Small cell lung cancer (SCLC) is a highly malignant lung cancer with a very poor prognosis. Clinical treatment options for SCLC are still limited, especially for patients who have failed first or ...second line therapy. Anlotinib is a potentially beneficial new treatment option for SCLC. The aim of this meta-analysis is to evaluate the efficacy and safety of anlotinib-containing regimen for the treatment of SCLC.
We will search SinoMed, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed for relevant articles that may meet the criteria published before March 31, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of anlotinib-containing regimen for the treatment of SCLC. Clinical randomized controlled trials comparing anlotinib-containing regimens with other treatment regimens for advanced SCLC will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.
The results of this study will provide evidence of anlotinib-containing regimens for advanced SCLC, and provide clinicians and patients with another convenient and effective treatment regimen for SCLC. This meta-analysis will be submitted to a peer-reviewed journal for publication.
This meta-analysis will provide clinical evidence of anlotinib-containing regimens for advanced SCLC, which may or may not be found for anlotinib use.
INPLASY202110034.
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•A co-sintering method for the fabrication of W alloy/steel composite structure is presented.•The base materials exhibit high relative density and good mechanical ...properties.•Microstructural analysis reveals the formation mechanism of in-situ formed reaction layer at W alloy/steel interface.•The high shear strength of W alloy/steel composite structure is benefited from the interfacial microstructure.
In this study, tungsten alloy/steel composite structure has been successfully fabricated by co-sintering method using hot isotactic pressing (HIP). The microstructure and mechanical properties of co-sintered samples were investigated systematically. Experimental results show that dense co-sintered base materials were obtained with good tensile properties (870 MPa for 90 W-4.2Ni-1.8Fe-4Cu alloy and 1350 MPa for 30CrMnSiNi2A steel). The co-sintered joint contains five regions: the W alloy matrix, the diffusion-affected zone of the W alloy (η-carbides contain Fe3W3C and Fe6W6C), the reaction interlayer, the diffusion-affected zone of the steel ((Ni, Fe, Cu) solid solution), and the steel matrix. The interlayer shows solidification structure, which is composed of Fe0.64Ni0.36, Cu0.81Ni0.19, Fe3W3C and Fe2W Laves phases. The η-carbides transitional belt with thickness of 4–6 μm formed along the W grain boundaries at the interfacial region between W alloy and interlayer, which is the weakest area of the interface according to the TEM and nanoindentation test results. Furthermore, the formation mechanism of the interfacial structure is deeply discussed. The interfacial shear and tensile strengths of the co-sintered specimen is 310 MPa and 148 MPa, respectively. This technique provides a reliable method of efficient preparation of tungsten alloy/steel composite structure.
BackgroundMicrobiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided ...transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules.MethodsThis was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve.ResultsA total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826).ConclusionEBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.
Linezolid, moxifloxacin, rifapentine, rifabutin, cycloserine, clofazimine, bedaquiline, levofloxacin, prothionamide, and ethionamide are commonly used second-line antituberculosis (anti-TB) drugs. To ...support therapeutic drug monitoring in regular clinical practice, the authors sought to develop a method based on ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) that would allow for the simultaneous quantification of multiple second-line anti-TB drugs in human serum.
Analytes were extracted from human serum by protein precipitation. UHPLC-MS/MS was performed using a gradient at a flow rate of 0.3 mL/min, and each sample was taken for 7.5 minutes. The mass spectrometry scanning mode used was electrospray ionization with multiple reaction monitoring in the positive mode.
Validation showed that endogenous substances in the sample did not interfere with the assay, and the relationship between X and Y was highly linear, with a coefficient of determination (R2) >0.9954 for each curve. The accuracy (85.0%-114.7%) and precision (intraday: 0.27%-9.32%; interday: 0.20%-7.66%) were less than 15.0%, and the internal standard-normalized matrix effects were consistent (coefficient of variation ≤4.40%). The analytes were stable in the final extract and human serum under various storage conditions (recovery: 87.0%-115.0%). The clinical applicability of the method was demonstrated by quantitative determination of analytes in serum samples obtained from patients with TB. Reproducibility of the drug concentrations measured in clinical samples was confirmed by incurred sample reanalysis.
A simple and reliable analytical method was developed and validated for the simultaneous determination of 10 anti-TB drugs in human serum using UHPLC-MS/MS. Quantitation of anti-TB drugs in clinical samples confirmed that the assay is suitable for therapeutic drug monitoring in regular clinical practice.
This study used a two-stage light gas gun to launch reactive fragments at high speeds into steel plates with different grain sizes (large and small). In addition, utilizing material characterization ...technologies like SEM, EBSD, and TEM, the microstructure evolution of steel plates with varying grain sizes was measured and analyzed both before and after impact. The results indicate that small-grain steel plates are more prone to intergranular or transgranular crack propagation, and they produce more macroscopic and microscopic cracks on the perforated surface under high-speed impact than large-grain steel plates. At the grain boundaries of both large and small grains of steel plate, as well as high-density dislocations, the impact process produces a significant number of minor angles with local misorientation ranging from 2 to 10°. A small-grain steel plate has an obvious grain boundary-strengthening effect. Small grains are more likely than large grains to cause changes in the crystal structure of BCC-HCP close to the perforation, and some grains form a lot of nanoscale elongated structures with the same crystal structure as the matrix. The interaction between dislocations or the emission of a large number of dislocation cells from grain boundaries may occur within some of the larger grains. The study's findings, which are illustrated in this article, can be used as a reference to understand how grain size influences the steel plates' microstructure changes after impacts.
