathological evaluation, suggesting a need to evaluate Hhex as a potential target for therapeutic intervention.

Background: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China., Methods: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0., Results: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%)., Conclusion: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

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 modified 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 outflow 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 outflow of the MHV.

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 < 0.05). By ROC curve analysis, the obvious elevation of the ATP value one wk after transplantation had better sensitivity and specificity in diagnosing the AR. The ATP sensitivity rate for early AR was 85.7% and specificity rate 80.9% when the cutoff value was 407 μg/L. The ATP value collected on the day of AR occurrence has apparently positive correlation with the rejection acting index (RAI) (p < 0.01). After the intravenous glucocorticoid therapy, all the ARs were reversed and the ATP value declined significantly compared with the control group and that on the day when AR occurred (p < 0.01)., Conclusions:   During the early postoperative period (especially at first week after liver transplantation), the elevation of ATP levels within CD4(+) T lymphocytes has good sensitivity and specificity in diagnosing the AR at early stage. And the degree of AR has positive relationship with ATP value. After the intravenous glucocorticoid therapy, the obvious declination of AR might be used in evaluating the effectiveness of anti-rejection treatment., (© 2011 John Wiley & Sons A/S.)

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4(+) effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4(+) T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4(+) T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3(+) cells in splenic CD4(+) T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4(+)CD25(-) T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection.

Tacrolimus (Tac, FK506) is a widely used T-cell-targeted immunosuppression drug known as a calcineurin inhibitor. However, its pharmacologic effects on T-helper type 17 (Th17) cells have not been fully elucidated. Herein, we demonstrate that Tac inhibits Th17 cell differentiation and proliferation, and expression of IL-17 messenger RNA. The proposed mechanism is that Tac inhibits calcineurin and T-cell receptor stimulation-induced cell division. Because Th17 cells participate in allograft rejection, the results of the present study suggest a novel model of immunosuppression effects of Tac. In addition, they provide further implications for the therapeutic immunosuppression effects of Tac on allograft rejection., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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., (© 2009 John Wiley & Sons A/S.)

Objective: To investigate the possible relationship between variation of coxsackievirus B3 (CoxB3) VP1 sequence from cerebrospinal fluid of children with severe and mild central nervous system (CNS) infection and damage to CNS in children from Shandong province., Methods: The enteroviruses were detected using VP1 typing and sequencing primer for enteroviruses from 73 enterovirus-infected cases confirmed by detection of cerebrospinal fluid by enteroviruses common primer. VP1 sequences (450 nucleotides) were determined and analyzed for 21 CoxB3 enteroviruses strains isolated in Qingdao and Binzhou, and were compared with that of BLAST search procedures from GeneBank in NCBI. The variation of VP1 gene and amino acids sequence of CoxB3 enteroviruses was analyzed for severe and mild CNS infection., Results: The nucleotide homogeneity of these CoxB3 appeared to be 97% - 99%, however, the homogeneity among different genotypes were 83% - 76%. Replacement of glutamine by histidine at amino acid locus 856 of VP1 CoxB3 was found in 4 cases with severe encephalitis. There were different variation in VP1 nucleotide sequence of CoxB3 in 3 cases with mild encephalitis and 14 cases with meningitis, but amino acids sequences had no regular variation. The modified Glasgow's coma score was below 7 in all the 4 cases with severe encephalitis. Of these 4 cases, 3 had consciousness disturbance for less than 3 days. Lethargy, restlessness and psychiatric symptoms were major manifestations, of whom 3 also had dysphagia, 1 had encephalatrophy obviously, Glasgow's coma score was 3, deep coma lasted for 9 days, and had concomitant fatal epileptic attacks. Of these 4 cases, 2 completely recovered, 1 had high muscle tone, 1 remained under anti-epileptic drug treatment at follow-up 6 months later., Conclusion: There were a small epidemic of CoxB3 CNS infection in children in 2005 in this area. The amino acid variation of CoxB3 VP1 possibly caused increased viral virulence and caused damage to CNS.

