Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous “inflammation brake.” We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.

Background: Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. Methods: With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Results: Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. Conclusions: This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.

Background: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. Methods: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Results: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. Conclusions: The results of this paper show that the occurrence of irAEs is associated with patients’ OS. irAEs occurrence can prolong patients’ OS. irAEs occurrence may serve as a surrogate marker for ICIs.