Compared with the cases in Wuhan, 80 imported cases of COVID-19 in Jiangsu Province exhibited mild or moderate symptoms and no obvious gender susceptivity, lower proportion of liver dysfunction and abnormal CT imaging and higher frequency nucleic acid detection. AbstractBackground. We aimed to report the clinical characteristics of imported coronavirus disease-19 in Jiangsu Province. Methods.We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with WHO interim guidance in three Grade ⅢA hospitals of Jiangsu from Jan 22 to Feb 14, 2020. Real time RT-PCR was used to detect the new coronavirus in respiratory samples. Results.Of the 80 patients infected with COVID-19, 41 patients were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. 9 patients were unconfirmed until a third-time nucleic acid test. 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 cases (78.75%) and 51 cases (-63.75%) respectively.Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (-68.75%) showed abnormal, 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Up to now, 21 cases were discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. Conclusions.Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptivity. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that of Wuhan.Notably, infected patients may be falsely excluded based on two consecutively negative respiratory pathogenic nucleic acid test results.

BackgroundAt present, the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been a focal point.MethodsTo assess the factors associated with severity and prognosis of patients infected with SARS‐CoV‐2, we retrospectively investigated the clinical, imaging and laboratory characteristics of confirmed 280 cases of novel coronavirus disease (COVID‐19) from 20 January to 20 February 2020.ResultsThe median age of patients in the mild group was 37.55 years, whilst that in the severe group was 63.04 years. The proportion of patients aged over 65 years in the severe group was significantly higher than that of the mild group (59.04% vs. 10.15%, P < 0.05). 85.54% of severe patients had diabetes or cardiovascular diseases, which was significantly higher than that of the mild group (51.81% vs. 7.11%, P = 0.025; 33.73% vs. 3.05%, P = 0.042). Patients in the mild group experienced earlier initiation of antiviral treatment (1.19 ± 0.45 vs. 2.65 ± 1.06 days in the severe group, P < 0.001). Our study showed that comorbidity, time from illness onset to antiviral treatment and age >=65 were three major risk factors for COVID‐19 progression, whilst comorbidity and time from illness onset to antiviral treatment were two major risk factors for COVID‐19 recovery.ConclusionsThe elderly and patients with underlying diseases are more likely to experience a severe progression of COVID‐19. It is recommended that timely antiviral treatment should be initiated to slow the disease progression and improve the prognosis.

Transcription and splicing are functionally coupled, resulting in highly efficient splicing of RNA polymerase II (RNAP II) transcripts. The mechanism involved in this coupling is not known. To identify potential coupling factors, we carried out a comprehensive proteomic analysis of immunopurified human RNAP II, identifying >100 specifically associated proteins. Among these are the SR protein family of splicing factors and all of the components of U1 snRNP, but no other snRNPs or splicing factors. We show that SR proteins function in coupling transcription to splicing and provide evidence that the mechanism involves cotranscriptional recruitment of SR proteins to RNAP II transcripts. We propose that the exclusive association of U1 snRNP/SR proteins with RNAP II positions these splicing factors, which are known to function early in spliceosome assembly, close to the nascent pre-mRNA. Thus, these factors readily out-compete inhibitory hnRNP proteins, resulting in efficient spliceosome assembly on nascent RNAP II transcripts.

The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29−0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.

BackgroundStem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF).MethodshPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis.ResultshPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig livers (Groups III, IV).ConclusionsOur data revealed that hPMSCs could not only differentiate into hepatocyte-like cells in vitro and in vivo, but could also prolong the survival time of ALF pigs. Regarding the transplantation pathways, the left branch of the portal vein inside the liver was superior to the jugular vein pathway. Thus, hPMSCs transplantation through the portal vein by B-ultrasonography may represent a superior approach for treating liver diseases.

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Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate liver injury. Here, the protective effect of MSCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was investigated. In this study, we illustrated a novel mechanism that ferroptosis, a newly recognized form of regulated cell death, contributed to CCl4-induced ALI. Subsequently, based on the in vitro and in vivo evidence that MSCs and MSC-derived exosomes (MSC-Exo) treatment achieved pathological remission and inhibited the production of lipid peroxidation, we proposed an MSC-based therapy for CCl4-induced ALI. More intriguingly, treatment with MSCs and MSC-Exo downregulated the mRNA level of prostaglandin-endoperoxide synthase 2 (Ptgs2) and lipoxygenases (LOXs) while it restored the protein level of SLC7A11 in primary hepatocytes and mouse liver, indicating that the inhibition of ferroptosis partly accounted for the protective effect of MSCs and MSC-Exo on ALI. We further revealed that MSC-Exo-induced expression of SLC7A11 protein was accompanied by increasing of CD44 and OTUB1. The aberrant expression of ubiquitinated SLC7A11 triggered by CCl4 could be rescued with OTUB1-mediated deubiquitination, thus strengthening SLC7A11 stability and thereby leading to the activation of system XC− to prevent CCl4-induced hepatocyte ferroptosis. In conclusion, we showed that MSC-Exo had a protective role against ferroptosis by maintaining SLC7A11 function, thus proposing a novel therapeutic strategy for ferroptosis-induced ALI.

Human placenta-derived mesenchymal stem cells (hPMSCs) reside in a physiologically low-oxygen microenvironment. Hypoxia influences a variety of stem cell cellular activities, frequently involving hypoxia-inducible factor-2 alpha (HIF-2α). This research showed that hPMSCs cultured in hypoxic conditions (5% O2) exhibited a more naïve morphology and had a higher proliferative capability and higher HIF-2α expression than hPMSCs cultured in normoxic conditions (21% O2). Similar to the hypoxic cultures, hPMSCs over-expressing HIF-2α showed higher proliferative potential and higher expression of CCND1 (CyclinD1), MYC (c-Myc), POU5F1 (Oct4) and the components of the MAPK/ERK pathway. In contrast, these genes were down-regulated in the HIF-2α-silenced hPMSCs. After adding the MAPK/ERK inhibitor PD0325901, cell growth and the expression of CCND1 and MYC were inhibited. Furthermore, the chromatin immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA) showed that HIF-2α bound to the MAPK3 (ERK1) promoter, indicative of its direct regulation of MAPK/ERK components at the transcriptional level during hPMSC expansion. Taken together, our results suggest that HIF-2α facilitated the preservation of hPMSC stemness and promoted their proliferation by regulating CCND1 and MYC through the MAPK/ERK signaling pathway.