The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

/pdf/plasma-hsp90-levels-in-patients-with-systemic-sclerosis-and-1ftthcf8xe.pdf

Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study.

[Crohn's disease].

Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis.

BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with the inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) reached clinical response, with an increase of CD8+ T cells and B cells. No significant change of any subset was detected in non-response cases. In multivariate analysis, post-treatment decrease of CD8+ T cells and B cells and increase of CD4+/CD8+ ratio were indicated as independent predictors for poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.

Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia

Background Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. Results Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P Conclusion Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.

/pdf/clinical-characteristics-of-refractory-covid-19-pneumonia-in-57y3l59dkf.pdf

Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China.

Pancreatic Injury Patterns in Patients With Coronavirus Disease 19 Pneumonia.

The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis.

Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies Epidemiological studies were included, and identified studies were evaluated for risk of biasA narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes 20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight This study indicated a positive association between UPFs consumption and risk of several health outcomes Large-scale prospective designed studies are needed to confirm our findings

/pdf/consumption-of-ultra-processed-foods-and-health-outcomes-a-2a8ou5uw5i.pdf

Qiu Zhao

Papers

Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia

Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China.

Pancreatic Injury Patterns in Patients With Coronavirus Disease 19 Pneumonia.

The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis.

Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies