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Background We investigated whether the outcome of organs from donors after circulatory death (DCD) can be improved by the addition of mcc950 to the perfusate of the hypothermic machine perfusion (HMP) system and intravenous mcc950 injection after transplantation in a pig liver transplantation model. Methods Thirty-six healthy Bama mini pigs randomized into 3 groups. All the DCD livers were preserved in an HMP system after 2 hours of simple cold storage. In HMP-Postop group, mcc950 was added to the perfusate; in the control group and Postop group, the perfusate was normal LPS. After transplantation, the pigs in the Postop group and HMP-Postop group were intravenously administered 3 mg/kg mcc950, at the time of reperfusion and on day 2 and day 3 after transplantation. During the 3-day follow-up period, general operative characteristics, and serological markers and histological features related to ischemia reperfusion injury were examined. Results The HMP-Postop group suffer the lightest ischemia reperfusion injury (IRI), and functioned best after transplantation. Model for the Early Allograft Function Score (predictor of long-term survival), degree of injury in the hepatocytes and rate of apoptosis was lowest in the HMP-Postop group. Further, in the HMP-Postop group, the nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 inflammasome pathway activation was lowest, and the level of IL-1β was lowest. Postop group functioned better than control group, but not comparable with HMP-Postop group. Conclusions The outcome of DCD organs can be improved by the addition of mcc950 to the perfusate of the HMP system and intravenous injection of mcc950 after transplantation.

Background Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death (DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. Methods We divided 195 Sprague-Dawley rats into five groups: the control (n = 39), warm ischemic time (WIT) 15 min (n = 39), WIT 30 min (n = 39), WIT 45 min (n = 39), and WIT 60 min (n = 39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemia-related damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio (LPR) was calculated. Results The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. Conclusion Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.

We report the clinical and laboratory findings and successful management of seven patients with critical coronavirus disease 2019 (COVID-19) requiring mechanical ventilation (MV). The patients were diagnosed based on epidemiological history, clinical manifestations, and nucleic acid testing. Upon diagnosis with COVID-19 of critical severity, the patients were admitted to the intensive care unit, where they received early noninvasive–invasive sequential ventilation, early prone positioning, and bundle pharmacotherapy regimen, which consists of antiviral, anti-inflammation, immune-enhancing, and complication-prophylaxis medicines. The patients presented fever (n = 7, 100%), dry cough (n = 3, 42.9%), weakness (n = 2, 28.6%), chest tightness (n = 1, 14.3%), and/or muscle pain (n = 1, 14.3%). All patients had normal or lower than normal white blood cell count/lymphocyte count, and chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs. Nucleic acid testing confirmed COVID-19 in all seven patients. The median MV duration and intensive care unit stay were 9.9 days (interquartile range, 6.5–14.6 days; range, 5–17 days) and 12.9 days (interquartile range, 9.7–17.6 days; range, 7–19 days), respectively. All seven patients were extubated, weaned off MV, transferred to the common ward, and discharged as of the writing of this report. Thus, we concluded that good outcomes for patients with critical COVID-19 can be achieved with early noninvasive–invasive sequential ventilation and bundle pharmacotherapy.

Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multigene family with isoform-specific regulation of vascular smooth muscle (VSM) functions. In previous studies, we found that vascular injury resulted in VSM dedifferentiation and reduced expression of the CaMKIIγ isoform in medial wall VSM. Smooth muscle knockout of CaMKIIγ enhanced injury-induced VSM neointimal hyperplasia, whereas CaMKIIγ overexpression inhibited VSM proliferation and neointimal formation. In this study, we evaluated DNA cytosine methylation/demethylation as a mechanism for regulating CaMKII isoform expression in VSM. Inhibition of cytosine methylation with 5-Aza-2′-deoxycytidine significantly upregulated CaMKIIγ expression in cultured VSM cells and inhibited CaMKIIγ downregulation in organ-cultured aorta ex vivo. With the use of methylated cytosine immunoprecipitation, the rat Camk2g promoter was found hypomethylated in differentiated VSM, whereas injury- or cell culture-induced VSM dedifferentiation coincided with Camk2g promoter methylation and decreased expression. We report for the first time that VSM cell phenotype switching is accompanied by marked induction of thymine DNA glycosylase (TDG) protein and mRNA expression in injured arteries in vivo and in cultured VSM synthetic phenotype cells. Silencing Tdg in VSM promoted expression of CaMKIIγ and differentiation markers, including myocardin, and inhibited VSM cell proliferation and injury-induced neointima formation. This study indicates that CaMKIIγ expression in VSM is regulated by cytosine methylation/demethylation and that TDG is an important determinant of this process and, more broadly, VSM phenotype switching and function.NEW & NOTEWORTHY Expression of the calcium calmodulin-dependent protein kinase II-γ isoform (CaMKIIγ) is associated with differentiated vascular smooth muscle (VSM) and negatively regulates proliferation in VSM synthetic phenotype (VSMSyn) cells. This study demonstrates that thymine DNA glycosylase (TDG) plays a key role in regulating CaMKIIγ expression in VSM through promoter cytosine methylation/demethylation. TDG expression is strongly induced in VSMSyncells and plays key roles in negatively regulating CaMKIIγ expression and more broadly VSM phenotype switching.

