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Background The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented burden on the delivery of intensive care services worldwide. Research Question What is the global point estimate of deaths and risk factors for patients who are admitted to ICUs with severe COVID-19? Study Design and Methods In this systematic review and meta-analysis Medline, Embase, and the Cochrane library were searched up to August 1, 2020. Pooled prevalence of participant characteristics, clinical features, and outcome data was calculated with the use of random effects models. Subgroup analyses were based on geographic distribution, study type, quality assessment, sample size, end date, and patient disposition. Studies that reported in-hospital mortality rate of adult patients (age >18 years) with confirmed COVID-19 admitted to an ICU met study eligibility criteria. Critical evaluation was performed with the Newcastle Ottawa Scale for nonrandomized studies. Results Forty-five studies with 16,561 patients from 17 countries across four continents were included. Patients with COVID-19 who were admitted to ICUs had a mean age of 62.6 years (95% CI, 60.4-64.7). Common comorbidities included hypertension (49.5%; 95% CI, 44.9-54.0) and diabetes mellitus (26.6%; 95% CI, 22.7-30.8). More than three-quarters of cases experienced the development of ARDS (76.1%; 95% CI, 65.7-85.2). Invasive mechanical ventilation was required in 67.7% (95% CI, 59.1-75.7) of case, vasopressor support in 65.9% (95% CI, 52.4-78.4) of cases, renal replacement therapy in 16.9% (95% CI, 12.1-22.2) of cases, and extracorporeal membrane oxygenation in 6.4% (95% CI, 4.1-9.1) of cases. The duration of ICU and hospital admission was 10.8 days (95% CI, 9.3-18.4) and 19.1 days (95% CI, 16.3-21.9), respectively, with in-hospital mortality rate of 28.1% (95% CI, 23.4-33.0; I2 = 96%). No significant subgroup effect was observed. Interpretation Critically ill patients with COVID-19 who are admitted to the ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global death from severe COVID-19 is

MicroRNAs (miRNAs/miRs) are 19–25 nucleotide-long, non-coding RNAs that regulate the expression of target genes at the post-transcriptional level. In the present study, the role of miR-340 in breast cancer (BC) was investigated. The overexpression of miR-340 significantly inhibited the proliferation, migration and invasion of human breast MDA-MB-231 cancer cells in vitro. The Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) gene was identified as a target of miR-340; its expression was downregulated by overexpression of miR-340 by binding to its 3′-untranslated region. The short interfering RNA-mediated silencing of ROCK1 was also performed, which phenocopied the effects of miR-340 overexpression. An inhibitor of miR-340 was used to suppress miR-340 expression, which led to increased expression of ROCK1, thus improving the proliferation, migration and invasion of MDA-MB-231 cells. Data from the present study suggest that miR-340 inhibits MDA-MB-231 cell growth and its downregulation may lead to the progression and metastasis of BC. Thus, miR340 may act as a tumor-suppressor agent that could serve a key role in the diagnosis and therapy of BC.

