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Mitochondrial dysfunction is a salient feature of myocardial ischemia/reperfusion injury (MIRI), while the potential mechanism of mitochondrial dynamics disorder remains unclear. This study sought to explore whether activation of Adenosine monophosphate-activated protein kinase (AMPK) could alleviate MIRI by regulating GTPase dynamin-related protein 1 (Drp1)-mediated mitochondrial dynamics. Isolated mouse hearts in a Langendorff perfusion system were subjected to ischemia/reperfusion (I/R) treatment, and H9C2 cells were subjected to hypoxia /reoxygenation (H/R) treatment in vitro . The results showed that AICAR, the AMPK activator, could significantly improve the function of left ventricular, decrease arrhythmia incidence and myocardial infarction area of isolated hearts. Meanwhile, AICAR increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) content in myocardial homogenate. Mechanistically, AICAR inhibited the phosphorylation of Drp1 at Ser 616 while enhanced phosphorylation of Drp1 at Ser 637. In addition, AICAR reduced the expression of inflammatory cytokines including TNF-ɑ, IL-6, and IL-1β , as well as mitochondrial fission genes Mff and Fis1 , while improved the expression of mitochondrial fusion genes Mfn1 and Mfn2 . Similar results were also observed in H9C2 cells. AICAR improved mitochondrial membrane potential (MMP), reduced reactive oxygen species (ROS) production, and inhibited mitochondrial damage. To further prove if Drp1 regulated mitochondrial dynamics mediated AMPK protection effect, the mitochondrial fission inhibitor Mdivi-1 was utilized. We found that Mdivi-1 significantly improved MMP, inhibited ROS production, reduced the expression of TNF-a, IL-6, IL-1β, Fis1 , and Mff , and improved the expression of Mfn1 and Mfn2 . However, the protection effect of Mdivi-1 was not reversed by AMPK inhibitor Compound C. In conclusion, this study confirmed that activation of AMPK exerted the protective effects on MIRI, which were largely dependent on the inhibition of Drp1-mediated mitochondrial fission.

This study aimed to evaluate the cost-effectiveness of osimertinib vs docetaxel and bevacizumab in third-line treatment in EGFR T790M resistance mutation advanced non–small cell lung cancer in China from the perspective of the health care system. To explore modeling uncertainty, 2 different model methods (a Markov model and a partitioned survival [PS] model) were developed to simulate costs and health outcomes during a lifetime. Both models consisted of 3 health states: progression-free survival, postprogression survival, and death. Efficacy and safety data of osimertinib vs docetaxel and bevacizumab in patients who had acquired EGFR T790M resistance mutation were derived from a key head-to-head clinical trial. Cost and utility values were derived from local charges, the literature, the China Drug Bidding Database, and patients’ health care documents. Two scenario analyses and sensitivity analyses were performed to explore the robustness of the results. In the Markov model, compared with docetaxel and bevacizumab, osimertinib yielded 0.69 additional quality-adjusted life-years (QALYs) at an additional cost (in US dollars) of $17,311 for an incremental cost-utility ratio (ICUR) of $25,463 per QALY. In the PS model, osimertinib yielded an additional 0.69 QALYs with an incremental cost of $17,827 for an ICUR of $25,951 per QALY. From the Markov model, the ICUR was $29,416 per QALY in scenario 1 and $25,543 per QALY in scenario 2. From the PS model, the ICUR was $30,264 per QALY and $25,947 per QALY for scenarios 1 and 2, respectively. In the probabilistic sensitivity analysis, osimertinib treatment had a 21%–63% probability of being cost-effective at a willingness-to-pay threshold of $9777 to $29,330 per QALY (1–3 times the gross domestic product per capita). The findings from the present analysis suggest that osimertinib could be cost-effective vs docetaxel and bevacizumab in third-line treatment in EGFR T790M resistance mutation advanced non–small cell lung cancer in China. •The model projected that both the average time of progression free survival and overall survival was longer with osimertinib vs. docetaxel-bevacizumab.•Osimertinib, as a third-line treatment option, resulted in a gain of 0.69 quality-adjusted life-years and 1.21 life-years, increased costs of US$17,490.32, resulting in an incremental cost-effectiveness ratio of US$25,462.84/quality-adjusted life-year and US$14,490.63/life-year compared with docetaxel-bevacizumab.•The use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental costutility.

Background In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. Methods A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. Results Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. Conclusion Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Objective: We conducted a large-scale meta-analysis and subgroup analysis to compare the effect of fixed-dose combination (FDC) therapy with that of free-equivalent combination (FEC) therapy on medication adherence. Methods: Studies published in Web of Science, PubMed, Cochrane Library, ScienceDirect, and Embase up to May 2022 were identified according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary assessed outcomes were the medication possession ratio (MPR) and proportion of days covered (PDC). We investigated the probability of being adherent to the prescribed treatment (MPR or PDC ≥80%) or the average estimate of these two parameters. Studies reporting such results were included in this meta-analysis. The summary measures were reported as the risk ratio (RR) and the weighted mean difference (MD) with 95% of confidence interval (CI) using the random-effects model of DerSimonian and Laird. The quality of the cohort studies was assessed using the Newcastle-Ottawa scale. Results: Of the 1,814 screened studies, 61 met the predefined inclusion criteria. The meta-analysis of the results showed that compared to FEC, FDC significantly improved the medication compliance of patients by 1.29 times (95% CI:1.23–1.35, p < 0.00001). I 2 of 99% represent high heterogeneity across studies. The mean difference in medication adherence between FDC and FEC was 0.10 (95% CI: 0.06–0.14, p < 0.00001) with an I 2 estimate of 100%. Subgroup analyses were performed for studies that reported adherence outcomes according to disease type, period of evaluation and compliance indicators. A sensitivity analysis was conducted to exclude the results of low-quality studies, as well as studies in which there was ambiguity in the method of calculating the estimator. Conclusion: Analysis of the assessed parameters for the intention-to-treat and subgroup populations suggests that FDC can improve adherence to treatment and its advantages over FEC may increase over time. Further research is needed to better understand how medical conditions affect the impact of reduced pill burden on adherence, particularly in diseases other than cardiovascular disease and type 2 diabetes mellitus.

This paper considers output-based adaptive event-triggered control of saturated system with the dynamic anti-windup compensator. An adaptive event-triggered condition with a time-varying threshold function is proposed, under which the system has better performance in saving communication resources. A dynamic anti-windup compensator is employed to overcome the potential performance degradation caused by input saturation. For the prescribed dynamic anti-windup compensator, an optimization problem is proposed for enlarging the domain of attraction. Moreover, if dynamic anti-windup compensator is not given in advance, co-design of the dynamic anti-windup compensator and adaptive event-triggered condition is developed. In addition, the Zeno behavior is excluded by calculating the minimum triggering time interval. Finally, the theoretical result is verified by numerical simulation.

This paper addresses the co-design of anti-windup compensator and a novel saturation-based dynamic event-triggered condition for asymmetric saturated system. Asymmetric saturation frequently appears in practical systems, which may seriously degrade the system performance. For the systems with undetectable state, dynamic output feedback controller is employed in this paper. A saturation-based dynamic event-triggered mechanism related to the upper and lower bounds of asymmetric saturation is proposed in this paper, which has better performance in reducing the event-triggered number than static event-triggered condition. In addition, the minimum triggering time interval is calculated to avoid Zeno behavior. An optimization problem is formulated to maximize estimated stable region for the closed-loop system. Finally, the proposed results are illustrated by a numerical example.

Atrial fibrillation (AF) is a common clinical arrhythmia, primarily associated with the risk of stroke and various thromboembolic events, imposing significant clinical and economic burdens on patients and societies. This study aimed to review the relevant pharmacoeconomic evaluations of novel oral anticoagulants (NOACs) compared to vitamin K antagonists (VKAs) in patients with AF and explore the influencing factors and general trends of economic evaluations. This review qualitatively analyzed the basic characteristics, model structure, and basic results of all included studies. Moreover, a cross-sectional and longitudinal comparative analysis of costs, health outcomes, and cost-effectiveness results of studies in the United States, China, and the United Kingdom was conducted. Additionally, this study employed multivariate binary logistic regression to explore the influencing factors and general trends of the cost-effectiveness between NOACs and VKAs across all included studies. A total of 103 studies were included, comprising 218 comparisons between NOACs and VKAs. Total costs and health outcomes measured in studies with different countries and baseline characteristics exhibited considerable variations. However, NOACs generally had higher total costs than VKAs and resulted in more health outcomes for patients. The binary logistic regression analysis revealed that the country's economic development level, study perspective, and cycle length significantly influenced cost-effectiveness results. In high-income countries, NOACs are generally considered cost-effective, while VKAs may remain an attractive strategy in middle- and low-income countries. Additionally, factors such as drug prices, patient baseline characteristics, and model settings could impact the costs, health outcomes, and cost-effectiveness results of studies. Conducting relevant pharmacoeconomic research based on specific populations and study contexts is essential.

