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Background: Differences between virtual bronchoscopic navigation (VBN) systems and their impacts on the diagnostic yield of transbronchial biopsy (TBB) of peripheral pulmonary nodules (PPNs) remain unclear. Objectives: To compare the Synapse 3D system (Version 4.4, Fujifilm, Japan) and DirectPath system (Version 2.0, Olympus, Japan) in the VBN application of PPNs. Design: Retrospective study with self-paired design and exploratory study with retrospective cohort design. Methods: The study analyzed patients with PPNs using the Synapse 3D system (Group S) and DirectPath system (Group D) and compared differences between the two groups in bronchial tree reconstruction, navigation pathway planning, and VBN-assisted TBB of PPNs. Results: In all, 289 patients were analyzed ultimately. Bronchial tree reconstruction quality was better in Group S ( p 0.05). Conclusion: Synapse 3D system (Version 4.4) and DirectPath system (Version 2.0) had their own merits. Localization success rate and diagnostic yield of VBN-assisted TBB were of no statistical difference for these two VBN systems. Improvements in segmentation algorithms of VBN systems and using the most suitable chest CT scan data for them may be the breakthrough to improve the efficiency of VBN, especially for poor experienced interventional physicians.

Abstract Acquired bronchobiliary fistula (ABBF) is very rare among the complications that occur in patients with hepatocellular carcinoma (HCC) after treatment. Although surgery and drainage have been the main methods for treating ABBF for a long time, they are not entirely suitable for patients with refractory ABBF resulting from HCC therapy. In this study, we present four cases of ABBF caused by HCC treatment, who were treated using selective bronchial occlusion (SBO). Among the 4 patients with ABBF treated with SBO, 3 cases successfully blocked ABBF with SBO, and the treatment success rate was 75%. All successfully treated patients reported disappearance of symptoms of bilioptysis and cough was alleviated. No life‐threatening adverse reactions were reported following SBO intervention, and no deaths occurred. We believe that the use of video bronchoscopy to place a self‐made silicone plug in the bronchus to treat refractory ABBF is a feasible palliative treatment, which can significantly improve the condition of ABBF patients.

Introduction: Congenital bronchial atresia (CBA), as a rare developmental abnormality of the lung, is usually asymptomatic and is accidently discovered in most cases. Currently, no standardized guidelines for the treatment or management of CBA have been established. Case presentation: A 22-year-old male soldier was referred to Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University due to chest tightness and shortness of breath after repeated strenuous activities. Contrast-enhanced computed tomography (CT) revealed an 18mm × 11mm solitary, well-circumscribed, and solid nodule with no enhancement in the right upper lobe (RUL), and emphysematous changes distributed throughout the RUL. A flexible bronchoscopic examination showed extrinsic compression stenosis in the bronchial opening of the right middle lobe (RML). After three-dimensional (3D) reconstruction CT and a multidisciplinary consultation, a diagnosis of CBA in the anterior segment (B3) of RUL was established. Subsequently, thoracoscopic right upper lobectomy was performed and resulted in an improved respiratory capacity 6 months after surgery. To date, the patient has good quality of life without any complication. Conclusion: This study underscores the role of bronchoscopy, 3D reconstruction CT, and a multidisciplinary consultation in the diagnosis of CBA, and highlights that a thoracoscopic intervention should be considered in such case.

PurposeTo evaluate the operability and safety of bronchoscopic domestic one-way endobronchial valves (EBV) on animals.MethodsNine pigs were randomly assigned (2:1) to receive domestic one-way EBV (the experimental group, n = 6) and Zephyr® EBV (the control group, n = 3). Routine blood tests, arterial blood gases, and CT scans of the lungs were performed 1 day pre-procedure in addition to 1 week and 1 month post-procedure to assess changes in blood markers and lung volumes. At 1 month post-procedure, the animals were sacrificed, followed by removal of all valves via bronchoscopy. Pathological examinations of critical organs were subsequently performed.ResultsA total of 15 valves were placed in the experimental group and 6 valves were placed in the control group, without serious complications. Routine blood tests and arterial blood gas examinations at 1 day pre-procedure, 1 week post-procedure, and 1 month post-procedure did not differ significantly in both groups. No EBV displacement was noted under bronchoscopy, and the valve was smoothly removable by bronchoscope at 1 month post-procedure. At 1 week post-procedure, varying degrees of target lung lobe volume reduction were observed on lung CT in both groups. Lung volume reduction was achieved at 1 month post-procedure in both groups, without significant statistical difference. Although 3 cases in the experimental group and 1 case in the control group developed varying degrees of pneumonia, the inflammatory response did not increase over time during the experimental period. Pathological examination revealed no significant abnormal changes in the critical organs for both groups.ConclusionOur results demonstrate that domestic EBV is safe and reliable for endobronchial application in general-grade laboratory white pigs. The safety of domestic EBV is similar to that of Zephyr® EBV, with good ease of use and operability. This kind of domestic EBV can meet the safety evaluation requirements for animal testing.

