MicroRNA expression profile of human umbilical vein endothelial cells in response to coxsackievirus A10 infection reveals a potential role of miR-143-3p in maintaining the integrity of the blood-brain barrier.

Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus-host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood-brain barrier (BBB) integrity.

Retrospectively analyze and compare the efficacy and safety of thoracoscopic-assisted Nuss repair of pectus excavatum under intubation anesthesia and non-intubation anesthesia.

Background: Thoracoscopic-assisted Nuss repair is a commonly used method for treating pectus excavatum, which has always been performed under tracheal intubation and general anesthesia. However, general anesthesia with endotracheal intubation can produce intubation and anesthetic drug related complications. In non-intubation anesthesia, laryngeal mask is used instead of tracheal intubation without muscle relaxants and small doses of sedative and analgesic drugs. Therefore, non-intubation anesthesia can reduce complications and speed up postoperative recovery. This study retrospectively analyzed the clinical impact of these two anesthesia methods on thoracoscopic-assisted Nuss repair for the treatment of pectus excavatum. Methods: A total of 115 pectus excavatum patients who underwent thoracoscopic-assisted Nuss procedure repair in the Department of Thoracic Surgery of Yunnan First People's Hospital from January 2017 to January 2022 were included. All subjects in this study underwent thoracoscopic assisted Nuss repair in the same thoracic surgical team. According to different anesthesia methods, they were divided into non-intubation anesthesia group (n=62) and intubation anesthesia group (n=53). The intubation time, intraoperative mean heart rate, postoperative complications, postoperative first oral food intake, water intake, ambulation, defecation time, postoperative blood drawing results, postoperative hospital stay and total hospitalization cost were compared between the two groups. Results: There were no significant differences in clinical characteristics and preoperative examination indexes between the two groups, which were comparable. Compared with the intubation anesthesia group, the non-intubation anesthesia group had less anesthesia intubation time, lower intraoperative mean heart rate, less postoperative complications, such as pneumothorax, pleural effusion, and lung infection. In the non-intubation anesthesia group, the first time to eat, drink, get out of bed, and defecate were all earlier. Routine blood results 24 h after surgery indicated that the non-intubation anesthesia group had lower white blood cell, neutrophil and lymphocyte, an earlier postoperative discharge time, and lower total hospitalization expenses. Conclusions: Non-intubation anesthesia in thoracoscopic-assisted Nuss procedure for the repair of pectus excavatum can make the postoperative recovery of patients faster and has better safety and efficacy.

SV-VATS exhibits dual intraoperative and postoperative advantages.

BACKGROUND: The merits of spontaneous ventilation video-assisted thoracic surgery (SV-VATS) are still controversial. Our team retrospectively evaluated the intraoperative and postoperative advantages of this surgical approach, comparing with mechanical ventilation video-assisted thoracic surgery (MV-VATS). METHODS: We did a single center retrospective study at the First Affiliated Hospital of Yunnan Province. 244 patients were eventually assigned to the SV-group and MV-group, and their intraoperative indicators and thoracic surgery postoperative data were included in the comparison. RESULTS: The SV-group exhibited markedly less intraoperative bleeding and postoperative thoracic drainage, and the bleeding volume was correlated with the volume and duration of drainage. Further analysis showed that, patients undergoing SV-VATS had less activation of white blood cells and neutrophils after surgery, but they also had lower serum albumin concentrations. Risks of short-term postoperative complications, including inflammatory reactions, malignant arrhythmias, constipation, and moderate or more pleural effusions, were also significantly reduced in the SV-group. Additionally, hospitalization cost was lower in the SV-group than that in the MV-group. CONCLUSIONS: SV-VATS is suitable for various types of thoracic surgery, and effectively reduce intraoperative bleeding and postoperative thoracic drainage. With less postoperative inflammatory response, it reduces the risk of short-term postoperative complications. It is also able to help to reduce the financial burden of patients.

Characteristics of BRCA1/2 pathogenic germline mutations in chinese NSCLC patients and a comparison with HBOC.

