Explore the vast range of titles available.

Objective: Camrelizumab is the first domestic PD-1inhibitor approved to be combined with chemotherapy as a first-line therapy for advanced nonsquamous non–small-cell lung cancer (NSCLC) in China. The purpose of this study was to determine whether using camrelizumab in the first-line setting is cost-effective in China when compared with traditional chemotherapy or the imported PD-1inhibitor pembrolizumab. Material and Methods: A Markov model was built to simulate 3-week patient transitions over a 30-year horizon from the perspective of the Chinese healthcare system. Health states included stable disease, first progression, second progression, and death. A direct comparison between first-line camrelizumab in combination with pemetrexed and carboplatin (CPC) and pemetrexed plus carboplatin (PC) was performed by calculating transition probabilities from the CameL trial. An indirect comparison between first-line CPC and pembrolizumab in combination with pemetrexed and platinum (PPP) was performed by calculating transition probabilities using a network meta-analysis. Costs in the Chinese setting were collected from the local public database and literatures. Sensitivity analyses explored the uncertainty around model parameters. Results: In the primary analysis, first-line CPC gained an additional 0.41 quality-adjusted life-years (QALYs) with an incremental cost of$3,486 compared with PC, resulting in an incremental cost-effectiveness ratio (ICER) of $ 8,378 per QALY gained. In the secondary analysis, first-line PPP yielded an additional 0.10 QALYs at an incremental cost of$6,710, resulting in an ICER of $ 65,563 per QALY gained. Conclusion: For Chinese patients with advanced nonsquamous NSCLC without targetable genetic aberrations, our primary analysis results supported first-line CPC as a cost-effective treatment compared with traditional PC chemotherapy. The findings of our secondary analysis suggested that first-line PPP would not be a cost-effective option compared with first-line CPC. This analysis provided strong evidence for promoting the widespread use of first-line CPC in China and, to some extent, stimulated the enthusiasm for the development of domestic cancer drugs.

Aqueous Zn‐ion batteries (AZIBs) are regarded as a promising alternative to the widely used lithium‐ion batteries in large‐scale energy storage systems. The researches on the development of novel aqueous electrolyte to improve battery performance have also attracted great interest since the electrolyte is a key component for Zn2+ migration between cathode and anode. Herein, we briefly summarized and illuminated the recent development tendency of aqueous electrolyte for AZIBs, then deeply analyzed its existing issues (water decomposition, cathode dissolution, corrosion and passivation, and dendrite growth) and discussed the corresponding optimization strategies (pH regulation, concentrated salt solution, electrolyte composition design, and functional additives). The internal mechanisms of these strategies were further revealed and the relationships between issues and solutions were clarified, which could guide the future development of aqueous electrolytes for AZIBs. This review reveals the internal mechanisms of these strategies and clarifies the relationships between different issues and solutions for aqueous Zn‐ion batteries.

For wave loads on cylinders constituting a long but finite array in the presence of incident waves, variations in the magnitude of the load with the non-dimensional wavenumber exhibit interesting features. Towering spikes and nearby secondary peaks (troughs) associated with trapped modes have been studied extensively. Larger non-trapped regions other than these two are termed Region III in this study. Studies of Region III are rare. We find that fluctuations in Region III are regular; the horizontal distance between two adjacent local maximum/minimum points, termed fluctuation spacing, is constant and does not change with non-dimensional wavenumbers. Fluctuation spacing is related only to the total number of cylinders in the array, identification serial number of the cylinder concerned and wave incidence angle. Based on the interaction theory and constructive/destructive interference, we demonstrate that the fluctuation characteristics can be predicted using simple analytical formulae. The formulae for predicting fluctuation spacing and the abscissae of every peak and trough in Region III are proposed. We reveal the intrinsic mechanism of the fluctuation phenomenon. When the diffraction waves emitted from the cylinders at the ends of the array and the cylinder concerned interfere constructively/destructively, peaks/troughs are formed. The fluctuation phenomenon in Region III is related to solutions of inhomogeneous equations. By contrast, spikes and secondary peaks are associated with solutions of the eigenvalue problem. This study of Region III complements existing understanding of the characteristics of the magnitude of wave load. The engineering significances of the results are discussed as well.

