MicroRNA-191 acts as a tumor promoter by modulating the TET1-p53 pathway in intrahepatic cholangiocarcinoma.

Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miR-191, play an important role in tumorigenesis; but expression and biological functions of miR-191 in ICC remain to be established. This study investigated the functions and underlying mechanisms of miR-191 in ICC. ICC miRNA profiles were generated in five pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative RT-PCR. The miR-191-associated mechanisms in ICC were investigated in vitro and in vivo, and clinical outcomes associated with miR-191 were correlated in 84 patients. Our results showed that miR-191 expression was significantly increased in ICC compared with the adjacent normal bile duct tissues (P < 0.001). Overexpression of miR-191 promoted proliferation, invasion, and migration of cholangiocarcinoma cells in vitro and in vivo. The elevated miR-191 expression reduced the expression level of ten-eleven translocation 1 (TET1)-a direct target gene of miR-191 in ICC, which catalyzes demethylation. The reduced TET1 expression level allowed the methylated CpG-rich regions at the p53 gene transcription start site stay methylated, leading to reduced p53 expression level, which compromises p53's anticancer vigor. Finally, miR-191 was found to be an independent risk factor for poor prognosis in patients with ICC (overall survival, hazard ratio = 3.742, 95% confidence interval 2.080-6.733, P < 0.001; disease-free survival, hazard ratio = 2.331, 95% confidence interval 1.346-4.037, P = 0.003). CONCLUSION: Our results suggest that overexpressed miR-191 is associated with ICC progression through the miR-191/TET1/p53 pathway. (Hepatology 2017;66:136-151).

Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies.

BACKGROUND: Studies investigating the association between hepatitis C virus (HCV) infections and the occurrence of cholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma (ICC), have shown inconsistent findings. Although previous meta-analyses referred to HCV and CCA, they mainly focused on ICC rather than CCA or extrahepatic cholangiocarcinoma (ECC). Since then, relevant new studies have been published on the association between HCV and ICC. Since the different anatomic locations of CCA have distinct epidemiologic features and different risk factors, it is necessary to evaluate the relationship between HCV infection and ICC, ECC, and CCA. METHODS: Relevant studies were identified by searching PUBMED, EMBASE, and MEDLINE databases prior to 1 August 2013. Pooled risk estimates were calculated with random-effects models using STATA 11.0. RESULTS: A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias. CONCLUSIONS: HCV infection is associated with the increasing risk of CCA, especially ICC.

Characterization of mesenchymal stem cells under the stimulation of Toll-like receptor agonists.

Infective factors cause the perpetuation of inflammation as a result of the permanent exposure of the immune system to exogenous or endogenous products of virus or bacteria. Mesenchymal stem cells (MSCs) can be exposed to this infective environment, which may change the characteristics and therapeutic potency of these MSCs. MSCs have the ability to repair damaged and inflamed tissues and regulate immune responses. In this study, we demonstrated that MSCs express functional Toll-like receptors (TLR) 3 and 4, the Toll-like receptor families that recognize the signals of viral and bacterial mimics, respectively. The specific stimulations did not affect the self-renewal and apoptosis capabilities of MSCs but instead promoted their differentiation into the adipocytes and osteoblasts with the TLR3 ligand. The reverse of these results were obtained with the TLR4 ligand. The migration of the MSCs to stimulate either of the two specific ligands was inhibited at different times, whereas the immunogenicity and immunosuppressive properties of the MSCs were not weakened unlike in the MSCs group. These results suggest that TLR3 and TLR4 stimulation affect the characterization of MSCs.

Liver transplantation as a treatment for complicated bile duct injury.

