Objectives To determine the patterns of chest computed tomography (CT) evolution according to disease severity in a large coronavirus disease 2019 (COVID-19) cohort in Jiangsu Province, China. Methods This retrospective cohort study was conducted from January 10, 2020, to February 18, 2020. All patients diagnosed with COVID-19 in Jiangsu Province were included, retrospectively. Quantitative CT measurements of pulmonary opacities including volume, density, and location were extracted by deep learning algorithm. Dynamic evolution of these measurements was investigated from symptom onset (day 1) to beyond day 15. Comparison was made between severity groups. Results A total of 484 patients (median age of 47 years, interquartile range 33-57) with 954 CT examinations were included, and each was assigned to one of the three groups: asymptomatic/mild (n = 63), moderate (n = 378), severe/critically ill (n = 43). Time series showed different evolution patterns of CT measurements in the groups. Following disease onset, posteroinferior subpleural area of the lung was the most common location for pulmonary opacities. Opacity volume continued to increase beyond 15 days in the severe/ critically ill group, compared with peaking on days 13-15 in the moderate group. Asymptomatic/mild group had the lowest opacity volume which almost resolved after 15 days. The opacity density began to drop from day 10 to day 12 for moderately ill patients. Conclusions Volume, density, and location of the pulmonary opacity and their evolution on CT varied with disease severity in COVID-19. These findings are valuable in understanding the nature of the disease and monitoring the patient's condition during the course of illness. Key Points • Volume, density, and location of the pulmonary opacity on CT change over time in COVID-19. • The evolution of CT appearance follows specific pattern, varying with disease severity. Keywords Coronavirus. Multidetector computed tomography. Viral pneumonia Abbreviations AI Artificial intelligence CI Confidence interval COVID-19 Coronavirus disease 2019 CT Computed tomography GGO Ground-glass opacity ICU Intensive care unit IQR Interquartile range SaO 2 Arterial oxygen saturation SD Standard deviation VOI Volume of interest Electronic supplementary material The online version of this article (

ObjectivesTo determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China.Design and settingRetrospective, multicentre cohort study performed at 24 hospitals in Jiangsu, China.Participants625 patients with COVID-19 enrolled between 10 January and 15 March 2020.ResultsOf the 625 patients (median age, 46 years; 329 (52.6%) men), 37 (5.9%) were children (18 years or younger), 261 (41.8%) young adults (19–44 years), 248 (39.7%) middle-aged adults (45–64 years) and 79 (12.6%) elderly adults (65 years or older). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease and diabetes comorbidities increased with age (trend test, p<0.0001, p=0.0003, p<0.0001 and p<0.0001, respectively). Fever, cough and shortness of breath occurred more commonly among older patients, especially the elderly, compared with children (χ2 test, p=0.0008, 0.0146 and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both p<0.0001). Older patients had many significantly different laboratory parameters from younger patients. Elderly patients had the highest proportion of severe or critically-ill cases (33.0%, χ2 test p<0.0001), intensive care unit use (35.4%, χ2 test p<0.0001), respiratory failure (31.6%, χ2 test p<0.0001) and the longest hospital stay (median 21 days, Kruskal–Wallis test p<0.0001).ConclusionsElderly (≥65 years) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure and the longest hospital stay, which may be due partly to their having a higher incidence of comorbidities and poor immune responses to COVID-19.

Objectives Growth differentiation factor 11 (GDF11), an emerging secreted member of the TGF‐beta superfamily, plays essential roles in development, physiology and multiple diseases; however, its role during adipogenic differentiation and the underlying mechanisms remains poorly understood. Materials and methods Bone marrow‐derived human mesenchymal stem cells (hMSCs) and 3T3‐L1 pre‐adipocytes were induced with adipogenic culture medium supplementing with different concentrations of recombinant GDF11 (rGDF11 0, 10, 50, 100 ng mL −1 ). Oil Red O staining, qRT‐PCR analysis, Western blot analysis and immunofluorescence staining were performed to assay adipogenesis. Results For both hMSCs and 3T3‐L1 pre‐adipocytes, the presence of rGDF11 leads to a dose‐dependent reduction of intracellular lipid droplet accumulation and suppressed adipogenic‐related gene expression. Mechanically, GDF11 inhibits adipogenesis by activating Smad2/3‐dependent TGF‐beta signalling pathway, and these inhibitory effects could be restored by SB‐431542, a pharmacological TGF‐beta type I receptor inhibitor. Conclusions Taken together, our data indicates that GDF11 inhibits adipogenic differentiation in both hMSCs and 3T3‐L1 pre‐adipocytes by activating Smad2/3‐dependent TGF‐beta signalling pathway.

Background Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China. Methods Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation. Results A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO 2 ), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03–1.09), lymphocyte count (10 9 /L) (OR 0.25, 95%CI 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51). Conclusions Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.