Background Lateral habenula nucleus (LHb) has recently been noted for its role in stress-induced depressive disorder. Yet little is known about the mechanisms by which external stimuli or depression induces pathological alteration in the LHb. Methods Chronic unpredictable mild stress (CUMS) was employed to model depressive-like behaviors in adult rats. We examined expressions of DNA methyltransferases (Dnmts) mRNA and protein and global DNA methylation levels in LHb of CUMS-induced depressive rats. Then 5-aza-2′-deoxycytidine (5-aza), a Dnmts inhibitor, was infused into the LHb of native rats to test the effects of hypomethylation in the LHb. The gene expressions in the LHb and the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in dorsal raphe nucleus (DRN) were examined in 5-aza infusion rats by quantitative real-time PCR and high performance liquid chromatography, respectively. Results Rats were exposed to CUMS for 21 days and depressive-like behaviors were induced as expected. We observed significant decrease in mRNA and protein expressions of Dnmt1 and DNA hypomethylation in LHb of depressive rats. These phenomenon suggests that CUMS-induced depressive-like behaviors are related with DNA hypomethylation in the LHb. Local 5-aza infusion into LHb of native rat resulted in global DNA hypomethylation in the LHb and induced depressive-like behaviors which are featured with lack of interest and investment in the environment, behavioral despair and anhedonia. Moreover, DNA hypomethylation in the LHb increased transcription of β calcium/calmodulin dependent protein kinase II and glutamate receptor 1 in the LHb and attenuated the levels of 5-HT and 5-HIAA in the DRN. Our data suggested that alteration of DNA methylation in the LHb may control 5-HT neuronal activity in the DRN to regulate emotional state. Conclusions DNA hypomethylation in the LHb is involved in the development of depressive-like behavior and suitable methylation state contributes to the emotional stabilization.

Vascular smooth muscle (VSM) expresses calcium/calmodulin-dependent protein kinase II (CaMKII)-δ and -γ isoforms. CaMKIIδ promotes VSM proliferation and vascular remodeling. We tested CaMKIIγ function in vascular remodeling after injury. CaMKIIγ protein decreased 90% 14 d after balloon injury in rat carotid artery. Intraluminal transduction of adenovirus encoding CaMKIIγC rescued expression to 35% of uninjured controls, inhibited neointima formation (>70%), inhibited VSM proliferation (>60%), and increased expression of the cell-cycle inhibitor p21 (>2-fold). Comparable doses of CaMKIIδ2 adenovirus had no effect. Similar dynamics in CaMKIIγ mRNA and protein expression were observed in ligated mouse carotid arteries, correlating closely with expression of VSM differentiation markers. Targeted deletion of CaMKIIγ in smooth muscle resulted in a 20-fold increase in neointimal area, with a 3-fold increase in the cell proliferation index, no change in apoptosis, and a 60% decrease in p21 expression. In cultured VSM, CaMKIIγ overexpression induced p53 mRNA (1.7 fold) and protein (1.8-fold) expression; induced the p53 target gene p21 (3-fold); decreased VSM cell proliferation (>50%); and had no effect on expression of apoptosis markers. We conclude that regulated CaMKII isoform composition is an important determinant of the injury-induced vasculoproliferative response and that CaMKIIγ and -δ isoforms have nonequivalent, opposing functions.—Saddouk, F. Z., Sun, L.-Y., Liu, Y. F., Jiang, M., Singer, D. V., Backs, J., Van Riper, D., Ginnan, R., Schwarz, J. J., Singer, H. A. Ca2+/calmodulin-dependent protein kinase II-γ (CaMKIIγ) negatively regulates vascular smooth muscle cell proliferation and vascular remodeling.

Better efficacy for predicting the risk of transplantation rejection could be achieved by intergenic interactions among single nucleotide polymorphisms (SNPs) compared with one SNP. In this study, we explored the forewarning function of interactions among SNPs in nucleotide excision repair (NER) genes. Thirty-eight polymorphisms in eight NER genes were genotyped by Sequenom MassARRAY platform, including XPA, XPC, DDB2, XPB (ERCC3), XPD (ERCC2), ERCC1, XPF (ERCC4), and XPG (ERCC5). The haplotype analysis suggested that XPA rs3176629-rs2808668 C-T and ERCC5 G-C-C-T and G-C-T-C (OR = 1.81, 7.72 and 3.46, respectively) increased the risk of transplantation rejection; while ERCC5 rs2094258-rs751402-rs2296147-rs1047768 A-C-T-T decreased the risk (OR = 0.35). Multiple logistic regression and multifactor dimensionality reduction (DMR) analyses consistently revealed intergenic interactions among ERCC2 rs50871, ERCC5 rs1047768, and XPC rs2228001 SNPs for the risk of transplantation rejection. Taken together, the interactions among XPC rs2228001, ERCC2 rs50871 and ERCC5 rs1047768 SNPs were associated with the risk of transplantation rejection.