BACKGROUND/AIMS: Bile duct injury during cholecystectomy can be successfully managed by biliary reconstruction in the majority of patients. However it can also lead to potentially severe complications with unpredictable long-term results and in fact a proportion of these cases may even require liver transplantation. METHODOLOGY: In recent years, two cases of complicated bile duct injury after the failure of traditional surgical interventions were admitted to our hospital. Both patients underwent liver transplantation successfully, and the detailed clinical data was analyzed retrospectively. RESULTS: Bile duct injury (Strasberg type E4) in one patient was caused by laparoscopic cholecystectomy associated with proper hepatic artery injury; after the failure of an initial Roux-en-Y hepaticojejunostomy, the patient underwent classical orthotopic liver transplantation. Bile duct injury (Strasberg type D) in the other patient was caused by abdominal trauma in his childhood. After several unsuccessful surgical interventions, the patient finally developed secondary biliary cirrhosis twelve years later. He therefore underwent a living related liver transplantation. The outcome of both patients was satisfactory. CONCLUSIONS: Liver transplantation should be considered when bile duct injury has occurs concomitant with severe vascular injury or secondary biliary cirrhosis appears after failure of surgical intervention.

Differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation.

The aim of this study was to investigate the differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation (LDLT). Twenty patients who underwent LDLT (the L group) and 42 patients who underwent whole liver transplantation (the W group) were enrolled, and colored Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90. The changes in the portal blood flow velocity (PBV) and portal blood flow volume (PBF) were monitored. The graft and spleen sizes were measured with angiographic computed tomography, and upper endoscopy was used to measure esophageal varices on PODs 14, 30, and 90. Although the portal venous pressure (PVP) decreased after graft implantation, it was higher in the L group with a smaller graft size ratio (25.7 ± 5.1 cm H2O for the L group and 18.5 ± 4.6 cm H2O for the W group, P < 0.05). PBF and PBV increased in both the W and L groups on POD 1 after transplantation; however, the PBF and PBV peaks were significantly higher in the W group. The postoperative PVP and graft volume were greatly related to PBF on POD 1. Grafts in the L group regenerated rapidly after the operation, and the volume increased from 704 ± 115 to 1524 ± 281 mL as early as 1 month after transplantation. A rapid improvement in splenomegaly was observed in both groups. An improvement in esophageal varices was observed in the W group on POD 14 after transplantation, whereas no change was observed in the L group. The portal venous flow in patients with portal hypertension showed a high perfusion state after LDLT, but in contrast to whole liver transplantation, the PVP elevation after LDLT postponed the closing time of the collateral circulation and affected the recovery from splenomegaly.

[Effect of electroacupuncture on intestinal Toll-like receptor 4 and nuclear factor-kappa B in obese rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on intestinal Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in obese rats, so as to explore the mechanism of action of acupuncture in losing weight. METHODS: A total of 50 male Wistar rats were randomly divided into control and model groups. High-fat feed was used to establish a rat model of obesity, and after modeling, the 24 rats were randomly divided into model group, TLR4 inhibitor group, and EA group, with 8 rats in each group. The rats in the EA group were given EA at "Guanyuan" (CV4), "Zhongwan "(CV12), "Zusanli" (ST36), and" Fenglong" (ST40), 10 minutes each time, 3 times a week, and those in the TLR4 inhibitor group were given intraperitoneal injection of TAK-242 three times a week; the course of treatment was 8 weeks for both groups. Body weight and blood glucose were measured every two weeks. Co-immunoprecipitation was used to observe the interaction between TLR4 and NF-κB p65 in the intestinal tissue; electrophoretic mobility shift assay was used to measure the activity of NF-κB p65; Western blot was used to measure the protein expression of TLR4, phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (p-IκBα), and NF-κB p65; quantitative real-time PCR was used to measure the mRNA expression of TLR4, NF-κB p65, and IκBα. RESULTS: Compared with the control group, the model group had significant increases in body weight, blood glucose, and protein and mRNA expression of TLR4 and NF-κB p65 (P<0.01, P<0.05), as well as significant enhancement in the interaction between TLR4 and NF-κB p65 and activity of NF-κB p65 (P<0.05，P<0.01). Compared with the model group, the EA group had a significant reduction in body weight (P<0.05), both of the EA group and the TLR4 inhibitor group had significant reductions in blood glucose, and protein and mRNA expression of TLR4, p-IκBα， and NF-κB p65 (P<0.05，P<0.01), as well as significant reductions in the activity of NF-κB p65 (P<0.01). CONCLUSION: EA can effectively regulate intestinal TLR4, inhibit the interaction between TLR4 and NF-κB p65, and reduce the activity of NF-κB p65, which may be a potential mechanism of EA in reducing body weight and blood glucose in obese rats.