Background: The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs. Methods: The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1. Results: An analysis of 46 studies with a total of 7252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4 % (95 % CI: 69.9%–76.7 %), with significant heterogeneity detected among studies (I2 = 90 %, P 2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1 % (95 % CI: 2.1%–4.3 %), 0.4 % (95 % CI: 0.1%–0.7 %) and 1.1 % (95 % CI: 0.5%–2.0 %), respectively. Conclusions: r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

Abstract The Wnt pathway is frequently dysregulated in many cancers, underscoring it as a therapeutic target. Wnt inhibitors have uniformly failed in clinical trials. Here, we report a mechanism of WNT pathway activation through the Semaphorin 3 C neurodevelopmental program in glioma stem-like cells. Sema3C directs β-catenin nuclear accumulation in a Rac1-dependent process, leading to transactivation of Wnt target genes. Sema3C-driven Wnt signaling occurred despite suppression of Wnt ligand secretion, suggesting that Sema3C drives canonical Wnt signaling independent of Wnt ligand binding. In a mouse model of glioblastoma, combined depletion of Sema3C and β-catenin partner TCF1 extended animal survival more than single target inhibition alone. In human glioblastoma, Sema3C expression and Wnt pathway activation were highly concordant. Since Sema3C is frequently overexpressed in glioblastoma, Sema3C signaling may be a significant mechanism of resistance to upstream Wnt pathway inhibitors. Dual targeting of Sema3C and Wnt pathways may achieve clinically significant Wnt pathway inhibition.

Background: Low oxygen saturation (LOS) is a frequent occurrence for patients with post-tuberculosis tracheobronchial stenosis (PTTS) during bronchoscopic procedures. However, there are currently no systematic assessment tools to predict LOS risk in PTTS patients during bronchoscopy. Objectives: This study aimed to develop an effective preoperative predictive model to guide clinical practice. Design: Retrospective cohort study. Methods: Data was retrospectively collected from PTTS patients who underwent bronchoscopic interventions between January 2017 and December 2022. Among all patients included in this study, patients between January 2017 and December 2021 were used as training cohort for the logistic regression model, and patients between January 2022 and December 2022 were utilized as validation cohort for internal validation. We used consistency index (C-index), goodness-of-fit test and calibration plot to evaluate the model performance. Results: A total of 465 patients who met the inclusion criteria were enrolled in the study. The overall incidence of LOS was 26.0% (121/465). Comorbidity, degree of stenosis, bronchoscopist level, thermal ablation therapy, balloon dilation, and airway stenting, as independent risk factors for the presence of LOS, were used to construct the nomogram prediction model. The C-index of training cohort was 0.827 (95% CI, 0.786–0.869), whereas that of validation cohort was 0.836 (95% CI, 0.757–0.916), combining with the results of the calibration plot and goodness-of-fit test, demonstrating that this model had good predictive ability. Conclusion: The predictive model and derived nomogram with good predictive ability has been developed to preoperatively predict the risk of LOS in PTTS patients during bronchoscopy, allowing for individualized interventions for high-risk patients.

This paper presents a backpropagation neural network (BPNN) approach based on the sparse autoencoder (SAE) for short-term water demand forecasting. In this method, the SAE is used as a feature learning method to extract useful information from hourly water demand data in an unsupervised manner. After that, the extracted information is employed to optimize the initial weights and thresholds of the BPNN. In addition, to enhance the effectiveness of the proposed method, data reconstruction is implemented to create suitable samples for the BPNN, and the early stopping method is employed to overcome the BPNN overfitting problem. Data collected from a real-world water distribution system are used to verify the effectiveness of the proposed method, and a comparison with the BPNN and other BPNN-based methods which integrate the BPNN with particle swarm optimization (PSO) and the mind evolutionary algorithm (MEA), respectively, is conducted. The results show that the proposed method can achieve fairly accurate and stable forecasts with a 2.31% mean absolute percentage error (MAPE) and 320 m3/h root mean squared error (RMSE). Compared with the BPNN, PSO–BPNN and MEA–BPNN models, the proposed method gains MAPE improvements of 5.80, 3.33 and 3.89%, respectively. In terms of the RMSE, promising improvements (i.e., 5.27, 2.73 and 3.33%, respectively) can be obtained. HIGHLIGHTS To enhance the performance of the BPNN, the SAE is introduced to extract useful features in an unsupervised manner.; An effective framework which integrates the BPNN with the SAE and early stopping technique is proposed for water demand forecasting.; The proposed method is verified by comparing with the BPNN and similar methods which integrate the BPNN with PSO and the MEA, respectively.;