Aims and background Hepatobiliary cystadenoma and cystadenocarcinoma are rare cystic lesions of the liver. The aim of the study was to discuss the clinical features, diagnostic methods and surgical treatment of hepatobiliary cystadenoma and cystadenocarcinoma in our hospital. Methods Six patients with hepatobiliary cystadenomas and four with hepatobiliary cystadenocarcinomas were evaluated. We collected detailed clinical data, and all patients were followed. Results Three patients of the 6 with cystadenomas and 2 patients of the 4 with cystadenocarcinomas had marked elevation of CA19-9 (average, 707.0 U/ml and 1078.5U/ml, respectively). CT scan with contrast revealed typical lesions in all 10 cases, i.e., cyst-occupying lesions with separations in the liver. All patients with hepatobiliary cystadenoma were treated by partial hepatectomy. None of them recurred at a mean follow-up of 40 months. Three patients with hepatobiliary cystadenocarcinoma underwent hepatectomy, without recurrence or metastasis at a mean follow-up of 32 months. Conclusions Tumor markers (CA19-9) and imaging findings may be helpful for an early diagnosis. Complete resection is still the best choice. Even for hepatobiliary cystadenocarcinoma, considering the low malignant grade, we suggest that for the best prognosis radical excision should be attempted.

Granular cell tumor is rare and accounts for approximately 0.5 % of all soft tissue tumors. The malignant granular cell tumor, especially cutaneous malignant granular cell tumor is extremely rare. The present case is the first patient of primary cutaneous malignant granular cell tumor reported from China in English. A review of the literature is performed, and the presentation, position, pathological diagnosis, treatment and prognosis of the patients with cutaneous malignant granular cell tumor of the reported cases before is analysed.

Aims We have compared hypothermic oxygenated machine perfusion (HOPE) with simple cold storage (SCS) in liver preservation with a porcine model of donor after cardiac death (DCD). Methods A DCD model was developed in 10 hybrid pigs by apnea. Livers were harvested after 30 min of warm ischemia (WI) and randomly preserved using HOPE (HOPE group, five pigs, dual perfusion via portal vein and hepatic artery) or SCS (SCS group, five pigs) methods. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, lactic acid, and pyruvic acid were measured by microdialysis analyzer. Results Histological morphology of liver tissue was significantly affected by 30 min of WI. HOPE significantly delayed histological morphology change and cell apoptosis. Release of ALT and AST was significantly higher in SCS group compared to HOPE group (p

Airway smooth muscle (ASM) is a key target cell in allergen-induced asthma known to contribute to airway hyperresponsiveness (AHR) and chronic airway remodeling. Changes in ASM calcium homeostasis have been shown to contribute to AHR although the mechanisms and Ca(2+) signal effectors are incompletely understood. In the present study, we tested the function of ASM multifunctional protein kinase Ca(2+)/calmodulin-dependent kinase II (CaMKII) isoforms CaMKIIδ and CaMKIIγ in allergen-induced AHR and airway remodeling in vivo. Using a murine model of atopic asthma, we demonstrate that CaMKIIδ protein is upregulated in ASM derived from ovalbumin (OVA)-treated animals compared to controls. A genetic approach to conditionally knock out smooth muscle CaMKIIδ and CaMKIIγ in separate Cre-loxp systems was validated, and using this loss-of-function approach, the function of these CaMKII isoforms was tested in ovalbumin (OVA)-induced airway remodeling and AHR. OVA treatment in control mice had no effect on ASM remodeling in this model of AHR, and CaMKIIδ knockouts had no independent effects on ASM content. However, at 1 day post-final OVA challenge, OVA-induced AHR was eliminated in the CaMKIIδ knockouts. OVA-induced peribronchial inflammation and bronchoalveolar lavage fluid (BALF) levels of the Th2 cytokine IL-13 were significantly decreased in the CaMKIIδ knockouts. Unexpectedly, we found increased peribronchial eosinophils in the smooth muscle CaMKIIδ knockouts compared to control animals at 1 day post-final challenge, suggesting that lack of ASM CaMKIIδ delays the progression of AHR rather than inhibiting it. Indeed, when AHR was determined at 7 days post-final OVA challenge, CaMKIIδ knockouts showed robust AHR while AHR was fully resolved in OVA-challenged control mice. These in vivo studies demonstrate a role for smooth muscle CaMKIIδ in promoting airway inflammation and AHR and suggest a complex signaling role for CaMKIIδ in regulating ASM function. These studies confirm the diverse roles of ASM cells as immune effectors that control AHR and call for further studies into CaMKIIδ-mediated signaling in ASM cells during disease.

MicroRNAs could mediate the targeted coding gene and the targeted non-coding RNA to form endogenous competition, which have an important regulatory role in tumorigenesis of many types of cancer, including hepatocellular carcinoma. The goal of this study was to characterize the role of miR-200b in the pathogenesis of hepatocellular carcinoma. We identified miR-200b that was predicted to regulate RhoA and circ_000839. Our data establish that miR-200b is expressed at a relatively low level in hepatocellular carcinoma ( p

Background Expanded criteria donors (ECDs) are currently accepted as potential sources to increase the donor pool and to provide more chances of kidney transplantation for elderly recipients who would not survive long waiting periods. Hypothermic machine perfusion (HMP) is designed to mitigate the deleterious effects of simple cold storage (CS) on the quality of preserved organs, particularly when the donor is in a marginal status. Methods We compared the transplant outcomes in patients receiving ECD kidneys with either HMP or CS graft preservation. Articles from the MEDLINE, EMBASE and Cochrane Library databases were searched and all studies reporting outcomes from HMP versus CS methods of kidney preservation were included in this meta-analysis. The parameters analyzed included the incidence of delayed graft function (DGF), primary non-function (PNF) and one-year graft and patient survival. Results A total of seven studies qualified for the review, involving 2374 and 8716 kidney grafts with HMP or CS preservation respectively, all from ECD donors. The incidence of delayed graft function (DGF) was significantly reduced with an odd ratio(OR) of 0.59 (95% CI 0.54–0.66, P

