Background Telemedicine has been used widely in China and has benefited a large number of patients, but little is known about the overall development of telemedicine. Objective The aim of this study was to perform a national survey to identify the overall implementation and application of telemedicine in Chinese tertiary hospitals and provide a scientific basis for the successful expansion of telemedicine in the future. Methods The method of probability proportionate to size sampling was adopted to collect data from 161 tertiary hospitals in 29 provinces, autonomous regions, and municipalities. Charts and statistical tests were applied to compare the development of telemedicine, including management, network, data storage, software and hardware equipment, and application of telemedicine. Ordinal logistic regression was used to analyze the relationship between these factors and telemedicine service effect. Results Approximately 93.8% (151/161) of the tertiary hospitals carried out telemedicine services in business-to-business mode. The most widely used type of telemedicine network was the virtual private network with a usage rate of 55.3% (89/161). Only a few tertiary hospitals did not establish data security and cybersecurity measures. Of the 161 hospitals that took part in the survey, 100 (62.1%) conducted remote videoconferencing supported by hardware instead of software. The top 5 telemedicine services implemented in the hospitals were teleconsultation, remote education, telediagnosis of medical images, tele-electrocardiography, and telepathology, with coverage rates of 86.3% (139/161), 57.1% (92/161), 49.7% (80/161), 37.9% (61/161), and 33.5% (54/161), respectively. The average annual service volume of teleconsultation reached 714 cases per hospital. Teleconsultation and telediagnosis were the core charging services. Multivariate analysis indicated that the adoption of direct-to-consumer mode (P=.003), support from scientific research funds (P=.01), charging for services (P<.001), number of medical professionals (P=.04), network type (P=.02), sharing data with other hospitals (P=.04), and expertise level (P=.03) were related to the effect of teleconsultation. Direct-to-consumer mode (P=.01), research funding (P=.01), charging for services (P=.01), establishment of professional management departments (P=.04), and 15 or more instances of remote education every month (P=.01) were found to significantly influence the effect of remote education. Conclusions A variety of telemedicine services have been implemented in tertiary hospitals in China with a promising prospect, but the sustainability and further standardization of telemedicine in China are still far from accomplished.

Background For patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after curative resection, the effects of various postoperative adjuvant therapies are not summarized in detail, and the comparison between the effects of various adjuvant therapies is still unclear. Thus, we collected existing studies on postoperative adjuvant therapies for patients with HCC with MVI after curative resection and analyzed the effects of various adjuvant therapies. Method We collected all studies on postoperative adjuvant therapy for patients with HCC with MVI after curative resection from PubMed, EMBASE, Cochrane Library and SinoMed ending on May 1, 2019. Overall survival (OS) and disease-free/recurrence-free survival (RFS) between each group were compared in these studies by calculating the pooled hazard ratio (HR) and 95% confidence interval (CI). All statistical analyses were assessed by two authors independently. Result A total of 13 studies were included in this study, including 824 postoperative adjuvant transarterial chemoembolization (pa-TACE) patients, 90 postoperative radiotherapy patients, 57 radiofrequency ablation (RFA)/re-resection patients, 16 sorafenib patients and 886 postoperative conservative treatment patients. The results showed that pa-TACE significantly improved OS and RFS compared with postoperative conservative treatment in patients with HCC with MVI after curative resection (HR: 0.64, 95% CI: 0.55–0.74, p < 0.001; HR: 0.70, 95% CI: 0.62–0.78, p < 0.001, respectively). There was no significant difference in OS between pa-TACE and radiotherapy in patients with HCC with MVI (HR: 1.75, 95% CI: 0.92–3.32, p = 0.087). RFS in patients with HCC with MVI after pa-TACE was worse than that after postoperative adjuvant radiotherapy (HR: 2.29, 95% CI: 1.43–3.65, p < 0.001). The prognosis of pa-TACE and RFA/re-resection in patients with MVI with recurrent HCC had no significant differences (HR: 0.65, 95% CI: 0.09–4.89, p = 0.671). Adjuvant treatments significantly improved the OS and RFS of patients compared with the postoperative conservative group (HR: 0.580, 95% CI: 0.480–0.710, p < 0.001; HR: 0.630, 95% CI: 0.540–0.740, p < 0.001, respectively). Conclusion Compared with postoperative conservative treatment, pa-TACE, postoperative radiotherapy and sorafenib can improve the prognosis of patients with hepatocellular carcinoma with microvascular invasion after curative resection. Postoperative radiotherapy can reduce the recurrence of patients with HCC with MVI after curative resection compared with pa-TACE.

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BDH2 is a short-chain dehydrogenase/reductase family member involved in several biological and pathological processes, including the utilization of cytosolic ketone bodies, immunocyte regulation and tumor progression. In this study, we first revealed that BDH2 was downregulated in HCC tissues by qRT-PCR and immunohistochemistry analysis and that low BHD2 expression was significantly associated with poor overall survival, poor tumor differentiation, increased tumor size, venous invasion and an advanced BCLC stage. Moreover, the results of a univariate analysis and multivariate analysis revealed that BDH2 may be regarded as an independent prognostic marker. As a member of a gene family involved in ketone metabolism, BDH2 upregulated the level of β-HB in liver cells as well as the level of H3 histone acetylation. Functional analysis showed that BDH2 expression inhibited tumor cell growth, proliferation and migration. The results of the mechanistic analysis revealed that BDH2 induced mitochondrial apoptosis and inhibited autophagy through the unfolded protein response. Therefore, BDH2 may be a new HCC prognostic marker and a useful treatment target.

