We aimed to explore the molecular substrate underlying EGFR‐TKI resistance and investigate the effects of N‐acetylcysteine (NAC) on reversing EGFR‐TKI resistance. In the current research, the effects of NAC in combination with gefitinib on reversing gefitinib resistance were examined using CCK‐8 assay, combination index (CI) method, matrigel invasion assay, wound‐healing assay, flow cytometry, western blot, and quantitative real‐time PCR (qRT‐PCR). CCK8 assay showed that NAC plus gefitinib combination overcame EGFR‐TKI resistance in non‐small cell lung cancer (NSCLC) cells by lowering the value of half maximal inhibitory concentration (IC50). CI calculations demonstrated a synergistic effect between the two drugs (CI < 1). Matrigel invasion assay and wound healing assay demonstrated a decrease in migration and invasion ability of PC‐9/GR cells after NAC and gefitinib treatment. Flow cytometry displayed enhanced apoptosis in the combination group. Western blot and qRT‐PCR revealed that increased E‐cadherin and decreased vimentin in the combination group. When PP2 was administered with gefitinib, the same effects were seen. Our findings suggest that NAC could restore the sensitivity of gefitinib‐resistant NSCLC cells to gefitinib via suppressing Src activation and reversing epithelial‐mesenchymal transition.
BackgroundThe association of clinical risk factors, in particular deep vein thrombosis (DVT), with risk stratification for pulmonary embolism (PE) remains to be identified. We therefore aimed to establish the relationship between risk stratification of PE patients and DVT of lower extremities.MethodsIn this retrospective study, 93 out of 485 PE patients with uncompleted clinical data were excluded, resulting in 392 patients included for analysis. Based on the ESC criteria, 24, 171, and 197 patients were categorized into high (6.1%), intermediate (43.6%), and low risk (50.3%) subgroups, respectively.ResultsDVT was detected in 304 patients (77.6%). The incidence of DVT in patients with high and intermediate risk PE was much lower than in those patients with low risk PE (67.2% vs 87.8%, P < .0001). Further analyses of the 304 patients with DVT showed higher incidence of high and intermediate risk PE in patients with isolated distal DVT than proximal DVT (59.0% vs 39.1%, P = .005), with asymptomatic DVT than symptomatic DVT (63.0% vs 36.8%, P < .0001), and with bilateral DVT than unilateral DVT (54.5% vs 39.9%, P = .03). Stepwise logistic regression showed that symptomatic or asymptomatic DVT was an independent risk factor for risk stratification of PE patients with DVT (0.320, 95% confidence interval, 0.186‐0.550).ConclusionsPatients with high and intermediate risk PE presented lower incidence of DVT compared with patients with low risk PE. In PE patients with comorbid DVT, asymptomatic DVT is an independent risk factor for high and intermediate risk of PE.
Energy harvesting for self-powered wireless sensor networks (WSNs) is increasingly needed. In this paper, a self-powered WSN node scenario is proposed and realized by coupling the electric charge extraction interface circuit, power management module, and wireless communication module. Firstly, the output power of an optimized self-powered energy extraction circuit is compared with different energy extraction circuits under various loads and excitation amplitudes theoretically. Then, an energy-harvesting setup is established to validate the load-carrying capacity and working condition of the self-powered optimized synchronized switch harvesting on inductor (SP-OSSHI) circuit. It gives guidance to select and estimate the appropriate energy-consuming level for the sensor and modules. Finally, by connecting the energy-harvesting system, power management element, and sensing part together, a self-powered wireless sensor node is accomplished. Under 18 Hz resonant excitation, the whole self-powered system transmits 32 bytes of data every 30 seconds including the acceleration and environment temperature. This prototype strongly proves the feasibility of the self-powered WSN node. These research results have potential to be used in different application fields.