One transcription factor mediator of Ca(2+)-signals is cAMP response element-binding protein (CREB). CREB expression and/or activity negatively correlates with vascular smooth muscle (VSM) cell proliferation and migration. Multifunctional Ca(2+)/calmodulin-dependent protein kinases, including CaMKII, have been demonstrated to regulate CREB activity through both positive and negative phosphorylation events in vitro, but the function of CaMKII as a proximal regulator of CREB in intact cell systems, including VSM, is not clear. In this study, we used gain- and loss-of-function approaches to determine the function of CaMKIIδ in regulating CREB phosphorylation, localization, and activity in VSM. Overexpression of constitutively active CaMKIIδ specifically increased CREB phosphorylation on Ser(142) and silencing CaMKIIδ expression by siRNA or blocking endogenous CaMKII activity with KN93 abolished thrombin- or ionomycin-induced CREB phosphorylation on Ser(142) without affecting Ser(133) phosphorylation. CREB-Ser(142) phosphorylation correlated with transient nucleocytoplasmic translocation of CREB. Thrombin-induced CREB promoter activity, CREB binding to Sik1 and Rgs2 promoters, and Sik1/Rgs2 transcription were enhanced by a kinase-negative CaMKIIδ2 (K43A) mutant and inhibited by a constitutively active (T287D) mutant. Taken together, these studies establish negative regulation of CREB activity by endogenous CaMKIIδ-dependent CREB-Ser(142) phosphorylation and suggest a potential mechanism for CaMKIIδ/CREB signaling in modulating proliferation and migration in VSM cells.

BACKGROUND/AIMS There are studies that report that liver metastases rarely occur in patients with cirrhosis. This study evaluates the relationship between the incidence of liver metastases from colorectal cancer (CRC) and chronic hepatitis virus infection in patients. METHODOLOGY Three hundred and fifty-four cases of advanced CRC from our hospital were evaluated. The patients were divided into a chronic hepatitis virus infection group and a non-hepatitis virus infection group. The two groups were compared regarding the incidence of colorectal liver metastases and survival. The criterion of colorectal liver metastases was based on liver CT examination and intraoperative exploration results. RESULTS There were two cases with colorectal liver metastases among the seventy cases of the chronic hepatitis virus infection group. The rate of liver metastases was 2.86%. There were 48 cases with colorectal liver metastases among 284 cases of the non-hepatitis virus infection. The rate of liver metastases was 16.9%. The incidence of colorectal liver metastases between the two groups was significantly different (p

The majority of pancreatic insulinomas are of small size and conventional imaging examinations such as percutaneous ultrasonography (US), Computerized Tomography (CT) and MRI usually fail to reveal the lesion. In this article we describe the potential role of combining arteriography with CT, which is superior to single arteriography or CT.A 45-year-old man who suffered from significant catecholaminergic and neuroglycopenic symptoms, such as hypodynamia, sweating, impaired memory and confusion, was diagnosed with insulinoma by biochemical tests. The serum level of glucose of fast in the morning was as low as 1.2 mmol/L, coincident with the low serum level of glucose; the serum level of insulin was 28.77 mIU/L. The fasting insulin-to-glucose ratio was higher than 0.4. The C-peptide of 1097.62 pmol/L was higher than normal. The lesion was not identified on US, CT scan or arteriography. However the combination of arteriography with CT revealed the small insulinoma located at junction of the body and the tail of the pancreas, about 1.0 x 0.8 cm.Intraoperative ultrasound (IOUS) verified the lesion which located in the posterior and superior aspect of the pancreas and spleen-preserving distal pancreatectomy was performed. Histopathology confirmed the diagnosis. After the surgery the patient underwent a good recovery and was discharged two weeks later. He has developed no further episodes of hypoglycemia two years after the surgery.Combining arteriography with CT is a valuable examination for insulinoma, and IOUS is helpful to verify the lesion. Entire excision of the lesion is the best way of treatment.

Background. Three commonly used sutures were tested in a pig model of bile duct anastomosis to assess their relative contributions to inflammation and scarring.Methods. Thirty pigs were randomised to bile duct division and anastomosis with either polyglyconate (Maxon), polyglactin 910 (Vicryl) or polypropylene (Prolene). Half the animals were sacrificed at two weeks and the remainder at 23 weeks. Anastomoses were assessed by cholangiography, scanning electron microscopy and light microscopy.Results. There was less short term histological reaction with the two monofilament materials, Prolene and Maxon, compared to the braided suture Vicryl. Maxon was associated with less long term inflammation than Prolene, was found to handle better, and has an advantage over Prolene by being absorbable.Conclusion. Maxon is an optimal suture for bile duct anastomoses. Its long term absorption characteristics make it suitable for situations where bile duct healing may be delayed.