Pancreatic cancer is a disease of the elderly. Surgical resection is usually offered to patients in early stage disease; however, pancreatic resection in the elderly is controversial.MEDLINE, EMBASE and Cochrane Library, were searched for studies comparing short- and long-term outcomes of elderly (above the age of 70) with non-elderly patients (below the age of 70) following pancreatic resection for pancreatic adenocarcinoma over the period from the inception of electronic database to 2017. Twelve articles documenting 4860 patients were included. A meta-analysis of data on patient characteristics, operative techniques, and perioperative outcomes were analysed. Our primary endpoint was postoperative mortality, defined as 30-day mortality or in-hospitalisation mortality.There were 919 patients in the elderly group and 3941 patients in the non-elderly group. Elderly patients had worse ASA scores (p 0.001) and more cardiovascular comorbidities (p = 0.002). Tumour size, T-stage, N-stage and tumour grade were similar between the elderly and non-elderly group (p 0.05). Fewer elderly patients received a concomitant venous resection with their pancreatectomy (RR0.80, p = 0.003, I2 = 0%), achieved a negative margin status (RR0.76, p = 0.02, I2 = 28%) and underwent adjuvant chemotherapy treatment (RR0.69, p 0.001, I2 = 42%). Overall complication (RR1.15, p 0.001, I2 = 47%), in particular, respiratory complications (RR2.33, p = 0.004, I2 = 39%), was higher in the elderly group. There was no difference in postoperative pancreatic fistula formation, postoperative haemorrhage, intraabdominal abscess and length of hospital stay between both groups (p 0.05). Postoperative mortality was similar between both groups (p = 0.17). Subgroup analysis according to the time of enrolment (2000, ≥2000) showed a significant subgroup effect (Chi2 = 3.44, p = 0.06, I2 = 70.9%) and revealed that postoperative mortality in the elderly group improved over time (Before 2000: n = 1654, subtotal RR2.27, p = 0.02, I2 = 0%; From 2000 onwards: n = 3206, subtotal RR1.00, p = 0.99, I2 = 0%).Fewer elderly patients received chemotherapy and portal vein resection to achieve a clear margin. Pancreatic resection of pancreatic adenocarcinoma can be performed safely on elderly patients with acceptable risks in experienced centres by specialist hepatobiliary surgeons. Age alone should not be the only determinant for the selection of patients for surgical treatment of pancreatic adenocarcinoma.

RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real‑time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

Dysregulation of microRNAs (miRNAs) plays a critical role in cancer progression. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-135b in breast cancer and to validate whether miR-135b could regulate proliferation of breast cancer cells by effecting specific targets in the Hippo pathway. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to quantify the expression levels of miR-135b in both breast cancer tissues and cell lines. To characterize the function of miR-135b, MTT assays, colony formation assays, cell migration assays, cell invasion assays, and cell cycle assays were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-135b, in corroboration with western blot assays. Finally, we verified the changes of cellular function after transfection of LATS2-siRNA. Our experiments indicate that expression of miR-135b was commonly upregulated in breast cancer specimens and breast cancer cells when compared with that in adjacent normal tissues and non-malignant breast epithelial cells. Enforced expression of miR-135b can regulate cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-135b directly bound to the 3'-untranslated region (3'-UTR) of LATS2 (large tumor suppressor kinase 2), a critical gene in the Hippo pathway. Western blot analysis verified that miR-135b regulated the expression of LATS2 at protein levels. Further study demonstrated that the downstream gene of LATS2 in the Hippo pathway, such as cyclin-dependent kinase 2 (CDK2) and Phospho-Yes-associated protein (p-YAP), can also be regulated by miR-135b and LATS2 axis. Knockdown of endogenous LATS2 can mimic the result of miR-135b up-regulation in breast cancer. Taken together, our findings reveal that the miR-135b and LATS2 axis may be a potential therapeutic target for breast cancer in the future.

Background. Fine needle aspiration cytology (FNAC) and fine needle nonaspiration cytology (FNNAC) are useful cost-effective techniques for preoperatively assessing thyroid lesions. Both techniques have advantages and disadvantages, and there is controversy over which method is superior. This meta-analysis was performed to evaluate the differences between FNAC and FNNAC for diagnosis of thyroid nodules.Methods. Primary publications were independently collected by two reviewers from PubMed, Web of Science, Google Scholar, EBSCO, OALib, and the Cochrane Library databases. The following search terms were used: fine needle, aspiration, capillary, nonaspiration, sampling without aspiration, thyroid, and cytology. The last search was performed on February 1, 2015.Results. Sixteen studies comprising 1,842 patients and 2,221 samples were included in this study. No statistically significant difference was observed between FNAC and FNNAC groups with respect to diagnostically inadequate smears, diagnostically superior smears, diagnostic performance (accuracy, sensitivity, specificity, negative predictive value, and positive predictive value), area under the summary receiver operating characteristic curve, average score of each parameter (background blood or clot, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and retention of appropriate architecture), and total score of five parameters.Conclusion. FNAC and FNNAC are equally useful in assessing thyroid nodules.