BackgroundTransbronchial lung biopsy guided by radial probe endobronchial ultrasonography with a guide sheath (EBUS-GS-TBLB) is becoming a significant approach for diagnosing peripheral pulmonary lesions (PPLs). We aimed to explore the clinical value of the resistance of the probe to pass through the lesion in the diagnosis of PPLs when performing EBUS-GS-TBLB, and to determine the optimum number of EBUS-GS-TBLB.MethodsWe performed a prospective, single-center study of 126 consecutive patients who underwent EBUS-GS-TBLB for solid and positive-bronchus-sign PPLs where the probe was located within the lesion from September 2019 to May 2022. The classification of probe resistance for each lesion was carried out by two bronchoscopists independently, and the final result depended on the bronchoscopist responsible for the procedures. The primary endpoint was the diagnostic yield according with the resistance pattern. The secondary endpoints were the optimum number of EBUS-GS-TBLB and factors affecting diagnostic yield. Procedural complications were also recorded.ResultsThe total diagnostic yield of EBUS-GS-TBLB was 77.8%, including 83.8% malignant and 67.4% benign diseases (P=0.033). Probe resistance type II displayed the highest diagnostic yield (87.5%), followed by type III (81.0%) and type I (61.1%). A significant difference between the diagnostic yield of malignant and benign diseases was detected in type II (P = 0.008), whereas others did not. Although most of the malignant PPLs with a definitive diagnosis using EBUS-GS-TBLB in type II or type III could be diagnosed in the first biopsy, the fourth biopsy contributed the most sufficient biopsy samples. In contrast, considerably limited tissue specimens could be obtained for each biopsy in type I. The inter-observer agreement of the two blinded bronchoscopists for the classification of probe resistance was excellent (κ = 0.84).ConclusionThe probe resistance is a useful predictive factor for successful EBUS-GS-TBLB diagnosis of solid and positive-bronchus-sign PPLs where the probe was located within the lesion. Four serial biopsies are appropriate for both probe resistance type II and type III, and additional diagnostic procedures are needed for type I.

Abstract Background The insertion of self-expandable metallic stents (SEMS) for post-tuberculosis tracheobronchial stenosis (PTTS) was controversial. This study aimed to evaluate the efficacy and safety of SEMS for treating PTTS, and developed a scoring system for predicting the occurrence of restenosis after stenting in PTTS patients. Methods We conducted a retrospective review of 87 patients who were diagnosed with PTTS and experienced SEMS insertion between January 2000 and December 2017. All procedures were performed via flexible bronchoscopy under conscious sedation and local anesthesia. Results A total of 85 SEMS were successfully placed in 77 patients. Comparing with pre-stenting, there were significant improvements in the lumen diameters of the stenotic segment, mMRC scale and lung function after short-term SEMS placement. During the long-term (average 163.32 months) follow-up, 48 patients (62.3%) did not develop restenosis after stenting; the other 29 patients (37.7%) developed and eventually, 12 remained under interventional therapies and 11 had bronchial atresia. Multivariate Cox regression analysis revealed that the difference value between SEMS length and the stenosis-segment length, stenosis type, and the number of pre-stenting thermal ablation were independently related to restenosis occurrence and were subsequently used to establish the Restenosis Score. The model’s development group (0.83, 95% CI 0.74–0.92) and external validation set (0.94, 95% CI 0.77–1.00) showed excellent discrimination. Conclusion SEMS placement could serve as a safe and effective treatment option for most patients with PTTS. Further, we built a prediction model depending on the independent predictors of restenosis occurrence, the Restenosis Score. This validated tool might provide a decision support and a better management for PTTS patients who underwent SEMS implantation.

Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.

A hybrid model based on the mind evolutionary algorithm is proposed to predict hourly water demand. In the hybrid model, hourly water demand data are first reconstructed to generate appropriate samples so as to represent the characteristics of time series effectively. Then, the mind evolutionary algorithm is integrated into a back propagation neural network (BPNN) to improve prediction performance. To investigate the application potential of the proposed model in hourly water demand forecasting, real hourly water demand data were applied to evaluate its prediction performance. In addition, the performance of the proposed model was compared with a traditional BPNN model and another hybrid model where the genetic algorithm (GA) is used as an optimization algorithm for BPNN. The results show that the proposed model has a satisfactory prediction performance in hourly water demand forecasting. On the whole, the proposed model outperforms all other models involved in the comparisons in both prediction accuracy and stability. These findings suggest that the proposed model can be a novel and effective tool for hourly water demand forecasting. HIGHLIGHTS A unified framework is developed to select input variables for an hourly water demand forecasting model.; Mind evolutionary algorithm, a novel and powerful optimization algorithm, is used to obtain the optimal initial weights and thresholds for the back propagation neural network.; A hybrid model coupling mind evolutionary algorithm and back propagation neural network is proposed to predict hourly water demand.;

