Estimating the Economic Impact of Levalbuterol's Potential Transition From the National Reimbursement Drug List for the Treatment of Pediatric Asthma in China: A Budget Impact Analysis.

Background Levalbuterol is a short-acting ß2-agonist (SABA) indicated for treating or preventing asthma exacerbation. It was included in the 2020 Chinese National Reimbursement Drug List (NRDL). This study estimates the economic impact of levalbuterol's status change within and withdrawal from the NRDL in treating pediatric asthma from a publicly funded medical insurance perspective. Methodology A prevalence-based budget impact model was developed. The analysis compared a world with a levalbuterol scenario to a world without levalbuterol. Epidemiological data were obtained from the existing literature. Cost data were estimated based on the drug dosage in clinical trials, real-world settings, and expert opinions. Scenario analysis considered the same length of stay (LOS) in the two groups. One-way sensitivity analyses were carried out to show the impact of varying individual parameters. Results In the base-case analysis, compared to the world without scenario, the preservation of levalbuterol resulted in cost savings of ¥82.8 million in China over three years. In the scenario analysis, savings decreased to ¥76.1 million over three years. Sensitivity analysis showed that, for the most part, the results were robust to changes in input parameter values. Conclusions Using levalbuterol may lead to substantial cost savings for Chinese society.

Cost-Utility Analysis of Berberine Chemoprevention for Colorectal Cancer After Polypectomy.

Background Chemoprevention, such as berberine, has been developed as an alternative or complementary strategy to colonoscopy surveillance and has shown promise in reducing the morbidity and mortality of colorectal cancer. This study aims to evaluate the cost-effectiveness of berberine for postpolypectomy patients from the US third-party payer. Methods A Markov microsimulation model was developed to compare the cost and efficacy of berberine to no intervention, colonoscopy, and the combination of berberine and colonoscopy in postpolypectomy patients. Results After simulating 1 million patients, the study found that colonoscopy alone had a mean cost of $16,391 and mean quality-adjusted life-years (QALYs) of 16.03 per patient, whereas adding berberine slightly reduced the mean cost to $15,609 with a mean QALY of 16.05, making it a dominant strategy. Berberine therapy alone was less effective than colonoscopy alone, with a higher mean cost of $37,480 and a mean QALY of 15.32 per patient. However, berberine therapy was found to be a dominant strategy over no intervention. Conclusions Adding berberine to colonoscopy is the most cost-saving and effective approach for postpolypectomy patients. For patients who refuse or have limited access to colonoscopy, berberine alone is likely to be a dominant strategy compared to no intervention.

Comparison of surgical and oncological outcomes between different surgical approaches for overweight or obese cervical cancer patients.

The purpose was to investigate the safety and advantages of different surgical approaches applied to overweight or obese cervical cancer patients by comparing their surgical and oncological outcomes. This is a retrospective cohort study. 382 patients with a body mass index of at least 24.0 kg/m2 and stage IB-IIA (The International Federation of Gynecology and Obstetrics, FIGO 2009) cervical cancer were enrolled, and then were divided into three groups: open radical hysterectomy (ORH) group, laparoscopic radical hysterectomy (LRH) group, and robot-assisted radical hysterectomy (RRH) group according to the surgical approach. IBM SPSS version 25.0 was used to analyze data. There were 51 patients in ORH group, 225 patients in LRH group and 106 patients in RRH group. In the comparison of surgical outcomes, compared to LRH and ORH, RRH had the shortest operating time, the least estimated blood loss, the shortest postoperative hospital stay, and the shortest recovery time for bowel function (P < 0.05). In the comparison of postoperative complications, ORH has the highest rate of postoperative infection and wound complication compared to LRH and RRH (P < 0.05), and RRH has the highest proportion of urinary retention. After a median follow-up time of 61 months, there was no statistically significant difference between the three groups in terms of 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate, (P = 0.262, P = 0.453). In patients with overweight or obese cervical cancer, the long-term outcomes of the three surgical approaches were comparable, with RRH showing significant advantages over ORH and LRH in terms of surgical outcomes.

Immunohistochemical markers Ki67 and P16 help predict prognosis in locally advanced cervical cancer.

