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Background Immune-related genes (IRGs) are highly relevant to the progression and prognosis of esophageal squamous cell carcinoma (ESCC). A prognostic signature could be reliable in stratifying ESCC patients according to the risk score, which may help manage systematic treatments. In this study, a systematic and reliable immune signature was developed to estimate the prognostic stratification in ESCC. Methods Ribonucleic acid (RNA) expression data of 79 ESCC samples from the Cancer Genome Atlas (TCGA) database and 269 normal esophageal mucosal samples from the Genotype-Tissue Expression (GTEx) project database were downloaded from the University of California, Santa Cruz (UCSC) website to form a TCGA-GTEx dataset. First, we screened differentially expressed genes (DEGs) and then filtered IRGs based on the Immunology Database and Analysis Portal (ImmPort) database to obtain immune-related DEGs (IRDEGs). Next, a novel prognostic signature based on IRDEGs was developed using multivariable Cox analysis. Immune infiltration status was evaluated via single-sample gene set enrichment analysis (ssGSEA). ESCC tissues were grouped into three clusters in terms of immune infiltration (Immunity-L, Immunity-M, and Immunity-H) by applying an unsupervised hierarchical clustering algorithm. Finally, the samples were divided into high- and low-risk groups using the median of the risk score scores for GSEA pathway enrichment analysis in the three clusters. Results The prognostic signature based on IRDEGs (FCER1G, ISG20, and EGFR) performed moderately in prognostic predictions, with a concordance index (C-index) value of 0.73 [95% (confidence interval) CI: 0.63–0.84, P=2.02E-05] and an area under the curve (AUC) value of 0.817. The xenobiotic metabolism pathway was significantly enriched and up-regulated both in the high-risk group of the immunity-M and immunity-H clusters. Conclusions The novel immune-related prognostic signature we constructed has a good prognostic, predictive ability and can be used as an independent prognostic indicator. Our study provides clinicians with a quantitative tool to predict the probability of individual survival time and helps clinicians select targets for immunotherapies and individualized treatment strategies for ESCC patients.

Background The therapeutic response and prognosis of patients with non-small cell lung carcinoma (NSCLC) are widely related to immunity. To improve the prognosis of patients and provide reliable information to guide appropriate personalized treatment strategies, it is necessary to identify reliable prognostic or predictive indicators closely related to tumor phenotype and immune traits in NSCLC. Methods Based on The Cancer Genome Atlas (TCGA)-NSCLC mRNA expression profile data, a novel approach combining differential gene expression analysis, single-sample gene set enrichment analysis (ssGSEA), and weighted gene co-expression network analysis (WGCNA) was used to screen hub genes. Subsequently, the regulator of hemoglobinization and erythroid cell expansion (RHEX) was identified as a key gene using the log-rank test and confirmed in the ArrayExpress database. The relationship between RHEX and clinicopathological parameters was analyzed using the Wilcoxon rank-sum test. More importantly, through gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithms, and with reference to the Tumor IMmune Estimation Resource (TIMER) database, we explored the relevant pathways of RHEX and its relationship with tumor-infiltrating immune cells (TICs). Finally, we depicted the association between RHEX and immunomodulators in the TCGA and a web portal TISIDB. Results The RHEX mRNA expression levels in tumor tissues were lower than those in normal tissues and declined with the progression of NSCLC. Meanwhile, RHEX overexpression was associated with high immune infiltration levels and a favorable clinical prognosis. RHEX may participate in tumor microenvironment (TME) regulation through multiple tumor-immune related pathways, especially the JAK-STAT signaling pathway. Furthermore, RHEX expression affected the infiltrating abundance of multiple TICs and positively correlated with most of the immunomodulators in NSCLC. Conclusions Our study is the first to propose that RHEX is an immune-related gene with prognostic value in NSCLC and reveals the underlying mechanism between RHEX and tumor-immune system interactions. These results ultimately provide guidance for prognosis and immunotherapy for NSCLC patients.