General anesthetics are believed to induce amnesia. However, propofol can ameliorate cognitive deficits induced by electroconvulsive therapy (ECT), a treatment for mental disorders. This study aimed at investigating the possible molecular mechanism as well as the effects of propofol on learning-memory impairment in depressed rats induced by ECS (electroconvulsive shock, the analog of ECT to animals). Rats were treated with ECS (or sham ECS) pretreated with intraperitoneal injection of propofol (100 mg/kg) (or normal saline, 0.01 l/kg) after being treated with chronic unpredictable mild stresses to reproduce an animal model of depression. Sucrose preference test, open field test, and Morris water maze were used to assess behavioral changes. Hippocampal glutamate (Glu) and γ-aminobutyric acid (GABA) levels were measured with liquid chromatography, and glutamic acid decarboxylase 65 (GAD65) was assayed immunohistochemically. Additionally, rats undergoing ECS that were pretreated with pentobarbital sodium (45 mg/kg) were included for behavioral tests and electroencephalogram recording for comparison with rats undergoing ECS that were pretreated with propofol or normal saline. ECS rats pretreated with propofol or pentobarbital sodium exhibited similar decreased seizure durations as compared with ECS rats pretreated with normal saline. ECS pretreated with normal saline aggravated learning-memory deficits whereas ECS pretreated with propofol or pentobarbital sodium did not. Rats undergoing ECS pretreated with propofol showed better memory than those undergoing ECS after pretreatment with pentobarbital sodium. ECS pretreated with normal saline downregulated the ratio of Glu/GABA and upregulated GAD65 expression; all these molecular changes were nearly normalized to the level of control group by ECS pretreated with propofol. There were no significant differences of depressive behaviors between groups treated with ECS. The data suggest that propofol alleviated ECS-induced learning-memory impairment without interfering with the antidepressant efficacy of ECS, possibly by inhibiting excessive expression of GAD65 and maintaining the balance between glutamatergic and GABAergic amino acids neurotransmitters in the hippocampus.

To evaluate the correlations between MELD score and left ventricular function in patients with end-stage liver disease.A total of 92 patients who prepared for orthotopic liver transplantation from January 2002 to May 2008 were enrolled in this study. Of these Patients, 75 were males and 17 were females, and the mean age was 50.3+/-9.5 years; 85 were cirrhosis, 7 were cirrhosis with primary liver cancer. Preoperative information, including biochemical parameters, coagulation parameters, indicators of hepatitis virology, two-dimensional echocardiography and electrocardiogram were collected. According to MELD (the Model for End-stage Liver Disease) scoring system, these subjects were categorized into three groups: MELD score is less than or equal to 9 points (31 cases, 33.7%); 10 is less than or equal to MELD score is less than or equal to 19 points (45 cases, 48.9%); MELD score is more than or equal to 20 points (16 cases, 17.4%). The relationships between MELD score and classification and cardiac function were determined by chi-square test, analysis of variance, rank sum test and correlation analysis, et al.MELD score was significantly correlated with left atrial diameter (LAD), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), aortic flow (AF), cardiac output (CO), QRS interval (QRSI) and corrected QT interval (QTc) (r = 0.317, 0.341, 0.228, 0.387, 0.325, 0.209 and 0.347, respectively; P value less than 0.01, respectively); except QRSI, these variables and left ventricular posterior wall thickness (LVPWT) were also correlated with INR (a MELD component) (r = 0.282, 0.319, 0.322, 0.435, 0.275, 0.320 and 0.237, respectively; P value less than 0.01, respectively); LAD, LVEDD, AF, CO and QTc were correlated with serum total bilirubin (r = 0.241, 0.219, 0.357, 0.246 and 0.253, respectively; P value less than 0.05, respectively); IVST and E/A ratio (A blood flow [from left atrium to left ventricular] velocity ratio between early diastole [E wave] and late diastole[A wave] ) were correlated with serum creatinine (r = 0.216 and -0.343; P value less than 0.05 and 0.01); the proportion of E/A is less than or equal to 1 in all subjects was 46.7% (43/92), and 48.4% (15/31), 35.6% (16/45) and 75.0% (12/16) in each group, besides, there was statistically significant difference between 10 is less than or equal to MELD score is less than or equal to 19 points group and MELD score is more than or equal to 20 points group (X2 = 7.359, P = 0.009).There are different degrees of left ventricular structure, function and electrophysiological changes in patients with end-stage liver disease, these anomalies also will be increased with the MELD score increasing.

To investigate the characteristic findings of autoimmune pancreatitis (AIP) to increase the recognition of AIP.From February 2002 to April 2008, a total of 14 cases of AIP were reviewed by clinical, imaging, serologic, histopathologic features and treatment response. There were 13 male and 1 female, with a mean age of 53 years. The main clinical manifestations included progressive obstructive jaundice in 11 cases, upper abdomen pain in 3 cases.Diffuse enlargement of pancreas and diffuse narrowing of the main pancreatic duct (MPD) were observed in 11 cases, while 3 patients showed localized pancreatic head enlargement and focal narrowing of the MPD. Distal common bile duct stenosis was found in all cases. Increased expression of serum immunoglobulin G was found in 7 patients. Autoantibody test was positive in 5 of 12 patients. Nine of 14 patients with AIP had extrapancreatic organ involvement. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Seven earlier patients were treated initially with surgical laparotomy or resection for suspected malignancy. Steroid therapy was given to the other patients and was responsive. There were 4 recurrences after initial treatment.AIP should be a differential diagnosis in pancreatic head mass in order to avoid unnecessary resection.

Thrombosis of the gallbladder vein occurs rarely, and few clinical features have been reported. We report here with a case of gallbladder vein thrombosis presenting as acute peritonitis in a 75-year-old man.The old man with sudden continuous abdominal pain resorted to the emergency room and treated for peritonitis associated with acute cholecystitis. The treatment failed to slow the progress of the disease, and massive ascites appeared with thickening of the gallbladder wall. Laparotomic investigation was conducted later.Pathologically, thrombosis of the gallbladder vein was diagnosed.The thrombosis of the gallbladder vein is characterized by thickening of the gallbladder wall, ascites, and sudden continuous abdominal pain. The causes of deep vein thrombosis at this unusual site vary.

