No abstract

Highlights d Down-regulation of ACOT12 is correlated with metastasis and poor prognosis of HCC d ACOT12 functionally suppresses HCC metastasis d ACOT12 regulates acetyl-coA metabolism and histone acetylation d Down-regulation of ACOT12 promotes HCC metastasis by epigenetic induction of TWIST2

This study was aimed to examine the prognostic value of preoperative neutrophils, platelets, lymphocytes, monocytes and calculated ratios in patients with laryngeal squamous cell cancer (LSCC). From January 2007 to December 2011, 979 patients with LSCC were enrolled in our study. Preoperative neutrophils, platelets, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the independent prognostic relevance of these hematological parameters by Cox regression models in disease-free survival (DFS) and cancer-specific survival (CSS). We found patients in the highest tertile of NLR (>2.40), PLR (>111.00) were at significantly higher risk of DFS and CSS (P<0.05) compared with those in the lowest tertile after multivariate analysis, whereas presenting significantly higher risk in the lowest tertile of lymphocytes (<1.60×109/L) and LMR (<3.50). Additionally, the tertile category of NLR as well as PLR increased and lymphocytes as well as LMR decreased in shorter DFS and CSS by the Kaplan-Meier method and the log-rank test. In conclusion, this study indicated that preoperative lymphocytes, NLR, PLR and LMR were significantly associated with LSCC progression, DFS and CSS, and these hematological parameters could be considered independent prognostic values for patients with LSCC.

Coronavirus disease 2019 (COVID-19) pandemic may exert adverse impacts on sleep among populations, which may raise awareness of the burden of sleep disturbance, and the demand of intervention strategies for different populations. We aimed to summarize the current evidence for the impacts of COVID-19 on sleep in patients with COVID-19, healthcare workers (HWs), and the general population. We searched PubMed and Embase for studies on the prevalence of sleep disturbance. Totally, 86 studies were included in the review, including 16 studies for COVID-19 patients, 34 studies for HWs, and 36 studies for the general population. The prevalence of sleep disturbance was 33.3%–84.7%, and 29.5–40% in hospitalized COVID-19 patients and discharged COVID-19 survivors, respectively. Physiologic and psychological traumatic effects of the infection may interact with environmental factors to increase the risk of sleep disturbance in COVID-19 patients. The prevalence of sleep disturbance was 18.4–84.7% in HWs, and the contributors mainly included high workloads and shift work, occupation-related factors, and psychological factors. The prevalence of sleep disturbance was 17.65–81% in the general population. Physiologic and social-psychological factors contributed to sleep disturbance of the general population during COVID-19 pandemic. In summary, the sleep disturbance was highly prevalent during COVID-19 pandemic. Specific health strategies should be implemented to tackle sleep disturbance.

Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes and cardiac fibroblasts in AMI mice. Moreover, adenovirus mediated knockdown of Mirt1 was employed to clarify its roles in AMI mice or cultured cardiac fibroblasts. The cardiac functions and infarct size of AMI mice were examined, and tissues and cultured cells were collected and processed for histology and biochemical examination. Results: We demonstrated that Mirt1 was mainly expressed in cardiac fibroblasts, and that knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo. Furthermore, knockdown of Mirt1 in cardiac fibroblasts not only attenuated the apoptosis of cardiomyocytes, but also suppressed the migration of macrophages under hypoxia in vitro. NF-κB signaling pathway, activated under hypoxia, was also inhibited by Mirt1 knockdown in fibroblasts. Conclusions: Knockdown of Mirt1 attenuates AMI injury presumably by decreasing cardiomyocytes apoptosis and reducing inflammatory cell infiltration. These effects could be attributed, at least partly, to inhibition of the NF-κB pathway, resulting in decreased expression of inflammatory factors.

Previously (Shan et al, 2005), we reported that adenoviral vector-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to minipig parotid glands following irradiation (IRti) transiently restored salivary flow to near normal levels. This study evaluated a serotype 2, adeno-associated viral (AAV2) vector for extended correction of IR (single dose; 20 Gy)-induced, parotid salivary hypofunction in minipigs. Sixteen weeks following IR, parotid salivary flow decreased by 85-90%. AAV2hAQP1 administration at week 17 transduced only duct cells and resulted in a dose-dependent increase in salivary flow to ∼35% of pre-IR levels (to ∼1ml/10min) after 8 weeks (peak response). Administration of a control AAV2 vector or saline, was without effect. Little change was observed in clinical chemistry and hematology values after AAV2hAQP1 delivery. Vector treated animals generated high anti-AAV2 neutralizing antibody titers by week 4 (∼1:1600) and significant elevations in salivary (∼15%), but not serum, GM-CSF levels. Following vector administration, salivary [Na+] was dramatically increased, from ∼10mM to ∼55 (at 4 weeks) and 39 mM (8 weeks). The findings demonstrate that localized delivery of AAV2hAQP1 to IR-damaged parotid glands leads to increased fluid secretion from surviving duct cells, and may be useful in providing extended relief of salivary hypofunction in previously irradiated patients.

Six women with elevated circulating levels of big big PRL (BBPRL) and apparently normal ovarian function were variously studied through a menstrual cycle and menstruation, through pregnancy and suckling, and during stimulation tests with TRH and suppression with bromocriptine. No significant changes in monomeric PRL were demonstrated during the menstrual cycle, but all subjects showed a small and significant rise in BBPRL during the preovulatory phase. High PRL levels were present in day 1 menstrual plasma, but BBPRL was only present in low concentrations. All subjects (n = 5) demonstrated a rise in both PRL and BBPRL during pregnancy, with a consistent tendency for PRL to increase to a proportionately greater extent than BBPRL. One subject exhibited a rise in PRL (by 93%), but not BBPRL, 30 min after suckling. TRH caused a brisk rise in PRL (by 363 +/- 116%) but only a sluggish rise in BBPRL (by 17.5 +/- 7.4%; n = 3). Bromocriptine rapidly suppressed PRL (by 81.8 +/- 34.4%), but only slowly suppressed BBPRL (by 21.0 +/- 8.7% after 6 h; n = 3). Plasma binding studies did not demonstrate any evidence of a circulating specific PRL-binding protein. These data indicate that plasma concentrations of BBPRL may vary under the influence of a number of factors, but are much less sensitive to TRH stimulation, bromocriptine suppression, pregnancy, and suckling than PRL. The occurrence of BBPRL does not seem to be due to a specific circulating binding protein.

The clinical significance of circulating cell-free DNA (cfDNA) integrity as diagnostic and surveillance biomarker in hepatocellular carcinoma (HCC) was investigated and compared to that of alpha fetoprotein (AFP). Liver cancer patients had lower cfDNA integrity than those with benign diseases (P = 0.0167) and healthy individuals (P = 0.0025). Patients with HCC and non-HCC liver cancers (P = 0.7356), and patients with benign diseases and healthy individuals (P = 0.9138) had comparable cfDNA integrity respectively. cfDNA integrity increased after hepatectomy in cancer patients (P = 0.0003). The AUCs for detecting HCC by cfDNA integrity and AFP were 0.705 (P = 0.005) and 0.605 (P = 0.156), respectively. We found cfDNA integrity decreased in HCC patients and has the potential as promising biomarker for HCC diagnosis and treatment surveillance.