Background. Environmental particulate matter exposure can cause various respiratory problems including aggravated asthma, decreased lung function and increased respiratory symptoms. However, the molecular mechanisms underlying PM-induced lung inflammation are incompletely understood. Effective therapeutic strategies are required.Results. A mouse model of particulate matter-induced lung inflammation was used to identify the pathology and the molecular mechanisms for particulate matter-induced lung inflammation. The mouse model revealed that particulate matter induced neutrophil-dominated lung inflammation. Neutrophils derived from particulate matter-instilled mice showed decreased apoptosis and elevated Bcl-2 expression. Further studies in vav-Bcl-2 transgenic mice made it clear that Bcl-2 overexpression caused a marked increase in neutrophils in bronchoalveolar lavage fluid. Furthermore, we found that the Bcl-2 inhibitor ABT-199 reduced particulate matter-induced lung inflammation, and induced apoptosis of neutrophils in particulate matter-induced lung inflammation mice model.Conclusions. Particulate matter-induced lung inflammation is mediated in part by inhibition of apoptosis of inflammatory cells. Bcl-2 is responsible for the reduced apoptosis of inflammatory cells in particulate matter-induced lung inflammation. The Bcl-2 selective inhibitor ABT-199 reduces particulate matter-induced lung inflammation by inducing the apoptosis of neutrophils and might be a promising drug for the treatment of particulate matter-induced lung inflammation.
These authors contributed equally to this workPurpose: To compare overall survival (OS) and progression-free survival (PFS) between microwave ablation (MWA) and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) smaller than 5 cm. Methods: Patients with solitary HCC smaller than 5cm who initially underwent MWA or TACE were identified in Chinese PLA General Hospital from June 2010 to October 2015. Propensity score matching (PSM) was performed with a 1:1 matching protocol. OS and PFS were compared by using the log-rank test. After matching, subgroup analysis based on tumor size (≤3cm/3.1-5cm) was also conducted. Prognostic factors for OS and PFS were assessed with Cox proportional hazard regression model. Results: A total of 202 patients (MWA, n=120; TACE, n=82) were identified. After matching, 116 patients were included (58 patients for each treatment group). MWA provided significantly better OS and PFS than TACE for both the entire cohort (OS, P<0.001; PFS, P<0.001) and the matched cohort (OS, P=0.015; PFS, P<0.001). Subgroup analysis showed that among patients with tumor of 3cm or less, the MWA group had significantly better OS (P=0.027) and PFS (P=0.008) than the TACE group. Multivariate Cox regression analysis showed TACE was associated with worse OS (hazard ratio, 2.385; 95% CI: 1.427, 3.985; P=0.001) and PFS (hazard ratio, 2.567; 95% CI: 1.820, 3.622; P<0.001). Conclusion: MWA outperformed TACE for solitary HCC smaller than 5cm in OS and PFS. For single tumors less than 5cm, especially those smaller ones (≤3cm), priority should be given to MWA when making treatment options between MWA and TACE. Precis' StatementThis paper reported the comparative results in therapeutic effectiveness between MWA and TACE for solitary HCC smaller than 5cm.