AimMitophagy is the regulated process that targets damaged or dysfunctional mitochondria for lysosomal‐mediated removal. This process is an essential element of mitochondrial quality control, and dysregulation of mitophagy may contribute to a host of diseases, most notably neurodegenerative conditions such as Parkinson's disease. Mitochondria targeted for mitophagic destruction are molecularly marked by the ubiquitination of several outer mitochondrial membrane (OMM) proteins. This ubiquitination is positively regulated, in part, by the mitochondrial‐targeted kinase PINK1 and the E3 ubiquitin ligase Parkin. In contrast, the reverse phenomenon, deubiquitination, removes ubiquitin from Parkin substrates embedded in the OMM proteins, antagonizing mitophagy. Recent evidence suggests that the mitochondrial deubiquitinase USP30 negatively regulates Parkin‐mediated mitophagy, providing opportunities to identify USP30 inhibitors and test for their effects in augmenting mitophagy. Here we will characterize a USP30 inhibitor and demonstrate how the pharmacological inhibition of USP30 can augment stress‐induced mitophagic flux.MethodsWe have conducted mitophagy and mitochondrial analyses in cultured cells. We have determined the plasma pharmacokinetics of the USP30 inhibitor in mice and conducted analyses using the mt‐Keima mice to measure in vivo mitophagy directly.ResultsThe compound has minimal mitochondrial toxicity in cultured cells and is tolerated well in mice. Interestingly, we demonstrated tissue‐specific induction of mitophagy following USP30 pharmacological inhibition. In particular, pharmacological inhibition of USP30 induces a significant increase in cardiac mitophagy without detriment to cardiac function.ConclusionOur data support the evidence that USP30 inhibition may serve as a specific strategy to selectively increase mitophagic flux, allowing for the development of novel therapeutic approaches.

Depression amongst the elderly population is a worldwide public health problem, especially in China. Affected by the urban–rural dual structure, depressive symptoms of the elderly in urban and rural areas are significantly different. In order to compare depressive symptoms and its influencing factors among the elderly in urban and rural areas, we used the data from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS). A total of 7690 participants at age 60 or older were included in this study. The results showed that there was a significant difference in the prevalence estimate of depression between urban and rural elderly (χ2 = 10.9.76, p < 0.001). The prevalence of depression among rural elderly was significantly higher than that of urban elderly (OR -unadjusted = 1.88, 95%CI: 1.67 to 2.12). After adjusting for gender, age, marital status, education level, minorities, religious belief, self-reported health, duration of sleep, life satisfaction, chronic disease, social activities and having income or not, the prevalence of depression in rural elderly is 1.52 times (OR = 1.52, 95% CI: 1.32 to 1.76) than that of urban elderly. Gender, education level, self-reported health, duration of sleep, chronic diseases were associated with depression in both urban and rural areas. In addition, social activities were connected with depression in urban areas, while minorities, marital status and having income or not were influencing factors of depression among the rural elderly. The interaction analysis showed that the interaction between marital status, social activities and urban and rural sources was statistically significant (divorced: coefficient was 1.567, p < 0.05; social activities: coefficient was 0.340, p < 0.05), while gender, education level, minorities, self-reported health, duration of sleep, life satisfaction, chronic disease, social activities having income or not and urban and rural sources have no interaction (p > 0.05). Thus, it is necessary to propose targeted and precise intervention strategies to prevent depression after accurately identifying the factors’ effects.

The increase of fungal infectious diseases and lack of safe and efficacious antifungal drugs result in the urgent need of new therapeutic strategies. Here, we repurposed the lovastatin (LOV) as a synergistic antifungal potentiator to itraconazole (ITZ) against Candida albicans planktonic cells and biofilms in vitro for the first time. Mutants from ergosterol biosynthesis pathway were employed and key gene expression profiles of ergosterol pathway were also measured. LOV single treatment was unable to inhibit C. albicans strains except the ERG3 and ERG11 double mutant. LOV and ITZ combination was capable of inhibiting the C. albicans planktonic cells and biofilms synergistically including the ITZ resistant mutants. The synergistic antifungal ability was stronger in either ERG11 or ERG3 dysfunctional mutants compared to wild type. The combination lost the synergistic activities in the ERG11 and ERG3 double mutant, while it was sensitive to LOV single treatment. The expression of HMG1, encoding HMG-CoA the target of LOV, was significantly upregulated in ERG11 and ERG3 double mutant strain by the treatment of the combination at 1.5 and 3 h. The combination also significantly increased the HMG1 expression in mutants from ergosterol pathway compared with wild type. The ERG11 and ERG3 gene expressions were upregulated by ITZ and its combination with LOV, but seemingly not by LOV single treatment after 1.5 and 3 h. The combination of LOV and ITZ on C. albicans planktonic cells and biofilms highlights its potential clinical practice especially against the azole drug-resistant mutants.

No abstract