The changes in metabolomics profile induced by intermittent theta burst stimulation in major depressive disorder: an exploratory study.

BACKGROUND: Recently, there has been an ongoing interest in the mechanism of intermittent theta burst stimulation (iTBS) in major depressive disorder. Studying the metabolite changes induced by iTBS may help to understand the mechanism. METHODS: Eleven participants with major depressive disorder received 10 days iTBS treatment. Magnetic resonance imaging (MRI) was used to target the region of the left dorsolateral prefrontal cortex (DLPFC) in each participant. We analyzed the effects of iTBS on metabolites using high-throughput profiling and assessed its impact on depressive symptoms. These analyses were considered exploratory, and no correction for multiple comparisons was applied. RESULTS: Among the 318 measured metabolites, a significant increase in cystine, asymmetric dimethylarginine (ADMA), 1-methylhistidine, indoleacetic acid (IAA), diethanolamine (DEA), dopa, riboflavin-5'-monophosphate (FMN), and a significant decrease in alphalinolenic acid (ALA), gamma-linolenic acid (GLA), serotonin, linoleic acid (LA) (p < 0.05) were detected in the patients after iTBS treatment. In Pearson correlation analysis, the plasma levels of LA, FMN and ADMA at baseline were significantly related to the reduction rate of the 17-item Hamilton Depression Rating Scale and the Patient Health Questionnaire-9 scores (p < 0.05). CONCLUSIONS: Our study highlights that LA, FMN, ADMA and their relationship with oxidative stress, may be key factors in the antidepressant efficacy of iTBS.

Malignant cancer may increase the risk of all-cause in-hospital mortality in patients with acute myocardial infarction: a multicenter retrospective study of two large public databases.

BACKGROUND: Acute myocardial infarction (AMI) and cancer are diseases with high morbidity and mortality worldwide, bringing a serious economic burden, and they share some risk factors. The purpose of this study was to determine the effect of cancer on the all-cause in-hospital mortality of patients with AMI. METHODS: This multicenter retrospective study analyzed patients with AMI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD) in the United States. Patients were divided into two groups based on whether they had concomitant malignant cancer: cancer and noncancer groups. The outcome was all-cause in-hospital mortality. The association between the two groups and their outcomes were analyzed using Kaplan-Meier and Cox proportional-hazards regression models. Propensity score matching (PSM) and propensity score based inverse probability of treatment weighting (IPTW) were used to further adjust for confounding variables to verify the stability of the results. RESULTS: The study included 3,034 and 5,968 patients with AMI from the MIMIC-IV database and the eICU-CRD, respectively. Kaplan-Meier survival curves indicated that the probability of in-hospital survival was lower in patients with cancer than in those without cancer. After adjusting for potential confounding variables using multivariable Cox proportional hazards regression, the risk of all-cause in-hospital mortality was significantly higher in the cancer than the noncancer group, and the HR (95% CI) values for the cancer group were 1.56(1.22,1.98) and 1.35(1.01,1.79) in the MIMIC-IV database and the eICU-CRD, respectively. The same results were obtained after using PSM and IPTW, which further verified the results. CONCLUSIONS: Among the patients with AMI, the all-cause in-hospital mortality risk of those with cancer was higher than those without cancer. Therefore, when treating such patients, comprehensive considerations should be made from a multidisciplinary perspective involving cardiology and oncology, with the treatment plan adjusted accordingly.

Development and validation of a simple nomogram for predicting the short-term prognosis of patients with pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a disease caused by blood clots, tumor embolism, and other emboli within the pulmonary arteries. Various scoring scales are used for PE. One such same is the PESI, but it has 12 variables, making it inconvenient for clinical application. OBJECTIVES: The aim of this study was to develop a new simple nomogram model to assess 30-day survival in PE patients. The new nomogram makes it easier and faster for clinicians to assess the prognosis of patients with PE. METHODS: We collected data about the patients with PE from the Medical Information Mart for Intensive Care-III (MIMIC-III) database and used the receiver operating characteristic (ROC) curve, area under the ROC curve (AUROC), calibration plot, integrated discrimination improvement (IDI), and decision curve analysis (DCA) to evaluate the predictive power of the new model, and compared these with the PESI. RESULTS: According to the multivariable Cox regression model results, alongside the actual clinical conditions, we included the following seven variables: race, bicarbonate, age, tumor, systolic blood pressure (SBP), body temperature, and oxygen saturation (Spo2). The AUROC of the new model was greater than 0.70. Its IDI exceeded 0, but with P-value>0.05. CONCLUSION: The predictive performance of the new model was not worse than the PESI, but the new model only has seven variables, and is therefore more convenient for clinicians to use.

Competing risk analysis of cardiovascular death in patients with primary gallbladder cancer.