Abstract Colorectal carcinoma (CRC) has a high morbidity and mortality. Current studies have confirmed a variety of microRNA polymorphisms were associated with tumor susceptibility, however, the mechanisms are still unknown. In this study, we were aimed to clarify how polymorphism rs2682818 participated in the progression of CRC. First of all, the differential expression of miR-618 was assessed by quantitative real-time polymerase chain reaction in CRC patients with different genotypes of polymorphism rs2682818, including homozygous (TT) genotype, homozygous (GG) genotype and heterozygous (TG) genotype. Secondly, plasmids carried miR-168 precursor sequences harboring rs2682818 (SNP type) or without rs2682818 (wild type) were transfected into 293T cells to verify that polymorphism rs2682818 affected miR-618 expression. Thirdly, CCK-8 assay, flow cytometry assay, transwell assay and mouse xenograft assay were performed to measure the biological functions of miR-618 in CRC. Fourthly, the candidate target genes of miR-618 which were predicted by bioinformatics tools were verified by luciferase reporter assay. Finally, in order to explain the potential molecular mechanisms, western blotting was performed to demonstrate the differential expression and phosphorylation of pathway related proteins. The results showed that miR-618 was down-regulated in colon cancer, especially in CRC patients with rs2682818 GG homozygous genotype. Higher expression of mature miR-618 occurred in patients with TT homozygous genotype, and these patients usually had a longer survival time. Moreover, miR-618 mimic obviously impaired the growth and invasion ability of CRC cells, and miR-618 mimic also remarkably promoted CRC cell apoptosis. Our luciferase experiments confirmed that TIMP1 was a target of miR-618 in CRC cells. Knockdown of TIMP1 also significantly inhibited the malignant cytological features of CRC, including malignant growth and invasion as well as apoptosis resistance. In summary, polymorphism rs2682818 participated in the progression of CRC via affecting the expression of mature miR-618 in CRC cells, and miR-618 inhibited the progression of CRC via targeting TIMP1expression.

Abstract Intratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.

The capacitance characteristics of magnetorheological fluids (MRFs) were studied experimentally based on simulation analysis. The nonlinear relationship between the capacitance of MRFs and electric field frequency was measured by the self-made circuit device. The effects of magnetic induction intensity and particle volume fraction on the capacitance characteristics of MRFs were investigated. The results show that the nonlinear dependence of the capacitance of an MRF on frequency induced by the effect of tunnel current decreases with the increase in frequency. The capacitance of an MRF is directly related to the particle structures. The capacitance of the MRF with a chain particle structure is greater than that of the MRF with a random particle distribution. The smaller the clearance between the adjacent particles, the greater the capacitance of the MRF. The network particle structure and particle contact will reduce the capacitance of an MRF. The capacitance of an MRF increases with the increment of external magnetic field. The capacitance of an MRF with higher particle volume fraction is smaller than that of an MRF with lower particle volume fraction.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients’ follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.

Objective:To evaluate the effect of visual input on static balance function, by assessing the posture control of young healthy subjects with eyes open and closed using the plantar pressure analysis technique.Methods:A total of sixty-six young, healthy adults were recruited in the study. They were instructed to stand at a fixed position on the FreeMed plantar pressure analysis test board. The subject's pelvis was swung in four directions including front, back, left and right, to make their foot pressure evenly distributed. The pressure data of the soles was recorded in eyes open and closed states for 30 seconds, respectively. The collected data was processed using the Freestep plantar pressure analysis system. The ball length, ellipse area, average velocity, average X, average Y, ellipse tilt angle, ellipse eccentricity, maximum swing, minimum swing, and total plantar load, forefoot load, and hind foot load of the left and right lower limbs were obtained.Results:There were significant differences in the ellipse area (P< 0.05), the average Y(P< 0.001) and the maximum swing (P< 0.001) of the subjects in the two states of eyes open and closed. Compared with eyes open condition, the ellipse area decreased, the average Y decreased, and the maximum swing increased during eyes closed condition. According to the scatter plot distribution of center of pressure (COP), it was found that the COP distribution was more concentrated with the eyes open than that with eyes closed. Comparing the two conditions (eyes open and eyes closed), the subjects'left foot forefoot load (P< 0.001), right foot forefoot load (P< 0.001), left foot hind foot load (P< 0.001) and right foot hind foot load (P< 0.001) were significantly different. Compared with the eyes open, the left-foot forefoot load and the right-foot forefoot load increased both, while the left-foot hind foot load and the right-foot hind foot load decreased. In the comparison of the two status of the left lower limb and the right lower limb, the subject's overall load on the left foot in the eyes open state was reduced compared with the right lower limb (P=0.030); the overall load on the left foot was also lower than that on the right side in eyes closed. The difference of the lower limbs decreased was statistically significant (P=0.021). In the comparison of the forefoot and hind foot in eyes open and closed, the hind foot load was significantly greater than the forefoot load (P< 0.001).Conclusion:The findings of this experiment indicated that normal young subjects could adjust the balance function under different visual input status by changing the ellipse area and swing amplitude. The kinematics and dynamics parameters analyzed by plantar pressure analysis can be used for quantitative and clinical evaluation of static balance function.

Abstract The knowledge of airway length is the theoretical basis in the diagnosis and management of airway disease. The objective of this study is to measure the length of trachea and left and right main bronchus in Chinese Shanghai population. A total of 153 consecutive adult patients with minor pulmonary disease in Xinhua hospital were enrolled for bronchoscopy examination. Measurements were conducted on head and neck neutral position and height, weight and age for each patient were recorded either. Student t test and multiple linear regression was used to compare means between males and females and to analyze correlation among height, weight, sexual dimorphism and the lengths of the trachea and bronchus. The lengths of the trachea and left main bronchus are significantly different between male and female patients (P