ObjectiveTo observe clinical therapeutic effects of acupuncture combined with music therapy for treatment of cerebral palsy.MethodsSixty children with cerebral palsy were randomly divided into an acupuncture group (Group Acup.) and an acupuncture plus music group (Group Acup.+ M). Simple acupuncture was applied in Group Acup., and acupuncture at 5 groups of points plus music were applied in Group Acup. +M. The treatment was given once every two days with 3 treatments weekly, and 36 treatments constituted a therapeutic course. Therapeutic effects including movement improvement were observed for comparison after 3 courses of treatments.ResultsThe comprehensive functions were elevated in both groups, and the total effective rate in Group Acup. + M was obviously better than that in Group Acup (P

To summarize the experience in the managements of portal vein thrombosis (PVT) and to evaluate the impact of PVT on intraoperative course and postoperative outcome in liver transplantation.Between May 1995 and September 2007, 194 orthotopic liver transplantations were performed, of which 24 cases presented portal vein thrombosis. There were 12 patients with grade I, 9 with grade II, 2 with grade III and 1 with grade IV. The management of PVT depended mainly on its extent. Ligation of the collateral circulation, especially spontaneous or surgical splenorenal shunt, was made as approaches to improve portal flow.Heparin or low-molecule-weight heparin as a prophylactic anticoagulation therapy was maintained during and after operation if prothrombin time is less than eighteen seconds. Follow-up Doppler ultrasonography was used daily in the early postoperative period. Risk factors and variables associated with the transplant and the post-transplant period were analyzed and compared with 170 patients transplanted without PVT.Surgical techniques were eversion thromboendovenectomy in 21 patients with PVT grades I and II, extra-anatomic mesenteric graft in 2 with grade III, and anastomosis to a collateral vein in 1 with grade IV. The study demonstrated more RBC transfusions [(15.2 +/- 11.8) U vs. (8.6 +/- 6.6) U, P = 0.006], longer surgery procedures [(492 +/- 89) min vs. (403 +/- 105) min, P = 0.001] and hospital stay [(32.4 +/- 13.5) d vs. (22.1 +/- 9.1) d, P = 0.001] in the PVT group. However, there were no differences in overall morbidity (58.3% vs. 50.6%, P = 0.478), hospital mortality (8.3% vs.6.5%, P = 0.73) and 1-year survival (87.5% vs. 89.4%, P = 0.778). The incidence of rethrombosis was higher in the PVT group (8.3% vs.1.2%, P = 0.021). Two cases rethrombosis were successfully cured by percutaneous thrombolysis, balloon angioplasty, and stent placement.Portal thrombosis is associated with greater operative complexity and rethrombosis, but has no influence on overall morbidity and mortality in liver transplantation.

To study the prevention and treatment of biliary complications after orthotopic liver transplantation.Clinical data of 183 recipients who had received liver transplantation between May 1995 and December 2006 were retrospectively analyzed.Biliary complications occurred in 15 patients (15/183, 8.2%). The incidence for short-term and long-term complication were 6.0% (11/183) and 2.2% (4/183) respectively. No biliary complications was due to hepatic artery thrombosis(HAT). Four cases who received PTC(percutaneous transhepatic cholangiography) with stent insertion,8 cases who received ERCP( endoscopic retrograde cholangiopancreatography) with stent insertion and 1 who received Roux-en-Y choledochojejunostomy for anastomotic stricture were successfully cured. Two cases required relaparotomy died for fungus infection eventually. The mortality due to biliary complications was 1.1%.The rapid combined abdominal organ harvesting technique could shorten the ischemia time and ameliorate the injury due to vascular and bile duct variances, which could reduce the incidence of biliary complication. PTC and (or) ERCP combined with stent insertion were main procedure for biliary complications not related to HAT after liver transplantation.

To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) transplantation.Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg x d(-1)) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg x kg(-1) on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction.No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 +/- 11 micromol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g x d(-1)) for 3 days. OKT3 (0.5 mg x d(-1)) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued.Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

To investigate the effects of nitric oxide (NO) on reperfusion injury following pancreaticoduodenal transplantation in rats.The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-arginine (L-Arg) group received intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-Arginine methyl ester (L-NAME) group received intravenous injection of L-NAME at a dose of 10 mg/kg, and control group received saline. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) determined by enzyme-linked immunosorbant assay, expression of CINC mRNA detected by Northern blot assay, and myeloperoxidase (MPO) activity in the pancreas graft were measured. Histological observation was performed.The amount of NO in the L-Arg group was higher than in the control group, while in the L-NAME group was lower than in the control group (P0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with significant difference among groups. Expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group was lower than in the control group, the L-NAME group was higher than control group (P0.05). MPO activity in the L-Arg group obviously decreasd compared with other groups. The pancreas inflammation was ameliorated in L-Arg group, and pancreas damage was aggravated in L-NAME group.L-Arg can increase the amount of NO and inhibit the elevation of CINC, CINC mRNA expression, and early neutrophil accumulation in the transplanted pancreas. NO has protective effects on the ischemia/reperfusion injury of pancreaticoduodenal transplantation.