Purpose MiR-654-3p plays important roles in many types of malignant tumours. However, the biological function of miR-654-3p in non-small cell lung cancer (NSCLC) remains unknown. In this study, the role of miR-654-3p in NSCLC was investigated. Methods qRT-PCR was used to evaluate the level of miR-654-3p in NSCLC tissues and cell lines, while Cell Counting Kit-8, Annexin V/propidium iodide dual staining or TUNEL staining were used to investigate proliferation and apoptosis of NSCLC cells. Luciferase assays and Western blotting were performed to validate potential targets of miR-654-3p. Results MiR-654-3p levels were significantly decreased in NSCLC patients and cell lines and were significantly correlated with the tumour size and tumour node metastasis stage of NSCLC patients. In A549 cells, miR-654-3p overexpression significantly increased apoptosis and inhibited growth both in vivo and in vitro, while downregulation of miR-654-3p had the opposite effects. In addition, polo-like kinase 4 (PLK4) was shown to be a target gene of miR-654-3p that is negatively regulated by miR-654-3p in A549 cells. Furthermore, PLK4 was observed to be highly expressed in NSCLC tissues and cells, and PLK4 overexpression abolished the inhibitory effects of miR-654-3p overexpression on NSCLC cell proliferation. Finally, the animal experiment results further demonstrated that miR-654-3p inhibits tumour growth and regulates PLK4 expression. Conclusion Our results demonstrate that miR-654-3p functions as a growth-suppressing miRNA by targeting PLK4 in NSCLC.

PURPOSE OF REVIEW An increasing number of patients are turning to cannabis and cannabinoids for management of their palliative and nonpalliative cancer pain and other cancer-related symptoms. Canadians have a legal framework for access to medical cannabis, which provides a unique perspective in a setting lacking robust clinical evidence. This review seeks to delineate the role of cannabis and cannabinoids in cancer pain management and offers insight into the Canadian practice. RECENT FINDINGS A cohort study using nabiximols on advanced cancer pain in patients already optimized on opioids, over 3 weeks, demonstrated improved average pain score. A large observational study of cancer patients using cannabis over 6 months demonstrated a decreased number of patients with severe pain and decreased opioid use, whereas the number of patients reporting good quality of life increased. SUMMARY Good preclinical animal data and a large body of observational evidence point to the potential efficacy of cannabinoids for cancer pain management. However, there are relatively weak data pointing to clinical efficacy from clinical trial data to date. In Canada, the burgeoning cannabis industry has driven the population to embrace a medicine before clinical evidence. There remains a need for high-quality randomized controlled trials to properly assess the effectiveness and safety of medical cannabis, compared with placebo and standard treatments for cancer-related symptoms.

Accurate clinical staging is crucial to managing esophageal cancer. [Patients with esophageal cancer who underwent concurrent [Thirty-five patients (ranging from 44-83 years old with a median age of 63.5 years) were evaluated in our study. In treatment-naive patients (n=25), [[

Spontaneous ventilation video-assisted thoracic surgery (SV-VATS) is reported to have superior or equal efficacy on postoperative recovery to mechanical ventilation VATS (MV-VATS). However, perioperative safety of the SV-VATS blebectomy is not entirely demonstrated.We performed a noninferiority, randomized controlled trial (No. NCT03016858) for primary spontaneous pneumothorax patients aged 16 to 50 years undergoing a SV-VATS and the MV-VATS procedure. The trial was conducted at 10 centers in China from April 2017 to January 2019. The primary outcome was the comparison of intra- and postoperative complications between SV-VATS and MV-VATS procedures. Secondary outcomes included total analgesia dose, change of vital sign during surgery, procedural duration, recovery time, postoperative visual analog pain scores, and hospitalization length.In this study, 335 patients were included. There was no significant difference between the SV-VATS group and the MV-VATS group in the intra- and postoperative complication rates (17.90% vs 22.09%; relative risk, 0.81; 95% confidence interval, 0.52-1.26; P = .346). The SV-VATS group was associated with significantly decreased total dose of intraoperative opioid agents; that is, sufentanil (11.37 μg vs 20.92 μg; P .001) and remifentanil (269.78 μg vs 404.96 μg; P .001). The SV-VATS procedure was also associated with shorter extubation time (12.28 minutes vs 17.30 minutes; P .001), postanesthesia care unit recovery time (25.43 minutes vs 30.67 minutes; P = .02) and food intake time (346.07 minute vs 404.02 minutes; P = .002). Moreover, the SV-VATS procedure deceased the anesthesia cost compared with the MV-VATS ($297.81 vs $399.81; P .001).SV-VATS was shown to be noninferior to MV-VATS in term of complication rate and in selected patients undergoing blebectomy for primary spontaneous pneumothorax.