Abstract Nuclear matrix‐associated proteins (NMPs) play critical roles in regulating chromatin organization and gene transcription by binding to the matrix attachment regions (MARs) of DNA. However, the functional significance of NMPs in glioblastoma (GBM) progression remains unclear. Here, we show that the Special AT‐rich Binding Protein‐2 (SATB2), one of crucial NMPs, recruits histone acetyltransferase CBP to promote the FOXM1‐mediated cell proliferation and tumor growth of GBM. SATB2 is preferentially expressed by glioma stem cells (GSCs) in GBM. Disrupting SATB2 markedly inhibited GSC proliferation and GBM malignant growth by down‐regulating expression of key genes involved in cell proliferation program. SATB2 activates FOXM1 expression to promote GSC proliferation through binding to the MAR sequence of FOXM1 gene locus and recruiting CBP to the MAR. Importantly, pharmacological inhibition of SATB2/CBP transcriptional activity by the CBP inhibitor C646 suppressed GSC proliferation in vitro and GBM growth in vivo. Our study uncovers a crucial role of the SATB2/CBP‐mediated transcriptional regulation in GBM growth, indicating that targeting SATB2/CBP may effectively improve GBM treatment.

The tumour microenvironment plays an important role in promoting glioblastoma. Here, the authors show that glioma stem cells secrete WISP1, which promotes both the survival of the stem cells and tumour-associated macrophages.

Abstract Background A number of JmjC domain-containing histone demethylases have been identified and biochemically characterized in mammalian models and humans. JMJD2A is a transcriptional co-factor and enzyme that catalyzes the demethylation of histone H3 lysine 9 and 36 (H3K9 and H3K36). Here in this study, we reported the role of JMJD2A in human glioma. Methods Quantitative real-time PCR and western blot were performed to analyzed JMJD2A expression in glioma. Log-rank was performed to plot the survival curve. JMJD2A was knocked or overexpressed with lentivirus. Cell proliferation and colony formation were performed to assess the effects of JMJD2A on glioma cell growth. Xenograft experiment was performed the evaluate the growth rate of glioma cells in vivo. The signaling pathway was analyzed with western blot and mTOR was inhibited with rapamycin. Results Quantitative real-time PCR and western blot experiments revealed higher expression of JMJD2A and lower levels of H3K9me3/H3K36me3 in glioma tissues than that in normal brain tissues. We showed that knockdown of JMJD2A expression attenuated the growth and colony formation in three lines of glioma cells (U251, T98G, and U87MG), whereas JMJD2A overexpression resulted in opposing effects. Furthermore, we performed in vivo xenograft experiments and our data demonstrated that JMJD2A knockdown reduced the growth of glioma T98G cells in vivo. Further mechanism study implicated that JMJD2A activated the Akt-mTOR pathway and promoted protein synthesis in glioma cells via promoting phosphoinositide-dependent kinase-1 (PDK1) expression. The activation of the Akt-mTOR pathway was also validated in human glioma tissues. Finally, we showed that inhibition of mTOR with rapamycin blocked the effects of JMJD2A on protein synthesis, cell proliferation and colony formation of glioma cells. Conclusions These findings demonstrated that JMJD2A regulated glioma growth and implicated that JMJD2A might be a promising target for intervention.

Tensors are powerful tools for representing and processing multidimensional data. In this paper, an algorithm of dimension reduction for multidimensional data is proposed. We consider both the global and local structures of the data to fully extract important features. Multiplying a tensor by a matrix in mode-n can change the size of a certain dimension of the tensor. Therefore, for the global structure, we use a matrix to span a subspace to minimize the distance between the tensor data and its projection on the subspace for each mode. For local structure, we construct a dimensionality reduction algorithm for tensor data based on local homeomorphism to keep the continuous dependency relationship of the original high-dimensional tensor data unchanged after dimensionality reduced in each locality. The proposed algorithm achieves dimensionality reduction by combining the global subspace projection distance minimum and local homeomorphism, which realizes global variance maximization and maintains the local non-linear geometric structure at the same time. The proposed algorithm performs good feasibility while compared with other advanced algorithms in classification and clustering experiments.

To ensure the safety of ships and bridges at the same time during collisions, a new type of bridge pier protection system is proposed, in which one is composed of corrugated steel plates, bolts, and corrugated steel pipes (CSP), and the other is composed of ordinary steel plates, bolts, and corrugated steel pipes (OSP). To study their anticollision performance, a pendulum impact test and numerical simulation were carried out. Comparing the test results with the simulation results, it was shown that the simulation results are basically consistent with the test results. Then, the influence curves of the impact velocity, specimen thickness, weight, and frequency are analysed to evaluate the anticollision performance of CSP/OSP and optimize their structure. When the impact energy is low, the peak values of the lateral impact force and lateral displacement of the column equipped with OSP are all smaller than those of the column equipped with CSP. When the impact energy is high, the peak values of the lateral impact force and lateral displacement of the column equipped with OSP are larger than those of the column equipped with CSP. However, under the same impact energy, the total energy peak value of the CSP specimen is larger than that of the OSP specimen. Results can provide a certain numerical analysis basis for the structural design and research of new types of corrugated steel protection system for bridge pier.