To investigate the impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the long-term survival of renal transplantation recipients.A total of 443 patients who received renal allografts from 1992 to 2002 were analyzed. Outcome and survival were compared among four groups retrospectively.Twelve patients were positive for both hepatitis B surface antigen (HBsAg) and HCV antibody (anti-HCV) (group 1), 18 were HBsAg-positive and anti-HCV-negative (group 2), 26 were HBsAg-negative and anti-HCV-positive (group 3) and 387 were negative for both markers (group 4). The mean follow-up period was 6.1 +/- 2.8 years (range, 0.5-10 years) for all patients. Group 2 had significantly higher liver-related complications (38.9%) and liver-related death (16.7%) than did group 4 (0%, P0.01). Among all patients, 4 HBsAg-positive patients had fulminant hepatitis and died within two years of transplantation. Three patients (group 2) who died were seropositive for HBeAg and/or HBV DNA and none had a history of or positive serologic marker to indicate hepatitis of other etiologies. One (group 1), two (group 2), and one patient (group 3) developed liver cirrhosis respectively, and hepatocellular carcinoma occurred in two patients (group 2) and one patient (group 3). Despite high liver-related mortality in HBV-infected patients, no significant differences among the four groups in the long-term graft and patient survivals were demonstrated. The presence of HBsAg or anti-HCV was not associated with poor prognosis as determined by Cox regression analysis.HBV or HCV infection is not a contraindiction to kidney transplantation in Chinese patients. However, it should be noted that serious liver-related complications may occur and limit survival in patients infected with HBV and/or HCV after kidney transplantation.

Islet transplantation is considered a potentially curative treatment for diabetic mellitus. The aim of this study was to assess the feasibility of islet transplant through the spleen.Both donor and recipient Wistar rats (BW150+/-20 g) were provided by the Animal Center of China Medical University, Shenyang, China. Islets were isolated and purified with the modified Minnesota program. 600-800IE graft islets were handpicked and transplanted through the spleen of diabetic recipients. Blood glucose and insulin were evaluated after operation every other day. IVGTT was performed 10 days after transplantation.300-400IE islet was procured from one donor rat. Secretion index (SI) of the glucose stress was 5.59+/-0.62, showing the graft functioning well. The diabetic rats restored normal blood glucose levels of 3.4-5.4 mmol/L (mean 4.8 mmol/L). Their insulin levels were as normal as 8.5-12.2 microIU/ml. The K value of IVGTT in the rats after transplantation was similar to the normal one.The islets can be transplanted successfully through the spleen, while avoiding the complications caused by traditional transplantation through the portal vein, such as bleeding and portal vein hypertension. The graft islets loss can be reduced because of less centrifugation and mechanic pressure. In conclusion, transplantation through the spleen is a simple and feasible method.

To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK).Seventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction.1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued.Reasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

To study the changes of canine Oddi sphincter (SO) function after pancreas transplantation with bladder drainage and the effect on the graft function.Normal canine SO, transplant canine SO and canine SO in vitro manometry were performed by triple lumen catheter. At the same time, pancreas endocrine and exocrine function after transplantation were determined. After transplantation, anti-reflux function of graft SO was also measured.Endocrine and exocrine function of all the transplanted dogs showed that pancreas graft function was good. Basal pressure of SO in control group was (18.5 +/- 2.8) mm Hg (1 mm Hg = 0.133 kPa). The contraction frequency was (9.7 +/- 1.5) per min, the contraction amplitude was (47.1 +/- 5.5) mm Hg, the motility index was (236 +/- 56). After transplantation, basal pressure increased to (27.8 +/- 2.8) mm Hg, frequency increased to (13.1 +/- 1.9) per min, amplitude decreased significantly to (8.3 +/- 1.8) mm Hg. There was no significant difference of motility index. Basal pressure of SO in vitro increased significantly to (37.2 +/- 5.1) mm Hg. Phasic contraction was not absent. After transplantation, the pressure in the bile duct residual did not increase in accordance with the increase of bladder pressure.After pancreas transplantation with bladder drainage, Basal pressure and frequency of canine SO could increase while amplitude could decrease, which provide the anti-reflux function of graft SO and may serve as an obstacle to pancreatic juice flow.

Post-transplantation pancreatitis and graft thrombosis are two major complications of pancreas transplantation that contribute to morbidity, mortality, and graft loss. Nitric oxide(NO) is a potent vasodilator agent formed when L-arginine (L-Arg) is converted to L-citrulline by the action of NO synthase (NOS), and plays a major role in microcirculatory changes. We therefore investigated the effect of L-Arg on reperfusion injury following pancreaticoduodenal transplantation in rats.The homologous male Wistar rat model of heterotopic total pancreaticoduodenal transplantation was used. The L-Arg-treated rats received the intravenous injection of L-Arg 5 minutes before and after reperfusion at a dose of 200 mg/kg while the N-Nitro-L-arginine methyl ester (L-NAME)-treated rats at a dose of 10 mg/kg. The amount of NO in the pancreas graft was measured. Serum concentration of cytokine-induced neutrophil chemoattractant (CINC) was determined by enzyme-linked immunosorbant assay, the expression of CINC mRNA was detected by Northern blot assay in the pancreas graft, and the activity of myeloperoxidase (MPO) was measured. Histological examination was performed.The amount of NO was higher in the L-Arg group than in the control group, while it was lower in the L-NAME group than in the control group (P0.05). The peak of serum CINC concentration occurred 3 hours after reperfusion with the difference among the groups being significant. The expression peak of CINC mRNA in the pancreas graft occurred 3 hours after reperfusion. The expression level in the L-Arg group (7.66+/-1.53 microg/L) was lower than in the control group (26.31+/-2.01 microg/L), while in the L-NAME group (34.18+/-3.12 microg/L) it was higher than that in the control group (P0.05). The activity of MPO in the L-Arg group was obviously decreased as compared with in the other groups. The pancreas inflammation was ameliorated when L-Arg was administered, whereas the pancreas damage was aggravated when L-NAME was administered.L-Arg can increase the amount of NO and inhibit the elevation of CINC, the CINC mRNA expression and early neutrophil accumulation in the pancreas. NO has protective effects on ischemia/reperfusion injury in pancreaticoduodenal transplantation.

