[Potential Source Environments for Microbial Communities in Wastewater Treatment Plants (WWTPs) in China].

To better understanding the microbial composition of activated sludge (AS), unique OTUs and their indicators were examined and SourceTracker was used to identify possible source environments for AS communities to thrive in 15 cities across China, based on 16S rRNA gene sequencing. This may help reveal the underlying mechanisms of AS community composition formations in various areas. The results indicated that the dominant phyla in AS in each city were similar; Proteobacteria, Bacteroidetes, and Chloroflexi made up 94.53%-97.04% of the whole microbial communities. Geographic location and environmental conditions were identified as having an effect on microbial compositions. Cities located toward to the edge of China or along the coast tended to harbor more unique OTUs. Moreover, the composition of indicators in wastewater treatment plants (WWTPs) near the sea were more similar, while no indicators were detected in WWTPs in Chengdu and Chongqing. Source environments for AS microbial communities also depended on location and environmental conditions. Overall, microbes from 'plant' and 'soil' sources accounted for a large proportion of the AS microbial communities in each city, while bacteria from 'marine' sources were only detected in coastal AS communities. Cities with more rivers and lakes tended to have more bacteria originating from 'fresh water' sources. Since most of the WWTPs in China play a role in treating industrial wastewater, industrial wastewater was also an important source environment. However, few bacteria originating from the human digestive system were identified in the AS communities. Moreover, a large proportion of bacteria (36%-70%) originated from unknown sources not included in the source database, such as sewage infrastructure, indicating that the source database will need to be expanded in the future.

Azaphilone Alkaloids with Anti-inflammatory Activity from Fungus Penicillium sclerotiorum cib-411.

Nine new azaphilone alkaloids, penazaphilones A-I (1-9), were isolated from the solid fermented rice culture of Penicillium sclerotiorum cib-411. The structures of compounds 1-9 were elucidated based on HRESIMS, NMR, and CD spectroscopic data. The structures of 5 and 8 were confirmed by X-ray crystallographic analyses. Biological evaluation showed that compounds 1, 5, 6, and 8 inhibited the production of nitric oxide (NO) on RAW 264.7 cells stimulated by lipopolysaccharide with IC50 values of 15.29, 9.34, 9.50, and 7.05 µM, respectively. Meanwhile, they did not exhibit obvious cytotoxicity at a concentration of 50.0 µM.

Hydroxycinnamoylmalated flavone C-glycosides from Lemna japonica.

Three previously undescribed flavone C-glycosides (1-3), along with seven known ones (4-10), were isolated and characterized from the smallest flowering aquatic plant, Lemna japonica. On the basis of spectroscopic analysis and alkaline hydrolysis, compounds 1-3 were identified to be luteolin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (1), apigenin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (2), and luteolin 6-C-(2″-O-trans-coumaroyl-d-malate)-ß-glucoside (3). Compounds 1-3 are characteristic of a trans-coumaroyl-d-malate or trans-caffeoyl-d-malate linked to C-2″ of the glucose, which was reported for the first time. Compounds 1-3 exhibited weak cytotoxicity against HepG-2, SW-620, and A-549 cell lines, with IC50 values between 42.5 and 19.2µg/ml, and moderate antioxidant activity. Meanwhile compound 3 displayed moderate nematocidal activity with an EC50 value of 1.56mg/ml.

MiR-486-5p negatively regulates oncogenic NEK2 in hepatocellular carcinoma.

NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion. Consequently, patients exhibiting high NEK2 expression had poorer prognosis. This was corroborated by our multivariate analysis that showed NEK2 to be an independent prognostic factor for HCC patient survival. Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. Tumor xenograft data from Balb/c nude mice demonstrated that HCC cells with high NEK2 expression formed larger tumors than those with low NEK2 expression. Finally, we showed that miR-486-5p suppressed NEK2 by directly binding to its transcript 3'UTR. We also demonstrated an inverse relationship between miR-486-5p and NEK2 expression in HCC patients. These findings suggest miR-486-5p negatively regulates NEK2, which is a critical prognostic indicator of HCC patient survival after liver transplantation.

Prognostic value of combined preoperative fibrinogen and neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation.

OBJECTIVES: Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil-lymphocyte ratio (NLR). RESULTS: Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. MATERIALS AND METHODS: Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. CONCLUSIONS: Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing.