OBJECTIVE: To investigate the relationship between Ki-67 and P16 expression levels after neoadjuvant chemotherapy, and the clinicopathological characteristics and prognosis of patients with locally advanced cervical cancer. METHODS: Patients with FIGO 2009 stage IB2 or IIA2 cervical cancer, who underwent neoadjuvant chemotherapy combined with radical hysterectomy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and December 2019, were identified retrospectively to correlate postoperative Ki-67 and P16 expression levels with clinicopathological factors. The optimal threshold for predicting recurrence was analysed using receiver operating characteristic (ROC) curves for the Ki-67 index, and univariate and multi-factorial Cox regression analysis were used to investigate the association between clinicpathological features including Ki-67 and P16 and recurrence-free survival. RESULTS: In total, 334 patients were included after screening. The cut-off value of Ki-67 for determining recurrence was 67.5 % according to the ROC curve. On multi-factorial Cox analysis, lymphatic vascular space (p = 0.003) and Ki-67 index (p = 0.005) were shown to increase the risk of recurrence, and were independent prognostic factors for recurrence, while the expression of P16 was not significantly associated with the risk of recurrence (p = 0.097, odds ratio = 0.319). Patients with cervical cancer in the high Ki-67 expression group (Ki-67 ≥ 67.5 %) had lower recurrence-free survival and overall survival than patients in the low Ki-67 expression group (Ki-67 < 67.5 %) (p = 0.001 and 0.036, respectively). CONCLUSION: The expression levels of Ki-67 and P16 after neoadjuvant chemotherapy for locally advanced cervical cancer correlated with tumour differentiation. High expression of Ki-67 (Ki-67 ≥ 67.5 %) may indicate poorer recurrence-free survival and overall survival.

Cyclodextrin-Mediated Cholesterol Depletion Induces Adiponectin Secretion in 3T3-L1 Adipocytes.

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-ß-cyclodextrin (MßCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MßCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MßCD-induced adiponectin secretion. MßCD-induced adiponectin secretion was reduced after 10 µg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann-Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MßCD-induced adiponectin secretion. Furthermore, treatment with 1 µM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MßCD-induced adiponectin secretion. Finally, MßCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MßCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.

Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model.

Objective: To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI). Methods: To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China's per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI. Results: During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD -1,418), lixisenatide (USD -1,713), semaglutide (USD -4,298), and liraglutide (USD -4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05). Conclusion: Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate.

Impact of Environmental Uncertainties and Strategic Flexibility in Innovation Activities on NEV Battery Recycling Firms in China.

Due to the popularization and development of new energy vehicles (NEVs) worldwide, power batteries that have been used are being retired and replaced. In China's battery recycling industry, the legal NEV battery recycling enterprises are at a negative financial performance. Based on theory of organizational adaptation, the key to innovation performance and sustainable development is recognition of the environment and strengthening organizational flexibility. This study empirically explores the bidirectional dynamic relationships among heterogeneous environmental uncertainties, innovation activities, firm growth and strategic flexibility in Chinese NEV battery recycling firms. A total of 1040 sample data were collected from 2015 to 2021. The research results demonstrate that environmental uncertainty (EU), strategic flexibility (SF) and innovation activities (INNO) all had impacts on firm growth (FG). Specifically, INNO had strongly negative effects in the short term, and in the long term, it will bring a positive effect to FG; the impact of EPU was more important than market uncertainty (MU) to FG and innovation activities. This could be due to the dependence of the Chinese NEV battery recycling industry on government policy. However, MU has a strong impact on SF. Moreover, the levels of SF should be reasonable, otherwise it could be a burden to enterprises. There also exists the bidirectional dynamic relationships between FG and INNO. This study contributes a non-core perspective to strategic flexibility research by revealing the complex environmental mechanism, and to the Chinese NEV battery recycling industry we provide a theoretical basis and practical guidance for government and firms on how to apply SF to promote innovation and realize growth in the present business environment.

Prediction of individual mortality risk among patients with chronic obstructive pulmonary disease: a convenient, online, individualized, predictive mortality risk tool based on a retrospective cohort study.