Objective: To explore the effects of astilbin on the maturation and immunologic function of mouse bone marrow-derived dendritic cells (DCs)., Methods: Mouse bone marrow cells were cultured with recombinant mouse granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) for 5 days to get immature DCs (imDCs), then the imDCs was cultured in the presence of 1 microg/mL lipopolysaccharide (LPS) or LPS (1 microg/mL) plus astilbin (25, 50, 100 microg/mL) for 48 h. Then, the cells were harvested, and the apoptosis, immunophenotypes and antigen phagocytosis capability of imDCs in LPS, and low-, medium- and high-dose astilbin groups were analyzed by flow cytometry. Contents of p40 subunit of interleukin-12 (IL-12p40) in the supernatants were detected with enzyme-linked immunosorbent assay (ELISA). The stimulatory activity of the harvested cells on allogeneic T cells in mixed lymphocyte reactions (MLR) was tested by incorporation of 3H-thymidine, and the contents of IL-2, IL-4, IL-10 and interferon-gamma (INF-gamma) in the supernatants of MLR were examined by ELISA., Results: At the concentrations of 25 to 100 microg/mL, astilbin exhibited no toxicity on co-cultured DCs. Compared with the lipopolysaccharide, low-, medium- and high-dose astilbin could decrease the expression levels of major histocompatibility complex-Ia (MHC-Ia), CD40, CD80 and CD86 molecules in DCs. DCs in the low-, medium- and high-dose astilbin groups exhibited weaker capabilities for antigen phagocytosis and less contents of IL-12p40 in the supernatants than in the LPS group. Furthermore, low-, medium- and high-dose astilbin showed weak activities in stimulating the proliferation of allogeneic T cells as compared with the LPS (P<0.05). Compared with the LPS, low-, medium- and high-dose astilbin could decrease IL-2 and INF-mu secretion from T cells in MLR but had no effect on IL-10 secretion., Conclusion: Astilbin can inhibit maturation of mouse bone marrow-derived DCs with dose-dependent effect and exert negative effects on immunologic function of the DCs.

Background: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors., Methods: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening., Results: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72-0.92] and 0.68 (95% CI 0.58-0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine > or = 1.5 mg/dl., Conclusions: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.

Purpose: To evaluate current selection criteria for patients undergoing liver transplantation (LT) in response to hepatocellular carcinoma (HCC), and to analyze the prognostic factors for successful transplantation., Methods: We evaluated the outcome of 1,078 consecutive patients with HCC from the Shanghai Multi-Center Collaborative LT Group who underwent LT over a 6-year period. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Multivariate study with Cox's proportional hazard model was used to evaluate the prognosis-relative aspects., Results: We determined that expansion of Milan criteria to include: a solitary lesion < or = 9 cm in diameter, no more than three lesions with the largest < or = 5 cm, a total tumor diameter < or = 9 cm without macrovascular invasion, lymph node invasion and extrahepatic metastasis (referred to as the "Shanghai criteria"), resulted in overall survival (OS) and disease-free survival (DFS) rates that were similar to the Milan criteria. Multivariate analysis using the Cox proportional hazards regression model showed that the Child-Pugh-Turcotte classification (P = 0.010, 0.000), tumor differentiation (P = 0.001, 0.000), tumor size (P = 0.000, 0.000) and number (P = 0.014, 0.016), macrovascular invasion (P = 0.022, 0.000) and alpha-fetoprotein (AFP) levels (P = 0.031, 0.003) were independent predictors of OS and DFS, while post-LT chemotherapy (OS, P = 0.000) and tumor encapsulation (DFS, P = 0.038) were independent predictors of OS or DFS., Conclusion: Shanghai criteria expanded the current criteria while maintaining similar survival.