Role of splanchnic hemodynamics in liver regeneration after living donor liver transplantation.

The aim of this study was to investigate the changes in splanchnic hemodynamics after LDLT and their relationship with graft regeneration. Eighteen patients with LDLT December 2006 and June 2008 were enrolled, and color Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90 after transplantation. The changes in the portal blood flow mean velocity (PBV) and portal blood flow volume (PBF) were monitored, and their effects on hepatic function were observed simultaneously. Graft sizes were measured on PODs 7, 30, and 90 after the operation. The regeneration rates of grafts were calculated. PBF increased in the recipient group from 1081.17 +/- 277.50 to 2171.44 +/- 613.15 mL/minute, and PBV increased from 15.01 +/- 5.67 to 56.00 +/- 22.11 cm/s; they were both significantly higher than those in the donor group (P < 0.01). On POD 1, serum aspartic aminotransferase, alanine aminotransferase, and total bilirubin all peaked; however, these indices in patients with PBF/graft weight (GW) > 300 mL/minute . 100 g were significantly higher than those in patients with PBF/GW < 300 mL/minute . 100 g. Livers in the recipient group regenerated rapidly. The graft regeneration rate reached 119.40% +/- 28.21% as early as 1 month post-transplantation. PBF and PBV on PODs 1 and 3 were greatly related to liver regeneration at 30 days. The portal venous flow in patients with portal hypertension after LDLT showed a high perfusion state, which could promote graft regeneration, but PBF/GW after the operation should be controlled below 300 mL/minute . 100 g in order to protect grafts from hyperperfusion injury.

[Diagnosis and treatment of multiple endocrine neoplasia type 1 related pancreatic endocrine tumors].

OBJECTIVE: To summarize the experience on diagnosis and treatment of multiple endocrine neoplasia type 1 (MEN-1) related pancreatic endocrine tumors (PET). METHODS: From January 2004 to December 2007, there were 10 patients of MEN-1 related PET were treated in Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital. There were 2 males and 8 females, aged from 11- to 49-years-old. They were diagnosed by laboratory tests, imaging examinations and genes sequencing. Drug therapy, surgery and follow-up were applied on the patients. RESULTS: There were 9 patients having insulinomas including 2 cases of multiple insulinomas and 1 case presenting an insulinoma, multiple nonfunctional PET and malignant duodenum gastrinoma with liver metastasis. The other patient was diagnosed as glucagonoma clinically. Five cases had family history and MEN-1 gene mutation was detected in 9 patients. Seven patients accepted nine operations. Twelve insulinomas, four nonfunctional PET and one duodenum gastrinoma were found in the operations. All patients were followed up from 1 month to 11 years, and 9 patients with good conditions and 1 patient died. CONCLUSIONS: Well recognizing PET and MEN-1, early diagnosing MEN-1 related PET, appropriately surgical intervention will prove patients' life quality and will help for prolonging patients' survival time.

[The retrospective analysis of surgical outcome of portal hypertension].