Non-invasive strategies for monitoring posttuberculosis (TB) tracheobronchial stenosis (PTTS) are clinically important but currently lacking. Transforming growth factor-β1 (TGF-β1) and procollagen type I N-propeptide (PINP) have been identified as markers of fibrosis. The present study aimed to investigate the clinical significance of serum TGF-β1 and PINP in PTTS. Serum samples were collected from 119 patients with tracheobronchial TB after the condition was treated for at least 6 months (59 patients with airway stenosis and 60 patients with no stenosis). Serum TGF-β1 and PINP levels were measured using ELISA and compared between the groups. Relationships between serum TGF-β1 and PINP levels and clinical characteristics, interventional bronchoscopy and outcomes of airway stenosis were analysed. The correlation between TGF-β1 and PINP, and their diagnostic efficacy for airway stenosis were also analysed. The TGF-β1 and PINP levels in the airway stenosis group were higher than those in the non-stenosis group. Furthermore, airway stenosis with atelectasis or mucus plugging was associated with higher TGF-β1 levels, and airway stenosis with atelectasis, mucus plugging, right main bronchus stenosis or severe airway tracheal stenosis was associated with higher PINP levels. In addition, TGF-β1 and PINP levels increased after interventional bronchoscopy therapy and airway stenosis with recurrent stenosis was associated with higher baseline levels of both markers. Finally, TGF-β1 levels were positively correlated with PINP levels in patients with airway stenosis. The area under the receiver operating characteristic curve of TGF-β1 and PINP for distinguishing airway stenosis from non-stenosis cases was 0.824 (95% CI: 0.748-0.900) and 0.863 (95% CI: 0.796-0.930), respectively. Therefore, TGF-β1 and PINP are potential biomarkers that may be useful for diagnosing and monitoring PTTS.
Background: In the patients with pulmonary embolism (PE), PE itself can cause haemoptysis and other reasons can also cause haemoptysis. Therefore, the clinical characteristics and the causes of haemoptysis are lacking. Methods: A retrospective analysis was performed that involved screening 583 PE patients and determining that haemoptysis occurred in 141 cases. Of these, eight cases were omitted due to anticoagulation-related haemoptysis or unavailable data, leaving 133 cases that were enrolled in final analysis (127 acute and 6 chronic case of PE). We classified the acute PE patients who combined with diseases which can cause haemoptysis to non-simple group (n = 61) and those without these diseases to simple group (n = 66). Results: The incidence of haemoptysis in PE patients was 23.75%. In the simple group, the amount of haemoptysis ≤ 5 mL was 80.30% (53/66) and ≤ 20 mL was 90.91% (60/66). In the non-simple group who combined with lung cancer, the amount of haemoptysis ≤ 5 mL was 68.4% (26/38) and ≤ 20 mL was 86.8% (33/38). Further analyses revealed that the amount of haemoptysis in the non-simple group was larger than that in the simple group (median 5 [5-125] vs. 5 [5-5], p < 0.001; volume ≥ 100 mL: 29.5% vs. 6.1%, p< 0.001). Among all the PE patients, chronic thromboembolic pulmonary hypertension (CTEPH), PE combined with tuberculosis (TB) and PE combined with bronchiectasis were independent risk factors for the amount of haemoptysis ≥ 100 mL (OR = 15.00, (95% CI: 2.235-100.652); 12.00, (3.101-46.437); 60.00, (6.552-549.441), respectively). Conclusions: The haemoptysis caused by acute PE or PE combined with lung cancer was mild and was characterised by blood in sputum. PE combined with TB, bronchiectasis and CTEPH are associated with moderate to massive haemoptysis, with a greater risk of haemoptysis ≥ 100 mL.
The representation of three-dimensional objects with point clouds is attracting increasing interest from researchers and practitioners. Since this representation requires a huge data volume, effective point cloud compression techniques are required. One of the most powerful solutions is the Moving Picture Experts Group geometry-based point cloud compression (G-PCC) emerging standard. In the G-PCC lifting transform coding technique, an adaptive quantization method is used to improve the coding efficiency. Instead of assigning the same quantization step size to all points, the quantization step size is increased according to level of detail traversal order. In this way, the attributes of more important points receive a finer quantization and have a smaller quantization error than the attributes of less important ones. In this paper, we adapt this approach to the G-PCC predicting transform and propose a hardware-friendly weighting method for the adaptive quantization. Experimental results show that compared to the current G-PCC test model, the proposed method can achieve an average Bjøntegaard delta rate of -6.7%, -14.7%, -15.4%, and -10.0% for the luma, chroma Cb, chroma Cr, and reflectance components, respectively on the MPEG Cat1-A, Cat1-B, Cat3-fused and Cat3-frame datasets.
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