Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

Individual dose recommendations for drug interaction between tacrolimus and voriconazole in adult liver transplant recipients: A semiphysiologically based population pharmacokinetic modeling approach.

The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy. METHODS: Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed. RESULTS: A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha-fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05). CONCLUSIONS: The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

Population Pharmacokinetic Modeling Combined With Machine Learning Approach Improved Tacrolimus Trough Concentration Prediction in Chinese Adult Liver Transplant Recipients.

This study aimed to develop and evaluate a population pharmacokinetic (PPK) combined machine learning approach to predict tacrolimus trough concentrations for Chinese adult liver transplant recipients in the early posttransplant period. Tacrolimus trough concentrations were retrospectively collected from routine monitoring records of liver transplant recipients and divided into the training data set (1287 concentrations in 145 recipients) and the test data set (296 concentrations in 36 recipients). A PPK model was first established using NONMEM. Then a machine learning model of Xgboost was adapted to fit the estimated individual pharmacokinetic parameters obtained from the PPK model with Bayesian forecasting. The performance of the final PPK model and Xgboost model was compared in the test data set. In the final PPK model, tacrolimus daily dose, postoperative days, hematocrit, aspartate aminotransferase, and concomitant voriconazole, were identified to significantly influence the clearance. The postoperative days along with hematocrit significantly influence the volume of distribution. In the Xgboost model, the first 5 predictors for predicting the clearance were concomitant with voriconazole, sex, single nucleotide polymorphisms of CYP3A4*1G and CYP3A5*3 in recipients, and tacrolimus daily dose, for the volume of distribution were postoperative days, age, weight, total bilirubin and graft : recipient weight ratio. In the test data set, the Xgboost model showed the minimum median prediction error of tacrolimus concentrations, less than the PPK model with or without Bayesian forecasting. In conclusion, a PPK combined machine learning approach could improve the prediction of tacrolimus concentrations for Chinese adult liver transplant recipients in the early posttransplant period.

[Effects of gravel content on runoff and sediment yield on Lou soil engineering accumulation slopes under simulated rainfall conditions.] / æ¨¡æ‹Ÿé™é›¨æ¡ä»¶ä¸‹ç ¾çŸ³å«é‡å¯¹å¡¿åœŸå·¥ç¨‹å †ç§¯ä½“å¡é¢äº§æµäº§æ²™çš„å½±å“.

To investigate the effects of gravel content on runoff and sediment yield on Lou soil accumulation slopes, we conducted indoor simulation rainfall experiments and examined the characteristics of runoff and sediment yield on accumulation slopes with five gravel contents (10%, 20%, 30%, 40%, 50%) under four rainfall intensities (1.0, 1.5, 2.0, 2.5 mm·min-1), with a no gravels slope as control. The average runoff rate under different test conditions ranged from 2.18 to 13.07 L·min-1. The average runoff rate was the maximum under the gravel content of 10% (or 20%) and the minimum under the 50% gravel content. The average flow velocity ranged from 0.06 to 0.22 m·s-1. The variation of flow velocity was complex. The smaller the gravel content, the larger the range of variation and the coefficient of variation. The average flow velocity reached the maximum when the gravel content was 10%. The presence of gravel effectively inhibited the sediment yield, and the sediment reduction benefit reached 84.2%. The rainfall intensity had more influence on the average sediment yield rate than gravel content. Results of partial correlation analysis showed that gravel content was significantly negatively correlated with the ave-rage runoff rate, the average flow velocity, and the average sediment yield rate. The relationships between the ave-rage sediment yield and the average runoff rate, the average flow velocity, and their interaction were all extremely significant linear functions, with the strongest relationship between the average sediment yield and the average runoff rate. This study could provide references for the control of soil erosion and the establishment of erosion models for engineering accumulations in Lou soil areas.

Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: A comparison of Michaelis-Menten and theory-based pharmacokinetic models.