OBJECTIVE: To retrospectively analyze the surgical outcome of portal hypertension and explore the risk-factors of long-term survival after operation. METHODS: The data of 149 patients (male 119, female 30, aged from 19 to 73 years old) with portal hypertension treated surgically from January 1996 to October 2007 was collected. Among these patients, there were 110 patients for Child A and 39 patients for Child B according to Child-Pugh classification. According to different surgical modality, all patients were divided into devascularization group (n = 85) and shunting group (n = 64). RESULTS: The follow-up rate was 78.8% and the average follow-up time was (46.3 +/- 30.4) months. The overall survival rates of 1-, 3-, 5- and 10-years were 95.6%, 88.7%, 83.4% and 65.1% respectively. Meanwhile the survival rates of 1-, 3-, 5- and 10-years in devascularization group and in shunting group were 95.4%, 87.7%, 80.6%, 56.3% and 95.8%, 90.1%, 86.8%, 72.6% respectively. There was no significant difference in survival rate between these two groups (P > 0.05). Child-Pugh classification has been the most important risk-factor that could influence long-term survival after operation by analysis of COX regression and it showed that the long-term survival time in Child A was longer than in Child B. The re-hemorrhage rates of 1-, 3- and 5-years in shunting group would be much better than in devascularization group. The rate of postoperative encephalopathy in devascularization group and shunting group was 6.9% and 6.1% respectively and there was no significant difference (P > 0.05). The portal venous pressure and flow of portal vein decreased significantly after shunting operation (P < 0.05). CONCLUSIONS: The mainly sole risk-factor of long-term survival for portal hypertension has been the classification of Child-Pugh, not surgical procedure. The individualized proximal splenorenal shunt is much better than devascularization in controlling variceal hemorrhage.

[Protective effect of heme oxygenase-1 induction in vivo to pancreas islet xenograft].

OBJECTIVE: To study the protective effect of islet xenograft and its possible mechanism of high expression of heme oxygenase-1 (HO-1) in donor pancreas islet induced by cobalt protoporphyrin (CoPP). METHODS: Male SD rats and C57BL/6 mouse were used as donors and recipients respectively. Donors were divided into 3 groups according to different pretreatment 24 hours before donation: control group (injected intraperitoneally with NaCl), induce group [injected intraperitoneally with cobalt-protoporphyrin (CoPP)], block group (injected intraperitoneally with CoPP and zinc protoporphyrin simultaneously). A modified approach was used for islet isolation.Recipients were rendered diabetic by intraperitoneal injection of streptozotocin. Islets were transplanted into mouse subrenal capsule. Postoperative mouse glycemia were monitored daily and normoglycemia time was compared among each group. The receptor mouse serum IL-10 was detected by ELISA approach, and real-time PCR was used to check the expression of IL-10 mRNA in islet graft tissues. The graft tissues were observed for the lymphocyte infiltration after HE staining. RESULTS: Diabetes mice accepted islets untreated, induced or blocked maintained the euglycemia for (9.3 +/- 1.4), (16.3 +/- 1.5) and (9.7 +/- 1.0) d respectively. The xeno-islets presented HO-1 over-expression survived much longer than that absent (P < 0.05), it was no significance between control group and block group (P > 0.05). The mouse islet serum IL-10 content after induction was (73.0 +/- 9.7) pg/ml, significantly higher than (30.6 +/- 3.9) pg/ml of the untreated group and (32.1 +/- 5.9) pg/ml of the blocked group (P < 0.05), there was no difference between control group and block group (P > 0.05). Moreover, the IL-10 mRNA expression up-regulated statistic significantly in HO-1 induced islet xeno-graft. Pathological examination showed that the graft lymphocyte infiltration of the induced group was obviously less serious than the other two groups. CONCLUSIONS: The higher expression of HO-1 induced by CoPP in vivo would significantly prolong graft survival time and its mechanism could be related to immune modulation of IL-10.

[A clinical study on splanchnic hemodynamic changes after orthotopic liver transplantation for patients with portal hypertension].