A new type of corrugated steel protection system (CSP) for the bridge pier is proposed to improve the impact resistance of the bridge pier and reduce the loss caused by the collision of the ship against the pier. A new bolt numerical simulation method and finite element model establishment method are proposed and verified by the impact test. The results show that the new method can effectively simulate the mechanical behavior of bolts and CSP. Parameters analysis was carried out subsequently by the verified finite element model which showed that the energy absorbing ability of CSP increases with corrugated steel pipe wall thickness and its weight decreases. It is concluded that CSP (2.0 mm) is the optimal structural type, and compared with the existing FRP Fender System. The results show that the energy absorbing ability of CSP (2.0 mm) is strong, and its final absorbed energy can reach 86.13% of the total energy of the model structural system (7.22 MJ).

The preferential sites of Cr in the μ -Co _7 W _6 phase and its influence on electronic properties were studied by first-principles calculations based on density functional theory. The calculation results of the formation energy and defect formation energy show that the stability of the system is enhanced when Cr occupies the Co site, which indicates that Cr tends to occupy the Co site of the system. By calculating the density of states, the Hamilton population of crystal orbital, the electron location function and the Bader charge distribution, the reason why Cr preferentially occupied the Co sites is further explained. This is primarily owing to the hybridization of the d-d orbitals of the Cr atom to its adjacent atoms.

Primary pulmonary nuclear protein of testis carcinoma is a rare and highly aggressive malignant tumor. It accounts for approximately 0.22% of primary thoracic tumors and is little known, so it is often misdiagnosed as pulmonary squamous cell carcinoma. No effective treatment has been formed yet, and the prognosis is extremely poor. This review aims to summarize the etiology, pathogenesis, diagnosis, treatment, and prognosis of primary pulmonary nuclear protein of testis carcinoma in order to better recognize it and discuss the current and innovative strategies to overcome it. With the increasing importance of cancer immunotherapy and tumor microenvironment, the review also discusses whether immunotherapy and targeting the tumor microenvironment can improve the prognosis of primary pulmonary nuclear protein of testis carcinoma and possible treatment strategies. We reviewed and summarized the clinicopathological features of all patients with primary pulmonary nuclear protein of testis carcinoma who received immunotherapy, including initial misdiagnosis, disease stage, immunohistochemical markers related to tumor neovascularization, and biomarkers related to immunotherapy, such as PD-L1 (programmed death-ligand 1) and TMB (tumor mutational burden). In the meanwhile, we summarized and analyzed the progression-free survival (PFS) and the overall survival (OS) of patients with primary pulmonary nuclear protein of testis carcinoma treated with PD-1 (programmed cell death protein 1)/PD-L1 inhibitors and explored potential population that may benefit from immunotherapy. To the best of our knowledge, this is the first review on the exploration of the tumor microenvironment and immunotherapy effectiveness in primary pulmonary nuclear protein of testis carcinoma.

Wayside acoustic detection is a promising technology for railway-vehicle bearing health monitoring due to its merits of non-conduct measurement, low cost, and early warning capacity. However, the diagnostic accuracy will be reduced by the problems of strong background noise and Doppler distortion. Considering the super spatial directivity ability of the microphone array, in this paper, a uniform rectangular array (URA) and an optimal spatial filter (OSF) based on the principle of minimum variance distortion-less response (MVDR) are designed to improve the diagnostic accuracy. Compared with the traditional single microphone and linear array, spatial directivity can be improved significantly so that the better anti-noise performance and higher diagnostic accuracy can be achieved. First, a URA consisting of 15 microphone elements arranged into five columns and three rows is designed to capture the wayside acoustic signal. Second, the direction angle of the target moving sound source with high accuracy is calculated at different times. Third, an OSF based on the principle of the MVDR is designed to extract the target sound source signal. Fourth, Doppler effect embedded in the filtered signal is eliminated using the MVDR spectrum estimation and resampling method. Finally, the diagnosis decision is made through an envelope spectrum analysis. The comparative simulation and experimental case studies are carried out to verify the effectiveness and improvement of the proposed method.

ObjectiveTo develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.MethodsTumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/Kb transgenic mice were immunized with peptides from HLA-A*02:01+patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity in vitro. The HLA-A*02:01+lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6nu/nu mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/Kb transgenic mice were adoptively transfused to verify their immunogenicity in vivo.ResultsMultiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both in vitro and in vivo using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.ConclusionNeoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.PrecisNeoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.

Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.

A fifty year old male was diagnosed with bronchial HPV. He was treated with local interventional treatment argon plasma coagulation and subcutaneous injections bevacizumab. Spraying of the regions followed with a specially designed catheter with interferon-α (2b). Systematic treatment of esomeprazole was also administered. After six months the patient is disease free and on close follow-up.

A report a case of a 63 year old male diagnosed with lung cancer adenocarcinoma. The patient had a right paratracheal mass diagnosed with EBUS-TBNA 22G. The patient had surgery, however 7 days after the billau catheter was removed pneumothorax was diagnosed which did not resolved. Bronchoscopy reveled two minor fistulas in the interior wall of the trachea. An additional surgery was performed in order to add muscle patches on the exterior part of the trachea. Unfortunately additional stent placement was placed after a silicon stent since the muscle patches failed. We chose a metallic auto expandable stent since after three months of follow up a small metastatic lesion was observed in the liver. Stent placement is an option for these patients and the right stent has to be placed for each case.

