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BackgroundSince December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and spread across the globe. The objective of this study is to build and validate a practical nomogram for estimating the risk of severe COVID-19.MethodsA cohort of 366 patients with laboratory-confirmed COVID-19 was used to develop a prediction model using data collected from 47 locations in Sichuan province from January 2020 to February 2020. The primary outcome was the development of severe COVID-19 during hospitalization. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data size and select relevant features. Multivariable logistic regression analysis was applied to build a prediction model incorporating the selected features. The performance of the nomogram regarding the C-index, calibration, discrimination, and clinical usefulness was assessed. Internal validation was assessed by bootstrapping.ResultsThe median age of the cohort was 43 years. Severe patients were older than mild patients by a median of 6 years. Fever, cough, and dyspnea were more common in severe patients. The individualized prediction nomogram included seven predictors: body temperature at admission, cough, dyspnea, hypertension, cardiovascular disease, chronic liver disease, and chronic kidney disease. The model had good discrimination with an area under the curve of 0.862, C-index of 0.863 (95% confidence interval, 0.801-0.925), and good calibration. A high C-index value of 0.839 was reached in the interval validation. Decision curve analysis showed that the prediction nomogram was clinically useful.ConclusionWe established an early warning model incorporating clinical characteristics that could be quickly obtained on admission. This model can be used to help predict severe COVID-19 and identify patients at risk of developing severe disease.

Inflammation can be activated as a defensive response by the attack of acute coronary syndrome (ACS) for ischemic tissue injury. The aim of the present study was to investigate the impact of ACS-activated inflammation on adipokine imbalance and the effects of statins on the crosstalk between inflammation and adipokine imbalance during ACS. In this study, 586 subjects were categorized into: (1) control group; (2) SA (stable angina) group; and (3) ACS group. Circulating levels of hs-CRP, adiponectin and resistin were measured by ELISA. Furthermore, forty C57BL/6 mice were randomized into: sham, AMI, low-statin (atorvastatin, 2 mg/kg/day) and high-statin (atorvastatin, 20 mg/kg/day) group. After 3 weeks, AMI models were established by surgical coronary artery ligation. Circulating levels and adipose expressions of adiponectin and resistin were assessed in animals. Besides, we investigate the effects of atorvastatin on ox-LDL-induced adipokine imbalance in vitro. As a result, we found that ACS patients had higher hs-CRP and resistin levels and lower adiponectin levels. Our correlation analysis demonstrated hs-CRP concentrations were positively correlated with resistin but negatively with adiponectin levels in humans. Our animal findings indicated higher circulating hs-CRP and resistin levels and lower adiponectin levels in AMI mice. Atorvastatin pre-treatment dose-dependently decreased hs-CRP and resistin levels but increased adiponectin levels in mice. The consistent findings were observed about the adipose expressions of resistin and adiponectin in mice. In study in vitro, ox-LDL increased cellular resistin expressions and otherwise for adiponectin expressions, which dose-dependently reversed by the addition of atorvastatin. Therefore, our study indicates that the ACS attack activates inflammation leading to adipokine imbalance that can be ameliorated by anti-inflammation of atorvastatin.

Xuezhikang (XZK), an extract of Chinese red yeast rice, is recommended as an optimal choice for patients with coronary heart disease (CHD) with markedly elevated triglyceride (TG) levels. This study was designed to compare the hypotriglyceridemic effects between XZK and simvastatin. The role of apolipoprotein A5 (apoA5), a key regulator of TG metabolism and a target gene of peroxisome proliferator-activated receptor α (PPARα), was to be identified in XZK-related hypotriglyceridemic actions. For these goals, hypertriglyceridemia of rats was induced by a high-fructose diet. In order to investigate the hypotriglyceridemic effects of XZK and simvastatin on these animals based on an equivalent low-density lipoprotein cholesterol (LDL-C) lowering power, we titrated their doses (XZK 80 mg/kg/d versus simvastatin 1 mg/kg/d) according to plasma LDL-C reduction of rats. Similarly, we titrated the target doses of the two agents (XZK 500 μg/ml versus simvastatin 10 μM) according to hepatocyte LDL receptor expressions, and then compared the effects of the two agents on TG and apoA5 of hepatocytes in vitro. Our results showed that XZK (80 mg/kg/d) had higher hypotriglyceridemic performance than simvastatin (1 mg/kg/d) on these animals albeit their equivalent LDL-C lowering power. Higher plasma apoA5 levels and hepatic apoA5 expressions were observed in rats treated with XZK (80 mg/kg/d) than simvastatin (1 mg/kg/d). Further, XZK (80 mg/kg/d) contributed to higher hepatic PPARα expressions of rats than simvastatin (1 mg/kg/d). Although the two agents led to an equivalent up-regulation of LDL receptors of hepatocytes, more TG reduction and apoA5 elevation were detected in hepatocytes treated with XZK (500 μg/ml) than simvastatin (10 μM). However, PPARα knockdown eliminated the above effects of XZK on hepatocytes. Therefore, our study indicates that XZK has greater hypotriglyceridemic performance than simvastatin in the setting of an equivalent LDL-C lowering power, which is attributed to more apoA5 up-regulation by this agent via the PPARα signaling pathway.

PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation.

Mammalian spermatogenesis comprises three successive phases: mitosis phase, meiosis phase, and spermiogenesis. During spermiogenesis, round spermatid undergoes dramatic morphogenesis to give rise to mature spermatozoon, including the condensation and elongation of nucleus, development of acrosome, formation of flagellum, and removal of excessive cytoplasm. Although these transformations are well defined at the morphological level, the mechanisms underlying these intricate processes are largely unknown. Here, we report that Iqcg, which was previously characterized to be involved in a chromosome translocation of human leukemia, is highly expressed in the spermatogenesis of mice and localized to the manchette in developing spermatids. Iqcg knockout causes male infertility, due to severe defects of spermiogenesis and resultant total immobility of spermatozoa. The axoneme in the Iqcg knockout sperm flagellum is disorganized and hardly any typical ("9+2") pattern of microtubule arrangement could be found in Iqcg knockout spermatids. Iqcg interacts with calmodulin in a calcium dependent manner in the testis, suggesting that Iqcg may play a role through calcium signaling. Furthermore, cilia structures in the trachea and oviduct, as well as histological appearances of other major tissues, remain unchanged in the Iqcg knockout mice, suggesting that Iqcg is specifically required for spermiogenesis in mammals. These results might also provide new insights into the genetic causes of human infertility.