Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins. OBJECTIVE: To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH. METHODS: We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis. RESULTS: A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79). CONCLUSION: Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.

Disulfiram in glioma: Literature review of drug repurposing.

Gliomas are the most common malignant brain tumors. High-grade gliomas, represented by glioblastoma multiforme (GBM), have a poor prognosis and are prone to recurrence. The standard treatment strategy is tumor removal combined with radiotherapy and chemotherapy, such as temozolomide (TMZ). However, even after conventional treatment, they still have a high recurrence rate, resulting in an increasing demand for effective anti-glioma drugs. Drug repurposing is a method of reusing drugs that have already been widely approved for new indication. It has the advantages of reduced research cost, safety, and increased efficiency. Disulfiram (DSF), originally approved for alcohol dependence, has been repurposed for adjuvant chemotherapy in glioma. This article reviews the drug repurposing method and the progress of research on disulfiram reuse for glioma treatment.

Modulation of Tumor Immune Microenvironment and Prognostic Value of Ferroptosis-Related Genes, and Candidate Target Drugs in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor, among which IDH1-wild type GBM has a poor prognosis. Recent studies have shown that ferroptosis-related genes (FRGs) are correlated with the development and progression of cancer. In GBM, the role of FRGs associated with IDH1 status as biological indicators and therapeutic targets remains to be clarified. Ten of FRGs (STEAP3, HSPB1, MAP1LC3A, SOCS1, LOX, CAPG, CP, GDF15, CDKN1A, and CD44) associated with IDH1 status in GBM were identified as key genes through screening by survival analysis and Random Forest using The Cancer Genome Atlas (TCGA) datasets, and the protein expressions of key genes were verified. Transwell and qPCR results showed that ferroptosis promoted the migration of glioblastoma cells and affected the expression of key genes. Our study established the ferroptosis-related prognostic model for GBM patients based on ten key genes by a different modeling method from previous study, the GSVA algorithm. Further, we took the methods of functional enrichment analysis, clinical characteristics, immune cell infiltration, immunomodulator, ESTIMATE and single nucleotide variant (SNV) analysis to study the molecular mechanisms of prognostic model and key genes. The results showed that ten key genes were strongly associated with immune-related factors and were significantly involved in the p53 signaling pathway, senescence and autophagy in cancer, and in the negative regulation of protein kinase activity. Moreover, potential therapeutic drugs were identified by Virtual Screening and Molecular Docking. Our study indicated that the novel ferrotosis-related prognostic model for GBM patients and key genes possessed the prognostic and therapeutic values.

Immunotherapeutic Value of MAP1LC3C and Its Candidate FDA-Approved Drugs Identified by Pan-Cancer Analysis, Virtual Screening and Sensitivity Analysis.

Background: The autophagy pathway within the tumour microenvironment can be regulated to inhibit or promote tumour development. In the fight against tumour growth, immunotherapy induces an anti-tumour immune response, whereas autophagy modulates this immune response. A key protein in the autophagy pathway, microtubule-associated protein 1 light chain 3 (MAP1LC3), has recently become a hotspot for tumour research. As a relatively novel member, the function of MAP1LC3C in tumours still need to be investigated. Therefore, the goal of this study was to look into the possible link between MAP1LC3C and immunotherapy for 33 kinds of human malignancies by using pan-cancer analysis. Methods: High-throughput sequencing data from The Cancer Genome Atlas, Genotype-Tissue Expression Project and Cancer Cell Line Encyclopedia databases, combined with clinical data, were used to analyze the expression of MAP1LC3C in 33 types of cancer, as well as patient prognosis and neoplasm staging. Activity scores were calculated using ssGSEA to assess the MAP1LC3C activity in pan-cancer. Associations between MAP1LC3C and the tumour microenvironment, including immune cell infiltration and immunomodulators, were analyzed. Moreover, tumour tissue ImmuneScores and StromalScores were analyzed using the ESTIMATE algorithm. Additionally, associations between MAP1LC3C and tumour mutational burden/microsatellite instability, were investigated. Finally, based on the expression and structure of MAP1LC3C, the United States Food and Drug Administration (FDA)-approved drugs, were screened by virtual screening, molecular docking and NCI-60 drug sensitivity analysis. Results: Our study found that MAP1LC3C was differentially expressed in tumour and normal tissues in 23 of 33 human cancer types, among which MAP1LC3C had prognostic effects in 12 cancer types, and MAP1LC3C expression was significantly correlated with tumour stage in four cancer types. In addition, MAP1LC3C activity in 14 cancer types was consistent with changes in transcription levels. Moreover, MAP1LC3C strongly correlated with immune infiltration, immune modulators and immune markers. Finally, a number of FDA-approved drugs were identified via virtual screening and drug sensitivity analysis. Conclusion: Our study investigated the prognostic and immunotherapeutic value of MAP1LC3C in 33 types of cancer, and several FDA-approved drugs were identified to be highly related to MAP1LC3C and can be potential cancer therapeutic candidates.

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials.

Statins are used in clinical practice to prevent from complications such as cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy and safety of statins are still controversial due to insufficient evidence from randomized controlled trials and inconsistent results of the existing studies. This meta-analysis aimed to systematically review the latest evidence on the time window and complications of statins in aSAH. The randomized controlled trials in the databases of The Cochrane Library, PubMed, Web of Science, Embase, CNKI, and Wanfang from January 2005 to April 2021 were searched and analyzed systematically. Data analysis was performed using Stata version 16.0. The fixed-effects model (M-H method) with effect size risk ratio (RR) was used for subgroups with homogeneity, and the random-effects model (D-L method) with effect size odds ratio (OR) was used for subgroups with heterogeneity. The primary outcomes were poor neurological prognosis and all-cause mortality, and the secondary outcomes were cerebral vasospasm (CVS) and statin-related complications. This study was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021247376). Nine studies comprising 1,464 patients were included. The Jadad score of the patients was 5-7. Meta-analysis showed that poor neurological prognosis was reduced in patients who took oral statins for 14 days (RR, 0.73 [0.55-0.97]; I 2 = 0%). Surprisingly, the continuous use of statins for 21 days had no significant effect on neurological prognosis (RR, 1.04 [0.89-1.23]; I 2 = 17%). Statins reduced CVS (OR, 0.51 [0.36-0.71]; I 2 = 0%) but increased bacteremia (OR, 1.38 [1.01-1.89]; I 2 = 0%). In conclusion, a short treatment course of statins over 2 weeks may improve neurological prognosis. Statins were associated with reduced CVS. Based on the pathophysiological characteristics of CVS and the evaluation of prognosis, 2 weeks could be the optimal time window for statin treatment in aSAH, although bacteremia may increase.

Risk Factors of Psychological Responses of Chinese University Students During the COVID-19 Outbreak: Cross-sectional Web-Based Survey Study.

BACKGROUND: COVID-19 is a highly contagious and highly pathogenic disease caused by a novel coronavirus, SARS-CoV-2, and it has become a pandemic. As a vulnerable population, university students are at high risk during the epidemic, as they have high mobility and often overlook the severity of the disease because they receive incomplete information about the epidemic. In addition to the risk of death from infection, the epidemic has placed substantial psychological pressure on the public. In this respect, university students are more prone to psychological problems induced by the epidemic compared to the general population because for most students, university life is their first time outside the structure of the family, and their mental development is still immature. Internal and external expectations and academic stress lead to excessive pressure on students, and unhealthy lifestyles also deteriorate their mental health. The outbreak of COVID-19 was a significant social event, and it could potentially have a great impact on the life and the mental health of university students. Therefore, it is of importance to investigate university students' mental health status during the outbreak of COVID-19. OBJECTIVE: The principal objective of this study was to investigate the influencing factors of the psychological responses of Chinese university students during the COVID-19 outbreak. METHODS: This study used data from a survey conducted in China between February 21 and 24, 2020, and the data set contains demographic information and psychological measures including the Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the compulsive behaviors portion of the Yale-Brown Obsessive-Compulsive Scale. A total of 2284 questionnaires were returned, and 2270 of them were valid and were used for analysis. The Mann-Whitney U test for two independent samples and binary logistic regression models were used for statistical analysis. RESULTS: Our study surveyed 563 medical students and 1707 nonmedical students. Among them, 251/2270 students (11.06%) had mental health issues. The results showed that contact history of similar infectious disease (odds ratio [OR] 3.363, P=.02), past medical history (OR 3.282, P<.001), and compulsive behaviors (OR 3.525, P<.001) contributed to the risk of mental health issues. Older students (OR 0.928, P=.02), regular daily life during the epidemic outbreak (OR 0.410, P<.001), exercise during the epidemic outbreak (OR 0.456, P<.001), and concern related to COVID-19 (OR 0.638, P=.002) were protective factors for mental health issues. CONCLUSIONS: According to the study results, mental health issues have seriously affected university students, and our results are beneficial for identifying groups of university students who are at risk for possible mental health issues so that universities and families can prevent or intervene in the development of potential mental health issues at the early stage of their development.