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

With increasingly stringent emissions limitation of greenhouse gas and atmospheric pollutants for ship, the direct injection of natural gas on the cylinder head with high-pressure injection is an effective method to make a high power output and decrease harmful gas emissions in marine natural gas dual fuel engines. However, the effects on mixing characteristics of high-pressure natural gas underexpanded jet have not been fully understood. Especially, the injection pressure is up to 30 MPa with large injection quantity and critical surrounding gas conditions for the low-speed two-stroke marine engine. Therefore, this research is focused on the flow and mixing process of the natural gas jet with high-pressure injection under the in-cylinder conditions of low-speed two-stroke marine engine. The gas jet penetration, the distribution of velocity and density, the equivalence ratio and air entrainment have been analyzed under different nozzle hole diameters by numerical simulation. The effects of surrounding gas conditions including pressure, temperature and swirl ratio on air entrainment and equivalence ratio distribution were studied in detail. From the numerical simulation, it is found that the mixing characteristics of natural gas jet can be improved under in-cylinder conditions of higher ambient temperature and swirl ratio, which is relevant to the low-speed two-stroke marine engine.

Purpose To observe the clinical application value of 68Ga-FAPI-04 PET/CT in the preoperative detection of lymph node metastasis and staging of esophageal cancer.Methods A prospective analysis of 29 surgical patients was performed. 68Ga-FAPI-04 PET/CT was performed within 1 week before the operation. All patients received enhanced CT during the same period. None of these patients had received preoperative treatment before the operation. The value of 68Ga-FAPI-04 PET/CT and enhanced CT in the diagnosis of lymph node metastasis and preoperative staging of esophageal cancer was compared according to postoperative pathology.Results Both 68Ga-FAPI-04 PET/CT and CT detected the primary tumor (29/29 cases). 637 lymph nodes were surgically removed, of which 37 lymph nodes were metastasized. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for lymph node metastasis detection were 71.1%, 99.4%, 97.8%, 90.0%, and 98.2%; The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CT for lymph node metastasis detection were 36.8%, 98.9%, 95.3%, 70.0%, and 96.1%, respectively.Conclusion 68Ga-FAPI-04 PET/CT is better than enhanced CT in diagnosing lymph node metastasis and determining lymph node staging in esophageal cancer.

Background The SVV tests the ability of a person to perceive the gravitational vertical. A tilt in SVV indicates vestibular imbalance in the roll plane, and thus injuries to the utricle or its connecting nerves. A validated bedside method (et, al., 2009, 72(19):1689–1692, Neurol, Zwergal) is the bucket method, in which the subject estimates the true vertical by attempting to properly align a straight line visible on the bottom of a bucket that is rotated at random by the examiner. In our study, the subjects need to align the plumb line on the Visual Vertical iOS app to the vertical direction. Methods Measurements of the SVV were made in 22 healthy subjects (16 females and 6 males). Each subject conducted 10 iterations of bucket test and 10 iterations of iOS app test. The reliability and validity of the iOS app was analyzed by SPSS21. Results Cronbach’s α for the plumb line method was 0.976, and the iOS app was 0.978. Statistical comparison of SVV values measured by the iOS app and the bucket method showed no significant difference in distribution (Mann Whitney U test U = 0.944). Conclusion The Visual Vertical iOS app is an effective and accessible substitute to the plumb line for the measurement of the validated bucket test.

This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells. The results were further validated in LK2 cells that matrine regulated apoptosis gene expressions, which were reversed by CCL21 treatment. Furthermore, matrine enhances the effects of cisplatin, 5-fluorouracil, and paclitaxel in A549 cells, and the anticancer effects exhibit a dosage-dependent manner. In summary, matrine induced cell apoptosis and enhanced the effects of anticancer drugs in NSCLC cells; the mechanism might be associated with the CCR7 signal.

Diphenhydramine (DPH) is an over-the-counter antihistamine medication commonly used for symptom management in palliative care. Despite the ease of access and perceived safety of DPH, there is documented evidence of potential for abuse of this medication. We present a case of a 61-year-old man with metastatic carcinoma of the distal esophagus, who was initially admitted with a pain crisis but subsequently developed a severe DPH withdrawal syndrome consisting of hyperactive delirium, autonomic dysfunction, and increased muscle tone. With careful selection of the antipsychotic agent loxapine, additional symptom management medications and scheduled tapering the patient was able to be discharged home for end-of-life care. We highlight the challenges of recognizing and managing a withdrawal syndrome in patients with terminal illnesses at end of life.