BACKGROUND: Developments in medical technology are resulting in continuous decreases in the cancer mortality rate of patients with gallbladder cancer, while non-cancer deaths in cancer patients are becoming more common. The main cause of this is cardiovascular mortality (CVM). The purpose of this study was to determine the CVM risk in patients with primary gallbladder cancer (PGC). METHODS: We extracted information on patients in the SEER database who were diagnosed with PGC from 2004 to 2015, compared CVM in patients with PGC with the general United States population, and calculated standardized mortality rates (SMRs) and the absolute excess risk. A competing risks model was used to identify and analyze the independent risk factors for cardiovascular death in patients with PGC. RESULTS: This study included 5925 patients, 247 of whom died from cardiovascular disease. The SMR of cardiovascular death in patients with PGC was 15.84 (95% confidence interval: 15.83-15.85), and the SMR was slightly lower in male than female patients. The competing risks analysis indicated that age, marital status, cancer cell differentiation, chemotherapy status, and year of diagnosis were risk factors for cardiovascular death in patients with PGC. CONCLUSIONS: The CVM risk is considerably higher in patients with PGC than in the general population. It is therefore very necessary to apply cardioprotective interventions to patients with PGC.

Anti-embolism devices therapy to improve the ICU mortality rate of patients with acute myocardial infarction and type II diabetes mellitus.

Background: Anti-Embolism (AE) devices therapy is an additional antithrombotic treatment that is effective in many venous diseases, but the correlations between this medical compression therapy and cardiovascular arterial disease or comorbid diabetes mellitus (DM) are still controversial. In this study we investigated the association between compression therapy and intensive care unit (ICU) mortality in patients with a first acute myocardial infarction (AMI) diagnosis complicated with type II DM. Methods: This retrospective cohort study analyzed all patients with AMI and type II DM in the Medical Information Mart for Intensive Care-IV database. We extracted the demographics, vital signs, laboratory test results, comorbidities, and scoring system results of patients from the first 24 h after ICU admission. The outcomes of this study were 28-day mortality and ICU mortality. Analyses included Kaplan-Meier survival analysis, Cox proportional-hazards regression, and subgroup analysis. Results: The study included 985 eligible patients with AMI and type II DM, of who 293 and 692 were enrolled into the no-AE device therapy and AE device therapy groups, respectively. In the multivariate analysis, compared with no-AE device therapy, AE device therapy was a significant predictor of 28-day mortality (OR = 0.48, 95% CI = 0.24-0.96, P = 0.039) and ICU mortality (OR = 0.50, 95% CI = 0.27-0.90, P = 0.021). In addition to age, gender and coronary artery bypass grafting surgery, there were no significant interactions of AE device therapy and other related risk factors with ICU mortality and 28-day mortality in the subgroup analysis. Conclusions: Simple-AE-device therapy was associated with reduced risks of ICU mortality and 28-day mortality, as well as an improvement in the benefit on in-hospital survival in patients with AMI complicated with type II DM.

Triptolide inhibits the migration and invasion of human prostate cancer cells via Caveolin-1/CD147/MMPs pathway.

Prostate cancer (PCa) is the second most common type of carcinoma and the 5th leading cause of cancer-related death in males. Triptolide, is a main and effective component of Tripterygium wilfordii Hook F, which exerts an broad-spectrum anti-malignant tumor function. However, the effect of triptolide on migration and invasion of human prostate cancer cells is still poorly understood. In this study, we demonstrated that triptolide significantly inhibited the proliferation, migration and invasion of prostate cancer cells in a time- and dose-dependent manner. Caveolin-1 (Cav-1) is regarded as a major structural protein of caveolae and participated in lipid transport, signal transduction and tumor progression. Triptolide treatment inhibited the expression of tumor promoter Cav-1 and reduced CD147 and MMPs activities at both mRNA and protein levels. Meanwhile, triptolide treatment combined with Cav-1 knockdown in PCa cells enhanced the effects of anti-migration and anti-invasion, and those effects were restored following Cav-1-rescued. Together, our research indicates that triptolide represses the migration and invasion through Cav-1/CD147/MMPs pathway in PCa cells, which gives a better understanding of triptolide in clinical aggressive prostate cancer therapy.

ST6Gal-I modulates docetaxel sensitivity in human hepatocarcinoma cells via the p38 MAPK/caspase pathway.

The ß-galactoside α2-6-sialyltransferase 1 (ST6Gal-I) is the principal sialyltransferase responsible for the addition of α2-6-sialic acid to the termini N-glycans on cell surface. Although ST6Gal-I in cancer cell resistance to chemotherapeutics agents has been previously reported, the role of ST6Gal-I in clinical drug resistance of hepatocellular carcinoma (HCC) is not fully understood. In this study, we found that knockdown of ST6Gal-I increased the sensitivity of hepatocarcinoma MHCC97-H cells to docetaxel treatment by instigating the process of apoptosis. Silencing ST6Gal-I expression decreased the survival rate of MHCC97-H cells after docetaxel treatment. Importantly, ST6Gal-I silencing resulted in an increasing of phospho-p38, Bax, Bad, cytochrome c and the cleaved caspase-9, 3 and PARP, while a decreasing of the anti-apoptotic protein Bcl-2. In addition, we found that p38 MAPK and caspase-3 inhibitors can reduce the enhanced apoptosis levels of MHCC97-H cells resulted by either ST6Gal-I silencing or docetaxel treatment. Conversely, exogenous expression of ST6Gal-I in hepatocarcinoma Huh7 cells inhibited apoptotic cell death and prevented docetaxel-induced apoptosis by inhibiting p38 MAPK mediated mitochondrial-dependent pathway. Taken together, these results indicate that ST6Gal-I might play a positive role in mediating the survival of human hepatocarcinoma cells and could be a potential target for gene and antitumor drugs therapy.