Effect of ursodeoxycholic acid administration after liver transplantation on serum liver tests and biliary complications: a randomized clinical trial.

BACKGROUND/AIMS: Endogenous hydrophobic bile acids are suspected to be one of the pathogenetic factors of biliary complications after orthotopic liver transplantation (OLT). This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum liver tests and the incidence of biliary complications. METHODS: 112 adult patients undergoing OLT from donation after cardiac death (DCD) were randomized to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients). Serum liver tests and serum bile acids of all patients and biliary bile acids in patients with T-tube drainage were determined during the 4 weeks after OLT. Biliary complications as well as patient and graft survival were analyzed during a mean follow-up of 41.6 months. RESULTS: UDCA treatment decreased ALT, AST and GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge and casts within the 1st year (p < 0.05). However, no differences in the incidence of other biliary complications as well as 1-, 3- and 5-year graft and patient survival were observed. CONCLUSIONS: UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT.

Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment.

This study sought to perform integrative analysis of the immune/methylation/autophagy landscape on breast cancer prognosis and single-cell genotypes. Breast Cancer Recurrence Risk Score (BCRRS) and Breast Cancer Prognostic Risk Score (BCPRS) were determined based on 6 prognostic IMAAGs obtained from the TCGA-BRCA cohort. BCRRS and BCPRS, respectively, were used to construct a risk prediction model of overall survival and progression-free survival. Predictive capacity of the model was evaluated using clinical data. Analysis showed that BCRRS is associated with a high risk of stroke. In addition, PPI and drug-ceRNA networks based on differences in BCPRS were constructed. Single cells were genotyped through integrated scRNA-seq of the TNBC samples based on clustering results of BCPRS-related genes. The findings of this study show the potential regulatory effects of IMAAGs on breast cancer tumor microenvironment. High AUCs of 0.856 and 0.842 were obtained for the OS and PFS prognostic models, respectively. scRNA-seq analysis showed high expression levels of adipocytes and adipose tissue macrophages (ATMs) in high BCPRS clusters. Moreover, analysis of ligand-receptor interactions and potential regulatory mechanisms were performed. The LINC00276&MALAT1/miR-206/FZD4-Wnt7b pathway was also identified which may be useful in future research on targets against breast cancer metastasis and recurrence. Neural network-based deep learning models using BCPRS-related genes showed that these genes can be used to map the tumor microenvironment. In summary, analysis of IMAAGs, BCPRS, and BCRRS provides information on the breast cancer microenvironment at both the macro- and microlevels and provides a basis for development of personalized treatment therapy.

Supercapacitive Performances of Ternary CuCo2S4 Sulfides.

Currently, ternary CuCo2S4 sulfides are intensively investigated as electrode materials for electrochemical capacitors due to their low cost, high conductivity, and synergistic effect. The research of CuCo2S4 materials for energy storage has gradually grown from 2016. The supercapacitive performances of CuCo2S4 electrodes for electrochemical capacitors are briefly reviewed in this work. The structure, morphology, and particle size of CuCo2S4 are related to the synthesis conditions and electrochemical performances. The thin films of CuCo2S4 nanostructures deposited on conductive substrates and their composites both show better properties than single CuCo2S4. CuCo2S4 and its composites reveal large potential for asymmetric capacitors, delivering high energy densities. However, there is still much new space remaining for future research. The possible development directions, challenges, and opportunities for CuCo2S4 materials are also discussed.

Post-transplant infection improves outcome of hepatocellular carcinoma patients after orthotopic liver transplantation.

