No abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The early diagnosis of HCC is greatly helpful to achieve long-term disease-free survival. However, HCC is usually difficult to be diagnosed at an early stage. The aim of this study was to create the prediction model to diagnose HCC based on gene expression programming (GEP). GEP is an evolutionary algorithm and a domain-independent problem-solving technique. Clinical data show that six serum biomarkers, including gamma-glutamyl transferase, C-reaction protein, carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 153, and carbohydrate antigen 199, are related to HCC characteristics. In this study, the prediction of HCC was made based on these six biomarkers (195 HCC patients and 215 non-HCC controls) by setting up optimal joint models with GEP. The GEP model discriminated 353 out of 410 subjects, representing a determination coefficient of 86.28% (283/328) and 85.37% (70/82) for training and test sets, respectively. Compared to the results from the support vector machine, the artificial neural network, and the multilayer perceptron, GEP showed a better outcome. The results suggested that GEP modeling was a promising and excellent tool in diagnosis of hepatocellular carcinoma, and it could be widely used in HCC auxiliary diagnosis. Graphical abstract The process to establish an efficient model for auxiliary diagnosis of hepatocellular carcinoma.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. Several studies reported that SATA4 (signal transducer and activator of transcription 4) polymorphisms were significantly associated with PBC susceptibility. In order to derive a more comprehensive estimation of the association between STAT4 and PBC risk, this meta-analysis was conducted. Thirteen eligible studies from 8 articles with a total number of 11,310 cases and 27,844 controls were included in this meta-analysis. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with fixed effects model or random effects model. The results showed statistically significant association between polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 and PBC risk under the allelic effect model (rs7574865, T vs. G, OR = 1.24, 95% CI 1.14-1.35; rs3024921, T vs. A, OR = 1.65, 95% CI 1.44-1.91; rs6752770, G vs. A, OR = 1.24, 95% CI 1.11-1.39; rs7601754, A vs. G, OR = 1.35, 95% CI 1.17-1.55; and rs10168266, T vs. C, OR = 1.31, 95% CI 1.22-1.41). Furthermore, the rs7574865 polymorphism was significantly associated with PBC risk under all genotype genetic models (dominant effect model: TT + TG vs. GG, OR = 1.43, 95% CI 1.19-1.71; recessive effect: TT vs. TG + GG, OR = 1.40, 95% CI 1.24-1.58; and co-dominant effect: TT vs. GG, OR = 1.67, 95% CI 1.37-2.02). The sensitivity analysis by omitting one study at a time showed that the results were stable. No publication bias was indicated from both Begg's test and Egger's weighted regression. This meta-analysis suggested that polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 were significantly associated with the risk of PBC.

BACKGROUND Nephrotic syndrome that is resistant to steroid therapy is termed refractory nephrotic syndrome (RNS), a condition that is associated with an increased risk of end-stage renal disease. Immunosuppressants are used to treat RNS; however, prolonged use may lead to significant adverse effects. Mizoribine (MZR) is a novel agent used in long-term immunosuppressive therapy, which has few adverse effects, but data on its long-term use in patients with RNS are unavailable. OBJECTIVE We propose a trial to examine the efficacy and safety of MZR compared with cyclophosphamide (CYC) in Chinese adult patients with RNS. METHODS This is a multicenter, randomized, controlled interventional study with a screening phase (1 week) and a treatment phase (52 weeks). This study has been reviewed and approved by the Medical Ethics Committees of all 34 medical centers that are participating. Patients with RNS consent to participation, and are enrolled and randomized to an MZR group or a CYC group (1:1 ratio), with each group receiving tapering doses of oral corticosteroids. Participants are assessed for adverse effects, and laboratory results are collected at 8 visits during the treatment phase (weeks 4, 8, 12, 16, 20, 32, 44, and 52 [exit visit]). Participants are able to withdraw voluntarily, and investigators are required to remove patients when there are safety concerns or deviations from the protocol. RESULTS The study started in November 2014 and was completed in March 2019. A total of 239 participants from 34 hospitals in China have been enrolled. Data analysis has been completed. The results are being finalized by the Center for Drug Evaluation. CONCLUSIONS This study examines the safety and efficacy of MZR as a long-term treatment approach for Chinese adults with RNS. It is the longest lasting and largest randomized controlled trial to examine MZR in Chinese patients. The results can help determine whether RNS should be considered as an additional indication for MZR treatment in China. CLINICALTRIAL ClinicalTrials.gov NCT02257697; https://clinicaltrials.gov/ct2/show/NCT02257697 INTERNATIONAL REGISTERED REPORT RR1-10.2196/46101