MicroRNA-200c Nanoparticles Sensitized Gastric Cancer Cells to Radiotherapy by Regulating PD-L1 Expression and EMT.

INTRODUCTION: Immuno-checkpoint inhibitors (ICIs) in advanced gastric cancer either as monotherapy or in combining strategies are rapidly evolving but still in early phase. Various efforts have been made to provide insights into regulating immune checkpoint molecule programmed cell death ligand-1 (PD-L1) expression to improve ICIs efficacy. The aim of this study was to investigate the effect and potential mechanism of miR-200c nanoparticles combined with radiotherapy in gastric cancer cells. METHODS: We prepared miR-200c-loaded nanoparticles (miR-200c NPs) to achieve targeted delivery of miR-200c to AGS cells. The roles of miR-200c NPs and radiotherapy in regulating the viability of AGS cells were assessed by CCK-8 toxicity test and Annexin V-FITC/PI apoptosis kit. Flow cytometry was used to analyze expression of PD-L1 and CD44 on the surface of AGS cells treated by miR-200c NPs and/or ionizing radiation. Enzyme-linked immunosorbent assay (ELISA) was used to test the level of transforming growth factor-beta 1 (TGF-ß1) secreted by AGS cells. The cooperation mechanism between miR-200c NPs and radiotherapy was also explored in vitro. RESULTS: Compared with naked miR-200c mimics, miR-200c NPs significantly downregulated PD-L1 expression of gastric cancer cells. The combination of miR-200c NPs and radiotherapy showed significantly synergistic inhibitory effect on gastric cancer cells by inhibiting immune escape mediated by PD-L1, reversing EMT phenotype as well as abrogating cancer stem cells (CSCs)-associated properties of tumor cells. CONCLUSION: MiR-200c NPs sensitized gastric cancer cells to radiotherapy by regulating PD-L1 expression and EMT.

Defender-Attacker Games with Asymmetric Player Utilities.

The presence of strategic attackers has become an important factor in the security and protection of systems, especially since the 9/11/2001 attacks, and considerable efforts have been dedicated to its study. When defending against the strategic attacker, many existing studies assume that the attacker would seek to minimize the defender's utility, which implies that the defender and attacker have symmetric utilities. However, the attacker's objective is determined by its own valuation of the system and target of the attack, which is not necessarily consistent with the defender's utility. If the attacker unexpectedly targets a different utility, then the defense strategy might no longer be optimal. In particular, the defense strategy could be inferior if the attacker's utility is not known to the defender. This study considers a situation where the defender's utility is the system survivability and the attacker's utility is the expected number of destroyed elements in the system. We investigate possible attack strategies under these two different utilities and compare (a) the conservative defense strategy when the attack utility is unknown to the defender with (b) the optimal defense strategy when the attack utility is known to the defender. We show that the conservative protection strategy is still optimal under asymmetric utilities when the contest intensity is smaller than one.

Preparation and Optimization Lipid Nanocapsules to Enhance the Antitumor Efficacy of Cisplatin in Hepatocellular Carcinoma HepG2 Cells.

This work aimed to develop and optimize several lipid nanocapsule formulations (LNCs) to encapsulate cisplatin (CDDP) for treatment of hepatocellular carcinoma. By comparing the effect of oil/surfactant ratio, lecithin content, and oil/surfactant type on LNC characteristics, two LNCs were selected as optimal formulations: HS15-LNC (Solutol HS 15/MCT/lecithin, 54.5:42.5:3%, w/w) and EL-LNC (Cremophor EL/MCT/lecithin, 54.5:42.5:3%, w/w). Both LNCs could effectively encapsulate CDDP with the encapsulation efficiency of 73.48 and 78.84%. In vitro release study showed that both LNCs could sustain the release CDDP. Moreover, cellular uptake study showed that C6-labeled LNCs could be effectively internalized by HepG2 cells. Cellular cytotoxicity study revealed that both LNCs showed negligible cellular toxicity when their concentrations were below 313 µg/mL. Importantly, CDDP-loaded LNCs exhibited much stronger cell killing potency than free CDDP, with the IC50 values decreased from 17.93 to 3.53 and 5.16 µM after 72-h incubation. In addition, flow cytometric analysis showed that the percentage of apoptotic cells was significantly increased after treatment with LNCs. Therefore, the prepared LNC formulations exhibited promising anti-hepatocarcinoma effect, which could be beneficial to hepatocellular carcinoma therapy.