BackgroundMitogen-activated protein kinase (MAPK) signaling pathways are implicated in inflammatory and apoptotic processes of cerebral ischemia and reperfusion (I/R) injury. Hence, MAPK pathways represent a promising therapeutic target. Exploring the full potential of inhibitors of MAPK pathways is a useful therapeutic strategy for ischemic stroke. Bilobalide, a predominant sesquiterpene trilactone constituent of Ginkgo biloba leaves, has been shown to exert powerful neuroprotective properties, which are closely related to both anti-inflammatory and anti-apoptotic pathways. We investigated the neuroprotective roles of bilobalide in the models of middle cerebral artery occlusion and reperfusion (MCAO/R) and oxygen-glucose deprivation and reoxygenation (OGD/R) of cerebral I/R injury. Moreover, we attempted to confirm the hypothesis that its protection effect is via modulation of pro-inflammatory mediators and MAPK pathways.MethodsMale Sprague-Dawley rats were subjected to MCAO for 2 h followed by reperfusion for 24 h. Bilobalide was administered intraperitoneally 60 min before induction of middle cerebral artery occlusion (MCAO). After reperfusion, neurological deficit scores, infarct volume, infarct weight, and brain edema were assessed. Ischemic penumbrae of the cerebral cortex were harvested to determine superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide, TNF-α, interleukin 1β (IL-1β), p-ERK1/2, p-JNK1/2, and p-p38 MAPK concentration. Similarly, the influence of bilobalide on the expression of nitric oxide, TNF-α, IL-1β, p-ERK1/2, p-JNK1/2, and p-p38 MAPK was also observed in an OGD/R in vitro model of I/R injury.ResultsPretreatment with bilobalide (5, 10 mg/kg) significantly decreased neurological deficit scores, infarct volume, infarct weight, brain edema, and concentrations of MDA, nitric oxide, TNF-α, IL-1β, and increased SOD activity. Furthermore, bilobalide (5, 10 mg/kg) pretreatment significantly down-regulated both p-JNK1/2 and p-p38 MAPK expression, whereas they had no effect on p-ERK1/2 expression in the ischemic penumbra. Supporting these observations in vivo, pretreatment with bilobalide (50, 100 μM) significantly down-regulated nitric oxide, TNF-α, IL-1β, p-JNK1/2, and p-p38 MAPK expression, but did not change p-ERK1/2 expression in rat cortical neurons after OGD/R injury.ConclusionsThese data indicate that the neuroprotective effects of bilobalide on cerebral I/R injury are associated with its inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation.

Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family and localizes to the cytoplasm. STAT4 is phosphorylated after a variety of cytokines bind to the membrane, and then dimerized STAT4 translocates to the nucleus to regulate gene expression. We reviewed the essential role played by STAT4 in a wide variety of cells and the pathogenesis of diverse human diseases, especially many kinds of autoimmune and inflammatory diseases, via activation by different cytokines through the Janus kinase (JAK)-STAT signaling pathway.

Background Lymph node metastasis (LNM) is an important factor for thyroid cancer patients’ treatment and prognosis. The aim of this study was to explore the clinical value of ultrasound features and radiomics analysis in predicting LNM in thyroid cancer patients before surgery. Methods The characteristics of ultrasound images of 150 thyroid nodules were retrospectively analysed. All nodules were confirmed as thyroid cancer. Among the assessed patients, only one hundred and twenty-six patients underwent lymph node dissection. All patients underwent an ultrasound examination before surgery. In the radiomic analysis, the area of interest was identified from selected ultrasound images by using ITK-SNAP software. The radiomic features were extracted by using Ultrosomics software. Then, the data were classified into a training set and a validation set. Hypothetical tests and bagging were used to build the model. The diagnostic performance of different ultrasound features was assessed, a radiomic analysis was conducted, and a receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic accuracy. Results Regarding the prediction of LNM, the ROC curves showed that the area under the curve (AUC) values of an irregular shape and microcalcification were 0.591 (P = 0.059) and 0.629 (P = 0.007), respectively. In the radiomics analysis, in the training set, the AUC value of LNM was 0.759, with a sensitivity of 0.90 and a specificity of 0.860. In the verification set, the AUC was 0.803, with a sensitivity of 0.727 and a specificity of 0.800. Conclusions Microcalcification and an irregular shape are predictors of LNM in thyroid carcinoma patients. In addition, radiomics analysis has promising value in screening meaningful ultrasound features in thyroid cancer patients with LNM. Therefore, the prediction of LNM based on ultrasound features and radiomic features is useful for making appropriate decisions regarding surgery and interventions before thyroid carcinoma surgery.

Background: To date, 14 single-nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). Aim: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. Methods: We performed a retrospective analysis of 1623 Han Chinese HBeAg-positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow-up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase-IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed.Results: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα-treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one-third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P-trend = 4.000 × 10 −4 ) andHBsAg loss (P-trend = 0.010) in PegIFNα-treated patients. However, none of the SNPs were associated with treatment response in NUCs-treated patients.Conclusions: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg-positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.