Purpose Willingness-to-pay (WTP) and willingness-to-accept (WTA) are widely used measures of individual preferences in valuing healthcare services; however, a persistent disparity between them, often with WTA exceeding WTP, raises concerns. This study aims to review empirical research evidence to achieve a comprehensive understanding of the disparity between WTA and WTP for health outcomes or healthcare goods and services. Methods A search was conducted in PubMed, Embase, Web of Science, and Scopus from inception to November 15, 2023, for empirical research articles reporting both WTA and WTP in the healthcare field. Data extracted from the included studies encompassed WTA and WTP values, participation response rates, and other study characteristics. Descriptive analyses were conducted to compare WTA/WTP ratios across studies, and chi-square tests were applied to examine differences in response rates where applicable. Results A total of 779 records were identified through database searches. After removing duplicates, 405 records remained for title and abstract screening. Of these, 70 articles were retrieved for full-text review, and 28 articles met the eligibility criteria for inclusion in the final qualitative analysis, encompassing 35 distinct studies or subgroups. The reported WTA/WTP ratios ranged from 0.14 to 29.19, with a median value of 1.61, indicating that individuals often demand higher compensation to give up healthcare benefits than they are willing to pay to obtain them. Among the empirical studies analyzed, 29 studies (82.86%) from 24 articles reported WTA values that exceeded WTP values, while 6 studies (17.14%) from the remaining 4 articles indicated WTA values lower than WTP values. Among the 14 studies reporting both WTA and WTP response rates, six studies indicated a significantly lower WTA response rate compared to the WTP response rate, whereas two studies found the WTA response rate to be significantly higher ( P  < 0.05). The WTP response rate was observed to range from 0.89 to 20.23 times that of the WTA response rate. Conclusions The results of this study suggest that losses in health outcomes or healthcare goods and services are valued differently than gains. The disparities between WTA and WTP are influenced by various factors, including the income effect and personal preferences. Individual preferences shape perceptions of WTA and WTP questions, resulting in varied response rates. Considering these disparities in the medical and healthcare fields can assist policymakers in making more informed decisions regarding the allocation of medical and health resources.

BackgroundTo evaluate the short-term efficacy, lung function, and oxidative stress levels between the robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery group (VATS) for non-small cell lung cancer (NSCLC).MethodsWe conducted a retrospective cohort study, selecting 248 NSCLC patients who underwent minimally invasive lobectomy at the Department of Thoracic Surgery, Gansu Provincial People’s Hospital, from August 2019 to February 2023. There were 105 patients in the RATS group and 143 patients in the VATS group. The patients in the two groups were subjected to 1:1 propensity score matching analysis (PSM), and the perioperative indicators were recorded. The levels of oxidative stress factors (superoxide dismutase, SOD; malondialdehyde, MDA) and inflammatory factors were measured 1 day before surgery and 3 days after surgery, respectively. Pulmonary function and patient quality of life were measured at 1 day preoperatively and 3 months postoperatively.ResultsThere are 93 patients in each group after PSM. Compared to the VATS group, the RATS group had shorter operation time, less intraoperative blood loss, greater number and groups of lymph nodes cleared, and shorter postoperative hospital stay. The SOD level in the RATS group was higher and the MDA level was lower than that in the VATS group after surgery. Postoperative inflammatory cytokine levels were less elevated in the RATS group than in the VATS group. At 3 months postoperatively, FVC%, FEV1%, and GQOLI-74 scores were higher in the RATS group than in the VATS group.ConclusionCompared to VATS lobectomy, RATS lobectomy has the advantages of shorter operative time, lesser bleeding, more lymph node dissection, faster postoperative recovery, and lesser impact on postoperative lung function. It is also capable of reducing the postoperative oxidative stress and inflammatory response, which can improve patients’ quality of life.

The frequent occurrence of space debris collision incidents has made research on autonomous satellite avoidance necessary. Against this backdrop, the paper presents a short-term autonomous space debris avoidance algorithm based on the Equivalent Linear Velocity Obstacle (ELVO) paradigm, which addresses the challenges of multiple debris scenarios and real-time decision-making. Error analysis and compensating terms are provided to enhance the algorithm’s accuracy. Simulations are proposed to validate the algorithm, and the simplified design reduces the online computational load, demonstrating its feasibility for future on-orbit usage.