[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.

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).

[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.

Heme Oxygenase-1 Promoter Polymorphism Protects Liver Allograft.

Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival (p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver (p < 0.01). Additionally, in recipients of small-carrier allografts, cold ischemia time (<10 h or ≥10 h) did not affect the total bilirubin significantly. Our study suggested a protective function of donor-derived heme oxygenase-1 gene promoter polymorphism on orthotopic liver allograft function after transplantation.

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).

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.

Prognostic evaluation of patients undergoing living-donor liver transplant by APACHE II and MELD scores.

OBJECTIVES: We hypothesized that the combination of APACHE II and Model for End-Stage Liver Disease systems would work satisfactorily in patients admitted to intensive care unit after living-donor liver transplant. MATERIALS AND METHODS: Data were retrospectively collected from the database of our surgical team. The study included 38 patients (hepatitis B virus cirrhosis, 47.4%; hepatocellular carcinoma, 28.9%; other diseases, 23.7%). Laboratory values were obtained. Vital signs, Glasgow Coma scale scores, and urine output were abstracted. Variables included age, sex, acute physiology score, APACHE II score, APACHE II-predicted intensive care unit and hospital mortality, predicted length of intensive care unit, and hospital stay. Patients' actual length of intensive care unit and hospital stays, intensive care unit and hospital discharge status, and discharge location were recorded. Standardized mortality ratios were calculated. Discrimination and calibration of APACHE II were assessed. All patients were divided into 3 groups: Model for End-Stage Liver Disease score: >25, 18 to 25, and <18. Predicted hospital mortality was calculated and compared. RESULTS: Mean APACHE II scores of survivors and non-survivors were 13.03 and 23.67. Mean risk of death was 7.05% and 25.07%. APACHE II scores and risk of death between survivors and non-survivors was significantly different (P <.001). The cutoff value of APACHE II score and Model for End-Stage Liver Disease score in the receiving operating characteristic curve was 20 and 25. Patients with APACHE II scores greater than 20 or Model for End-Stage Liver Disease scores greater than 25 had higher predicted hospital mortality after living-donor liver transplant. CONCLUSIONS: The modified APACHE II model provides an accurate prognosis of patients receiving a living-donor liver transplant. The combined application of Model for End-Stage Liver Disease score and APACHE II score can improve the predictive accuracy.

Outcomes of surgical approaches for gastric cancer with portal hypertension.

OBJECTIVE: The influence of surgical approaches on patients with gastric cancer with portal hypertension is unknown. The aim of the study was to investigate the outcomes in such patients who had undergone curative surgery for gastric cancer. PATIENTS AND METHODS: The clinical data of 60 patients with portal hypertension undergoing curative surgery for gastric cancer or simultaneous surgery for portal hypertension were retrospectively analyzed. RESULTS: Radical gastrectomy alone had no tremendous impact on postoperative liver function, but simultaneous surgery for portal hypertension affected patients' liver function dramatically (P<0.001). For those who underwent surgery for portal hypertension simultaneously, the incidence of complications on patients with Child's B was much higher than that of patients with Child's A (P<0.001). However, the incidence of complications did not differ between Child's A and Child's B patients who underwent radical gastrectomy alone. In addition, patients undergoing simultaneous surgery for portal hypertension displayed more severe complications than did those who underwent radical gastrectomy alone (P<0.001). Age, tumor stage, and simultaneous surgery for portal hypertension were the independent risk factors for the deterioration of liver function (P<0.05), and the survival time of patients undergoing simultaneous surgery for portal hypertension was significantly shorter than that of patients undergoing radical gastrectomy alone (P<0.05). CONCLUSION: Individualized selection of surgical approaches for the treatment of gastric cancer with portal hypertension should be decided by preoperative liver function. Simultaneous management of portal hypertension was not advocated.

Higher efficacy of antiviral therapy after major hepatectomy in patients with hepatitis B virus-related hepatocellular carcinoma of less than 3 cm.

OBJECTIVE: Little is known about the role of antiviral therapy for patients with hepatitis B who underwent curative hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess whether antiviral therapy after hepatectomy improves the prognosis of HCC in preoperatively antiviral-free patients. MATERIALS AND METHODS: This was a retrospective study of postoperative antiviral treatment in patients (n=87) who underwent curative hepatectomy for HCC. Clinicopathological features and disease-free survival (DFS) were assessed. Patients were followed up to monitor HCC recurrence (median of 31 months). RESULTS: In patients with HCC up to 3 cm (n=36), antiviral therapy reduced serum alanine transminase levels after 6 months of treatment (-26.3%, P<0.01). Among these patients, there was a significant prolongation of DFS in patients who received antiviral therapy after hepatectomy compared with those who did not (P=0.006). However, in patients with HCC greater than 3 cm (n=51), antiviral therapy did not decrease alanine transminase levels (+32.8%, P<0.01). In these patients, antiviral therapy had no effect on DFS (P>0.05). Using multivariate analysis, postoperative antiviral therapy was found to be an independent prognostic factor that was associated with a better DFS in patients with HCC up to 3 cm (odds ratio=0.220, 95% confidence interval: 0.120-0.434, P=0.008). CONCLUSION: Antiviral therapy improved the prognosis of hepatitis B virus-related HCC up to 3 cm. Antiviral therapy should be considered a standard postoperative adjuvant therapy of hepatitis B virus-related HCC.

