Molecular mechanism study of HGF/c-MET pathway activation and immune regulation for a tumor diagnosis model.

BACKGROUND: Hepatocyte growth factor (HGF) binds to the c-mesenchymal-epithelial transition (C-MET) receptor and activates downstream signaling pathways, playing an essential role in the development of various cancers. Given the role of this signaling pathway, the primary therapeutic direction focuses on identifying and designing HGF inhibitors, antagonists and other molecules to block the binding of HGF to C-MET, thereby limiting the abnormal state of other downstream genes. METHODS: This study focuses on the analysis of immune-related genes and corresponding immune functions that are significantly associated with the HGF/c-MET pathway using transcriptome data from 11 solid tumors. RESULTS: We systematically analyzed 11 different cancers, including expression correlation, immune infiltration, tumor diagnosis and survival prognosis from HGF/c-MET pathway and immune regulation, two biological mechanisms having received extensive attention in cancer analysis. CONCLUSION: We found that the HGF/c-MET pathway affected the tumor microenvironment mainly by interfering with expression levels of other genes. Immune infiltration is another critical factor involved in changes to the tumor microenvironment. The downstream immune-related genes activated by the HGF/c-MET pathway regulate immune-related pathways, which in turn affect the degree of infiltration of immune cells. Immune infiltration is significantly associated with cancer development and prognosis.

Application of Telemedicine Services Based on a Regional Telemedicine Platform in China From 2014 to 2020: Longitudinal Trend Analysis.

BACKGROUND: Telemedicine that combines information technology and health care augments the operational model of traditional medical services and brings new opportunities to the medical field. China promotes telemedicine with great efforts, and its practices in the deployment of telemedicine platforms and delivery of services have become important references for the research and development in this field. OBJECTIVE: Our work described in this paper focuses on a regional telemedicine platform that was built in 2014. We analyzed the system design scheme and remote consultations that were conducted via the system to understand the deployment and service delivery processes of a representative telemedicine platform in China. METHODS: We collected information on remote consultations conducted from 2015 to 2020 via the regional telemedicine platform that employs a centralized architectural system model. We used graphs and statistical methods to describe the changing trends of service volume of remote consultation, geographical and demographic distribution of patients, and waiting time and duration of consultations. The factors that affect consultation duration and patient referral were analyzed by multivariable linear regression models and binary logistic regression models, respectively. The attitudes toward telemedicine of 225 medical practitioners and 225 patients were collected using the snowball sampling method. RESULTS: The regional telemedicine platform covers all levels of medical institutions and hospitals in all 18 cities of Henan Province as well as some interprovince hospitals. From 2015 to 2020, 103,957 remote medical consultations were conducted via the platform with an annual increasing rate of 0.64%. A total of 86.64% (90,069/103,957) of medical institutions (as clients) that applied for remote consultations were tier 1 or 2 and from less-developed regions; 65.65% (68,243/103,945) of patients who applied for remote consultations were aged over 50 years. The numbers of consultations were high for departments focusing in the treatment of chronic diseases such as neurology, respiratory medicine, and oncology. The invited experts were mainly experienced doctors with senior professional titles. Year of consultation, tier of hospital, consultation department, and necessity of patient referral were the main factors affecting the duration of consultations. In surveys, we found that 60.4% (136/225) of medical practitioners and 53.8% (121/225) of patients had high satisfaction and believed that telemedicine is of vital importance for the treatment of illness. CONCLUSIONS: The development of telemedicine in China shows a growing trend and provides great benefits especially to medical institutions located in less developed regions and senior citizens who have less mobility. Cases of remote consultations are mainly for chronic diseases. At present, the importance and necessity of telemedicine are well recognized by both patients and medical practitioners. However, the waiting time needs to be further reduced to improve the efficiency of remote medical services.

Effectiveness of a Cloud-Based Telepathology System in China: Large-Sample Observational Study.

BACKGROUND: Whole-slide imaging allows the entire slide to be viewed in a manner that simulates microscopy; therefore, it is widely used in telepathology. However, managing the large digital files needed for whole-slide imaging is difficult. To solve this problem, we set up the Chinese National Cloud-Based Telepathology System (CNCTPS). CNCTPS has been running for more than 4 years and has accumulated a large amount of data. OBJECTIVE: The main purpose of this study was to comprehensively evaluate the effectiveness of the CNCTPS based on a large sample. The evaluation indicators included service volume, turnaround time, diagnosis accuracy, and economic benefits. METHODS: Details of 23,167 cases submitted to the CNCTPS from January 2016 to December 2019 were collected to analyze the service volume, turnaround time, and economic benefits. A total of 564 patients who visited the First Affiliated Hospital of Zhengzhou University and obtained final diagnoses were followed up to analyze the diagnostic accuracy of the CNCTPS. RESULTS: From 2016 to 2019, the service volume of the CNCTPS increased from 2335 to 9240, and the number of participating hospitals increased from 60 to 74. Consultation requests from county-level hospitals accounted for 86.57% (20,287/23,167). A total of 17,495 of 23,167 cases (75.52%) were confirmed, including 12,088 benign lesions, 5217 malignant lesions, and 190 borderline lesions. Of the cases, 3.85% (893/23,167) failed to be diagnosed for reasons such as poor slice quality and incomplete sampling. The median turnaround time was 16.93 hours and was shortened yearly (between 2018 and 2019: adjusted P=.01; other groups: adjusted P<.001); 82.88% cases were diagnosed in 48 hours. There was a discrepancy between the diagnosis and final diagnosis for 11 cases, including 4 false-positive cases and 7 false-negative cases. The sensitivity and specificity were 97.66% and 98.49%, respectively. The diagnostic accuracy of the system was 98.05%, with no statistical difference from the final diagnosis in the hospital (P=.55). By using this system, a total of US $300,000 was saved for patients every year. CONCLUSIONS: The novel cloud-based telepathology system has the potential to relieve the shortage of pathologists in primary hospitals. It can also simultaneously reduce medical costs for patients in China. It should, therefore, be further promoted to enhance the efficiency, quantity, and quality of telepathology diagnoses.

Involvement of long non-coding RNAs in the progression of esophageal cancer.

Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system with high incidence and mortality rate worldwide. Therefore, exploring the pathogenesis of EC and searching for new targeted therapies are the current research hotspot for EC treatment. Long non-coding RNAs (lncRNAs) are endogenous RNAs with more than 200 nucleotides, but without protein-coding function. In recent years, lncRNAs have gradually become the focuses in the field of non-coding RNA. Some lncRNAs have been proved to be closely related to the pathogenesis of EC. Many lncRNAs are abnormally expressed in EC and participate in many biological processes including cell proliferation, apoptosis, and metastasis by inhibiting or promoting target gene expression. LncRNAs can also regulate the progression of EC through epithelial-mesenchymal transformation (EMT), which is closely related to the occurrence, development, and prognosis of EC. In this article, we review and discuss the involvement of lncRNAs in the progression of EC.

Identification of esophageal cancer pathway deviation and construction of a diagnosis model using three kernel genes.

The purpose of this study is to better understand the role of interleukin 35 (IL35) in esophageal carcinoma by comparing the mRNA level in Barrett's esophageal mucosa and in matched normal squamous mucosa and to understand how the diagnosis model works with two other genes: hepatocyte nuclear factor 1B (HNF1B) and cAMP responsive element binding protein 3-like 1 (CREB3L1). By comparing carcinoma tissue and normal tissue samples, we extracted all the differentially expressed mRNAs. The bioinformatics analysis resulted in the discovery of three prominent genes. Eventually, the three genes were utilized to train a deep-learning model. An additional wet experiment was conducted to validate the effect of IL35. All the differentially expressed genes were enriched into nine groups, each of which has specific biological functions. Given that the three significant genes HNF1B, CREB3L1, and IL35 as diagnostic features, a deep-learning model was constructed, reaching an accuracy of 93% in the training set and 87% in the test set. Our findings suggest that IL35, along with the other two signatures, can distinguish esophageal tumor samples from normal samples precisely.

Integrated analysis of dysregulated long non-coding RNAs/microRNAs/mRNAs in metastasis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), largely remains a primary cause of cancer-related death worldwide. The molecular mechanisms in LUAD metastasis have not been completely uncovered. METHODS: In this study, we identified differentially expressed genes (DEGs), miRNAs (DEMs) and lncRNAs (DELs) underlying metastasis of LUAD from The Cancer Genome Atlas database. Intersection mRNAs were used to perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and co-expression network analysis. In addition, survival analyses of intersection mRNAs were conducted. Finally, intersection mRNAs, miRNAs and lncRNAs were subjected to construct miRNA-mRNA-lncRNA network. RESULTS: A total of 1015 DEGs, 54 DEMs and 22 DELs were identified in LUAD metastasis and non-metastasis samples. GO and KEGG pathway analysis had proven that the functions of intersection mRNAs were closely related with many important processes in cancer pathogenesis. Among the co-expression interactions network, 22 genes in the co-expression network were over the degree 20. These genes imply that they have connections with many other gene nodes. In addition, 14 target genes (ARHGAP11A, ASPM, HELLS, PRC1, TMPO, ARHGAP30, CD52, IL16, IRF8, P2RY13, PRKCB, PTPRC, SASH3 and TRAF3IP3) were found to be associated with survival in patients with LUAD significantly (log-rank P < 0.05). Two lncRNAs (LOC96610 and ADAM6) acting as ceRNAs were identified based on the miRNA-mRNA-lncRNA network. CONCLUSIONS: Taken together, the results may provide a novel perspective to develop a multiple gene diagnostic tool for LUAD prognosis, which might also provide potential biomarkers or therapeutic targets for LUAD.