Elevated Preoperative Serum Gamma-glutamyltranspeptidase Predicts Poor Prognosis for Hepatocellular Carcinoma after Liver Transplantation.

Gamma-glutamyltransferase (γ-GGT) is a membrane-bound enzyme that is involved in biotransformation, nucleic acid metabolism, and tumourigenesis. Elevated serum γ-GGT levels are related to an increased cancer risk and worse prognosis in many cancers. In the present study, we evaluated the prognostic value of preoperative serum γ-GGT in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). A total of 130 HCC patients after LT were included in the study. The optimal cut-off value of γ-GGT was 128U/L by receiver operating characteristic analysis, with a sensitivity and specificity of 60.0% and 72.9%, respectively. Elevated preoperative serum γ-GGT was significantly associated with high alpha-fetoprotein (AFP), large tumor size, and macro- and micro-vascular invasion. The 1-, 3-, 5-year disease-free survival (DFS) and overall survival (OS) rates of HCC patients in the γ-GGT > 128U/L group were poorer than those in the γ-GGT ≤ 128U/L group. Stratification analysis revealed that γ-GGT exhibited a greater predictive value for DFS and OS in HCC patients beyond the Milan criteria and no macro-vascular invasion. In conclusion, elevated preoperative serum γ-GGT was significantly associated with advanced tumor stage and aggressive tumor behaviors, and serum γ-GGT can be considered as a prognostic factor for HCC patients after LT, especially for patients beyond the Milan criteria or without macro-vascular invasion.

Prognostic value of preoperative peripheral monocyte count in patients with hepatocellular carcinoma after liver transplantation.

Prognostic value of peripheral monocyte, as a member of inflammatory cells, was widely being investigated. The aim of this study was to evaluate the prognostic value of preoperative peripheral blood monocyte count for hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) and the relationship between monocyte count and tumor-related characteristics. We retrospectively analyzed the clinical data of 101 HCC patients after LT. Preoperative monocyte count and demographic, clinical, and pathologic data were analyzed. The optimal cutoff value of monocyte count was 456/mm(3), with the sensitivity and specificity of 69.4 and 61.5 %, respectively. Elevated preoperative peripheral blood monocyte count was significantly associated with large tumor size. The 1-, 3-, and 5-year disease-free survival (DFS) (80.9, 70.1, and 53.3 % vs 55.1, 38.7, and 38.7 %, P = 0.007) and overall survival (OS) rates (95.7, 76.6, and 64.8 % vs 72.2, 44.1, and 36.1 %, P = 0.002) of HCC patients in the peripheral blood monocyte count ≤456/mm(3) group were higher than those in the peripheral blood monocyte count >456/mm(3) group. In conclusion, elevated preoperative peripheral blood monocyte count was significantly associated with advanced tumor stage and it can be considered as a prognostic factor for HCC patients after LT.

Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus -Associated Nephropathy after Renal Transplantation.

BACKGROUND: Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. METHODS: Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1-4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. RESULTS: After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25-34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. CONCLUSIONS: The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.

Indole Alkaloids from Chaetomium globosum.

Two new indole alkaloids chaetocochin J (1) and chaetoglobinol A (8), along with chetomin (2), chetoseminudin A (3), cochliodinol (9), and semicochliodinol (10), were isolated from the rice culture of the fungus Chaetomium globosum. Their structures were elucidated by spectral analysis. Three new epipolythiodioxopiperazines, chaetocochins G-I (5-7), were identified by the combination of UPLC and mass spectrometric analysis. Chaetocochin I contained two sulfur bridges, one formed by three sulfur atoms between C-3 and C-11a, and the other formed by four sulfur atoms between C-3' and C-6'. Chaetocochin I was readily transformed into chetomin (2), chetoseminudin A (3), chaetocochin D (4), chaetocochin G (5), and chaetocochin H (6) by losing sulfur atoms. Compounds 1-3, and 8 exhibited antibacterial activities against Bacillus subtilis with MICs of 25, 0.78, 0.78, and 50 µg/mL, respectively, but not against Gram-negative bacterium (Escherichia coli). Compounds 2 and 8 were inactive against Candida albicans, Fusarium graminearum, Fusarium vasinfectum, Saccharomyces cerevisiae, and Aspergillus niger even at the high concentrations of 200 and 100 µg/mL, respectively. Compound 8 showed free radical scavenging capacity against the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS(+•)), with IC50 values of 143.6 and 45.2 µM, respectively. The free radical scavenging capacity rates of compounds 1-3 on the DPPH and ABTS(+•) were less than 20% at the test concentrations (89.9-108.3 µM). The superoxide anion radical scavenging assay indicated that compounds 1-3, and 8 showed 14.8% (90.9 µM), 18.1% (90.9 µM), 51.5% (88.3 µM), and 30.4% (61.3 µM) superoxide anion radical scavenging capacity, respectively.