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.

Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function.

BACKGROUND: The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. METHODS: Islet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1ß level in serum and their mRNA and HO-1 mRNA and protein expression were examined. RESULTS: Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. CONCLUSIONS: The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.

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.

Surgical management of benign duodenal tumours.

BACKGROUND: While benign duodenal tumours are rare compared with malignant tumours, they comprise a wide variety of pathologies. Despite their diagnostic challenge, the optimal management of benign duodenal tumours remains undefined. We aimed to review the diagnosis and surgical treatment of benign duodenal tumours. METHODS: Records of all patients with post-operative pathological diagnosis of benign duodenal tumour were retrieved. Information on clinical presentations, diagnostic methods, tumour locations, surgical approaches, pathological results and patient outcomes were analysed. RESULTS: The operative spectrum included local resection in 8 cases, segmental duodenectomy in 1 case, subtotal gastrectomy in 1 case, papilla resection with sphincteroplasty in 3 cases and pancreaticoduodenectomy in 5 cases. The post-operative pathology results indicated 5 cases of adenoma, 2 cases of tubular adenoma, 2 cases of villous adenoma, 2 cases of tubulovillous adenoma, 2 cases of hamartoma and 1 case each of hamartomatous polyp, Brunner's adenoma, adenomyoma, fibromatosis and ectopic pancreas. Post-operatively, one patient died of unrelated disease, one case was lost in follow-up and the remaining patients survived recurrence-free with a good quality of life. CONCLUSION: The presentation of benign duodenal tumours is non-specific, with upper abdominal discomfort and upper gastrointestinal bleeding as common symptoms. Surgical resection is the preferable therapeutic choice with satisfactory prognosis.

Diagnosis and surgical treatment of multiple endocrine neoplasia.

BACKGROUND: Multiple endocrine neoplasia (MEN) is relatively rare. But more patients could be found by detailed examination. We discuss the diagnosis and surgical treatment of MEN. METHODS: The clinical data of 95 MEN cases were retrospectively analyzed. There were 30 cases of MEN1 including 19 cases from 6 families. The MEN1 gene mutation was detected in 81.48% of cases admitted after 1997. There were 22 cases of primary hyperparathyroidism (PHPT), 10 cases of enteropanceatic tumor including 9 cases of insulinoma, 15 cases of pituitary adenoma, 9 cases of adrenal adenoma, 2 cases of thymic carcinoid. Two patients had 4 glands involved, 3 patients had 3 glands involved, 16 patients had 2 glands involved, and 6 patients had only one gland involved. Three patients had neither clinical symptoms nor biochemical changes, and was diagnosed by MEN1 gene mutation. Six patients presented with nephrolithasis and 6 patients had impaired pancreatic endocrine function. There were 60 cases of MEN2a and 5 cases of MEN2b. 58 cases of MEN2a belongs to 19 kindreds. All MEN2a patients but one presented RET gene mutation in codon 634, and all MEN2b cases had mutation in codon 918. 48 cases of MEN2a had thyroid masses with elevated calcitonin levels. 27 patients had pheochromocytoma including 12 cases of multiple foci and 5 malignancy. 13 patients presented with hyperparathyroidism. 5 MEN2b patients had medullary thyroid carcinoma and mucosal ganglioneuromatosis with Marfanoid. Among them, 3 patients had bilateral pheochromocytoma. RESULTS: In MEN1, subtotal parathyroidectomy was performed in 12 patients with PHPT and one patient received parathyroid adenoma enucleation. Insulinomas were enucleated in 4 patients. Two patients underwent thymus tumor extirpation. Total thyroidectomy with bilateral dissection of regional lymph nodes was performed in 16 patients with MEN2a and nodule enucleation was performed in 9 patients. Twenty two MEN2a patients underwent pheochromocytoma enucleation including bilateral adrenal resection in 10 cases. 5 MEN2b patients underwent total thyroidectomy with bilateral lymph node dissection. Among them, 3 cases underwent bilateral adrenal operations. CONCLUSIONS: MEN varies in symptoms. Germline mutation test is helpful in establishing a diagnosis. Surgical management should be aimed at the improvement of life quality in MEN1 and prevention of the fetal tumors in MEN2.

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.

[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.

[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.

Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China.

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.