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As a cyclin-dependent kinase inhibitor, p16 INK4a plays a key role in cell cycle progression and cellular differentiation, and its expression is frequently altered in human cancers through epigenetically mediated transcriptional silencing. In this report, we demonstrate that p300 was able to induce cell cycle arrest, and this process was reversed by p16 INK4a silencing by RNA interference in HeLa cells. We also show that p300 was involved in activation of p16 INK4a expression in 293T cells. Specifically, p300 cooperated with Sp1 to stimulate both p16 INK4a promoter activity and mRNA expression. Co-immunoprecipitation and mammalian twohybrid assays revealed that p300 and Sp1 formed a complex through interaction between the Q domain of p300 and the N-terminal domain of Sp1. The chromatin immunoprecipitation assays verified that p300 was recruited to p16 INK4a promoter, and the histone acetyltransferase domain of p300 participated in p16 INK4a activation through inducing hyperacetylation of histone H4 at p16 INK4a gene. These data suggest that p300 plays a critical role in transcriptional regulation of p16 INK4a and in cell cycle arrest.

Background Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19). Purpose This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19. Study design Systematic review and meta-analysis Methods We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook. Results Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I 2 = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I 2 = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I 2 = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I 2 = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I 2 = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I 2 = 43.5%). The quality of evidence was very low to low. Conclusion The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.

BackgroundInflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia.MethodsPatients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman’s analysis.ResultsA total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman’s analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147).ConclusionsAmong the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX) therapy appears to be effective for ICH. The aim of this study was to perform a systematic review of DFX therapy for ICH patients and evaluate the efficacy and safety of DFX therapy for ICH patients. We searched Medline, Embase, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, all Chinese databases and the reference lists of all included studies and review articles. We then performed a systematic review of studies involving the administration of DFX following ICH. Only two studies were included, a prospective, randomized clinical trial and a prospective,observational cohort study with concurrent groups. Qualitative analysis of each study revealed one randomized controlled trial of moderate quality with a moderate risk of bias and one observational cohort study of moderate quality with a moderate risk of bias. DFX may be an effective treatment for edema in patients with ICH. However, due to the small number of trials and small sample sizes of these trials, insufficient evidence exists to determine the effect of DFX on neurologic outcomes after ICH and the safety of this intervention. Further investigation is required before DFX can become a routine treatment for ICH.