With the development of minimally invasive thoracoscopic and anesthesia control techniques, intravenous anesthesia with spontaneous ventilation video-assisted thoracic surgery (SV-VATS) has been increasingly employed in management of pleural effusion, bullectomy for pneumothorax, mediastinal biopsy, thymectomy and thymomectomy, wedge lung resections, anatomical lung resections for radical treatment of lung cancer and even more complex surgical procedures including tracheal resection and sleeve lobectomy (1-7) This changes in surgical strategies have been applied in the believe that SV-VATS can avoid adverse effects of mechanical ventilation and the residual effects of muscle relaxants, can achieve a faster recovery of respiratory muscle function and lower operative morbidity (7,8).

Background: Spontaneous ventilation VATS (SV-VATS) is reported to be associated with faster recovery and fewer complications than mechanical ventilation video-assisted thoracic surgery (MV-VATS). This study aimed to evaluate the effect of SV-VATS for patients with spontaneous pneumothorax. Methods: We performed a randomized controlled trial at 10 medical centers by recruiting primary pneumothorax patients undergoing SV-VATS and MV-VATS. Participants were randomly assigned (1:1), to receive non-intubated spontaneous ventilation (SV-VATS) or intubated mechanical one lung ventilation (MV-VATS). The primary outcome was the intraoperative surgery/anesthesia related accident rate, which was assessed according to incedences of intraoperative hypoxia, conversion to open surgery, conversion to intubation and other intraoperative adverse events that could happen in both groups. Other study outcomes included changes of vital signs, total analgesic dose, recovery time, post-operative complication rates, cost-effectiveness evaluation, etc. Findings: The trial began on Apr 10, 2017, and ended on Jan 03, 2019. During this time, 355 patients were assessed. After evaluation and randomization, 325 eligible patients were assigned to receive an SV-VATS (n=162) or MV-VATS (n=163) procedure. In the intention-to-treat analysis, there was no difference between the intraoperative accident rate of the SV-VATS (1.23%) and MV-VATS (1.23%) group (P=0.995). The SV-VATS group was associated with significantly decreased total dosage of both sufentanil (11.37 μg vs 20.92 μg; p

In order to improve the detection efficiency of SQL injection attack, this paper proposes a detection method of SQL injection attack based on sequence alignment algorithm. Needleman-Wunsch and its improved algorithm are used to carry out sequence alignment and then find out the best alignment results in the global-scope. Experiments show that 100% of the SQL injection attacks tested are detected in the detection rate; the algorithm has the minimum response delay compared with other types of SQL injection attacks. The detection method proposed in this paper can improve the detection effect quickly and effectively, and reduce the complexity of time and space.

BACKGROUND Propofol and midazolam are widely used for the sedation of bronchoscopy. This systematic review and meta-analysis is conducted to compare the efficacy of propofol and midazolam for bronchoscopy. METHODS The databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases are systematically searched for collecting the randomized controlled trials (RCTs) regarding the efficacy of propofol and midazolam for bronchoscopy. RESULTS This meta-analysis has included 4 RCTs. Compared with midazolam intervention in patients undergoing bronchoscopy, propofol intervention is associated with remarkably reduced recovery time [standard mean difference (SMD) = -0.74; 95% confidence interval (95% CI) = -1.04 to -0.45; P

Primary spontaneous pneumothorax (PSP) has an estimated incidence ranging from 17–24/100,000 and 1–6/100,000 among males and females, respectively (1,2). It usually occurs in tall thin individuals between 10–30 years of age, especially smokers (3).

Background The efficacy of thoracic paravertebral block for thoracoscopic surgery remains controversial. We conduct a systematic review and meta-analysis to explore the impact of thoracic paravertebral block on thoracoscopic surgery. Methods We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2018 for randomized controlled trials (RCTs) assessing the effect of thoracic paravertebral block on thoracoscopic surgery. This meta-analysis is performed using the random-effect model. Results Six RCTs involving 300 patients are included in the meta-analysis. Overall, compared with control group for thoracoscopic surgery, thoracic paravertebral block results in significantly reduced pain scores within 6 hours (Std. MD = -2.15; 95% CI = -3.67 to -0.62; P = .006), postoperative anesthesia consumption during 48 hours (Std. MD = -1.81; 95% CI = -3.05 to -0.58; P = .004), and hospital stay (Std. MD = -1.19; 95% CI = -2.13 to -0.26; P = .01), but has no important impact on pain scores at 24 hours (Std. MD = -1.10; 95% CI = -2.77-0.57; P = .20), and 48 hours (Std. MD = -1.25; 95% CI = -2.86-0.36; P = .13). Conclusions Thoracic paravertebral block can substantially enhance pain management for thoracoscopic surgery.