Bushenshugan Formula Attenuates the Development of Lung Cancer by Inhibiting Epithelial-Mesenchymal Transition.

BACKGROUND/AIMS: BushenShugan Formula (BSF) is a traditional Chinese medicine that has therapeutic effects on middle- and late-stage lung adenocarcinoma in clinical application. It was reported that Bushen Chinese medicine suppressed the onset of pre-metastatic niches in a murine model of spontaneous lung metastasis. However, the mechanisms of BSF on human lung adenocarcinoma remain unknown. METHODS: Cell proliferation was determined by CCK8 and colony formation. Cell apoptosis and cell cycle were detected by flow cytometry. Cancer stem cells properties were examined by spheroid body formation. The migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. The mRNA expressions were determined by qRT-PCR. Western blotting analysis showed the protein levels. RESULTS: BSF was shown to inhibit the proliferation of A549 cells in time- and concentration-dependent manners. Colony formation assays also indicated the antiproliferative effect of BSF against A549 cells. Cellular mechanistic studies demonstrated that BSF arrested the cell cycle in G2/M phase and induced apoptosis. Importantly, BSF could inhibit the epithelial-mesenchymal transition(EMT) of A549 cells through PI3K/AKT/NF-κB pathway. CONCLUSIONS: BSF effectively inhibited tumour growth, suggesting that it is a promising anticancer treatment for further clinical development.

Identification of an early diagnostic biomarker of lung adenocarcinoma based on co-expression similarity and construction of a diagnostic model.

BACKGROUND: The purpose of this study was to achieve early and accurate diagnosis of lung cancer and long-term monitoring of the therapeutic response. METHODS: We downloaded GSE20189 from GEO database as analysis data. We also downloaded human lung adenocarcinoma RNA-seq transcriptome expression data from the TCGA database as validation data. Finally, the expression of all of the genes underwent z test normalization. We used ANOVA to identify differentially expressed genes specific to each stage, as well as the intersection between them. Two methods, correlation analysis and co-expression network analysis, were used to compare the expression patterns and topological properties of each stage. Using the functional quantification algorithm, we evaluated the functional level of each significantly enriched biological function under different stages. A machine-learning algorithm was used to screen out significant functions as features and to establish an early diagnosis model. Finally, survival analysis was used to verify the correlation between the outcome and the biomarkers that we found. RESULTS: We screened 12 significant biomarkers that could distinguish lung cancer patients with diverse risks. Patients carrying variations in these 12 genes also presented a poor outcome in terms of survival status compared with patients without variations. CONCLUSIONS: We propose a new molecular-based noninvasive detection method. According to the expression of the stage-specific gene set in the peripheral blood of patients with lung cancer, the difference in the functional level is quantified to realize the early diagnosis and prediction of lung cancer.

Greenhouse gas emissions reduction in different economic sectors: Mitigation measures, health co-benefits, knowledge gaps, and policy implications.

To date, greenhouse gas (GHG) emissions, mitigation strategies and the accompanying health co-benefits in different economic sectors have not been fully investigated. The purpose of this paper is to review comprehensively the evidence on GHG mitigation measures and the related health co-benefits, identify knowledge gaps, and provide recommendations to promote further development and implementation of climate change response policies. Evidence on GHG emissions, abatement measures and related health co-benefits has been observed at regional, national and global levels, involving both low- and high-income societies. GHG mitigation actions have mainly been taken in five sectors: energy generation, transport, food and agriculture, household and industry, consistent with the main sources of GHG emissions. GHGs and air pollutants to a large extent stem from the same sources and are inseparable in terms of their atmospheric evolution and effects on ecosystem; thus, GHG reductions are usually, although not always, estimated to have cost effective co-benefits for public health. Some integrated mitigation strategies involving multiple sectors, which tend to create greater health benefits. The pros and cons of different mitigation measures, issues with existing knowledge, priorities for research, and potential policy implications were also discussed. Findings from this study can play a role not only in motivating large GHG emitters to make decisive changes in GHG emissions, but also in facilitating cooperation at international, national and regional levels, to promote GHG mitigation policies that protect public health from climate change and air pollution simultaneously.

Alkannin Inhibited Hepatic Inflammation in Diabetic Db/Db Mice.

BACKGROUND/AIMS: The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms. METHODS: An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA. The levels of the ROCK/NF-κB pathway were determined by Western blotting. RESULTS: The contents of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α were inhibited by ALK, metformin or fasudil in diabetic db/db mice. Further, Western blotting analysis showed that the expression of Rho, ROCK1, ROCK2, p-NF-κBp65, and p-IκBα was significantly reversed by ALK treatment. In human hepatic HepG2 cells, the hepatoprotective effects of ALK were further characterized. With response to palmitic acid-challenge, increased amounts of insulin, ALT, AST, TG, and TC were observed, whereas ALK pretreatment significantly inhibited their leakage in HepG2 cells without appreciable cytotoxic effects. The inflammation condition was recovered with ALK treatment as shown by changes of IL-1ß, IL-6 and TNF-α. Further, Western blotting analysis also suggested that ALK improves hepatic inflammation in a Rho-kinase pathway. CONCLUSION: The present study successfully investigated the role of Rho-kinase signalling in diabetic liver injury. ALK exhibited hepatoprotective effects in diabetic db/db mice, and it might act through improving hepatic inflammation through the Rho-kinase pathway.

Public health co-benefits of greenhouse gas emissions reduction: A systematic review.

BACKGROUND AND OBJECTIVES: Public health co-benefits from curbing climate change can make greenhouse gas (GHG) mitigation strategies more attractive and increase their implementation. The purpose of this systematic review is to summarize the evidence of these health co-benefits to improve our understanding of the mitigation measures involved, potential mechanisms, and relevant uncertainties. METHODS: A comprehensive search for peer-reviewed studies published in English was conducted using the primary electronic databases. Reference lists from these articles were reviewed and manual searches were performed to supplement relevant studies. The identified records were screened based on inclusion criteria. We extracted data from the final retrieved papers using a pre-designed data extraction form and a quality assessment was conducted. The studies were heterogeneities, so meta-analysis was not possible and instead evidence was synthesized using narrative summaries. RESULTS: Thirty-six studies were identified. We identified GHG mitigation strategies in five domains - energy generation, transportation, food and agriculture, households, and industry and economy - which usually, although not always, bring co-benefits for public health. These health gains are likely to be multiplied by comprehensive measures that include more than one sectors. CONCLUSIONS: GHG mitigation strategies can bring about substantial and possibly cost-effective public health co-benefits. These findings are highly relevant to policy makers and other stakeholders since they point to the compounding value of taking concerted action against climate change and air pollution.

Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer.

Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have differential expression in drug resistance of lung cancer, in which 10 lncRNAs were down regulated and 24 up regulated; 49 mRNAs were down regulated and 54 up regulated. LncRNAs-mRNAs expression network analysis revealed a role for lncRNAs in modulating cancer-related pathways. We also found that two pair lncRNAs and their subnetworks were highly related to drug resistance. NR_028502.1/NR_028505.1 were found differentially co-expressed with nine mRNAs, and highly correlated with better clinical outcome. NR_030725.1/NR_030726.1 co-expressed with eleven mRNAs, and were associated with poor survival in patients with lung cancer. Our work comprehensively identified expression signature of resistance-associated lncRNAs and their inter-regulated mRNAs in lung cancer.

Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform.

Based on our hospital database, the incidence of lung cancer diagnoses was similar in obstructive sleep apnea Syndrome (OSAS) and hospital general population; among individual with a diagnosis of lung cancer, the presence of OSAS was associated with an increased risk for mortality. In the gene expression and network-level information, we revealed significant alterations of molecules related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly available datasets to validate that the late-stage lung adenocarcinoma patients showed higher expression HK2 and GBE1 than early-stage ones. In terms of prognostic features, a survival analysis revealed that the high GBE1 and HK2 expression group exhibited poorer survival in lung adenocarcinoma patients. By analyzing and integrating multiple datasets, we identify molecular convergence between hypoxia and lung cancer that reflects their clinical profiles and reveals molecular pathways involved in hypoxic-induced lung cancer progression. In conclusion, we show that OSAS severity appears to increase the risk of lung cancer mortality.

Research on the functions of developing telemedicine service and establishing regional medical conjoined system.

This article introduces the technical requirements, standards, operation models, the domestic development status and problems of developing telemedicine technology, the necessity of establishing regional medical system, and the conception of cloud model, respectively. Based on the analysis of cardiovascular treatment cases in our hospital, this article suggests that developing telemedicine service and establishing regional medical conjoint system is the necessary direction of the domestic medical development. As with all kinds of difficulties, one can learn from the success cases and formulate practical and feasible measures according to the practical reality of different areas in China.