Objective To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. Design Retrospective cohort study. setting A designated hospital for patients with covid-19 in Zhejiang province, China. ParticiPants 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19

Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression.

As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified in silico. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remains severe. As the National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital of the Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province. Based on the present expert consensus carried out by the National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on “Four-Anti and Two-Balance” for clinical practice. The “Four-Anti and Two-Balance” strategy includes antivirus, anti-shock, anti-hypoxemia, and anti-secondary infection, and maintaining of water, electrolyte and acid/base balance and microecological balance. Simultaneously, an integrated multidisciplinary personalized treatment is recommended to improve therapeutic effects. The importance of early viral detection, dynamic monitoring of inflammatory indexes, and chest radiographs has been emphasized in clinical decision-making. Sputum was observed with the highest positive rate by reverse transcription-polymerase chain reaction (RT-PRC). Viral nucleic acids could be detected in 10% of the patients’ blood samples at the acute phase and 50% of patients had positive RT-PCR results in their feces. We also isolated live viral strains from feces, indicating potential infectiousness of feces. Dynamic cytokine detection was necessary to timely identify cytokine storms and for the application of the artificial liver blood purification system. The “Four-Anti and Two-Balance” strategy effectively increased cure rates and reduced mortality. Early antiviral treatment alleviated disease severity and prevented illness progression. We found that lopinavir/ritonavir combined with abidol showed antiviral effects against COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system was able to rapidly remove inflammatory mediators and block the cytokine storm. Moreover, it also contributed to the balance of fluids, electrolytes, and acids/bases and thus improved treatment efficacy during critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid administration was supported. Patients with an oxygenation index below 200 mm Hg were transferred to the intensive care unit. Conservative oxygen therapy was preferred and noninvasive ventilation (NIV) was not recommended. Patients with mechanical ventilation were strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was prescribed rationally and was not recommended, except for patients with a long course of disease, repeated fever, and elevated procalcitonin, similarly secondary fungal infections were of concern. Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased genus such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should; therefore, be assessed for all patients. Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infections due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established a dynamic assessment and warning for psychological crises. We also integrated Chinese medicine in the treatment to promote rehabilitation. We optimized nursing processes for severe patients to promote their rehabilitation. Since viral clearance patterns after severe acute respiratory syndrome coronavirus 2 infections remained unclear, 2 weeks quarantine for discharged patients was required, and a regular following-up was also needed. These Zhejiang experiences and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work is warranted to further improve strategies of prevention, diagnosis, and treatment for COVID-19.

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Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RAR fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RAR expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 × 109/L at relapse had better survival than those with WBC count over 10 × 109/L (P = .038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P = .01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.

A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin-angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO 2 /FiO 2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections.

Background-Oral anticoagulation therapy is the primary tool in reducing stroke risk in patients with nonvalvular atrial fibrillation but is underused. Patients nonpersistent with therapy contribute to this underuse. The objective of this study was to compare persistence rates in newly diagnosed nonvalvular atrial fibrillation patients treated with warfarin versus dabigatran as their oral anticoagulation. Methods and Results-US Department of Defense administrative claims were used to identify patients receiving warfarin or dabigatran between October 28, 2010, and June 30, 2012. Patient records were examined for a minimum of 12 months before index date to restrict the analyses to those newly diagnosed with nonvalvular atrial fibrillation and naive-to-treatment, identifying 1775 on warfarin and 3370 on dabigatran. Propensity score matching was used to identify 1745 matched pairs. Persistence was defined as time on therapy to discontinuation. Kaplan-Meier curves were used to depict persistence over time. Cox proportional hazards model was used to determine the factors significantly associated with persistence. Using a 60-day permissible medication gap, the persistence rates were higher for dabigatran than for warfarin at both 6 months (72% versus 53%) and 1 year (63% versus 39%