High-power inductors are fundamental components in high-power DC–DC converters, with their performance being a crucial metric of converter efficiency. This paper presents an in-depth analysis of a novel calculation method for the air gap length in such inductors. Taking into account the effects of air gap diffusion and the winding magnetic field, an expression for the air gap diffusion radius is derived, focusing on a distributed air gap structure. Furthermore, models for calculating the air gap and winding reluctance are developed, grounded in electromagnetic field theory. An equivalent magnetic circuit model, formulated based on Kirchhoff's second law, facilitates the proposed method for air gap length calculation. This study also involves the development of 3D models for both discrete and decoupled integrated inductors. The comparison between simulation outcomes and calculated air gap lengths indicates a maximum error of less than 8%, with the minimum error being as low as − 0.79%. Compared with traditional methods, the calculation method proposed in this paper has significant advantages. Additionally, the discrepancy between calculated values and experimental measurements is found to be 1.11%. These results validate the accuracy and applicability of the theoretical analysis and calculation method, underscoring their significance in the design and optimization of high-power DC–DC converters.

To determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China. Using a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model. In the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model. In China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective.

Oral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC. A three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25, $9362 and 0.78, $33,814 and 0.45, $49,120 and 0.83, $63,064 and 0.81, $74,814 and 0.82, $81,995 and 0.82, $74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was $779576, $1534,347, $1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs. For oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab.

Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system. Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of$35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model. Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $ 28,749, resulting in an ICER of$28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $ 27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold. Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.

In order to further improve the power-generating capacity of the wave energy converter (WEC) of oscillating buoy type, this paper puts forward a novel type where the WEC can move and extract power in five degrees of freedom. We make a detailed hydrodynamic analysis of such WECs. Each buoy is modeled as a floating truncated cylinder with five degrees of freedom: surge, sway, heave, roll, and pitch, and there are relative motions among buoys in the array. Linear power take-off (PTO) characteristics are considered for simplicity. Under the linear wave theory, a semi-analytical method based on the eigenfunction expansion and Graf’s addition theorem for Bessel functions is proposed to analyze the hydrodynamic interactions among the WEC array under the action of incident waves, and the amplitude response and power extraction of the WEC array are then solved. After verifying the accuracy of hydrodynamic analysis and calculation, we make preliminary case studies, successively investigating the power-generating capacity of a single WEC, an array of two WECs, and an array of five WEC; then, we compare their results with the conventional heaving WECs. The results show that the WEC with five degrees of freedom can significantly improve the power extraction performance.

Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double‐hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery ligation (LPAL) with hypoxia exposure in C57BL/6 mice. Our detailed haemodynamic and histological evaluations post‐surgery demonstrated pronounced elevations in right ventricular systolic pressure (RVSP) (LPAL: 41.1 ± 4.63 mmHg, P = 0.005; LPx: 38.4 ± 2.95 mmHg, P = 0.002; Sham: 32.1 ± 2.21 mmHg) and pulmonary vascular wall thickness (LPAL: 56.9 ± 3.34%, P = 0.02; LPx: 54.3 ± 4.65%, P = 0.04; Sham: 44.8 ± 3.76%) compared to hypoxia‐exposed sham‐operated controls, reflecting a more severe PH phenotype. These novel models, which exhibit haemodynamic alterations akin to the established hypoxia with SU5416‐induced PH model as per published data, could offer a substantial contribution to future PH research and therapeutic development. What is the central question of this study? Existing mouse models of pulmonary hypertension (PH) under hypoxia exhibit only mild PH: can a mouse model of PH be established that exhibits a more severe PH phenotype? What is the main finding and its importance? Mouse models with more severe PH were successfully established through a combination treatment involving unilateral pneumonectomy or left pulmonary artery ligation followed by hypoxia exposure. This approach results in a more pronounced PH phenotype compared to traditional models that rely solely on hypoxia exposure.

The drilling and blasting method is widely used in tunnel engineering. The accompanying airblast may damage structures and annoy nearby occupants. The prediction of airblast overpressure ( p oa ) outside the tunnel is necessary to improve the safety of blasting works. A study of propagation characteristics of airblasts induced by tunnel blasting was carried out through experimental and numerical studies. The results indicate that the distributions of the p oa outside the tunnel were anisotropic, which does not conform to the decay law of an explosion in free-field. The propagation of airblasts induced by tunnel blasting is related to the airblast shape. The phenomenon that the p oa along the axial direction of the tunnel was higher than along other directions can be explained by the numerical results of the process of airblasts. The airblasts outside the tunnel traveled as a spherical wave, but the pressure was not uniformly distributed. After an airblast plane wave with high speed and high pressure inside the tunnel was transmitted out of the tunnel, its inertia strengthened the pressure in the axial direction. The airblast outside the tunnel is related to the propagation distance R out , the angle from the measurement to the tunnel axis α , and the pressure intensity p 0 at the tunnel portal. Subsequently, an ellipsoidal contour curve of the p oa outside the tunnel was plotted, and therefore a new prediction equation was validated by numerical results and field data. Finally, the newly proposed methodology guided the blast design.