Background and Objective: Tacrolimus, a calcineurin inhibitor widely used as a potent immunosuppressant to prevent graft rejection, exhibits nonlinear kinetics in patients with kidney transplantation and nephrotic syndrome. However, whether nonlinear drug metabolism occurs in adult patients undergoing liver transplantation remains unclear, as do the main underlying mechanisms. Therefore, here we aimed to further confirm the characteristics of nonlinearity through a large sample size, and determine the potential influence of nonlinearity and its possible mechanisms. Methods: In total, 906 trough concentrations from 176 adult patients (150 men/26 women; average age: 50.68 ± 9.71 years, average weight: 64.54 ± 11.85 kg after first liver transplantation) were included in this study. Population pharmacokinetic analysis was performed using NONMEM®. Two modeling strategies, theory-based linear compartmental and nonlinear Michaelis-Menten (MM) models, were evaluated and compared. Potential covariates were screened using a stepwise approach. Bootstrap, prediction-, and simulation-based diagnostics (prediction-corrected visual predictive checks) were performed to determine model stability and predictive performance. Finally, Monte Carlo simulations based on the superior model were conducted to design dosing regimens. Results: Postoperative days (POD), Aspartate aminotransferase (AST), daily tacrolimus dose, triazole antifungal agent (TAF) co-therapy, and recipient CYP3A5*3 genotype constituted the main factors in the theory-based compartmental final model, whereas POD, Total serum bilirubin (TBIL), Haematocrit (HCT), TAF co-therapy, and recipient CYP3A5*3 genotype were important in the nonlinear MM model. The theory-based final model exhibited 234 L h-1 apparent plasma clearance and 11,000 L plasma distribution volume. The maximum dose rate (V max ) of the nonlinear MM model was 6.62 mg day-1; the average concentration at steady state at half-V max (K m ) was 6.46 ng ml-1. The nonlinear MM final model was superior to the theory-based final model and used to propose dosing regimens based on simulations. Conclusion: Our findings demonstrate that saturated tacrolimus concentration-dependent binding to erythrocytes and the influence of daily tacrolimus dose on metabolism may partly contribute to nonlinearity. Further investigation is needed is need to explore the causes of nonlinear pharmacokinetic of tacrolimus. The nonlinear MM model can provide reliable support for tacrolimus dosing optimization and adjustment in adult patients undergoing liver transplantation.

Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.

Erratum to: Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

[Erratum to: BMB Reports 2012; 45(9): 509-514, PMID: 23010171] The BMB Reports would like to correct in the Figure 2 of BMB Rep. 2012; 45(9): 509-514 titled "Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells." The original version of this article unfortunately contained image assembling error in the Figure 2. The image for "GFP-Day13" group was inadvertently duplicated from that for "BT20-Day 5" group, and an incorrect image was used for "GFP-Day 17" group. This article has been updated to correct this error in Figure 2.

Left Hepatic Vein Preferential Approach Based on Anatomy Is Safe and Feasible for Laparoscopic Living Donor Left Lateral Sectionectomy.

We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors.

Expert consensus on management of metabolic disease in Chinese liver transplant recipients.

Metabolic disease, including diabetes mellitus, hypertension, dyslipidemia, obesity, and hyperuricemia, is a common complication after liver transplantation and a risk factor for cardiovascular disease and death. The development of metabolic disease is closely related to the side effects of immunosuppressants. Therefore, optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease. The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies. Emphasis is placed on the risk factors of metabolic diseases, the effect of immunosuppressants on metabolic disease, and the prevention and treatment of metabolic diseases.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

[Effects of chemical N fertilizer reduction combined with biochar application on soil organic carbon active components and mineralization in paddy fields of yellow soil.] / æ°®è‚¥å‡é‡é æ–½ç”Ÿç‰©ç‚­å¯¹é»„å£¤ç¨»ç”°åœŸå£¤æœ‰æœºç¢³æ´»æ€§ç»„åˆ†å’ŒçŸ¿åŒ–çš„å½±å“.

Reducing the application of chemical fertilizer and increasing fertilizer efficiency can contribute to the sustainable development of agriculture. To evaluate the impacts of N fertilizer reduction and biochar application on soil organic carbon active components and mineralization in yellow soil, an experiment was carried out with five different substitution rates of chemical N fertilizer by biochar under the same rate of N input, i.e., 0, 10%, 20%, 30%, 40% (CK, T1-T4). The results showed that chemical N fertilizer reduction combined with biochar application could significantly improve soil organic carbon (SOC), the magnitude of which was proportional to the amount of biochar application. Under the condition of 20% substitution rate (T2), soil microbial biomass carbon (MBC) and readily oxidized carbon (ROC) were the highest with 293.68 mg·kg-1 and 250.00 mg·kg-1, respectively, but the concentration of soil dissolved organic carbon (DOC) was the lowest. SOC mineralization rate reached the highest on the third day of incubation. Then, it decreased rapidly in the early period (day 3 of incubation to day 6), decreased slowly in the middle period (day 6 of incubation to day 18), and stabilized in the later period (day 18 of incubation to day 30). There was a logarithmic relationship between mineralization rate of soil organic carbon and incubation time. SOC cumulative mineralization amount and cumulative mineralization rate were the lowest in the T2 treatment with 0.66-0.86 g·kg-1 and 2.9%-4.0%, respectively. As the substitution rate of chemical N fertilizer by biochar increased, rice yield increased firstly and then decreased. Rice yield in the T2 treatment was the highest, which increased by 13.4% compared with the CK. The substitution of 20% chemical N fertilizer with biochar (5 t·hm-2) could effectively improve the contents of SOC, MBC, ROC, and rice yield, reduce the cumulative mineralization amount of organic carbon and cumulative mineralization rate, and enhance the capacity of soil carbon sequestration. Hence, it could be the most effective fertilizer practice for improving soil fertility and rice yield in paddy field of yellow soil in Guizhou Province.