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Background: Long non-coding RNAs are critical to hepatocellular carcinoma (HCC) developments. LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) is a new regulator in several tumors. However, the mechanism by which PITPNA-AS1 mediates the tumorigenesis of HCC remains unclear.Methods: RT-qPCR was used to detect the level of PITPNA-AS1 in HCC specimens and cells. The biological functions of PITPNA-AS1 were explored by several functional experiments in vivo and in vitro. The binding relationship among PITPNA-AS1, miR-448 and ROCK1 were studied by Luciferase assay and pull-down assays.Results: We found that PITPNA-AS1 expressions were distinctly upregulated in both HCC specimens and cell lines. High PITPNA-AS1 levels were an unfavorable biomarker for patients with HCC. Functionally, knockdown of PITPNA-AS1 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, PITPNA-AS1 functioned as competing endogenous RNA to increase ROCK1 expressions via sponging miR-448.Conclusion: The newly identified PITPNA-AS/miR-448/ROCK1 axis promoted the oncogenicity of HCC cells. This novel axis is likely to be a promising HCC therapeutic aim.

Background: Circular RNAs (circRNAs) are important for the process of cancer initiation and progression. However, the role of circRNAs in hepatocellular carcinoma (HCC) remains incompletely understood. Therefore, we further explored the expression network of circRNAs in HCC.Methods: Whole-transcriptome microarrays of HCC and paired normal liver tissues were obtained from the Gene Expression Omnibus (GEO) database. The structures of tumor-associated circRNAs were acquired by the Cancer-Specific CircRNA Database (CSCD). StarBase, circBank, and R packages (miRNAtap and multiMiR) were used to predict miRNA targets of circRNAs and downstream molecules of miRNAs.Expression relationships between RNA-RNA interactions were evaluated by data from The Cancer Genome Atlas (TCGA) and GEO databases. ClusterProfiler and DOSE R packages were used for pathway enrichment to explore the biological functions of potential target genes. Finally, a possible circRNA-miRNA-mRNA regulatory network was established based on the competing endogenous RNA (ceRNA) hypothesis. Results:The differentially expressed circRNAs (DECs) were matched with cancer-specific circRNAs in the CSCD database and a screening analysis was performed to obtain 5 cancer-specific circRNAs. A total of 329 possible target miRNAs for 5 cancer-specific circRNAs were predicted by the circBank database, and intersection analysis with differentially expressed miRNAs (DEmiRNAs) revealed that miR-6746-3p and miR-96-5p were the two most suitable miRNAs targets for our selected circRNAs. Further expression verification and prediction of base complementary paired binding sites demonstrated the hsa_circ_0039466/ miR-96-5p axis as a crucial pathway in HCC. Next, we found that FOXO1 and LEPR were two potential downstream molecules of the hsa_circ_0039466/miR-96-5p axis through target gene prediction analysis, differential expression analysis, and intersection analysis. The pathway enrichment results suggested that the hsa_circ_0039466/miR-96-5p axis affects the progression and outcome of HCC through the insulin resistance pathway. Finally, through multi-data crossover analysis and data analysis of HCC samples further confirmed the existence of the hsa_circ_0039466/miR-96-5p/FOXO1 ceRNA regulatory network and that the axis was closely related to clinical stage.Conclusions: Hsa_circ_0039466 facilitates the expression of FOXO1 by sponging miR-96-5p, and ultimately inhibits tumor progression. These results provide a theoretical basis for further understanding of the gene expression network of HCC.

Background Hepatocellular Carcinoma (HCC) is one of the major malignant tumors threatening human health. Lenvatinib resistance seriously restricts the efficacy of HCC, but the specific mechanism is not clear. Circular RNA (circRNA) plays an important role in the regulation of tumor drug resistance. Methods Key circRNA was screened by bioinformatics methods, and further identified by relevant validation experiments and HCC tissue samples. And, circRNA was evaluated as a diagnostic and prognostic marker for HCC progression at the clinical level. After then, through in vivo and in vitro experiments, the specific mechanism of the circRNA on the progression of HCC and lenvatinib resistance was explored at the molecular level. Results circRNA_0009792 (circRNA-mTOR) was highly expressed in HCC and is closely related to the prognosis of patients, which has good diagnostic value and clinical significance. In vivo and in vitro experiments showed that circRNA-mTOR could promote the progression of hepatocellular carcinoma and promote lenvatinib resistance by improving the stemness of HCC cells. Mechanismly, circRNA-mTOR could affect RNA-binding protein (PSIP1) nuclear translocation by specifically binding to it, and then which enhanced the stemness of HCC cells through PSIP1/c-Myc axis, hence promoting the progression of HCC and lenvatinib resistance. And furthermore, circRNA-mTOR at least partially induce lenvatinib resistance by increasing the expression of EGFR in HCC. Conclusions In conclusion, this study suggests that circRNA-mTOR can affect PSIP1/c-myc axis nuclear translocation, to make progress of HCC and the maintenance of steness of liver cancer cell to aggravate lenvatinib resistance, And partially increased EGFR over-expression to making chemo-resistance worse. CircRNA-mTOR has the potential to be a biomarker for the diagnosis and prognosis of HCC. This study provides a certain experimental basis for the targeted drug therapy of HCC, and puts forward new ideas, new insights and new methods in understanding the occurrence and development of HCC, and it is of great significance to seek new markers and targets for the diagnosis and treatment of HCC and reduce drug resistance.