Objective To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings and imaging features of coronavirus disease 2019 (COVID‐19) in pediatric patients. Methods A meta‐analysis was carried out to identify studies on COVID‐19 from December 25, 2019 to April 30, 2020. Results A total of 48 studies with 5829 pediatric patients were included. Children at all ages were at risk for COVID‐19. The main illness classification ranged as: 20% (95% CI: 14 to 26%, I 2 =91.4%) asymptomatic, 33% (95% CI: 23 to 43%, I 2 =95.6%) mild and 51% (95% CI: 42 to 61%, I 2 =93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45 to 57%, I 2 =78.9%) and cough 41% (95% CI: 35 to 47%, I 2 =81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64 to 75%, I 2 =58.5%), lymphopenia 16% (95% CI: 11 to 21%, I 2 =76.9%) and elevated creatine‐kinase MB (CK‐MB) 37% (95% CI: 25 to 48%, I 2 =59.0%). The frequent imaging features were normal images 41% (95% CI: 30 to 52%, I 2 =93.4%) and ground‐glass opacity 36% (95% CI: 25 to 47%, I 2 =92.9%). Among children under 1‐year old, critical cases account for 14% (95% CI: 13 to 34%, I 2 =37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18 to 67%, I 2 =0.0%) cases that may also need attention. Conclusions Pediatric patients with COVID‐19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1‐year old. This article is protected by copyright. All rights reserved.

Down-regulation of microRNA-26a (miR-26a) is associated with poor prognosis of hepatocellular carcinoma (HCC), but its functional mechanism in HCC remains unclear. In this study, we investigated the roles of miR-26a in tumor growth and metastasis of HCC and found that miR-26a was frequently down-regulated in HCC tissues. Down-regulation of miR-26a correlated with HCC recurrence and metastasis. Through gain-and loss-offunction studies, miR-26a was demonstrated to significantly inhibit in vitro cell proliferation, migration, and invasion. In addition, miR-26a induced G1 arrest and promoted apoptosis of HCC cells. Importantly, miR-26a suppressed in vivo tumor growth and metastasis in nude mice models bearing human HCC. Interleukin-6 (IL-6) was identified as a target of miR-26a. Knockdown of IL-6 induced effects on HCC cells similar to those induced by miR-26a. In contrast, IL-6 treatment abrogated the effects induced by miR26a up-regulation. Moreover, miR-26a dramatically suppressed expression of signal transducer and activator of transcription 3 (Stat3) target genes, including Bcl-2, Mcl-1, cyclin D1, and MMP2. IL-6 treatment antagonized this effect, while knockdown of IL-6 by IL-6 short hairpin RNA (shIL-6) induced inhibitory effects on the expression of p-Stat3 and its main target genes, similar to miR-26a. The messenger RNA and protein levels of IL-6 inversely correlated with miR-26a in HCCs. Patients with high miR-26a or low IL-6 in HCC tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR-26a, IL-6, and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Conclusion: miR-26a could suppress tumor growth and metastasis of HCC through IL-6-Stat3 signaling and is a novel prognostic marker and therapeutic target for HCC. (HEPATOLOGY 2013;58:158-170)

No abstract

In our previous study, osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of hepatocellular carcinoma (HCC). However, the mechanism by which OPN promotes metastasis of HCC is not understood. In this study, RNA interference mediated by viral vectors-which could induce a long-lasting down-regulation in gene expression-was applied to analyze the role of OPN in metastasis of HCC. Three lentiviral vectors encoding microRNA against OPN, Lenti.OPNi-1, Lenti.OPNi-2, and Lenti.OPNi-3, were constructed and found to down-regulate the OPN level by 62%, 78%, and 95%, respectively, in HCCLM3 cells which had an overexpression of OPN and a higher metastatic potential. Consequently, both Lenti.OPNi-2 and Lenti.OPNi-3 induced a significant decrease in matrix metalloproteinase ( H epatocellular carcinoma (HCC) is the third leading cause of cancer death in the world, and the second in China. 1,2 The extremely poor prognosis of patients with HCC is largely due to the high rate of tumor recurrence or intrahepatic metastasis after surgical resection. 3 Therefore, it is very important to search for molecular markers related to metastasis, which would provide new predictors as well

Routine abdominal drainage is unnecessary after elective hepatectomy using the crushing clamp method.

Purpose: To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.Experimental Design: MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.Results: MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.Conclusions: Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.

The incidence of LNM in operable HCC patients was low, and patients with LNM had a poorer prognosis. LNM status determined the disease-free survival but not the overall survival of HCC. The complete lymphadenectomy did not improve overall survival, as compared with chemotherapy or radiotherapy.

The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97-H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor-beta 1 (TGFb1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co-culture of MHCC97-H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC-treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm 3 vs 2223.75 ± 1000.60 mm 3 , P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFb1 and MMP-2 was significantly downregulated in the MSCtreated HCC cells. TGFb siRNA concurrently downregulated expression of TGFb and MMP-2 in HCC cells and blocked the MSC-induced proliferation and invasiveness of MHCC97-H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFb1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546-2553 H epatocellular carcinoma (HCC) is the third leading cause of cancer death in the world, and the second in China.(1,2)The extremely poor prognosis of HCC is largely due to the high rate of intra-hepatic metastases that develop through invasion of the portal vein and spread to other parts of the liver.(3,4) Therefore, exploring new therapeutic strategies to control the metastasis of HCC is the key issue for prolonging patient survival. Recently accumulated evidence indicating that bone marrow stem cells contribute to the development and progression of cancers might be helpful in the diagnosis and treatment of human cancers.(6-11) Bone marrow cells have also been found to be closely associated with liver diseases, and can indirectly influence hepatocarcinogenesis.(12) However, their significance with respect to HCC is far from fully understood.Mesenchymal stem cells (MSC) from adult bone marrow can be induced to differentiate into a variety of mesenchymal tissues both in vitro and in vivo.(13-15) They can even demonstrate sitespecific differentiation, and have unique immunological characteristics that allow persistence in a xenogeneic environment. (16) Therefore, MSC present an intriguing model in which to investigate the differentiation of stem cells, as well as cell and gene therapy applications. However, little is known about the functional contribution of MSC to tumor growth and progression, and the publish...