Jiang-lin Wang

Preprocedural Prediction Model for Contrast‐Induced Nephropathy Patients

Background Several models have been developed for prediction of contrast‐induced nephropathy (CIN); however, they only contain patients receiving intra‐arterial contrast media for coronary angiographic procedures, which represent a small proportion of all contrast procedures. In addition, most of them evaluate radiological interventional procedure‐related variables. So it is necessary for us to develop a model for prediction of CIN before radiological procedures among patients administered contrast media. Methods and Results A total of 8800 patients undergoing contrast administration were randomly assigned in a 4:1 ratio to development and validation data sets. CIN was defined as an increase of 25% and/or 0.5 mg/dL in serum creatinine within 72 hours above the baseline value. Preprocedural clinical variables were used to develop the prediction model from the training data set by the machine learning method of random forest, and 5‐fold cross‐validation was used to evaluate the prediction accuracies of the model. Finally we tested this model in the validation data set. The incidence of CIN was 13.38%. We built a prediction model with 13 preprocedural variables selected from 83 variables. The model obtained an area under the receiver‐operating characteristic (ROC) curve (AUC) of 0.907 and gave prediction accuracy of 80.8%, sensitivity of 82.7%, specificity of 78.8%, and Matthews correlation coefficient of 61.5%. For the first time, 3 new factors are included in the model: the decreased sodium concentration, the INR value, and the preprocedural glucose level. Conclusions The newly established model shows excellent predictive ability of CIN development and thereby provides preventative measures for CIN.

Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

Roles of periostin in proliferation and migration of vascular smooth muscle cells and the effect of atorvastatin on them

OBJECTIVE To investigate the expression of periostin in in vitro cultured vascular smooth muscle cells (VSMCs) induced by TGF-β1 and the relationship between periostin expression and the migration and proliferation of the VSMCs. Further, to investigate the effects of atorvastatin on the above-mentioned processes and the molecular mechanisms of atorvastatin inhibition of TGF-β1- induced periostin production. METHODS Rat aorta smooth muscle cells were cultivated by the method of tissue explants adherence. Cells of generation 3 to 6 were used as the experimental system. Primary cultured rat vascular smooth muscle cells were treated by TGF-β1 and different concentrations of atorvastatin,Y-2763 (Rho kinase inhibitor), or atorvastatin plus MVA for 24 hours. The expression of periostin was measured by RT-PCR and Western blot. A Boyden chamber assay was used to measure cell migration, and an MTT test was used to measure cell proliferation. RESULTS Periostin expression in rat VSMCs stimulated by TGF-β1 increased significantly (4.158 ± 0.515 vs 0.385 ± 0.031), VSMC migration(25 ± 4 vs 8 ± 2) and proliferation (0.85 ± 0.06 vs 0.32 ± 0.03) also increased significantly. Atorvastatin significantly inhibited TGF-β1-induced periostin production in rat VSMCs, as well as VSMC migration and proliferation, in a dose-dependent manner. Rho kinase inhibitor Y-27632 significantly inhibited TGF-β1-induced periostin production in rat VSMCs (2.082 ± 0.245). The inhibitory effect of atorvastatin on periostin upregulation induced by TGF-β1 was reversed by mevalonate (3.838 ± 0.326). CONCLUSION Periostin can promote rat VSMC migration and proliferation. Atorvastatin inhibition of periostin expression induced by TGF-β1 in VSMCs may be exerted by inhibition of the production of MVA and other isoprene compounds and by blocking the Rho/Rho kinase signaling pathway.

