Background: Immune checkpoint inhibitors-induced myocarditis presents unique clinical challenges. Here, we assessed post-marketing safety of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors by mining the real-world data reported in two international pharmacovigilance databases. Methods: We analyzed immune checkpoint inhibitors (ICIs)-associated fatal adverse drug events (ADEs) reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) collected from July 1, 2014 to December 31, 2019 and data from EudraVigilance (EV) database accessed on February 29, 2020. Three different data mining approaches were used to detect the signal of fatal myocarditis caused by ICIs. Results: Based on 7613 ICIs-related ADEs reported to the EV database and 5786 ICIs-associated ADEs submitted to the FAERS database, the most frequently reported ADE was ipilimumab-related colitis. For myocarditis, nivolumab-associated myocarditis was the most common. Among the five fatal toxic effects associated with ICIs, the lethality rate of myocarditis was the highest. Therefore, we further analyzed ICI-associated myocarditis and found that elderly patients and male patients were more likely to develop ICIs-related myocarditis. The results of signal detection showed that the risk signal of avelumab-related myocarditis detected by reporting odds ratio (ROR) method and proportional reporting ratios (PRR) method was the highest, whereas the signal strength of ipilimumab-related myocarditis detected by Bayesian confidence propagation neural networks (BCPNN) method was the strongest. Conclusion: The findings of this study indicated the potential safety issues of developing myocarditis when using ICIs, which were consistent with the results of previous clinical trials and could provide a reference for clinical workers when using ICIs.

Peritoneal metastasis is a malignant disease which originated from several gastrointestinal and gynecological carcinomas and has been leading to a suffering condition in patients for decades. Currently, as people have gradually become more aware of the severity of peritoneal carcinomatosis, new molecular mechanisms for targeting and new treatments have been proposed. However, due to the uncertainty of influencing factors involved and a lack of a standardized procedure for this treatment, as well as a need for more clinical data for specific evaluation, more research is needed, both for preventing and treating. We aim to summarize backgrounds, mechanisms and treatments in this area and conclude limitations or new aspects for treatments.

Background: Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection. Methods: Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting₁₃. C-urea breath test was performed to evaluate the eradication therap’s efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions. Results: Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of ₁₃C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period. Conclusions: Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.

Background: β‐asarone (β‐as), a compound extracted from Acorus calamus, has been found to have anticancer effects on a variety of human cancers. However, the potential effect of β‐as on bladder cancer (BCa) remains unknown.Methods: After exposure to β‐as, migration, invasion, and epithelial‐mesenchymal transition (EMT) of BCa were determined by wound healing, transwell, and Western blot assays. Expression of proteins involved in the EMT and ER stress were explored by Western blot assays. Nude mouse xenograft model was served as the model system in vivo.Results: The migration, invasion, and EMT of BCa were significantly inhibited after β‐as treatment. Further experiments revealed that endoplasmic reticulum (ER) stress is involved in β‐as‐mediated metastasis inhibition. In addition, β‐as significantly up‐regulated activating transcription factor 6 (ATF6), a branch of ER stress, and promoted its Golgi cleavage and nuclear localization. ATF6 silencing attenuated β‐as‐mediated metastasis and EMT inhibition in BCa cells.Conclusion: Our data suggests that β‐as inhibits migration, invasion, and EMT of BCa by activating the ATF6 branch of ER stress. Thus, β‐as represents a potential candidate for BCa treatment.

Purpose: The aim of this study was to investigate the role of BIRC5 for early diagnosis and prognosis in clear-cell renal cell carcinoma (ccRCC) by studying the expression of BIRC5 and the correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC. Methods: The BIRC5 expression in ccRCC tissues and normal kidney tissues was measured using the Cancer Genome Atlas database and the Human Protein Atlas database. The correlation between BIRC5 expression and clinicopathological parameters and prognosis in ccRCC was analyzed using UALCAN, the Kaplan-Meier plotter, GEPIA, and SurvExpress. Thirteen-paired ccRCC plasma samples were used to verify the BIRC5 early diagnosis value of ccRCC. Results: The BIRC5 expression is significantly higher in ccRCC than in normal kidney tissues, and is correlated with the clinical stage and pathological grade of ccRCC (p < 0.05). The result of analyzing the relationship between BIRC5 expression and outcomes in ccRCC indicates that a high BIRC5 expression is an independent prognostic factor affecting the overall survival and disease-free survival of ccRCC (p < 0.05). Compared with normal kidney tissues, the immunohistochemical test shows that BIRC5 is significantly upregulated in ccRCC tissues. mRNA expression levels of BIRC5 were significantly higher in the ccRCC plasma than normal (p < 0.05). Conclusions: The high expression of BIRC5 is an important indicator for the prognosis of ccRCC, which makes BIRC5 an effective biomarker for predicting the prognosis of patients in ccRCC. BIRC5 may be a great potential biomarker for early diagnosis of ccRCC.