Objective: To investigate the protective effects of astilbin on renal ischemia-reperfusion (IR) injury in rats., Methods: Twenty-four male SD rats, two months old, were randomly allocated into three groups: sham-operated group (n=8), untreated group (n=8) and astilbin group (n=8). Rats in the untreated group and the astilbin group underwent temporary renal artery occlusion to induce IR injury. The rats in the astilbin group were intraperitoneally injected with 12 mg/mL astilbin at a dose of 30 mg/kg from 3 day before IR injury until to be sacrificed once per day, and rats in the untreated group were injected with equal volume of normal saline at the same time. After 6-hour reperfusion, blood urea nitrogen (BUN) and serum creatinine (SCr) and histological changes of the renal tissues were detected to evaluate renal injury. Expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein in the renal tissues and the serum contents of interleukin-6 (IL-6) and IL-1beta were also measured with semi-quantitative reverse transcription-polymerase chain reaction, Western blotting or enzyme-linked immunosorbent assay., Results: Compared with the untreated group, BUN and SCr levels were significantly decreased in the astilbin group after 6-hour reperfusion (P<0.01), and similar results were also found in histological examination. The expressions of MCP-1 mRNA and protein in renal tissues in the astilbin group were lower than those in the untreated group. The serum contents of IL-6 and IL-1beta were decreased in the astilbin group as compared with the untreated group (P<0.01)., Conclusion: Astilbin can ameliorate kidney IR injury in rats by inhibiting the production of chemokine MCP-1 and cytokines IL-6 and IL-1beta.

Background: Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer worldwide, with more than half a million identified cases and about a similar number of subjects succumb to it each year. This study sought to evaluate our results of liver transplantation for HCC to identify prognostic factors., Methods: Between December 2001 and December 2006, 224 patients (205 men, 19 women; age range, 15-75 years) with HCC underwent orthotopic liver transplantation (OLT) at our center. All grafts were from deceased donors. There were 68 cases within Milan criteria (30.3%), 32 cases beyond Milan criteria but within UCSF (University of California, San Francisco) criteria (14.3%), and 124 cases beyond UCSF criteria (55.4%)., Results: The overall 1-, 3-, and 5-year patient cumulative survival rates were 82.5%, 60.1%, and 51.5%, respectively. The survival rates were comparable between patients within Milan and UCSF criteria, but were significantly greater than that of patients beyond UCSF criteria. Multivariate analysis revealed alpha fetoprotein (AFP) >or= 800 microg/L, vascular invasion, and poor tumor differentiation to be independent prognostic factors., Conclusion: OLT is a safe and effective treatment for hepatitis B virus-related HCC. Compared with Milan criteria, UCSF criteria successfully expanded the indication without deteriorating the prognosis significantly, while preoperative AFP >or= 800 microg/L, vascular invasion, and poor tumor differentiation indicated poor survival.

Background: Portal vein thrombosis (PVT) used to be a contraindication for liver transplantation (LT). This obstacle has been delt with following the improvement of LT-related techniques and therapeutic approaches to thrombosis. But the effect of PVT on LT outcomes is still controversial. We reviewed retrospectively the outcome of LT patients with PVT as well as risk factors and surgical management according to PVT grades., Methods: A total of 465 adult LTs were performed from December 2002 through December 2006. Operative findings and the result of preoperative ultrasonography and imaging were reviewed for PVT grading (Yerdel grading). Comparison of risk factors, variables associated with perioperative period and prognosis between recipients with and without PVT is based on the grades., Results: In the 465 LTs, 42 were operatively confirmed to have PVT (9.0%) (19 recipients with grade 1, 14 with grade 2, 7 with grade 3, and 2 with grade 4). Increased age and treatment of portal hypertension were associated with PVT. Grade 1 or 2 PVT was treated by direct anastomosis or single thrombectomy. In grade 3 PVT patients, the donor PV was directly anastomosed to the dilated branch of the recipient portal venous system or to the distal open superior mesenteric vein through an interposition vein graft if needed. Grade 4 PVT was managed by our modified cavoportal hemitransposition technique. The comparison between PVT patients and controls showed no significant difference in operative duration and blood transfusion (P>0.05). The flow rate of the PV was lower in the PVT patients (48.881+/-12.788 cm/s) than in the controls (57.172+/-21.715 cm/s, P<0.05). The PVT patients had such postoperative complications as renal failure and PV rethrombosis (P<0.05). The 1-year survival rates in PVT and non-PVT patients were 78.6% and 76.4% respectively (P>0.05); the 3-year survival rates were 58.8% and 56.4% respectively (P>0.05)., Conclusions: PVT is not contraindicated for LT if it is graded. PVT recipients may have post-transplantation complications like renal failure and PV rethrombosis, and operative difficulty and patient survival are similar to those in recipients without PVT. Development of therapeutic approaches and accumulation of experience in dealing with PVT further improve the outcomes of LT in PVT recipients.