Evaluating tacrolimus pharmacokinetic models in adult renal transplant recipients with different CYP3A5 genotypes

PurposeNumerous studies have been conducted on the population pharmacokinetics of tacrolimus in adult renal transplant recipients. It has been reported that the cytochrome P450 (CYP) 3A5 genotype is an important cause of variability in tacrolimus pharmacokinetics. However, the predictive performance of population pharmacokinetic (PK) models of tacrolimus should be evaluated prior to their implementation in clinical practice. The aim of the study reported here was to test the predictive performance of these published PK models of tacrolimus.MethodsA literature search of the PubMed and Web of Science databases ultimately led to the inclusion of eight one-compartment models in our analysis. We collected a total of 1715 trough concentrations from 174 patients. Predictive performance was assessed based on visual and numerical comparison bias and imprecision and by the use of simulation-based diagnostics and Bayesian forecasting.ResultsOf the eight one-compartment models assessed, seven showed better predictive performance in CYP3A5 extensive metabolizers in terms of bias and imprecision. Results of the simulation-based diagnostics also supported the findings. The model based on a Chinese population in 2013 (model 3) showed the best and most stable predictive performance in all the tests and was more informative in CYP3A5 extensive metabolizers. As expected, Bayesian forecasting improved model predictability. Diversity among models and between different CYP3A5 genotypes of the same model was also narrowed by Bayesian forecasting.ConclusionsBased on our results, we recommend using model 3 in CYP3A5 extensive metabolizers in clinical practice. All models had a poor predictive performance in CYP3A5 poor metabolizers, and they should be used with caution in this patient population. However, Bayesian forecasting improved the predictability and reduced differences, and thus the models could be applied in this latter patient population for the design of maintenance dose.

Dlitiazem inhibits the oxidative stress induced by angiotensin II through growth hormone secretagogue receptor type 1a in human umbilicus vein endothelial cells

Diltiazem has been used for post-transplant hypertension, but the mechanism underlying its protective effect of endothelial cells against angiotensin II (Ang II) - induced impairment remains unclear. Human umbilicus vein endothelial cells (HUVECs) were cultured and divided into seven groups: control, Ang II (10-6M), diltiazem (10-6M), [D-Lys3]-GHRP-6(25μM), diltiazem (10-6M)+Ang II (10-6M), losartan (10-6M)+Ang II (10-6M), [D-Lys3]-GHRP-6 (25μM) + Dil(10-6M)+Ang II (10-6M) groups. Nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) and p47 phox subunit of NADPH were evaluated. Results indicated that pre- treatment with diltiazem significantly decreased the intracellular ROS levels and increased NO production. Treatment with 10-6M Ang II for 24h induced a significant decrease in the mRNA and protein levels of eNOS, which was significantly increased by the pre-incubated with diltiazem (10-6M). Treatment with 10-6M Ang II for 24h induced a significant increase in the mRNA and protein levels of p47 phox subunit of NADHP oxidase, which was significantly decreased by the pre-incubated with diltiazem. However, all of these protective roles of diltiazem were attenuated by pre-incubation of [D-Lys3]-GHRP-6. The results reveal that diltiazem inhibits the Ang II - induced oxidative stress in HUVECs, which may be partly mediated by GHSR1a.

[Meta-analysis of proximal gastrectomy and total gastrectomy for cancer of cardia and fundus].

OBJECTIVE To assess the value of proximal gastrectomy (PG) and total gastrectomy (TG) for the treatment of cancer of cardia and fundus. METHODS Publications on comparision between PG and TG in the treatment of cancer of cardia and fundus were collected, the data from the publications were matched with the PG group and the TG group respectively according to its corresponding surgical resection, and the data on postoperative complications, motality and 5-year survival rate were meta-analyzed by fixed effect model and random effect model. RESULTS Thirteen reseaches on 2 219 patients were included in this study, 2 of which were randomly controlled studies. There were no significant differences in the postoperative complications (OR=1.00, 95%CI: 0.44-2.28,P>0.05) and mortality (OR=1.25, 95%CI: 0.62-2.48,P>0.05) between the PG group and the TG group, while there was significant difference in the 5-year survival rate (HR=0.87, 95%CI: 0.76-0.99,P=0.04). The 5-year survival rate in the TG group was higher than that in the PG group. CONCLUSION Total gastrectomy for the treatment of cancer of cardia and fundus has better long-term therapetic effect.