MicroRNAs (miRNAs) are involved in the pathogenesis of intrahepatic cholangiocarcinoma (ICC). However, the role of microRNA-31 (miR-31) in ICC has yet to be elucidated. In this study, we demonstrated that the expression of miR-31 was significantly upregulated in ICC tissues and the human ICC cell line HCCC-9810, when compared with that in normal adjacent tissues. Bioinformatic analysis and a dual-luciferase reporter assay revealed RAS p21 GTPase activating protein 1 (RASA1) to be a direct target of miR-31 in HCCC-9810 cells. Further investigation showed that the protein expression level of RASA1 was significantly decreased in ICC tissues, suggesting an inverse correlation between miR-31 and RASA1 expression during the tumorigenesis of ICC. Moreover, the forced downregulation of miR-31 by its inhibitor in HCCC-9810 cells significantly inhibited cell proliferation and promoted cell apoptosis. However, when the cells were cotransfected with miR-31 inhibitor and RASA1-specific small interfering RNA (siRNA), these changes were attenuated. Further analysis of the molecular mechanism showed that the activity of the RAS-mitogen-activated protein kinase (MAPK) signaling pathway was significantly decreased in miR-31-downregulated HCCC-8910 cells, while cotransfection with miR-31 inhibitor and RASA1-specific siRNA attenuated this effect. These results indicate that the downregulation of RASA1 by miR-31 promoted cellular proliferation and inhibited cellular apoptosis, partially by upregulating the activity of the RAS-MAPK signaling pathway in ICC. In conclusion, the present study revealed important regulatory functions of miR-31 and RASA1 in ICC, indicating that miR-31 and RASA1 may become promising diagnostic and/or therapeutic targets for ICC.
Background: Since the coronavirus disease-2019 (COVID-19) outbreak, intensive care unit (ICU) healthcare workers were responsible for the critical infected patients. However, few studies focused on the mental health of ICU healthcare workers. This study aimed to investigate the psychological impact of COVID-19 on ICU healthcare workers in China.Methods: We distributed the nine-item Patient Health Questionnaire (PHQ-9) and seven-item General Anxiety Disorder questionnaire (GAD-7) online to ICU healthcare workers in China. Respondents were divided into frontline and second-line according to whether they have contact with COVID-19 patients. Depressive and anxiety symptoms of all respondents were evaluated based on their questionnaire scores.Results: There were 731 ICU healthcare workers finally enrolled in our study, including 303 (41.5%) male, 383 (52.4%) doctors, and 617 (84.4%) aged 26–45 years. All in all, 482 (65.9%) ICU healthcare workers reported symptoms of depression, while 429 (58.7%) reported anxiety. There was no significant difference between frontline (n = 325) and second-line (n = 406) respondents in depression (P = 0.15) and anxiety severity (P = 0.56). Logistic regression analysis showed that being female, ICU work time >5 years, and night duty number ≥10 were risk factors of developing depressive and anxiety symptoms. Income reduction was separately identified as risk of anxiety. Additionally, ICU work time >5 years was also identified as risk of developing moderate–severe depressive and anxiety symptoms.Conclusions: Frontline ICU work was not associated with higher risk of depressive and anxiety symptoms during COVID-19 pandemic remission period in China. Actions like controlling night duty number, ensuring vacation, and increasing income should be taken to relieve mental health problem. Furthermore, we should pay close attention to those who had worked long years in ICU.
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with poor responsiveness to existing drug therapies. Therefore, novel treatment strategies against ICC are required to improve survival. The aim of this study was to demonstrate the role of fused-in-glioblastoma-c-ros-oncogene1 (FIG-ROS) fusion gene in ICC. ROS was positively expressed in ICC tissues and HUCCT1 cells. Plasmids expressing ROS- and FIG-specific shRNAs were constructed and transfected into HUCCT1 cells. The results showed that single transfection of ROS- or FIG-specific shRNA inhibited HUCCT1 cell proliferation, colony formation, cell cycle progression, migration and invasion, while inducing apoptosis. Moreover, the co-inhibition of ROS- and FIG-specific shRNA exhibited stronger effects on HUCCT1 cell proliferation, apoptosis, colony formation, cell cycle progression, migration and invasion, when compared to single inhibition of ROS and FIG. Furthermore, findings of this study suggested that the AKT signaling pathway was involved in the ROS-FIG-mediated biological processes of HUCCT1 cells. In summary, the results suggest that FIG-ROS plays an oncogenic role in ICC. Additionally, ROS1-6290 and FIG-363 segments may become effective therapeutic targets for ICC harboring ROS-FIG fusion protein.
Carotid cardiac output shows moderate agreement with TTE cardiac output; thus, its use may be considered as an alternative for estimating cardiac output in emergencies and when TTE cardiac output is unobtainable. However, in patients with septic shock, multiple trauma, and respiratory failure, the use of carotid cardiac output is not recommended.
Background. The association between sarcopenia at admission and mortality in patients with sepsis has not been comprehensively evaluated. We performed a meta-analysis to systematically evaluate the above association. Methods. This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intrastudy heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship. Results. Ten cohort studies including 2396 patients with sepsis were included, and 1496 (62.4%) of them had sarcopenia at presentation. Pooled results showed that compared to those without sarcopenia, septic patients with sarcopenia had a significantly increased early (in-hospital or 1-month) mortality risk (risk ration (RR): 2.14, 95% confidence interval (CI): 1.60–2.87,
P
< 0.001; I2 = 46%). Subgroup analyses showed consistent association between sarcopenia and increased acute mortality risk in septic patients which were not affected by study characteristics such as study design, country of the study, clinical settings, diagnostic criteria for sepsis, age, gender of the patients, and methods for diagnosis of sarcopenia (
P
for all subgroup analyses >0.05). Further meta-analyses showed that sarcopenia was also associated with increased mortality risk in septic patients at 3–6 months (RR: 2.13, 95% CI: 1.58–2.89,
P
< 0.001; I2 = 0%) and at 1 year (RR: 1.57, 95% CI: 1.09–2.24,
P
= 0.01; I2 = 29%). Conclusions. Current evidence suggests that sarcopenia may be a predictor of mortality in patients with sepsis.
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