To reduce the loss of life and property caused by the collision of a ship against a bridge pier, this study proposes a new type of anticollision facility. The facility uses corrugated steel plates and corrugated steel pipes (CSPs), or ordinary steel plates and corrugated steel pipes (OSPs), as structural elements to form a honeycomb structure, which can greatly improve the impact resistance of bridge piers and reduce any damage to ships. To evaluate the anticollision performance of the proposed anticollision facility, this work uses the CSPs and OSPs as study objects in the impact test research. A pendulum impact test system was utilized to compare and analyze the column with CSP and OSP specimens and the column without any anticollision facilities. Test results show that the CSP and OSP specimens have a relatively high energy dissipation effect. When the impact energy is small, the energy dissipation effect of the OSPs with the same plate thickness is stronger than that of the CSPs. When the impact energy is large, the energy dissipation effect of the CSPs with the same plate thickness is stronger than that of the OSPs. In addition, the extreme value analysis method is used to analyze the relationship curve between the peak value of the D1 lateral displacement and the specimen’s plate thickness, weight, and natural frequency; the optimal thickness, weight, and natural frequency values of the CSP and OSP specimens are also deduced. Taking the optimal value of the specimen’s natural frequency as a target, the structure of the CSP and OSP specimens is optimized. When the optimized plate thickness is 2.50 mm, the ratios of the optimal value of the specimen plate thickness, weight, and natural frequency to the optimal calculation value are all in the range of [0.80, 1.12]. OSP and CSP specimens are found to have the best energy dissipation effect. The peak value of the D1 lateral displacement of the top of the column equipped with the CSPs is at least 88.37% lower than that of the column without any anticollision facilities. For the top of the column equipped with the OSPs, the peak value of the D1 lateral displacement is at least 80.37% lower than that of the column without any anticollision facilities. Optimization results show that the extreme value analysis method is suitable for the optimal design of anticollision facilities for piers.

Nowadays we have novel therapies for advanced stage non-small cell lung cancer. Immunotherapy has been introduced in the market for several years and until now its administration is mostly based on the programmed death-ligand 1. First line treatment with immunotherapy can be administered alone if programmed death-ligand 1 expression is ≥ 50%. All therapies for advanced stage disease have advantages and disadvantages, immunotherapy until now has presented mild adverse effects when compared to chemotherapy. However; it is known to induce inflammatory response to different tissues within the body. In our case acute pneumothorax was induced after immunotherapy administration.

Background: Solitary tracheobronchial papilloma (STBP) is a rare benign tumor. Human papilloma virus (HPV) infection is associated with dysplasia and a high risk of carcinoma. Case 1: Sixty five year old male with hemoptysis and with coilocytic atypia, indicating the presence of HPV. Case 2: Thirty two year old female with a polypoid villoglandular bronchial structure and no cytoplasmic or nuclear atypia but prominent microvilli. Discussion: Tissue sample is the best sample in order to determine and distinguish the two entities, local treatment should be considered as first option when possible.

Introduction: Local treatment of the airways and lung parenchyma has been used in clinical practice for several years for a variety of diseases. Methods: A variety of endoscopic tools for local treatment exist, especially for treating malignancies. Using these endoscopic tools, one can administer drugs specifically designed for the airways. Discussion: This article presents all locally administered treatment options and provides useful insights for future local endoscopically applied treatments.

Introduction: Aerosolised drugs have been approved for several diseases such as cystic fibrosis and diabetes. Moreover; there are already drugs for pulmonary hypertension in aerosol form already on the market. Materials and methods: Two drugs for pulmonary hypertension (Tadalafil and Macitentan) were milled and transformed from tablets to powder. Three different jet-nebulizers with seven different residual cups were combined. Moreover, we used 3 different ultrasound nebulizers with two different release methods. Results: The drug and residual cup designs produce alone or jointly different MMAD diameters. The three large (10 mls) residual cups with the jet-nebulisers produced the smallest aerosol droplets. Both ultrasound nebulisers are capable of producing optimal size aerosol droplets ≤5 μm mmad. Conclusions: These two drugs can be easily administered as aerosol and an vivo clinical study will prove the safety for the airways.

Nowadays we have novel equipment for lung cancer diagnosis, however; due to lack of symptoms, lung cancer is still diagnosed at a late stage. Currently we have the following therapies for non-small cell lung cancer: a) non-specific cytotoxic agents, b) targeted therapies and c) immunotherapy. Each therapy has its own advantages and adverse effects. In the current case we will present a rare case of psoriacic arthritis that was presented after two cycles of nivolumab administration and we will also present a review of the literature. Keywords: Lung cancer, Adenocarcinoma, Convex endobronchial ultrasound, PD-L1, Targeted therapy

Trachea stenosis is observed either in benign or malignant situations. In cancer malignancy a tumor might obstruct the central airway in three different ways. Again granuloma tissue is usually observed after intubation or stent placement in order to manage a benign malformation of the trachea. In any case there are several tools and techniques that can be used either with surgery or endoscopically to manage such situation. We will focus on a hybrid technique in order to ventilate the patient while performing endoscopic management of granuloma tissue. Keywords: Trachea, Balloon dilation, Rigid scope, Endoscopy