Copper-Catalyzed Asymmetric Annulation Reactions of Carbenes with 2-Iminyl- or 2-Acyl-Substituted Phenols: Convenient Access to Enantioenriched 2,3-Dihydrobenzofurans.

We have developed a method for the highly diastereo- and enantioselective construction of 2,3-dihydrobenzofurans bearing tetrasubstituted carbon stereocenters by means of annulation reactions between carbenes and 2-iminyl- or 2-acyl-substituted phenols through catalysis by readily accessible copper(I)/bisoxazoline catalysts under mild conditions. These reactions feature a unique mechanism in which the copper catalyst serves a dual function: first it reacts with the diazo compound to generate a metal carbene, and second, upon formation of an oxonium ylide, it acts as a Lewis acid to activate the imine or ketone for diastereo- and enantioselective cyclization.

The SMYD3 VNTR 3/3 polymorphism confers an increased risk and poor prognosis of hepatocellular carcinoma in a Chinese population.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC. METHODS: A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. RESULTS: The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. CONCLUSION: This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.

MicroRNA-144 suppresses the expression of cytokines through targeting RANKL in the matured immune cells.

To investigate whether the microRNA-144 (miR-144) had immune regulation effect on matured immune cells, we firstly used quantitative RT-PCR (qRT-PCR) to detect the expression changes of miR-144 between the matured and immature dendritic cells (DCs), macrophages, and the peripheral blood mononuclear cells (PBMCs). Then we went on inspecting the expression changes of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs treated with miR-144 mimics or inhibitors using qRT-PCR, and also performed western blot to test phosphorylation state of ERK, JNK, p38 and p65 in these cells. Next, TargetScan was conducted to forecast the target gene of miR-144, receptor activator for nuclear factor-κB ligand (RANKL), and double luciferase reporter system was applied to research their banding sites. We also determined the expression changes of RANKL in the DCs treated with miR-144 mimics or inhibitors using qRT-PCR and ELISA, respectively. The siRNA of RANKL was synthesized and transfected into DCs to inspect how the immune regulation effect of miR-144 was conducted to inhibit the expression of TNF-α using qRT-PCR, and lastly we used flow cytometry to investigate whether this effect applied to Th17 cells. As results, we found that miR-144 was down-regulated in the matured DCs, macrophages and PBMCs of liver transplantation patients, and the miR-144 mimics could inhibit the expression levels of TNF-α, IL-1ß, IL-6 and IL-23 in the matured DCs. Furthermore, miR-144 interacted with RANKL at position 679-685 of RANKL 3'UTR, and suppressed the translation of RANKL mRNA to realize the negative-regulation. Besides, the silence of RANKL enhanced the suppression effect of miR-144 on TNF-α and this immune regulation effect was applied to Th17 cells, too. In conclusion, this study clearly illustrated that miR-144 could inhibit the expression of cytokine in matured immune cells through suppressing the translation of RANKL mRNA.

A quantitative assessment model of T-cell immune function for predicting risks of infection and rejection during the early stage after liver transplantation.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A + 0.019C + 1.322R (simplified into T = 2A + 3C + 200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity = 80%, specificity = 79.9%,AUC = 92.3%) and 1939.5 (sensitivity = 93.9%, specificity = 77.6%, AUC = 88.6%), relatively (p < 0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients.

The effect of adenovirus-mediated siRNA targeting BMPR-II on UHMWPE-induced osteoclast formation.

Aseptic loosening (AL) is the single most common complication of total joint arthroplasty. The critical factor may contribute to loosening is the adverse tissue response to wear debris. A growing body of literature suggests that BMPs influence the formation and activity of osteoclasts, and BMP signaling plays an important role in the osteoclast formation. In this study, we have employed an RNA interference approach by transfecting a small interfering RNA (siRNA) specific for BMPR-II, to determine the possible importance of this receptor as a target for UHMWPE (Ultra high molecular weight polyethylene) induced osteoclastogenesis in the air pouch model in vivo. Meanwhile, in order to further elucidation of the mechanism of BMPR-II signaling pathway in osteoclast formation, we investigated the effects of siBMPR-II toward RANKL induced osteoclast differentiation in vitro. The present study showed that locally injection of adenovirus-mediated siRNA targeting BMPR-II appears to be a feasible and effective candidate to treat or prevent wear debris-associated osteolysis. Furthermore, we revealed that the effects of BMPR-II signaling on osteoclast formation are mediated directly by osteoclast itself, as well as indirectly by altered expression of RANKL and OPG in osteoblast.

Biphasic effects of TGFß1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells.

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with TGFß1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFß1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of TGFß1 inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of TGFß1 potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGFß1 decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that TGFß1 inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in G(0)/G(1) phase. Our findings strongly suggest that TGFß1 may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells.