Prognostic model and ceRNA network of m7G- and radiosensitivity-related genes in hepatocellular carcinoma.

Background: Radiotherapy is an effective treatment for hepatocellular carcinoma (HCC). Recent studies indicated that N7-methylguanosine (m7G)-associated genes are involved in radioresistance and prognosis of HCC. However, the prognostic value and underlying mechanism of m7G-and radiosensitivity-associated genes are still lacking. Methods: The related statistics of HCC were downloaded from The Cancer Genome Atlas (TCGA). M7G- and radiosensitivity-associated genes were screened and evaluated using correlation, differential, univariate, and multivariate analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a prognostic model. Prognostic efficacy, functional analysis, immune cell infiltration,and drug sensitivity of the prognostic model were assessed. The ceRNA network was predicted and evaluated through the StarBase database, correlation analysis, expression analysis, and survival analysis. Result: METTL1, EIF3D, NCBP2, and WDR4 participated in prognosis model construction. The favorable prediction efficiency has been verified in both the training and verification sets. Different risk groups have differences in prognosis outcome, function analysis, immune cell infiltration, and drug sensitivity. NCBP2 can be used to predict the prognosis and has excellent potential in immunotherapy. A prognostic ceRNA network based on the NCBP2/miR-122-5p axis was established. Conclusion: The prognosis model of m7G- and radiosensitivity-related genes is constructed, and widely used in clinical prognosis, immunotherapy, and drug therapy. NCBP2, as a hub gene, may be a prognostic biomarker for HCC and is related to immunotherapy. Establishing the NCBP2/miR-122-5p axis helps study the mechanism of ceRNA and provides new ideas for finding a new candidate biomarker.

CircCRIM1 Ameliorates Endothelial Cell Angiogenesis in Aging through the miR-455-3p/Twist1/VEGFR2 Signaling Axis.

Background: Aging leads to vascular endothelial cell senescence. Decreased expression of VEGFA and VEGFR2 plays a crucial role in impairing angiogenesis in senescent endothelial cells. Noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), regulate endothelial cell proliferation, differentiation, apoptosis, and migration and participate in the occurrence and development of vascular diseases. However, the mechanism of noncoding RNAs in age-related vascular endothelial dysfunction remains unclear. Here, we aimed to identify the circRNA that is associated with VEGF/VEGFR2 signaling pathway activation in angiogenesis. Methods: Immunoblotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in vitro and in vivo experiments, luciferase assays, and chromatin immunoprecipitation followed by qRT-PCR (ChIP-qPCR) assays were performed to clarify the roles played by circCRIM1 in mouse aortic endothelial cell (MAEC) angiogenesis. Results: CircCRIM1 expression was downregulated in both an aging mouse model of lower limb ischemia in vivo and aging MAECs in vitro. Overexpressing circCRIM1 mediated through a plasmid or adeno-associated virus (AAV) reversed the downregulation of angiogenesis-related phenotype acquisition during aging. MiR-455-3p was confirmed to be a potential target of circCRIM1 through luciferase assays followed by RNA fluorescence in situ hybridization (FISH), which revealed the colocalization of circCRIM1 and miR-455-3p. CircCRIM1 was found to be a competitive endogenous RNA that sponged miR-455-3p and regulated angiogenesis-related phenotypes in MAECs. Furthermore, Twist1 was found to be downstream of miR-455-3p. A ChIP-qPCR assay showed that Twist1 promoted VEGFR2 expression by binding to the promoter region, playing a vital role in angiogenesis. Conclusions: Decreased expression of circCRIM1 impaired angiogenesis in aging via the miR-455-3p/Twist1/VEGFR2 axis. Our findings suggest that overexpression of circCRIM1 may be an effective therapeutic strategy for promoting ischemic lower limb blood flow recovery.

Circular RNA circGSE1 promotes angiogenesis in ageing mice by targeting the miR-323-5p/NRP1 axis.

