Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/ . Funding: This work was supported by the Fundamental Research Funds for the Central Universities (lzujbky-2020-sp11) and the Gansu Provincial COVID-19 Science and Technology Major Project, China.

The effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on the proliferation of hepatic stellate cells (HSCs) is largely unknown. The purpose of this study was to explore the mechanism of action of hUC‑MSCs on the proliferation of HSCs in vitro. The upper and lower double-cell co-culture system was established between hUC‑MSCs and HSCs in the experimental group. HSCs were cultured alone as a negative control group. Cell proliferation and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. Cell supernatants were harvested to determine the concentration of transforming growth factor-β1 (TGF-β1) by ELISA. mRNA and protein of TGF-β1, Smad3 and Smad7 in HSCs were determined by reverse transcription-polymerase chain reaction and western blotting, respectively. In the co-culture group, the proliferation of HSCs was significantly inhibited compared with the negative control group at 24 and 48 h (p<0.05). Apoptosis of HSCs in the co-culture group increased compared with that in the negative control group, which was more obvious at 48 h (p<0.05). The concentration of TGF-β1 in the co-culture group was significantly lower than in the HSCs cultured alone (p<0.05). After HSCs were co-cultured with hUC‑MSCs for 48 h, expression of TGF-β1 and Smad3 mRNA and protein was reduced and expression of Smad7 mRNA and protein was increased compared with the negative control group (p<0.05). hUC‑MSCs inhibited proliferation of HSCs, possibly through inhibiting TGF-β1 and Smad3 expression and increasing Smad7 protein expression.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM‑MSCs in liver cirrhosis in vitro. Human BM‑MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co‑culture system. Groups were divided into HSCs alone (control group) and the co‑culture system of BM‑MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)‑β1 and Smad7 mRNA expression were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. BM‑MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM‑MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF‑β1 in the supernatant at 24 h and 48 h in the co‑cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF‑β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF‑β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM‑MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs.

Introduction Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%–6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. Methods and analysis This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. Ethics and dissemination The study protocol has been approved by the ethics committees of the Sixth People’s Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. Trial registration number ChiCTR2300073864.