To investigate the effect of Astragalus Extractum on canine isolated kidney during hypothermia perfusion and preservation.Isolated kidneys in the control group were hypothermia perfused and preserved using conventional hypertonic adenine citrate solution (HC-A), and for those in the experimental group, using HC-A plus Astragalus extract instead. The changes of renal tissue construction were observed with light microscopy and electron microscopy. Moreover, the kidney transplantation model of dog was established to determine the changes of biochemical parameters before and after transplantation. Data were analysed synthetically.The ultrastructural injury in preserved kidney of the experimental group was significantly milder than that in the control group. Parameters determined in the early stage of transplantation showed that the blood creatinine level was significantly lower and the endogenous creatinine clearing value was higher in the experimental group than that in the control group, the difference was significant (P0.05).When Astragalus extractum is used in preserving kidney with hypothermia perfusion, it shows definite protective effect on the ischemic reperfusion injured kidney.

The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P0.0001) and outflow (P0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.

AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n = 6), transplant control group (n = 6), and aminoguanidine (AG) treatment group (n = 18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most significant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01).The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.

AIM: CMU-1 is a new preservation solution with a low potassium concentration as well as low viscosity that is highly effective in reducing preservation injury. The purpose of this experiment is to compare the protective effect of CMU-1 solution with that of UW during cold preservation and normothermic reperfusion. METHODS: Wistar rats were divided into two groups according to different preservation solution: CMU-1 group and UW group. After 6, 12 and 24 h cold storage of rat liver in different preservation solutions, the isolated perfused rat liver model was applied to reperfuse the liver for 120 min normothermically (37 °C) with Krebs-Henseleit solution, meanwhile the pH value of the preservation solution was measured. The perfusate was sampled for the evaluation of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). At the end of the reperfusion, all of the bile product was collected, energy metabolic substrate and histological examination were performed. RESULTS: After preserving for 6 h, pH value of both groups did not change; after 12 h, both decreased but with no significant difference. After 24 h, pH value in UW solution group significantly decreased. The total adenine nucleotides level and AEC in liver tissue decreased with preservation time, but they were higher in CMU-1 group. And the amount of bile product after perfusion for 120 min in CMU-1 group was much more than that in UW group. However, there were no significant differences in ALT and LDH levels between two groups. Histology showed no difference. CONCLUSION: The preservation effect of CMU-1 solution is similar with that of UW solution. However, CMU-1 solution shows some advantages over UW solution in energy meta-bolism, preventing intracellular acidosis and bile product.

AIM: To evaluate the viability and energy metabolism of long warm ischemically damaged pancreas during preservation by the UW solution cold storage method. METHODS: The pancreas grafts subjected to 30-120 min warm ischemia were preserved by the UW solution cold storage method for 24 h. The tissue concentrations of adenine nucleotides (AN) and adenosine triphosphate (ATP) and total adenine nucleotides (TAN) were determined by using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. RESULTS: The functional success rates of pancreas grafts of groups after 30 min, 60 min, 90 min, 120 min of warm ischemia were 100%, 100%, 67.7%, 0%, respectively. There was an excellent correlation between the posttransplant viability and tissue concentration of ATP and TAN at the end of preservation. CONCLUSION: The UW solution cold storage method was effective for functional recovery of the pancreas suffering 60-min warm ischemia. The tissue concentration of ATP and TAN at the end of 24 h preservation by the UW solution cold storage method would predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.

Between February 1984 and September 1987, endoscopic embolization (EE) was performed in 26 patients with esophageal varices. The effects of EE were evaluated with endoscopic findings according to the general rules for recording endoscopic findings on esophageal varices as specified by the Japanese Research Society for Portal Hypertension. 1) When the result was regarded as effective if a patient had Cw, F1, R-C sign (-), Li and Lm or disappearance of varices, the improvement was found in 66.7% for Color, 79.2% for R-C sign, 54.2% for Form and 45.8% for Location after EE. 2) Recurrence of varices was found in 50% of the patients (12/24) and 4 of 12 cases (33.3%) had rebleeding. 3) When the endoscopic findings before and after EE were compared between relapsed and unrelapsed cases, relapsed patients had more unfavorable endoscopic findings, furthermore, the extent of improvements was also worse than that of unrelapsed cases. 4) As complications, slight fever, dysphagia and epigastric pain were found in most cases, however, all were cured conservatively. In conclusion, EE is useful and safety tool for the improvement of endoscopic findings of the patients with esophageal varices.