The use of MRI in isolated pediatric nystagmus remains a gray area in clinical management. Many clinicians prefer to order an MRI to rule out intracranial pathology despite the lack of clinically significant findings in most cases. To assess the yield of MR imaging in isolated pediatric nystagmus and define a management algorithm to minimize avoidable MRI referrals and streamline MRI protocols. We reviewed the charts of 148 children who underwent neuro MRI for isolated nystagmus between January 2008 and September 2014. We noted nystagmus onset and clinical characteristics and compared them with the MRI features and visual electrophysiology results. We included 85 boys and 63 girls (total 148, average age at MRI 4.24 ± 4.19 years). Twenty-three (15.5%) children had abnormal intracranial findings on MRI including abnormal signal lesions (4.1%; n=6), Chiari I malformations (3.4%; n=5) and optic pathway glioma (2.0%; n=3). The time of onset of nystagmus was not associated with an abnormal MRI (P=0.2). Seventy children underwent visual electrophysiology testing but this test could not predict abnormality at MRI, either (P=0.12). Among children with isolated nystagmus, 15.5% had abnormalities on neuroimaging. Neither clinical characteristics of nystagmus nor the visual electrophysiology results allowed prediction of intracranial pathology. We were unable to formulate a management algorithm for the optimal sequence of investigations (MRI preceding visual electrophysiology or vice versa), but we discuss the use of gadolinium contrast agent and orbital sequences in isolated pediatric nystagmus.

Cartilage has a limited self-repair capability and the repair of large cartilage defects remains a challenge in clinic. This study aimed to investigate the effect of mesenchymal stem cells (MSCs) loaded three-dimensional bilayer collagen scaffold for cartilage repair. Cross-linked three-dimensional bilayer collagen scaffolds seeded with or without MSCs were implanted into large cartilage defects (4 mm in diameter; 3 mm in depth) in rabbit knees. The untreated cartilage defects served as control. The tissue response was evaluated at 6 and 12 weeks after implantation by general histology and semi-quantitative histological grading systems. In addition, the repaired tissues were evaluated by mechanical test at 12 weeks after implantation. The MSCs-loaded collagen scaffold group showed the most hyaline cartilage, highest histological scores and compressive modulus. Moreover, it showed a good integration with the subchondral bone and adjacent cartilage. The structure of the novel bilayer collagen scaffolds provided architectural support for the differentiation of MSCs and demonstrated successful induction of in vivo chondrogenesis. These findings suggested that MSCs-loaded bilayer collagen scaffold could be an appealing candidate to be used for cartilage regeneration.

Oncogenesis, development, invasion and metastasis of lung cancer are modulated by relative genes of lung cancer, and the expression, deletion or mutation of these genes are regulated by cell membrane signal transduction system and cell membrane ionic channels. The aim of this study is to explore the electrophysiological properties of human lung adenocarcinoma cell line A549 and cell proliferation affected by tetraethylammonium chloride (TEA), one potassium channel blocker, so as to know whether the voltage-gated potassium channels are required for the proliferation of A549 cell line.Ionic currents were recorded by whole-cell patch-clamp recording technique. The proliferation activity of A549 cells was measured by MTT assay.Membrane current was observed when cells were held at -70mV and test potentials ranged from -30 to +110mV. The current exhibited properties of voltage-dependent, outward rectification and no or little inactivation over the 500ms voltage pulse. Exposure of tumor cells to 10mmol/L TEA reduced the peak outward potassium current (evoked by depolarization to +110mV) from (1057.52±59.17)pA to (212.26±11.96)pA, the ratio of suppression was 79.92% (P0.01). Obvious inhibitive effect of TEA with different concentrations ranged from 20 to 60mmol/L on proliferation activity of the cells was found.The voltage-gated potassium channels exist in human lung adenocarcinoma cell line A549 and play a great role in proliferation of A549 cells. TEA can inhibit proliferation of A549 cell through blocking the potassium channels and the inhibition is dose-dependent.