Lung cancer is still underdiagnosed mainly due to lack of symptoms. Most patients are diagnosed in a late stage where unfortunately only systematic therapy can be applied. Fortunately in the last five years several novel therapies and combinations have emerged. However; in certain situations local therapeutics modalities have to be applied in order to solve emergency problems as in the case that we will present. Convex-EBUS probe was used along with a novel method of ventilation which keeps PCO2 concentration satisfyingly low. Keywords: Lung cancer, Interventional pulmonology, Ventilation, EBUS

In response to the problems of small working width and low operating efficiency of existing hydraulic scouring lotus root harvesters, a wide-width hydraulic scouring system was designed based on a wide-width self-propelled lotus root harvester. The main parameters of the key components were determined through theoretical analysis of the water flow energy of the hydraulic scouring system pipelines. An experimental study was also carried out on the main factors affecting the working performance of this hydraulic scouring system. Through hydrodynamic simulation tests, the effect of nozzle type and constriction section structure on the turbulence intensity at the nozzle outlet and the pressure loss per unit mass of fluid between the nozzle inlet and outlet sections were compared and analysed. The test yielded conical-cylindrical nozzle geometry parameters for nozzle inlet diameter of 40 mm, shrinkage angle of 30°, nozzle outlet straight section length of 20 mm, nozzle outlet diameter of 16 mm, the nozzle had better flushing performance. Single-factor tests were carried out with nozzle outlet pressure, scouring angle and nozzle height from the mud surface as influencing factors. Based on the optimum effective scour depth, a three-factor, three-level Box–Behnken central combination design test was completed. The primary and secondary factors affecting the effective scouring depth were obtained in the following order: nozzle height from the mud surface, nozzle outlet pressure, and scouring angle. Finally, the performance test of the hydraulic scouring system was completed. Results showed that when the nozzle outlet pressure of 0.30 MPa, the scouring angle of 60° and the nozzle height from the mud surface of 0 mm, the effective scouring depth was 395 mm, the lotus root floating rate was 90% and the damage rate was 5%, which meet the requirements of lotus root harvesting operations.

Non-small cell lung cancer is still diagnosed at late stage due to the lack of early symptoms and methods of diagnostic prevention. In the past ten years several targeted therapies have been introduced or explored. Tyrosine kinase inhibitors and immunotherapy are currently considered the most effective and safe therapies in comparison to the non-specific cytotoxic agents. Regarding tyrosine kinase inhibitors the adverse effects have been fully explored, however; on the other hand for immunotherapy there are still several issues to be clarified. We report a rare case of a patient with lung cancer adenocarcinoma who developed vitiligo throughout his body after nivolumab administration.

Endobronchial ultrasound endoscopy is a state of the art diagnostic endoscopic procedure for the thorax. Firstly it was designed mainly for the staging of lung cancer and of course for the diagnosis of suspicious findings in large central airways. The main limitation of the equipment is the diameter of the instrument and therefore it can only be guided through large airways. However; the diameter of the working channel also provides a large tissue sample nowadays with the 19G biopsy needle. We will provide our experience with the 22G needle of the endobronchial convex-probe in several medical situations of the thorax.

In the past decade novel agents are on the market for non-small cell lung cancer adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation is necessary in the everyday clinical practice for the oncologic patient. Immunotherapy is nowadays the novel therapy for advanced stage non-small cell lung cancer with two agents nivolumab and pembrolizumab. In the current case series we will present adverse effects from our centers and comment on the treatment and follow-up of the patients.

Guidelines for the treatment of non-small cell lung cancer adenocarcinoma positive in epidermal growth factor mutations indicate tyrosine kinase inhibitors. There are currently three tyrosine kinase inhibitors that can be used as first line treatment: gefitinib, erlotinib and afatinib. Regarding erlotinib and afatinib dosage can be modified in the case of severe adverse effects. In the case of disease relapse investigation for T790M mutation has to be made either with re-biopsy or liquid biopsy and osimertinib has to be administered when T790M is diagnosed. Based on a case series we indicate which is the best approach for T790M mutation.

Solitary Fibrous Tumor of the Pleura (SFTP) is a rare tumor of the pleura. Worldwide about 800 patients diagnosed with this oncological entity have been described in the existing literature. We report our center's 13 year experience. During this time three patients suffering from this rare disease have been treated in our department. All patients were asymptomatic and their diagnosis was initially triggered by a random finding in a routine chest x-ray. The diagnosis was set preoperatively through a needle biopsy under computer tomography (CT) guidance. The tumors were resected surgically though video-assisted thoracoscopic surgery (VATS) or thoracotomy. Because of the lack of specific guidelines due to the rarity of the disease a long-term, systematic follow-up was recommended and performed. Parallel an overview of the diagnostic and therapeutic procedures of the rare tumor is made.

Targeted therapies are on the market for the past five years and recently pembrolizumab was approved as first line treatment for patients with PD-L1 >50%. We present three cases of patients which had epidermal growth factor receptor positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50% overexpression.

In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.