Liver transplantation using organs from deceased organ donors: a single organ transplant center experience.

BACKGROUND: In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program. METHODS: From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively. RESULTS: Among the 29 donors, 24 were China Category II donors (organ donation after cardiac death), and five were China Category III donors (organ donation after brain death followed by cardiac death). The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422 (2-696) days. Among the five mortalities during the follow-up, three died of tumor recurrence. In terms of post-transplant complications, 9 recipients (34.6%) experienced early allograft dysfunction, 1 (3.8%) had non-anastomotic biliary stricture, and 1 (3.8%) was complicated with hepatic arterial thrombosis. None of these complications resulted in patient death. Notably, primary non-function was not observed in any of the grafts. CONCLUSION: With careful donor selection, liver transplant from deceased donors can be performed safely and plays a critical role in overcoming the extreme organ shortage in China.

Safety and efficacy of four steroid-minimization protocols in liver transplant recipients: 3-year follow-up in a single center.

OBJECTIVE: To evaluate the safety and efficacy of steroid-minimization therapy in liver transplantation (LT) recipients with hepatitis B virus-related diseases in China. METHODS: From March 2000 to June 2007, 502 adult LT recipients, mostly with hepatitis B (HBV)-related diseases, were enrolled in our study. Four study groups were setup according to the steroid-minimization protocols: tacrolimus (TAC) with 6 months steroids withdrawal (6M SW), TAC with 3 months SW (3M SW), TAC with 14 days SW (14d SW), and TAC with basiliximab induction and steroids avoidance (Bas SA). All patients were followed up for at least 36 months after LT. RESULTS: There were no significant differences in the overall 3-year survival rates of the patients and graft, and chronic rejection among the four groups (P = 0.092, P = 0.113 and P = 0.684, respectively). There was also no difference in acute rejection within 12 months after LT (P = 0.514). The 3-year recurrence rates of HBV infection and hepatocellular carcinoma (HCC) after LT were significantly different among all the groups (lowest in TAC/Bas SA group; P = 0.037 and P = 0.029, respectively). The overall incidence of infection was significantly higher in the 6M SW group (62.2% vs 56.1% in 3M SW, 30.5% in 14d SW, 20.5% in Bas SA; P < 0.01). By the end of the 3-year follow-up, more than 90% of the surviving patients could safely receive TAC monotherapy. CONCLUSION: Bas SA immunosuppressive protocol can be achieved safely in LT and reduce HBV infection and HCC recurrence and side effects of steroids after LT.

[Efficacy and safety of sorafenib in the prevention and treatment of hepatocellular carcinoma recurrences after liver transplantation].