Background: Retransplantation of the liver is required for several complications of primary grafting, such as primary allograft non-function, hepatic artery thrombosis, biliary problems, or chronic ductopenic rejection. Surgeons usually take regrafting as the only pathway to treat those patients who are considered to have a poor outcome after the first operation. Whether the retransplantation is early or late, further attempts at rescue with a second or more grafts are associated with higher mortality and morbidity. However, retransplantation plays a role in improving survival of the patients. Therefore, it is necessary to summarize the experiences in liver retransplantation, as well as the factors influencing operative effects., Method: The clinical data of 8 patients who received liver retransplantation in our center were analyzed retrospectively., Results: Complications of the biliary tract occurred in 5 of the 8 patients, chronic rejection in 2, and embolism in the hepatic artery in 1. Infections occurred in 7 patients before engraftment. Patient 1 had developed renal failure before the surgery, and he died of severe infection and multi-organ failure after transplantation. Patient 4 had a massive hemorrhage during the operation and also died of multi-organ failure after transplantation. Patient 7 developed intracranial hemorrhage and abdominal infection and died soon after transplantation. The other 5 patients recovered and discharged from the hospital., Conclusions: Liver retransplantation is the only measure that can be taken to save the lives of patients whose liver allograft fails to function. It is very important that the indications and time of retransplantation are carefully selected. Factors leading to harmful effects on retransplantation include the preoperative condition of the recipient, a difficult and prolonged operation, massive hemorrhage during the operation, and severe complications after the surgery.

Aim: To investigate the effect of human interleukin-4 (hIL-4) on the expression of E-selectin and ICAM-1 on bovine aortic endothelial cells(BAEC) activated with TNF-alpha., Methods: BAEC were cultured in different concentrations of hIL-4 for 2 h followed by treatment with 4 microg/L TNF-alpha for 6 h or 18 h. The expression of E-selectin and ICAM-1 on BAEC was detected by cell-ELISA. The effect of hIL-4 on viability of BAEC was detected by MTT colorimetry., Results: Pretreatment of BAEC with hIL-4 inhibited the expression of E-selectin and ICAM-1 on BAEC activated by TNF-alpha in a dose-dependent manner (P<0.01). Both TNF-alpha and hIL-4 had no effect on the viability of BAEC., Conclusion: hIL-4 can suppress the expression of E-selectin and ICAM-1 on BAEC activated by TNF-alpha, which may contribute to the xenotransplant immune tolerance associated with hIL-4.

Background: The effect of tacrolimus (FK506) and 5-fluorouracil (5-FU) on hepatocellular carcinoma remains elusive. The aim of this study was to assess the effect of tacrolimus on the proliferation, and apoptosis in liver cancer cell line of SMMC-7721 and its sensitivity to fluorouracil (5-FU)., Methods: The liver cancer cell line of SMMC-7721 was cultured in vitro, and the MTT assay was used to examine the antiproliferative effect of FK506. Flow cytometry (FCM) was used to examine the effect of 5-FU alone or in combination with FK506 on the apoptosis and cell cycle of SMMC-7721 cells., Results: FK506 produced concentration-dependent antiproliferative effect on SMMC-7721 cells at all experimental concentrations (P<0.05), but no effect on induction of apoptosis. 5-FU induced apoptosis in a concentration-dependent manner, whereas the percentage of G0/G1-phase cells and proliferation index (PI) were increased with the increased concentration of 5-FU. Pretreatment with FK506 for 2 hours enhanced the effect of 5-FU on the induction of apoptosis., Conclusions: FK506 inhibits the growth of SMMC-7721 cells and enhances their sensitivity to 5-FU. This may be associated with the synergic effect of FK506 and 5-FU in inducing apoptosis and G0/G1-phase stasis.