In this paper, the AUTODYN/Smoothed Particle Hydrodynamics (SPH) method was used to study the impact of reactive fragments on three-layer equidistant steel plates. The perforation characteristics of ...equidistant three-layer steel plates were investigated along with the parameters of combustion energy release from reactive fragments under varied impact velocities and shape conditions. The modification of the steel plates’ perforation diameter was investigated using the dimensional analysis approach. The shock wave pressure and chemical reaction characteristics were examined using the shock wave theory. The results show that within the examined impact velocity range, the perforation diameter initially increased and then decreased as the impact velocity of the reactive fragment rose. In addition, the perforation diameter was approximately 1.5–3 times the diameter of the reactive fragment. As the impact speed increased, the active reaction generated by the reactive fragments became more sufficient. The energy released contributed to the impact’s pressure rise; in addition, the temperature of the steel plate was raised in part by the reactive fragment impact, making the steel plate more prone to melting. The results of this investigation provide important support for a detailed understanding of the rules governing the failure of steel plates under the impact of reactive fragments as well as the combustion of reactive fragments under impact.
•Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with multidrug-resistant tuberculosis.•The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during ...treatment.•Bedaquiline remained detectable 52 weeks after discontinuation.•Combination with clofazimine during bedaquiline treatment increased the risk of QTc prolongation.•QTc prolongation was closely associated with the serum electrolytes (K+ and Na+).
To determine the safety and efficacy of bedaquiline for Chinese patients with multidrug-resistant tuberculosis (MDR-TB) based on serum concentration monitoring and to identify factors associated with QTc prolongation occurring during treatment.
Data were collected from 35 patients who received treatment regimens containing bedaquiline for MDR-TB from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography–mass spectrometry.
After completing the 24-week bedaquiline treatment course, 80.0% of the patients’ sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range 52–126 days). The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml at 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline.
Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with MDR-TB. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline.
The paper explores the possibility of reducing the sintering temperature of the 90W–7Ni–3Fe alloy by introducing Cu without sacrificing the comprehensive mechanical properties. The effect of Cu ...content on the sintering behavior, microstructure and mechanical properties of the 90W–7Ni–3Fe alloy was systematically investigated in the range from 1250 to 1350 °C. The results indicate that Cu significantly decreased the liquidus temperature of the 90W–7Ni–3Fe alloy, which directly influence the sintering behavior. With increasing of Cu content, the sintering behavior of the 90W–7Ni–3Fe alloy changed from solid to liquid phase sintering. The relative density of sintered alloys obtained at 1350 °C increased consistently from 81.61% without Cu to 98.85% with Cu concentration up to 5 wt.%. The X–ray diffraction (XRD) and transmission electron microscopy (TEM) results reveal that, Cu diffused with γ–(Ni, Fe) phase during sintering process and this results in the formation of the γ–(Ni, Fe, Cu) phase, which is well bonded with W grains. The formation process of γ–(Ni, Fe, Cu) phase is also discussed. The tensile strength and hardness of the 90W–7Ni–3Fe alloys were improved obviously by adding Cu. At 1350 °C, the tensile strength of alloys with 5 wt.% Cu is as high as 864 MPa, which was four times than that of the alloy without Cu.
Multidrug-resistant tuberculosis (MDR-TB) remains a main global health concern as there is no comprehensive therapeutic intervention yet and numerous adverse effects follow the therapeutic process. ...In recent years, linezolid has been frequently used for treating MDR-TB. However, peripheral neuropathy associated with linezolid has reduced patient compliance. The current study explored the mechanism underlying linezolid-induced peripheral neuropathy in MDR-TB. Autophagy plays a neuroprotective role against peripheral nerve injury. We hypothesized that autophagy might also play a neuroprotective role against linezolid-induced peripheral neuropathy. In this study, we collected 12 questionnaires from MDR-TB patients in our hospital, and 10 of them developed linezolid-induced pain. The pain is mainly concentrated in the feet and accompanied by numbness. Subsequently, we used Sprague-Dawley (SD) rats and Schwann cells (SCs) to explore the mechanism. We found that linezolid causes a sparse arrangement of sciatic nerve tissue with associated loss of neurons, myelin sheaths, and down-regulation of LC3B expression. These results were also confirmed by
in vitro
experiments, showing that linezolid inhibited the proliferation of SCs. And the expression of P-AKT and P62 was elevated, and the expression of LC3B declined compared with the control group. Moreover, chloroquine (CQ), an autophagy inhibitor, also exhibited experimental results similar to linezolid. In summary, we conclude that linezolid-induced peripheral neuropathy is associated with the inhibition of autophagy flux.
Powder metallurgy hot isostatic pressing (HIP) is a promising technology for producing complex ultrahigh strength steel (UHSS) components. In the present study, a kind of China UHSS, 30CrMnSiNi2A ...steel, was prepared by HIP with different processing temperatures. The microstructure and tensile properties of HIPed compacts were analyzed in depth via scanning electron microscopy, X–ray diffraction, electron back–scattered diffraction, transmission electron microscopy, tensile testing and nanoindentation experiment. Results show that all HIPed compacts are granular bainitic structure composed of bainitic ferrite matrix and M–A islands. With the HIP temperature increasing, the volume fraction of M–A islands decreases, and the average grain size increases. Besides, a harmful structure (that is prior particle boundaries, PPBs), which is composed of a great number of Mn–rich and Si–rich oxide inclusions, is formed in the HIPed compacts. Notably, increasing HIP temperature is beneficial to eliminate PPBs. The volume fraction of M–A islands, grain size and the state of PPBs together determine the tensile properties of HIPed compacts, in which the state of PPBs has a most significant impact. With the HIP temperature rising, the tensile fracture mode changes from inter–particle debonding to transgranular quasi–cleavage, which benefits from the elimination of PPBs.
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