Age is an important factor in many cardiovascular diseases, in which endothelial cells (ECs) play an important role. Circular RNAs (circRNAs) have been reported in many cardiovascular diseases, but their role in ageing EC-related angiogenesis is unclear. We aimed to identify a functional circRNA that regulates angiogenesis during ageing and explore its specific mechanism. In this study, we searched for differentially expressed circRNAs in old endothelial cells (OECs) and young endothelial cells (YECs) by circRNA sequencing and found that circGSE1 was significantly downregulated in OECs. Our study showed that circGSE1 could promote the proliferation, migration and tube formation of OECs in vitro. In a mouse model of femoral artery ligation and ischemia, circGSE1 promoted blood flow recovery and angiogenesis in the ischemic limbs of ageing mice. Mechanistically, we found that overexpressing circGSE1 reduced miR-323-5p expression, increased neuropilin-1 (NRP1) expression, and promoted proliferation, migration, and tube formation in OECs, while knocking down circGSE1 increased miR-323-5p expression, reduced NRP1 expression, and inhibited proliferation, migration, and tube formation in YECs. During EC ageing, circGSE1 may act through the miR-323-5p/NRP1 axis and promote endothelial angiogenesis in mice. Finally, the circGSE1/miR-323-5p/NRP1 axis could serve as a potential and promising therapeutic target for angiogenesis during ageing.

Rapid diagnosis of disseminated Mycobacterium mucogenicum infection in formalin-fixed, paraffin-embedded specimen using next-generation sequencing: A case report.

BACKGROUND: Mycobacterium mucogenicum (M. mucogenicum) belongs to the group of rapidly growing Nontuberculous mycobacteria. This microorganism is associated with a wide spectrum of infectious diseases. Due to a low detection rate or the time required for conventional culture methodology, a rapid and broad-spectrum method is necessary to identify rare pathogens. CASE SUMMARY: A 12-year-old immunocompetent girl presented with painful masses for five months. The first mass was found in the right upper quadrant of the abdomen, and was about 1 cm × 1.5 cm in size, tough but pliable in texture, with an irregular margin and tenderness. An abscess gradually formed and ulcerated with suppuration of the mass. Three new masses appeared on the back one by one. Chest computed tomography showed patchy and streaky cloudy opacities in both lungs. Needle aspiration of the abscess was performed, but the smear and conventional culture were negative, and the pathological examination showed no pathogens. We then performed next-generation sequencing using a formalin-fixed, paraffin-embedded specimen to identify the pathogen. A significantly high abundance of M. mucogenicum was detected. The patient's abscesses gradually decreased in size, while inflammation in both lungs improved following 12-wk of treatment. No recurrence was observed four months after the end of the one-year treatment period. CONCLUSION: Next-generation sequencing is a promising tool for the rapid and accurate diagnosis of rare pathogens, even when using a formalin-fixed, paraffin-embedded specimen.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

miR-1-3p suppresses the epithelial-mesenchymal transition property in renal cell cancer by downregulating Fibronectin 1.

PURPOSE: Renal cell cancer (RCC) is one of the primary causes of malignancy deaths all over the world. The most important cause of RCC-related mortality is metastasis. Epithelial-mesenchymal transition (EMT) plays an important role in metastasis of malignant tumors including RCC. miR-1-3p is confirmed to be decreased in many types of cancer. Nevertheless, the function of miR-1-3p in RCC metastasis and EMT process was still unclear. MATERIALS AND METHODS: In this study, information from clinical investigation, in vitro study, and in vivo study discovered miR-1-3p expression character and its status in RCC. The character of miR-1-3p in invasive and metastatic properties in vitro and in vivo was also inspected in RCC cells and xenograft tumor model, and expression levels of EMT markers were evaluated in RCC cells and tissues. RESULTS: miR-1-3p was proved to be decreased in RCC cell lines and tissues compared with normal renal cells and tissues. miR-1-3p expression level in RCC tissues was closely related with capsulation, lymph node metastasis, and vascular invasion. miR-1-3p was found to be able to block the EMT process in A498 and CAKI-1 RCC cells and tumors. Luciferase reporter assay and expression level rescue assays were employed to reveal that miR-1-3p inhibited the invasion and migration property of RCC cells by directly targeting Fibronectin 1. Upregulation of Fibronectin 1 partially reversed the suppressive effect of miR-1-3p on EMT process. CONCLUSION: In brief, this study has verified that miR-1-3p blocked the EMT process of RCC cells by reducing Fibronectin 1 expression. miR-1-3p/Fibronectin 1 axis may be considered as a new target for drug development of RCC.

[Analysis of clinical characteristic of 158 inpatients with dengue fever in Guangzhou area during the 2014 epidemic].