Objective: We discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation., Methods: Sixty-eight cases of chronic fulminant hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to prevent hepatitis B virus reinfection. Lamivudine was administered to two cases and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical examinations were performed., Results: One of two cases given lamivudine developed reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA was positive in one of the two cases. Three cases given adefovir developed no reinfection with HBV., Conclusion: Orthotopic liver transplantation is an effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG prevent hepatitis B virus reinfection.

Objective: To investigate the expression of heparanase mRNA and its relation with the clinicopathological features and angiogenesis in primary hepatocellular carcinoma (HCC)., Methods: Expression of heparanase mRNA was detected by RT-PCR in 51 HCC lesions, and microvessel density (MVD) was detected by immunohistochemical stain with a factor VIII-related monoclonal antibody., Results: Expression of heparanase mRNA was shown in 49.0% (25/51) HCC lesions. The positive rate of heparanase expression in tumors larger than 3 cm (63.6%, 21/33) was significantly higher than those in smaller tumors (22.2%, 4/18; P < 0.01). Heparanase expression was more frequent in highly invasive tumors (70.0%, 14/20) compared with moderately invasive tumors (46.7%, 7/15) and low invasive ones (25.0%, 4/16; P < 0.05). Moreover, heparanase expression in tumors with high MVD (62.5%, 20/32) was significantly higher than those in tumors with low MVD (26.3%, 5/19; P < 0.05)., Conclusion: Heparanase mRNA expression may be important for the growth, invasion and angiogenesis of hepatocellular carcinoma.

Objective: To evaluate the inhibitory effect of heparanase antisense oligodeoxynucleotide (AS-ODN) on the invasiveness of human mammary carcinoma cell line MDA435., Methods: The AS-ODN complementary to the start codon region of heparanase mRNA and its control, scrambled nonsense oligodeoxynucleotide (NS-ODN) were designed and synthesized and phosphorothioated. The ODNs were embedded in cationic liposome Lipofectin and transfected into MDA435 cells. The total RNAs and proteins were extracted from the cells 48 hours after transfection and then semi-quantitative RT-PCR and Western blotting were performed to evaluate the heparanase gene and protein expression levels respectively. The invasiveness of transfected MDA435 cells were measured quantitatively by Matrigel invasion assays., Results: The heparanase gene and protein expression and invasiveness of MDA435 cells treated with AS-ODN of different final concentrations were significantly decreased compared with that of the controls (P < 0.01). Besides, the inhibitory effects were significantly different between the cells treated with AS-ODN of different concentrations (P < 0.01). The invasiveness inhibition rates were 34.0%, 57.8% and 79.7% at the cells treated with AS-DON of the final concentrations of 0.1 micro mol/L, 0.2 micro mol/L, and 0.4 micro mol/L, respectively., Conclusion: Heparanase AS-DON complementary to the start codon region of heparanase mRNA has a significant inhibitory effect on the invasiveness of human mammary carcinoma cell line in a dose-dependent manner.

A review of 33 cases of cancer in the gastric remnant (CGR) including 6 cases in Xian is presented. The detection rate of CGR consisting of different interval groups was 3.16%. The average age was 52.4 years, and Male: female ratio was 10:1. The average interval from the previous operation to the detection was 13.9 years. The interval of the subgroup over 30 years of age at the first operation was shorter than that of the subgroup below 30 years. The highest incidence was found in anastomotic stoma (58.1%) and cardia (32.3%). Borrmann I was the most common pathological type. Confirmed diagnostic rate with fibergastroscope was 81.8%. It is imperative that physician should follow up the patients with stomach remnant. No matter what the results of gastrointestinal barium study may be, the patients should undergo fibergastroscopic examination. The pathogenesis of CGR is also discussed.