OBJECTIVE: To evaluate the efficacy and safety of sorafenib in the prevention and treatment of hepatocellular carcinoma (HCC) relapse after liver transplantation. METHODS: A retrospective cohort study was performed to assess the efficacy and safety of sorafenib for HCC. Forty-four patients who underwent liver transplant for HCC beyond Milan criteria form July 2007 to May 2010 were included study group (sorafenib, n = 22) and control group (without sorafenib, n = 22). The primary endpoints of the study were disease-free survival (DFS), overall survival (OS). Secondary outcomes included the rates of acute rejection and graft survival. RESULTS: The clinical data of 44 patients were completely collected. There were significantly differences between sorafenib group and control group in 1-year DFS (81.8% (n = 18) vs 63.6% (n = 14), P < 0.05) and OS (90.9% (n = 20) vs 72.7% (n = 16), P < 0.05) respectively. The acute rejection rates in Sorafenib were 13.6% (3/22), compared with 18.2% (4/22) in control group (P = 0.524) and 1-year graft survival in Sorafenib group were 86.4% (19/22), compared with 72.7% (16/22) in control group (P = 0.086). The overall incidence of treatment-related adverse events was 68.1% (n = 15) in sorafenib group and 31.8% (n = 7) in the control group (P < 0.01). Adverse events that were reported for patients receiving sorafenib were predominantly grade 1 or 2 in severity including diarrhea (45.5%, n = 10), liver dysfunction (40.9%, n = 9), hand-foot skin reaction (31.8%, n = 7) and pains of head and four limbs (22.7%, n = 5). Two patients with grade 3 adverse events in study group were stopped continuing to use the sorafenib. Three patients with the dose of 400 mg twice daily and 17 patients with the dose reduction of sorafenib continued to the study endpoint. CONCLUSION: Patients with HCC undergoing liver transplantation could get the benefits of Sorafenib in reducing the incidence of tumor recurrence and extending disease-free and overall survival time.

[Clinical characteristics, diagnosis and treatment of digestive tract leakage after orthotopic liver transplantation].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of digestive tract leakage after orthotopic liver transplantation (OLT). METHODS: Sixty-one recipients had digestive tract leakage in early stage after OLT among 1173 cases from January 2000 to December 2010. There were 55 male and 6 female patients, aging from 36 to 61 years, with a median of 45 years. Digestive tract leakage included bile leakage (46 cases), gastric leakage (5 cases), duodenal leakage (1 case), jejunal leakage (4 cases), ileal leakage (1 case) and colon transversum leakage (4 cases). Ten of recipients with gastrointestinal leakage had 1 to 3 times of abdominal surgery before OLT. Abdominal drainage was used in 28 cases with bile leakage, and additionally, endoscopic retrograde cholangiopancreatography, endoscopic nasobiliary drainage and stenting were performed for 8 of them, and surgical neoplasty for another 18 patients with bile leakage. Simple surgical neoplasty of perforation was performed for 13 patients with gastrointestinal leakage, and diverticulectomy and neoplasty for 1 case with duodenal leakage, and partial jejunostomy for one severe jejunal leakage. Nutritional support was administered for all of cases. RESULTS: The incidence rate of digestive tract leakage in early stage after OLT was 5.20% (61/1173). Intra-operative iatrogenic injury of gastrointestinal tract was occurred in 6 cases with gastrointestinal leakage. After treatment, 11 cases died of multiple organ failure resulted from severe infection, with mortality of 18.0% (11/61), including 4 cases with bile leakage, with the mortality of 8.6% (4/46), and 7 cases with gastrointestinal tract leakage, with the mortality of 46.6% (7/15). The remanent 50 cases through comprehensive treatment with a span of 1 to 3 months recovered and discharged healthily. No digestive tract leakage reoccurred in the follow-up of 6 to 84 months. CONCLUSIONS: The morbidity of digestive tract leakage in early stage after OLT is low, but its mortality is high, especially for gastrointestinal tract leakage. High dose corticosteroids therapy, history of abdominal operation and intra-operative iatrogenic injury may be high risk factor. Comprehensive treatment is crucial for improving prognosis.

Twenty-four hour steroid avoidance immunosuppressive regimen in liver transplant recipients.

OBJECTIVES: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. MATERIALS AND METHODS: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24 hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. RESULTS: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). CONCLUSIONS: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.

[A study of the efficacy and safety of using hepatitis B surface antigen-positive donors for liver transplantation].