OBJECTIVE: To investigate the clinical characteristics of the inpatients suffering from dengue fever in order to provide references for better diagnosis and treatment. METHODS: The clinical data of 158 dengue fever patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from July 23rd to October 31st, 2014 during the 2014 epidemic in Guangzhou area were retrospectively analyzed, including general clinical manifestations, conventional examinations, pathogenesis, and prognosis. RESULTS: The mean age of the 158 patients was ( 56 ± 20 ) years, with half of them over 60 years old (79 cases). Among them, 94 (59.49%) were male. (1) The common manifestations included fever (100%), headache (70.89%), myalgia/bone soreness (62.03%), and skin rash (54.43%). Bleeding and plasma leakage were found in 25.95% and 14.56% of the patients respectively. (2) Laboratory examination: leucopenia (75.32%) and thrombocytopenia (77.85%) were found, and alanine aminotransferase (ALT) and aspartate aminotransferase ( AST ) were elevated in 57.59% and 77.85% of the patients respectively. However, elevation of blood hematocrit was rare (1.27% ). (3) It was found that in the acute phase (0 - 5 days of the onset), serum dengue virus antibody IgM (DF-IgM) was positive in 63.54% of the patients (61/96), and 92.62% (113/122) of patients were dengue virus RNA ( DENA-RNA ) positive. (4) The rate of comorbidity in this study was 55.06% ( 87/158 ), including hypertension (27.22%) and type 2 diabetes (15.82%), which were the two most common co-morbidities. (5) All the patients were given supportive therapy to prevent complications. They were also isolated for more than 5 days after onset, and at least for 24 hours after subsidence of fever in addition. (6) The criteria for the diagnosis of severe dengue were fulfilled in 18 patients (11.39%). One patient died of massive hemorrhage from gastro-intestinal tract, and 1 patient voluntarily left hospital with untreated multiple organ dysfunction syndrome (MODS). Another 2 patients of dengue fever died from primary cardio-cerebrovascular disease, and the remaining 154 patients (97.47%) fully recovered with supportive therapy and complication prevention measures. CONCLUSIONS: The clinical manifestations of inpatients with dengue fever in this study were typical, and they manifested a higher incidence of severe illness. DENA-RNA could be a sensitive indicator for early pathogenic diagnosis. With symptomatic and supportive therapy, most patients had a good outcome. However, early diagnosis and clinical interventions of severe dengue still need further studies.

A case report of acute myocardial infarction concomitant with Standford type B aortic dissection.

BACKGROUND: Acute myocardial infarction (AMI) concomitant with aortic dissection (AD) is rare but a devastating situation if misdiagnosed as simply AMI, followed by anticoagulant or thrombolytic therapy. In such cases, Standford type B AD was extremely infrequent. OBJECTIVES: To present a case with apparent concordance with the patient's history, symptoms, cardiac enzymes that lead to diagnostic error. CASE REPORT: An 85-year-old man with chronic hypertension and coronary atherosclerotic heart disease presented in our emergency department with squeezing retrosternal chest pain and dyspnea. Elevated cardiac enzymes and electrocardiography result suggested acute non-ST-segment elevation myocardial infarction. Emergency coronary angiography demonstrated a 50-90% diffuse stenosis of the proximal and mid right coronary artery also confirmed the diagnosis. Stents were deployed thereafter. However, the patient was found to be concomitant with Standford type B AD by computed tomography angiography due to unrelieved chest pain and new onset of abdominal pain after the operation. The patient refused to have endovascular operation and died of hemorrhagic shock one week later. CONCLUSIONS: AD may cause AMI due to some indirect mechanisms, and it is of utmost importance to search for the existence of AD before reperfusion therapy in AMI patients. Aortic dissection detection risk score, transthoracic echocardiography and D-dimer help early identification of AD.

[Development of the role of micrornas regulation in osteogenesis].

OBJECTIVE: To review the progress, controversy and trend in the regulation and mechanism of the microRNAs (miRNAs) during the osteogenesis. METHODS: Recent literature concerning regulation and mechanism of the miRNAs during the osteogenesis was extensively reviewed, summarized and analyzed. RESULTS: Recently miRNAs was a hot topic for osteogenesis. More and more materials showed its important role in ossification, but its definite mechanism was not clear. CONCLUSION: Osteogenesis can be strengthened by miRNAs technology, which has a bright future and may also provide the molecular mechanism. The study on miRNAs of osteogenesis can provide a model to analyze and compare the osteogenetic effects of novel drugs.