BACKGROUND: Tumor recurrence after orthotopic liver transplantation (OLT) remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma (HCC), since very few factors or measures have shown impact on overcoming HCC recurrence after OLT. Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system. Post-transplant infection (PTI), a common complication, is deemed to be harmful for the liver transplant recipients from a short-term perspective. Nevertheless, whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified. AIM: To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT. METHODS: A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group (53 patients) and a non-PTI group (185 patients). Univariate analyses, including the differences of overall survival (OS), recurrence-free survival (RFS), and post-recurrence survival (PRS), between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method, and the differences were compared using the log rank test. The variables with a P-value < 0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model. RESULTS: The 1-, 3-, and 5-year OS and RFS rates of the whole cohort were 86.6%, 69.0%, and 63.6%, and 75.7%, 60.0%, and 57.3%, respectively. The 1-, 3-, and 5-year OS rates for the PTI patient group (96.0%, 89.3%, and 74.0%) were significantly higher than those for the non-PTI group (84.0%, 63.4%, and 60.2%) (P = 0.033). The absence of PTI was an independent risk factor for dismal OS (relative risk [RR] = 2.584, 95%CI: 1.226-5.449) and unfavorable RFS (RR = 2.683, 95%CI: 1.335-5.390). Subgroup analyses revealed that PTI remarkably improved OS (P = 0.003) and RFS (P = 0.003) rates of HCC patients with vascular invasion (IV), but did not impact on OS (P = 0.404) and RFS (P = 0.304) of patients without VI. Among the patients who suffered post-transplant tumor recurrence, patients with PTI showed significantly better OS (P = 0.026) and PRS (P = 0.042) rates than those without PTI. CONCLUSION: PTI improves OS and RFS of the transplant HCC patients at a high risk for post-transplant death and tumor recurrence, which is attributed to suppressive effect of PTI on HCC recurrence.

[Therapeutic effect of liver transplantation on acute liver failure].

OBJECTIVE: To evaluate the short-term and long-term outcomes of emergent liver transplantation recipients with acute liver failure and to identify factors that influenced these outcomes. METHODS: 318 consecutive patients who underwent liver transplantations between January 2001 and December 2004 were analyzed retrospectively (all the cases were followed up to December 2005). According to UNOS grading scale, all recipients preoperative status were evaluated. 54 patients were acute liver failure (Group I, UNOS 1 and 2A), and the other 264 cases were chronic liver diseases (Group II, UNOS 2B and 3). The postoperative effects in different groups were compared, including the survival rates, incidences of complications, rates and causes of retransplantation, rates and causes of death. RESULTS: Comparing UNOS2B/3 to UNOS1/2A, the perioperative mortality were 3.7%; 22.6%, the rate of complications 16.7%; 55.6%, 1 year survival rate 91.3%; 74.1%, 3 year survival rate 86.4%; 68.5%, the retransplantation rate 1.1%; 18.5% respectively. CONCLUSION: Since the technique of liver transplant is very advanced, the effect of surgery is mainly depended on the function of liver and other organs in patients. The recipients with UNOS2B/3 have better short-term and long-term outcomes as comparing to UNOS1/2A. In addition, the recipients with UNOS1/2A are burdened with much higher mortality.

Long noncoding RNA AFAP1-AS1 indicates a poor prognosis of hepatocellular carcinoma and promotes cell proliferation and invasion via upregulation of the RhoA/Rac2 signaling.

It has been shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes including cancer progression and metastasis. However, the biological functions and clinical significance of lncRNA AFAP1-AS1 in hepatocellular carcinoma (HCC) remain unclear. Expression of AFAP1-AS1 was analyzed in 78 HCC tissues by real-time PCR. The effect of AFAP1-AS1 on cell proliferation was examined by MTT assay, cell apoptosis was detected by flow cytometric analysis and cell invasion was determined by Transwell assay. RhoA/Rac2 signaling and downstream factors were verified by western blotting. HCC cells infected with si-AFAP1-AS1 were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. We found that increased expression of AFAP1-AS1 was significantly correlated with pathological staging (P=0.024) and lymph-vascular space invasion (LVSI) in HCC patients (P=0.007). Multivariate analyses indicated that AFAP1-AS1 represented an independent predictor for overall survival of HCC (P=0.029). Further experiments showed that knockdown of AFAP1-AS1 by si-AFAP1-AS1 decreased the proliferation and invasion in vitro and in vivo, induced cell apoptosis and blocked cell cycle in S phase via inhibition of the RhoA/Rac2 signaling. Taken together, our findings indicate that AFAP1-AS1 may promote the HCC development through upregulation of RhoA/Rac2 signaling and provide a potential therapeutic target for HCC.

Could Tumor Size Be A Predictor for Papillary Thyroid Microcarcinoma: a Retrospective Cohort Study.

