/pdf/coronaviruses-and-the-cardiovascular-system-acute-and-long-2ggmpj4qaj.pdf

Coronaviruses and the cardiovascular system: acute and long-term implications.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barre syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

https://www.tandfonline.com/doi/pdf/10.1080/22221751.2020.1825914

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

Background The influence of dexmedetomidine on postoperative delirium (POD) in adult surgical patients remains controversial. We aimed to analyse whether dexmedetomidine use could decrease POD incidence in this population and its relation to timing of dexmedetomidine administration and patient age. Methods We used random-effects modelled meta-analysis, trial sequential analysis, and followed Cochrane methodology with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). PubMed and Cochrane library were searched up to July 2017 for randomised controlled trials that analysed POD incidence of adult surgical patients (age ≥18 yr) after dexmedetomidine administration. Results Eighteen studies (comprising 3309 patients) were included. There was decreased risk of POD with dexmedetomidine use for the entire adult surgical population [odds ratio (OR) 0.35; 95% confidence interval (CI) 0.24–0.51)], with firm evidence from trial sequential analysis. Pre-specified subgroup analyses confirmed this result with firm evidence for cardiac and non-cardiac surgical patients, (OR 0.41; 95% CI 0.26–0.63) and (OR 0.33; 95% CI 0.18–0.59), respectively. We also found firm evidence for reduction of POD if dexmedetomidine is administered during the postoperative period (OR 0.30; 95% CI 0.21–0.44), in patients aged Conclusion Dexmedetomidine can reduce POD incidence for adult cardiac and non-cardiac surgical patients. The optimal dose and timing of dexmedetomidine and influence on other outcomes or particular patient populations with risk factors warrants further studies. Clinical trial registration PROSPERO: CRD42017072380.

Efficacy of perioperative dexmedetomidine on postoperative delirium: systematic review and meta-analysis with trial sequential analysis of randomised controlled trials

OBJECTIVES To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus. DESIGN Retrospective cohort study. SETTING A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017. PATIENTS A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization. CONCLUSIONS Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus.

Epigenetic alterations, such as histone modification, DNA methylation, and miRNA-mediated processes, are critically associated with various mechanisms of proliferation and metastasis in several types of cancer. To overcome the side effects and limited effectiveness of drugs for cancer treatment, there is a continuous need for the identification of more effective drug targets and the execution of mechanism of action (MOA) studies. Recently, epigenetic modifiers have been recognized as important therapeutic targets for hepatocellular carcinoma (HCC) based on their reported abilities to suppress HCC metastasis and proliferation in both in vivo and in vitro studies. Therefore, here, we introduce epigenetic modifiers and alterations related to HCC metastasis and proliferation, and their molecular mechanisms in HCC metastasis. The existing data suggest that the study of epigenetic modifiers is important for the development of specific inhibitors and diagnostic targets for HCC treatment.

https://www.mdpi.com/1422-0067/19/12/3978/pdf

The Epigenetic Regulation of HCC Metastasis

Background and objective
The clinical presentations and disease courses of patients hospitalized with either influenza A virus subtype H7N9 (H7N9) or 2009 pandemic H1N1 influenza virus were compared in a recent report, but associated cardiac complications remain unclear. The present retrospective study investigated whether cardiac complications in critically ill patients with H7N9 infections differed from those infected with the pandemic H1N1 influenza virus strain.
Methods
Suspect cases were confirmed by reverse transcription polymerase chain reaction assays with specific confirmation of the pandemic H1N1 strain at the Centers for Disease Control and Prevention. Comparisons were conducted at the individual-level data of critically ill patients hospitalized with H7N9 (n = 24) or pandemic H1N1 influenza virus (n = 22) infections in Suzhou, China. Changes in cardiac biochemical markers, echocardiography, and electrocardiography during hospitalization in the intensive care unit were considered signs of cardiac complications.
Results
The following findings were more common among the H7N9 group relative to the pandemic H1N1 influenza virus group: greater tricuspid regurgitation pressure gradient, sinus tachycardia (heartbeat ≥ 130 bpm), ST segment depression, right ventricular dysfunction, and elevated cardiac biochemical markers. Pericardial effusion was more often found among pandemic H1N1 influenza virus patients than in the H7N9 group. In both groups, most of the cardiac complications were detected from day 6 to 14 after the onset of influenza symptoms. Those who developed cardiac complications were especially vulnerable during the first four days after initiation of mechanical ventilation. Cardiac complications were reversible in the vast majority of discharged H7N9 patients.
Conclusions
Critically ill hospitalized H7N9 patients experienced a higher rate of cardiac complications than did patients with 2009 pandemic H1N1 influenza virus infections, with the exception of pericardial effusion. This study may help in the prevention, identification, and treatment of influenza-induced cardiac complications in both pandemic H1N1 influenza virus and H7N9 infections.

Cardiac complications associated with the influenza viruses A subtype H7N9 or pandemic H1N1 in critically ill patients under intensive care

Liver cancer is one of the most common types of cancer among human malignancies. Four and a half LIM domains 1 (FHL1), as a tumor suppressor gene, is frequently downregulated in multiple types of human cancer. However, the role and specific mechanisms of FHL1 as a tumor suppressor in liver cancer are poorly understood. The present study aimed to investigate the role and associated mechanisms of FHL1 in human liver cancer. The level of FHL1 mRNA in hepatocellular carcinoma (HCC) tissue specimens and cell lines derived from the human liver was determined using reverse transcription polymerase chain reaction and western blot analysis. The association between FHL1 expression and clinicopathological characteristics of patients with liver cancer was analyzed. Western blotting, small interfering RNA (siRNA) and chromatin immunoprecipitation were used to study the expression association of FHL1 and enhancer of zeste homolog 2 (EZH2) in human liver cancer and to explore the regulatory mechanism of FHL1 downregulation. Colony formation and migration assays were performed while FHL1 was overexpressed in Hep3B cells. The results showed that the expression of FHL1 mRNA in tumor tissue decreased, exhibiting a significant difference compared with the adjacent non-cancerous tissue (P<0.05). However, the downregulation of FHL1 was not significantly associated with the sex, age, hepatitis B virus infection status, tumor size, distant metastasis status or level of tumor differentiation of the patients. FHL1 was synergistically silenced by DNA methylation and histone modification, and 3-deanzaneplanocin A (DZNep), an inhibitor of EZH2, which is a histone methyltransferase of the polycomb repressive complex 2, which catalyzes histone H3 lysine 27 tri-methylation (H3K27me3). A significant association between FHL1 and EZH2 expression was identified in the female hepatocellular carcinoma (HCC) samples, but was not in the male HCC samples. FHL1 overexpression and DZNep treatment significantly suppressed the growth and migration of Hep3B cells by restoring FHL1 expression. H3K27me3 was significantly enriched at the FHL1 promoter region, as indicated by a chromatin immunoprecipitation assay, and associated with the epigenetic repression of the FHL1 tumor suppressor gene in HCC cell lines. In conclusion, the present study provides an insight into DNA methylation and EZH2-H3K27me3 epigenetic repression of FHL1 in human liver cancer.

/pdf/epigenetic-analysis-of-fhl1-tumor-suppressor-gene-in-human-1kwcdnrf8w.pdf

Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer.

Background. Tanshinone IIA sodium sulfonate (TSS) is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS-) induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6) in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3) and Beclin-1) were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

/pdf/tanshinone-iia-sodium-sulfonate-attenuates-lps-induced-1x5n32yebq.pdf

Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice.

Objective
To evaluate the efficacy and safety of dexmedetomidine for post-operative elder patients on mechanical ventilation (MV).


Methods
For this randomized controlled trial, 108 cases of post-operative patients on MV were enrolled and assigned into either dexmedetomidine group (n=54) or propofol group (n=54) for sedation. And propofol was used for rescue. The dose of sedation was regulated by Ramsay score for maintaining a sedative score of 3-4. In both groups, fentanyl was provided intravenously continually for analgesia. The amount of fentanyl was adjusted according to the numerical rating scale (NRS) score for maintaining an analgesic score of 0-3. The average Ramsay score, the frequency of propofol, the highest score of NRS, the total dosage of fentanyl and recovery time were compared. Additional outcomes included duration of mechanical ventilation and intensive care unit (ICU) length. And the incidence of delirium and cardiovascular adverse events were compared for two groups.


Results
No significant inter-group difference existed in the effectiveness of sedation. Compare with propofol group, the highest score of NRS decreased(1.8±1.12 vs 3.1±1.24, P<0.05), the total dosage of fentanyl significantly decreased(427.6±14.1 vs 658.4±27.3 μg, P<0.05) and recovery time became significantly shortened (0.3±0.02 h vs 1.1±0.3 h, P<0.05) in dexmedetomidine group. Median duration of mechanical ventilation in dexmedetomidine group(21.0 h, 95%CI: 18.6-21.4 h)was significantly shorter than that in propofol group(28.0 h, 95%CI: 25.6-30.4 h)(P<0.05). No inter-group differences existed in the ICU length of stay and the incidence of delirium. Two cases in dexmedetomidine group developed bradycardia while hypotension occurred in two cases of propofol group.


Conclusion
Sedative effects of dexmedetomidine are safe and effective for post-operative elder patients on MV. And it offers a better efficacy of analgesia and shorter durations of MV and recovery time. Butdexmedetomidine had no significant influence on the ICU length of stay or the incidence of delirium.


Key words: 
Ventilators, mechanical; Conscious sedation; Analgesia; Aged; Dexmedetomidine

Shenglan Liu

Papers

Cardiac complications associated with the influenza viruses A subtype H7N9 or pandemic H1N1 in critically ill patients under intensive care

Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer.

Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice.

[Sedative effects of dexmedetomidine in post-operative elder patients on mechanical ventilation].