Clinical Characteristics and Genotyping of Pediatric Adenovirus Pneumonia Disease and Coinfection in Southeast China.

Introduction: Human adenovirus (HAdV) is a common pathogen that can cause acute respiratory infections (ARIs) in children. Adenovirus pneumonia is the most severe respiratory disease associated with HAdV. Objective: We aimed to investigate the clinical characteristics of children hospitalized with adenovirus pneumonia in Quanzhou, China, in 2019. We also sought to determine the viral genotype in these cases and explore cases associated with severe adenovirus pneumonia. Methods: We collected oropharyngeal swabs from 99 children who were hospitalized with pneumonia in Quanzhou Women and Children's Hospital, these samples were tested for the presence of HAdV. Genotyping of the viruses was performed by real-time polymerase chain reaction. Logistic regression analysis was employed to analyze risk factors related to severe adenovirus pneumonia. The epidemiological data were examined using the Statistical Package for Social Sciences software (SPSS). Results: Among the 99 patients in our study, the median age was 21 months. We observed a 4% mortality rate among those diagnosed with adenovirus pneumonia. Adenovirus pneumonia often presents as a coinfection. Lactate dehydrogenase and neutrophil percentages of WBC's were significantly increased in patients with severe adenovirus pneumonia compared with mild HAdV disease. The predominant viral genotypes identified were type 3 and type 7. Conclusions: In the Quanzhou area of southeast China, the incidence of adenovirus pneumonia was found to be high among children younger than two years old. Type 7 HAdV was identified as the primary pathogen. A long duration of fever, dyspnea and digestive system complications were risk factors for severe adenovirus pneumonia after HAdV infection. Clinical Trial Registration number: ChiCTR2200062358.

CD58 acts as a tumor promotor in hepatocellular carcinoma via activating the AKT/GSK-3ß/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. METHODS: Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3ß/ß-catenin axis in HCC cells. RESULTS: CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3ß/ß-catenin signaling pathway by increasing phosphorylation of AKT or GSK3ß signaling, promoting expression of Wnt/ß-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. CONCLUSIONS: Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3ß/ß-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC.

Lenvatinib inhibited HCC cell migration and invasion through regulating the transcription and ubiquitination of UHRF1 and DNMT1.

Hepatocellular carcinoma (HCC) is one of the most common causes of malignancy-related deaths. Lenvatinib, as a multi-targeted tyrosine kinase inhibitor, has gained increasing attention for its antitumor activity. However, the effect and mechanisms of Lenvatinib on HCC metastasis are virtually unknown. In this study, we revealed that Lenvatinib inhibited HCC cell motility and epithelial mesenchymal transition (EMT), along with cell adhesion and extension. Concomitant high DNMT1 and UHRF1 mRNA levels were in HCC patients and indicated worse prognosis. On the one hand, Lenvatinib modulated the transcription of UHRF1 and DNMT1via negatively regulation of ERK/MAPK pathway. On the other hand, Lenvatinib downregulated DNMT1 and UHRF1 expression by promoting their protein degradation through ubiquitin-proteasome pathway, consequently, resulting in upregulation of E-Cadherin. Moreover, Lenvatinib attenuated Huh7 cell adhesion and metastasis in vivo. Our findings provided insight into the intriguing molecular mechanisms regarding the anti-metastasis effect of Lenvatinib in HCC.

ß-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. ß-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of ß-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. ß-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of ß-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use ß-Lapachone. This study provides novel preclinical evidence for ß-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients.

SOX13 regulates cancer stem-like properties and tumorigenicity in hepatocellular carcinoma cells.

Sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) proteins are pivotal transcriptional factors that play essential roles in embryonic development, cell fate decisions and cancer development. The molecular mechanism of SOX13, a member of the SOX family, in hepatocellular carcinoma (HCC) remains largely unknown. In the current study, we found that HCC cells were able to form spheroids in serum-free suspension culture and that SOX13 expression was upregulated in spheroids enriched for cancer stem cells (CSCs). Inhibition of SOX13 in HCC-LM3 and MHCC-97H cells decreased the expression of stemness-related genes; attenuated spheroid formation, anchor-dependent and anchor-independent cell proliferation and tumorigenicity; and enhanced sensitivity to drug treatment. Furthermore, based on analysis of TCGA dataset, the results indicated that SOX13 expression was obviously upregulated and closely associated with poor prognosis in HCC patients. Moreover, SOX13 was correlated with TAZ and CD24 expression. These data strongly demonstrated that SOX13 is involved in maintaining cancer stem-like properties in HCC cells and plays a critical role in HCC development.

A Meta-analysis and Systematic Review Comparing the Effectiveness of Traditional and Virtual Surgical Planning for Orthognathic Surgery: Based on Randomized Clinical Trials.

PURPOSE: To explore the advantages of virtual surgical planning (VSP) and traditional surgical planning (TSP) to determine whether the current VSP technique is superior to the TSP technique for orthognathic surgery. METHODS: An electronic search was carried out in the CENTRAL, PubMed, and Embase databases to identify randomized clinical trials (RCTs) that compared the VSP and TSP techniques regarding their surgical accuracy for hard tissue, prediction precision for soft tissue, required time for planning and surgery, cost and patient-reported outcomes. RESULTS: Eight articles from 5 RCTs, involving 199 patients, were identified. The findings showed that the VSP and TSP techniques were similar in surgical accuracy for hard tissue in the sagittal plane, although the VSP technique was significantly more accurate in certain reference areas, especially in the anterior area of the maxilla. Both the VSP and TSP techniques had significantly better surgical accuracy for the maxilla than for the mandible. The VSP technique showed clinically significantly greater precision for soft tissue prediction in the sagittal plane. Patients who were treated via the VSP technique presented a more symmetrical frontal view, regardless of whether hard or soft tissue was involved. The VSP technique required more time for software planning, but it showed an advantage in time savings when considering the entire preoperative process. Accompanied by the use of an accurate computer-aided splint, the VSP technique could effectively reduce the operative time. Apart from the initial financial investment of software and hardware, the total cost of the VSP technique was similar to that of the TSP technique. Patients who were treated via the VSP or TSP technique showed similar improvements in quality-of-life. CONCLUSIONS: Currently, the VSP technique has become a good alternative to the TSP technique for orthognathic surgery, especially regarding frontal-esthetic considerations. Studies reporting indicators with good representativeness and sensitivity using an identical comparative method are recommended.