CircAKT3 inhibits glycolysis balance in lung cancer cells by regulating miR-516b-5p/STAT3 to inhibit cisplatin sensitivity.

OBJECTIVE: Lung cancer was one of the most deadly cancers around the world. Circular RNA AKT3 (CircAKT3) was highly expressed in lung cancer and could inhibit cell proliferation, but there were few studies on the mechanism of specific regulation of drug resistance. Therefore, we aimed to provide new ideas and perspectives for the role of circAKT3 in the mechanism of tumor resistance. METHODS: The levels of circAKT3, miR-516b-5p and STAT3 in lung cancer tissues and cells were examined using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assays. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to examine the sensitivity of cells treated under different conditions to cisplatin (DDP). A glucose assay kit and lactate assay kit were used to assess glycolysis and lactate production of cells treated with different plasmids and 2-deoxy-glucose (2-DG). Western blot analysis was used to detect the expression level of the hypoxia-inducible factor (HIF-1α) in A549 and H1299 cells. Starbase 3.0 predicted a targeted relationship between circAKT3 and miR-516b-5p, STAT3 and miR-516b-5p, and the relationship was proved by a dual-luciferase reporter assay. Knockdown of circAKT3 was used to study the effects of circAKT3 on tumor development in vivo. RESULTS: The levels of circAKT3 and STAT3 were upregulated, miR-516b-5p was downregulation in lung cancer tissues and cells. Functionally, circAKT3 knockdown improved cell sensitivity to DDP, and repressed glycolysis in lung cancer cells. Meanwhile, inhibition of HIF-1α-dependent glycolysis attenuated the circAKT3-induced increase of chemo-resistance in A549 cells. Mechanistically, miR-516b-5p was found to possess some binding sites with circAKT3. Noticeably, the inhibitory action of circAKT3 knockdown on DDP resistance and glycolysis was overturned through inhibitor of miR-516b-5p in lung cancer cells. Furthermore, besides, circAKT3 knockdown suppressed lung tumor cell growth by the miR-516b-5p/STAT3 axis in vivo. CONCLUSIONS: CircAKT3 inhibit cisplatin sensitivity of lung cancer cells at least partly through regulating miR-516b-5p/STAT3 axis-mediated glycolysis balance, providing a possible long noncoding RNA -targeted therapy for lung cancer.

Prevalence of Venous Thromboembolism in Critically Ill Patients With Coronavirus Disease 2019: A Meta-Analysis.

Background: Accumulating evidence suggests that coronavirus disease 2019 (COVID-19) is associated with hypercoagulative status, particularly for critically ill patients in the intensive care unit. However, the prevalence of venous thromboembolism (VTE) in these patients under routine prophylactic anticoagulation remains unknown. A meta-analysis was performed to evaluate the prevalence of VTE in these patients by pooling the results of these observational studies. Methods: Observational studies that reported the prevalence of VTE in critically ill patients with COVID-19 were identified by searching the PubMed and Embase databases. A random-effect model was used to pool the results by incorporating the potential heterogeneity. Results: A total of 19 studies with 1,599 patients were included. The pooled results revealed that the prevalence of VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE) in critically ill patients with COVID-19 was 28.4% [95% confidence interval (CI): 20.0-36.8%], 25.6% (95% CI: 17.8-33.4%), and 16.4% (95% CI: 10.1-22.7%), respectively. Limited to studies, in which all patients received routine prophylactic anticoagulation, and the prevalence for VTE, DVT, and PE was 30.1% (95% CI: 19.4-40.8%), 27.2% (95% CI: 16.5-37.9%), and 18.3% (95% CI: 9.8%-26.7%), respectively. The prevalence of DVT was higher in studies with routine screening for all patients, when compared to studies with screening only in clinically suspected patients (47.5% vs. 15.1%, P < 0.001). Conclusion: Critically ill patients with COVID-19 have a high prevalence of VTE, despite the use of present routine prophylactic anticoagulation.

Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China.

INTRODUCTION: Over 40,000 cases of coronavirus (CoV) disease 2019 (COVID-19) have been confirmed in China. The causative agent, 2019 novel CoV (2019-nCoV), has spread rapidly to more than 25 countries worldwide. Human-to-human transmission has accounted for most of the infections outside Wuhan. Most studies to date on COVID-19 have focused on disease etiology and the genomics of 2019-nCoV, with few reports on the epidemiologic and clinical characteristics of infected patients. METHODS: We report early clinical features of 26 patients with confirmed COVID-19 who were admitted to Liaocheng Infectious Disease Hospital in Shandong Province. RESULTS: The median age of the 26 patients with COVID-19 in this study was 42 years. The most common occupation was retail staff (16 patients, 61.54%), with 11 patients or their family members working at the same supermarket. Only 2 patients had visited Wuhan since December 2019; the other cases of 2019-nCoV infection arose from patient-to-patient transmission. Twelve patients had more than one sign or symptom; however, seven patients had no sign or symptom. The average time from symptom onset to admission was 4.5 days. CT revealed signs of bronchitis in 2 patients and unilateral and bilateral pneumonia in 9 and 15 patients, respectively. The patients received the following treatments: antiviral therapy (100%), Chinese medicine (76.92%), antibiotics (50%), gastric mucosal protection (19.23%), immunotherapy (7.69%), and glucocorticoids (3.85%). Most patients (25/26) required ≥1 treatment. DISCUSSION: In contrast to previous reports, most patients (24/26) had not been in close contact with individuals from Wuhan. Additionally, 11 patients or their family members worked at the same supermarket, suggesting active viral transmission in a location frequented by a large number of people. Close monitoring is essential for preventing the large-scale spread of the virus in such places.