OBJECTIVE: To study the regularity of splanchnic hemodynamic changes after orthotopic liver transplantation (OLT) for patients with portal hypertension. At the same time, effect of such changes on splenomegaly, hypersplenism, collateral circulation and the postoperative liver function was discussed. METHODS: Between June 2002 and October 2005, 173 liver transplantations were performed. In 38 patients with portal hypertension undergoing OLT, the following parameters were measured before surgery and subsequently at 1, 3, 5, 7 days, 1, 6 months and 1, 2, 3 years after operation by using Color Doppler sonography: portal blood flow mean velocity (PBV), portal blood flow volume (PBF), hepatic artery resistance indexes (HA-RI) and spleen size. The same parameters were measured in 8 patients with acute liver failure and 20 healthy controls. Meanwhile to observe liver function and varicose vein of esophagus. RESULTS: In cirrhotics, PBV and PBF increased immediately after transplantation [from (13.7 +/- 4.2) cm/s to (58.4 +/- 25.2) cm/s and from (958 +/- 445) ml/min to (3024 +/- 1207) ml/min respectively, P < 0.05]. HA-RI also augmented [from (0.65 +/- 0.11) to (0.74 +/- 0.12), P < 0.05]. PBV returned to normal values after 6 months, PBF returned to normal value after 2 years. Spleen size decreased significantly, but splenomegaly persisted after 3 years. In addition the esophagogastric varix ameliorated significantly. CONCLUSIONS: Abnormal splanchnic hemodynamic changes for patients with portal hypertension still will long-term exist after OLT, but does not effect recovery of hypersplenism, esophagogastric varix and liver function.

Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury.

AIM: To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury. METHODS: From November 2005 to December 2006, eight patients with biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury were admitted to our hospital. Their clinical data were analyzed retrospectively. RESULTS: Bile duct injury was caused by cholecystectomy in the eight cases, including seven cases with laparoscopic cholecystectomy and one with mini-incision choleystectomy. According to the classification of Strasberg, type E1 injury was found in one patient, type E2 injury in three, type E3 injury in two and type E4 injury in two patients. Both of the type E4 injury patients also had a vascular lesion of the hepatic artery. Six patients received Roux-en-Y hepaticojejunostomy for the second time, and one of them who had type E4 injury with the right hepatic artery disruption received right hepatectomy afterward. One patient who had type E4 injury with the proper hepatic artery lesion underwent liver transplantation, and the remaining one with type E3 injury received external biliary drainage. All the patients recovered fairly well postoperatively. CONCLUSION: Roux-en-Y hepaticojejunostomy is still the main approach for such failed surgical cases with bile duct injury. Special attention should be paid to concomitant vascular injury in these cases. The optimal timing and meticulous and excellent skills are essential to the success in this surgery.

Preliminary clinical experience in liver retransplantation.

BACKGROUND: The past several decades have witnessed increasingly successful rates of liver transplantation. However, retransplantation remains the only choice for patients with irreversible graft failure after primary transplantation. This article aimed to summarize our clinical experience in liver retransplantation. METHODS: From June 2002 to December 2005, a total of 185 cases of liver transplantation including 8 cases of retransplantation were performed in our hospital. The clinical data were analyzed retrospectively. RESULTS: The rate of liver retransplantation was 4.32%. Retransplantation was indicated for the following reasons: biliary complication (3 cases), chronic rejection (2), hepatic artery thrombosis (1), uncontrollable acute rejection (1) and hepatitis B recurrence (1). The mean model of end-stage liver disease (MELD) scores before primary transplantation and retransplantation were 15.6 and 23.9, respectively (P<0.05). The MELD score reflected the severity of liver disease more precisely than the Child classification. The mean interval between the first and second transplantation was 316 days (78-725 days). The first three patients, with mean interval of 101 days, died of severe infection combined with multiple organ failure after retransplantation. The patients who underwent retransplantation more than six months after the first transplant had better outcomes. The one-year survival rate for retransplantation in our group was 62.5%. CONCLUSIONS: Liver retransplantation is the only means of saving the patient with hepatic allograft failure. Understanding of the indications for retransplantation, careful selection of operation timing, excellent surgical skills and meticulous postoperative management all contribute to the success of each case of retransplantation.

[Research of rat small intestinal mesentery lymphoid tissue stimulating allograft mixed lymphocyte reaction].