OBJECTIVE: To evaluate the outcomes of liver transplant recipients who received liver allografts from hepatitis B surface antigen (HBsAg)-positive donors. METHODS: The medical records of 23 male patients (median age, 42.5 years; range: 29-61) who received HBsAg-(+) liver allografts in our organ transplant center were retrospectively analyzed. All patients had confirmed diagnosis of end-stage liver disease (ESLD) secondary to hepatitis B virus (HBV) infection, including 13 HBsAg(+)/HBeAg(-)/HBcAb(+) cases and 10 HBsAg(+)/HBeAb(+)/HBcAb(+) cases. After transplantation, all patients were administered oral entecavir and intravenous anti-hepatitis B immunoglobulin (HBIG) (2000 IU/d during the first week), along with a steroid-free immune suppression regimen. HBV-related antigen and antibody and HBV DNA were detected on post-transplantation days 1, 7, 14, 21, and 30. The liver allografts were monitored by ultrasound imaging. After discharge, monthly follow-up recorded liver function, renal function, acute rejection, infections, vascular complications, biliary complications, HBV recurrence, cancer recurrence, and patient survival. RESULTS: Two of the recipients died from severe perioperative pneumonia. The remaining 21 recipients were followed-up for 10 to 38 months, and all 21 patients remained HBsAg(+). One recipient developed biliary ischemia and required a second liver transplantation at five months after the primary transplantation. Three recipients (all primary) died from tumor recurrence at 9, 14, and 18 months post-transplantation, respectively. All other recipients survived and had acceptably low HBV DNA copy levels. Color Doppler imaging showed good graft function and normal texture. The patient and graft survival rates were 78.3% (18/23) and 73.9% (17/23), respectively. The recurrence rate of HBV infection was 100% (23/23). In surviving patients, no liver function abnormality, graft loss, or death was found to be related to the recurrence of HBV infection. CONCLUSION: Liver transplantation using HBsAg(+) liver grafts was safe for patients with ESLD secondary to HBV infection.

Steroid elimination within 24 hours after orthotopic liver transplantation: effectiveness and tolerability.

BACKGROUND: Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients. METHODS: Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups. RESULTS: There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05). CONCLUSION: Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.

Sirolimus conversion in liver transplant recipients with calcineurin inhibitor-induced complications: efficacy and safety.

OBJECTIVES: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. MATERIALS AND METHODS: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. RESULTS: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. CONCLUSIONS: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.

FlyExpress: visual mining of spatiotemporal patterns for genes and publications in Drosophila embryogenesis.

SUMMARY: Images containing spatial expression patterns illuminate the roles of different genes during embryogenesis. In order to generate initial clues to regulatory interactions, biologists frequently need to know the set of genes expressed at the same time at specific locations in a developing embryo, as well as related research publications. However, text-based mining of image annotations and research articles cannot produce all relevant results, because the primary data are images that exist as graphical objects. We have developed a unique knowledge base (FlyExpress) to facilitate visual mining of images from Drosophila melanogaster embryogenesis. By clicking on specific locations in pictures of fly embryos from different stages of development and different visual projections, users can produce a list of genes and publications instantly. In FlyExpress, each queryable embryo picture is a heat-map that captures the expression patterns of more than 4500 genes and more than 2600 published articles. In addition, one can view spatial patterns for particular genes over time as well as find other genes with similar expression patterns at a given developmental stage. Therefore, FlyExpress is a unique tool for mining spatiotemporal expression patterns in a format readily accessible to the scientific community. AVAILABILITY: http://www.flyexpress.net CONTACT: s.kumar@asu.edu.

[Experiences of liver retransplantation for postoperative diffuse biliary strictures].

OBJECTIVE: To investigate the feasibility and management of retransplantation for diffuse biliary strictures occurring after initial liver transplantation. METHODS: The clinical data of 53 consecutive liver retransplantation patients at our hospital from January 2001 to December 2009 were collected and analyzed retrospectively. Among them, 20 (37.7%) were due to diffuse biliary strictures. RESULTS: Diffuse biliary strictures appeared at 3 - 16 months after initial transplantation. The mean time was 6.3 months. The specific types included intra-hepatic diffuse biliary strictures (n = 16) and multi-strictures involving both intra- & extra-hepatic biliary ducts (n = 4). Retransplantation was performed after a failure of intervention or/and other comprehensive treatments. Among them, 14 were cured and 6 died from peri-operative complications including serious abdominal infection & MODS (multiple organ dysfunction syndrome) (n = 3, 50%), biliary fistula (n = 2, 33.3%) and hepatic artery embolism (n = 1, 16.7%). These patients were followed up for a mean time of 1.8 years (range: 1 - 5 years). The accumulative survival rates at 1, 3 and 6 months were 80.0%, 75.0% and 70.0% respectively. CONCLUSIONS: Liver retransplantation is the ultimate treatment for diffuse biliary strictures after liver transplantation. The survival rate is associated with operative timing, surgical techniques and peri-operative management.