BACKGROUND AND PURPOSES: The pathogenic BRCA1/2 germline mutations contributed to Hereditary Breast and Ovarian Cancer (HBOC) susceptibility. The features of BRCA1/2 germline mutations in non-small cell lung cancer (NSCLC) have not been systematically studied. Here we performed the first study investigating the characteristics of pathogenic BRCA1/2 germline mutations in Chinese NSCLC patients and compared them with those from Chinese HBOC. METHODS: Information on BRCA1/2 germline mutations from 9010 Chinese NSCLC patients were collected from available studies and analyzed, and compared with the BRCA1/2 germline mutations from Chinese HBOC BRCA1/2 database (LOVD database, 20,523 patients). RESULTS: 19 (20 carriers, 0.22 %) pathogenic BRCA1 and 60 (66 carriers, 0.73 %) pathogenic BRCA2 germline mutations from NSCLC were identified. The carrier frequency of BRCA1/2 in Chinese NSCLC patients (86/9010 = 0.95 %) was significantly lower than that in Chinese breast and ovary cancer patients (1481/20,523 = 7.2 %) (P < 0.001). We found that frameshift and nonsense mutations were the predominant types of BRCA1/2 mutation in NSCLC, with no obvious hot spot mutations. No significant difference in the ratio of frameshift and nonsense mutations was found between BRCA1 and BRCA2 in NSCLC. 5 out of 19 mutations in BRCA1 and 23 out of 60 mutations in BRCA2 were novel mutations found in NSCLC that have never been reported in Chinese HBOC. A trend of higher percentage of BRCA1 nonsense mutations in the carriers was revealed in NSCLC compared with HBOC, while no such difference was found in BRCA2 in all types of mutations. CONCLUSIONS: BRCA1/2 germline mutations from NSCLC exhibited distinct characteristics compared with those from HBOC in Chinese population, including lower carrier frequency than HBOC, higher ratio of nonsense mutations and carriers than HBOC, and novel BRCA1/2 germline mutations never found in HBOC.

The performance of the SHOX2/PTGER4 methylation assay is influenced by cancer stage, age, type and differentiation.

Aim: To investigate the clinicopathological factors affecting the mSHOX2/mPTGER4 assay performance and its application in lung cancer detection in Chinese population. Materials & methods: A total of 455 subjects were recruited in this case-control study (302 untreated lung cancer patients, 153 normal subjects). Blood samples were collected before therapy and the mSHOX2/mPTGER4 level was measured with Epi proLung assay. Results: The mSHOX2/mPTGER4 sensitivity was 75.6% at 84.8% specificity. Both markers showed stage-dependent sensitivity. mSHOX2 was more sensitive to small-cell lung cancer and mPTGER4 was more sensitive to poorly differentiated lung cancer. Sensitivity increased with age but was not affected by sex. The mPRGER4/mSHOX2 sensitivity was significantly higher than that of protein markers. Conclusion: The mSHOX2/mPTGER4 assay showed some values with more limitations in lung cancer early detection.

NUSAP1 knockdown inhibits cell growth and metastasis of non-small-cell lung cancer through regulating BTG2/PI3K/Akt signaling.

Non-small-cell lung cancer (NSCLC) is the most common malignancy along with high mortality rate worldwide. Recently, nucleolar and spindle-associated protein 1 (NUSAP1) has been reported to be involved in the malignant progression of several cancers. However, in NSCLC, the biological function of NUSAP1 and its molecular mechanism have not been reported. Here, our findings indicated that the NUSAP1 messenger RNA expression level was remarkably upregulated in NSCLC tissues compared with that of adjacent normal tissues. We also found that NUSAP1 gene expression was notably upregulated in NSCLC cell lines (A549, 95-D, H358, and H1299) compared with that of normal human bronchial epithelial cell line (16HBE). Subsequently, the biological function of NUSAP1 was investigated in A549 and H358 cells transfected with NUSAP1 small interfering RNA (siRNA), respectively. Results showed that NUSAP1 knockdown inhibited NSCLC cell proliferation, and promoted cell apoptosis. Furthermore, the number of cell migration and invasion was significantly suppressed by NUSAP1 knockdown. In addition, our results indicated that NUSAP1 knockdown increased the gene expression of B-cell translocation gene 2 (BTG2), but decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated serine/threonine kinase (p-AKT). BTG2 siRNA partly abrogates the effect of NUSAP1 knockdown on BTG2 gene expression. Fumonisin B1 (FB1), a AKT activator, reversed the effect of NUSAP1 knockdown on the biological function in NSCLC. Taken together, NUSAP1 knockdown promotes NSCLC cell apoptosis, and inhibits cell proliferation, cell migration, and invasion, which is associated with regulating BTG2/PI3K/Akt signal pathway. Our findings suggest that NUSAP1 is a promising molecular target for NSCLC treatment.