OBJECTIVE: To evaluate the effect of the small intestinal mesenteric lymphoid tissues stimulating mixed lymphocyte reaction with dendritic cells (DC) and peripheral blood monocyte cells (PBMC), and observe the changes of the MHC molecular expression on DC. METHODS: DC, PBMC and mixed lymphocyte were separated to culture from SD rats. Lymphoid tissue suspension was adopted from small intestinal mesentery of Wistar rats. In the mixed lymphocyte reaction (MLR), the cellular proliferation of small intestinal mesenteric lymphoid tissue antigen act on DC and PBMC was detected with cell counting of CCK-8 assay, the same assay used in small intestinal mesenteric lymphoid tissue antigen and ovalbumin (OVA) acting on DC. FACS analysis was performed after lymphoid tissue suspension stimulating DC to observe the MHC molecular expression. RESULTS: In the lymphoid tissue suspension, 91% of the cells was lymphocyte, others including granulocyte, plasmocyte, epithelium. The effect of stimulating mixed lymphocyte proliferation were higher in DC groups than in PBMC groups with the small intestinal mesenteric lymphoid tissue (P < 0.05). In the proportion of DC and mixed lymphocyte >or= 1:100 groups, the mixed lymphocyte proliferation were higher in the small intestinal mesenteric lymphoid tissues groups than in the OVA groups (P < 0.05). After stimulated by the small intestinal mesenteric lymphoid tissue, DC expressed higher MHC-I and -II molecules than control groups. CONCLUSIONS: The small intestinal mesenteric lymphoid tissue has high antigenicity; the antigen presenting ability of DC was much stronger than granulocytes; DC expresses high MHC-I and MHC-II molecules after stimulated by mixed lymphoid tissue suspension.

[Clinical analysis of infectious complications following abdominal cluster transplantation].

OBJECTIVE: To investigate the characteristic and management of postoperative infection in abdominal cluster transplantation. METHODS: Preliminary experience of two cases of abdominal cluster transplantation including small intestine was reviewed. RESULTS: Combination of five immunosuppressive agents based on tacrolimus was used. Severe Gram-negative bacillus infections occurred. The majority of invasive fungal infections was due to Candida species. Cytomegalovirus (CMV) infection increased monocytes and caused eosinopenia and an inversion of the CD4(+) to CD8(+) cell ratio in recipient I, and human CMV matrix proteins pp71 (CMV-pp71) was detected and identified in bile by PCR. Microabscesses in liver transplant biopsies were presented. CONCLUSIONS: Infectious complications after cluster transplantation were complicated. Strategies to optimize the immunity suppression protocol and early diagnosis and treatment will be important to reduce infection after abdominal cluster transplantation.

[Effects of selenium valence states and application concentrations on plant growth, ascorbate-glutathione cycle in Citrus junos cv. Ziyang Xiangcheng]. / 硒的价态与浓度对香橙幼苗生长和AsA-GSH循环的影响.

Potted Citrus. junos cv. Ziyang Xiangcheng seedlings were used to study the effects of selenium (Se) valence states (Se6+ and Se4+) on plant growth and antioxidants and antixodases in ascorbate(AsA)-glutathione (GSH) cycle. The results showed that Se6+ and Se4+ (from 1.0 mg·L-1 to 8.0 mg·L-1) stimulated the seedling growth by increasing plant height, leaf areas, and fresh or dry mass. Applying Se6+significantly increased plant Se levels mainly in leaf, and applying Se4+ slightly increased Se content mainly in root. Certain valence states and concentrations of Se increased leaf chlorophyll and hydrogen peroxide (H2O2) content. Se6+≤2.0 mg·L-1 treatments enhanced the activates of glutathione reductase (GR) and glutathione peroxidase (GPX), and the contents of GSH and oxidized glutathione (GSSG), while Se6+≥4.0 mg·L-1 treatments reduced the antioxidant contents and antixodase activities of GSH cycle. Moreover, Se4+≤ 2.0 mg·L-1 treatments increased the activities of dehydroascorbate reductase (DHAR) and ascorbate peroxidase (APX), and resulted in higher AsA/[AsA+dehydroascorbic acid (DHA)] ratio. When Se4+≥4.0 mg·L -1, the antioxidant contents and antixodase activities of GSH cycle were increased. Together, this study showed that different valence states and application concentrations of Se showed different influences on AsA-GSH cycle in citrus, and 2.0 mg·L-1 Se6+ and 4.0 mg·L-1 Se4+ were the best concentrations for plant growth.