BACKGROUND: Central lymph node metastasis(CLNM) is common in papillary thyroid microcarcinoma (PTMC). The aim of this study was to define the pathohistologic risk grading based on surgical outcomes. MATERIALS AND METHODS: Statistical analysis was performed to figure out the optimal cut-off values of size in preoperative ultrasound images for defining the risk of CLNM in papillary thyroid microcarcinoma. Receiver operating characteristic curves (ROC) studies were carried out to determine the cutoff value(s) for the predictor(s). All the patients were divided into two groups according to the above size and the clinic-pathological and immunohistochemical parameters were compared to determine the significance of findings. RESULTS: The optimal cut-off value of tumor size to predict the risk of CLNM in papillary thyroid microcarcinoma was 0.575 cm (area under the curve 0.721) according to the ROC curves. Significant differences were observed on the multifocality, extrathyroidal extension and central lymph node metastasis between two groups which were divided according to the tumor size by the cutoff values. Patients in two groups showed different positive rate and intensity of Ki67. CONCLUSIONS: The size of PTMC in ultrasound images are helpful to predict the aggressiveness of the tumors, it could be an easy predictor for PTMC prognosis and assist us to choose treatment.

[Portal venous and enteric drainage in simultaneous pancreas kidney transplantation].

OBJECTIVE: To summarize the initial experience of simultaneous pancreas kidney transplantation (SPK) with portal venous and enteric drainage. METHODS: Between Jane 2001 and Jane 2003, SPK were performed in 5 patients. Systemic venous-enteric drainage (SED) was used in the first 2 patients and portal venous-enteric drainage (PED) in the last 3 cases. All patient were immunosuppressed with quadruple therapy, which included anti-CD25 mAb (Zenapax/Simulect) induction therapy, FK506, mycophenolate mofetil (MMF), and prednisone baseline therapy. The complications were analyzed. RESULTS: Serum glucose and renal function of the 5 cases were normal and no further insulin was needed within 7 days post-operation. No technique complications such as duodenal fistula and thrombosis were observed, One episode of acute rejection of kidney allograft occurred in one patient with SED, and resolved with a bolus corticosteroids. One case with SED and one with PED were died of sepsis and FK506 toxicity 4 weeks after transplantation. The death occurred with functioning pancreas graft. No latter complications were observed in the 3 survived patients with excellent graft functions. CONCLUSIONS: Both methods of SED and PED can be performed successfully and with no latter complications. But with its potential physiologic and immunologic advantages, PED might be a standard procedure for SPK.

[The effects of ADAM28 on HDPC biological characteristics].

PURPOSE: To study the effects of ADAM28 gene on the proliferation, differentiation and apoptosis of human dental papilla cells(HDPC) and analyze the possible mechanism. METHODS: Cell culture, gene transfection, MTT, flow cytometry (FCM) and enzyme kinetics method were used to study the effects of ADAM28 on HDPC biological characteristics. SNK test of SPSS12.0 software package was used for statistical analysis. RESULTS: ADAM28 eukaryotic plasmid was transfected into HDPC successfully, HDPC proliferation activity, proliferation index(PI) and ALP secretion activity in eukaryotic plasmid group were significantly higher than those in pcDNA3.1(+) group, untransfected group, and apoptosis cell percentage in eukaryotic plasmid group was lower than that in the control groups.There were significant differences between them (P<0.01). CONCLUSION: ADAM28 could significantly promote the proliferation and ALP secretion of HDPC, inhibit HDPC apoptosis. Supported by National Natural Science Foundation of China (Grant No.30572046).

[The construction of ADAM28 eukaryotic expression plasmid and expression after transfected into HDFC].

PURPOSE: To construct a disintegrin and metalloproteinase (ADAM28) eukaryotic expression plasmid and detect the expression of ADAM28 gene in human dental follicle cells (HDFC) after eukaryotic plasmid was transfected into HDFC. METHODS: Gene rebuilt technique was used to construct ADAM28 eukaryotic expression plasmid, cell culture and gene transfection into HDFC mediated by Lipofectamine2000, immunofluorescence, RT-PCR and Western blot were used to detect the expression of ADAM28 in HDFC. RESULTS: ADAM28 eukaryotic plasmid was constructed, identified successfully and transiently transfected into HDFC for 72 hours. The detection verified that HDFC of eukaryotic plasmid group all expressed ADAM28 protein, and no expression was found in two control groups. CONCLUSIONS: ADAM28 could be correctly translated and expressed in HDFC, which might be used for further study of biological functions of ADAM28 in odontogenic cells.