Abdominal cluster transplantation and management of perioperative hemodynamic changes.

BACKGROUND: Multivisceral transplantation (MTX, or cluster transplantation) is defined as the transplantation of three or more abdominal organs en bloc, namely the liver together with the pancreatoduodenal complex, the stomach as well as the small bowel with/without the right hemicolon. Up to May 1999, only 72 cases were reported to the Intestinal Transplant Registry. Organ cluster transplantation may carry with complex hemodynamic alterations. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of multivisceral transplantation and the management of hemodynamic changes. METHODS: A Swan-Ganz catheter was placed to assist in monitoring the patients' hemodynamic status. After the transplantation, the 2 patients were closely observed in the intensive care unit in terms of vital signs;disseminated intravascular coagulation (DIC) including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and D-dimer, and arterial blood gas; and quantity and characteristics of drainage. Additionally, intra-abdominal hemorrhage was supervised by bedside B-ultrasonography or enhanced computed tomography (CT) examination. Whole blood viscosity was monitored 2 weeks after transplantation. The blood flow of the hepatic artery and portal vein and arterial resistant index were assessed routinely by Doppler ultrasonography. RESULTS: Hemodynamic changes were observed during perioperation. Liver and renal function recovered within one week after transplantation. Enteral feedings and oral intake were gradually increased with a reciprocal decrease in parenteral nutrition. Despite systemic antibiotics were given according to the results of frequent cultures, patient 1 died from cytomegalovirus (CMV) infection 4 months after transplantation and patient 2 died of a systemic sepsis 2 months after the operation. CONCLUSIONS: Many factors contribute to the success of multivisceral transplantation. In order to maintain hemodynamics stable during perioperation, preoperative coagulatory function should be corrected, and stable circulation, serum electrocyte balance, and normal body temperature should be kept during the operation in addition to the treatment of intra-abdominal hemorrhage and making up for the loss of body fluid. However, complications, infection and rejection are barriers for the improvement of graft survival.

[Pharmacokinetics of mycophenolic acid in Chinese patients with liver transplant].

AIM: To investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients. METHODS: Thirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software. RESULTS: The plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients. CONCLUSION: In view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

[Clinical degree of the superior mesenteric vein involvement with the surgery in the pancreas uncinate process carcinoma].

OBJECTIVE: To create the clinical degree of the superior mesenteric vein (SMV) involvement in pancreas uncinate process carcinoma (PUPC) and its clinical significance to be discussed. METHODS: According to the contiguous relationship between the SMV and the PUPC, the clinical degree of SMV involvement in PUPC are as followings four grades, 1 grade, the grade of clear boundary. 2 grade, the grade of fuzzy boundary. 3 grade, the grade of dissolved boundary. 4 grade, the grade of SMV infringed. The coherence between the type under the CT scan (Tx) and the type under the inoperative judgement (Sx) were analyzed with Kappa-test. RESULTS: There is a significant difference between the grade of SMV involvement and the surgery. The resection rate is 100% in 1st grade, 97.4% in 2nd grade, 65.8% in 3rd grade and 21.7% in 4th grade. There is coherent in the degree judgement between the CT scan and the inoperative inspection (U = 15.96, P < 0.01). CONCLUSIONS: There is clinical significance to establish the degree of SMV involvement in PUPC. It is helpful for clinician to accurately know its anatomic characteristic and decide more reasonable surgical strategy.

Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial.

Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50-0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27-0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9<466 U/ml were more responsive to chemotherapeutic agents than those with CA19-9≥571 U/ml (88.9% vs 0%, P<0.001). We conclude that the combination of GEM plus S-1 provides a better OS, PFS and response rate than S-1 monotherapy, but it did not significantly differ from GEM monotherapy. (ChiCTR-TRC-14004733).