Background: Chronic obstructive pulmonary disease (COPD) is a serious condition with a poor prognosis. No clinical study has reported an individual-level mortality risk curve for patients with COPD. As such, the present study aimed to construct a prognostic model for predicting individual mortality risk among patients with COPD, and to provide an online predictive tool to more easily predict individual mortality risk in this patient population. Patients and methods: The current study retrospectively included data from 1,255 patients with COPD. Random survival forest plots and Cox proportional hazards regression were used to screen for independent risk factors in patients with COPD. A prognostic model for predicting mortality risk was constructed using eight risk factors. Results: Cox proportional hazards regression analysis identified eight independent risk factors among COPD patients: B-type natriuretic peptide (hazard ratio [HR] 1.248 [95% confidence interval (CI) 1.155-1.348]); albumin (HR 0.952 [95% CI 0.931-0.974); age (HR 1.033 [95% CI 1.022-1.044]); globulin (HR 1.057 [95% CI 1.038-1.077]); smoking years (HR 1.011 [95% CI 1.006-1.015]); partial pressure of arterial carbon dioxide (HR 1.012 [95% CI 1.007-1.017]); granulocyte ratio (HR 1.018 [95% CI 1.010-1.026]); and blood urea nitrogen (HR 1.041 [95% CI 1.017-1.066]). A prognostic model for predicting risk for death was constructed using these eight risk factors. The areas under the time-dependent receiver operating characteristic curves for 1, 3, and 5 years were 0.784, 0.801, and 0.806 in the model cohort, respectively. Furthermore, an online predictive tool, the "Survival Curve Prediction System for COPD patients", was developed, providing an individual mortality risk predictive curve, and predicted mortality rate and 95% CI at a specific time. Conclusion: The current study constructed a prognostic model for predicting an individual mortality risk curve for COPD patients after discharge and provides a convenient online predictive tool for this patient population. This predictive tool may provide valuable prognostic information for clinical treatment decision making during hospitalization and health management after discharge (https://zhangzhiqiao15.shinyapps.io/Smart_survival_predictive_system_for_COPD/).

A Study on Paradoxical Leadership and Multiple Path Mechanisms of Employees' Bootleg Innovation.

Purpose: Based on the social cognitive theory and cognitive-affective system theory, the purpose of this study is to explore how and when paradoxical leadership enhances employees' bootlegging innovation. To achieve this purpose, the authors proposed a double-chain mediation model in this study. Methods: Data with 342 questionnaires were collected for effective matching between employees and leaders at two time nodes. The hypotheses were validated by structural equation modeling and bootstrap approaches. Results: Results indicate that paradoxical leadership has a significant and positive impact on employees' bootleg innovation. In addition, psychological capital and thriving at work play a partial mediating role between paradoxical leadership and employees' bootlegging behaviors respectively and a chain mediating role between the two together. Moreover, there is no significant difference among the three mediating paths. Conclusion: The present research advances our understanding of bootleg innovation with a focus on the specific role of paradoxical leadership. Our findings, and especially those related to the role of psychological capital and thriving at work, reveal the influence mechanisms of paradoxical leadership on employees' bootleg innovation. At the same time, it is useful for understanding what leadership style can effectively stimulate employees' bootleg innovation.

Investigation and research on elderly people's willingness to combine medical and health care and related factors in coastal cities in eastern China.

Background: The problem of global aging was becoming increasingly prominent. At present, the empty nest and miniaturization of family structure reduce the function of home-based elderly care. Methods: A questionnaire survey was conducted on 347 elderly people in multiple communities and nursing homes in eastern coastal cities of China, and 13 institutional staff members of eight nursing institutions that carried out the medical-nursing integration model were interviewed as the research objects. The survey mainly focuses on the basic characteristics of the elderly, the family support system, and the acceptance of medical care and health care. The influencing factors were screened by t test, univariate analysis and multivariate logistic regression analysis. SPSS software was used to test the reliability and validity of the questionnaire, and the Crobach's was 0.792, which can be considered that the questionnaire had good internal reliability. The classification of the questionnaire was reasonable, the reliability of the questionnaire was high, and the internal consistency of the scale was high. According to KMO and Bartlett test, KMO = 0.826, χ2 = 853.731, the degree of freedom was 36, and the P value was 0.000. Results: The proportion of male and female respondents was 48.1% and 51.9% respectively. Multivariate logistic regression analysis results showed that gender had no statistical significances on the degree of support for combine medical and health care in the elderly (P > 0.05). The results showed that gender, age, marital status, medical insurance type and old-age insurance type had little effect on the support of the combination of medical care and health care for the elderly (P > 0.05). Compared with the control group with education below primary school, the elderly with bachelor's degree or above are more willing to support the combination of medical care and health (P < 0.05). The registered residence type is more obvious than that of the urban residents (P < 0.05). Compared with the enterprise employees in the control group, the elderly who were employed as migrant workers before retirement were more willing to support the combination of medical care and health (P < 0.05). From the perspective of family monthly income, the elderly with family income ≥10,000 RMB have more obvious support for the combination of medical care and health than the elderly with family monthly income <3,000 RMB in the control group (P < 0.05). In terms of the degree of understanding, the degree of understanding and support in different degrees are significantly higher than that in the control group (P < 0.05). Conclusion: Through multivariate logistic regression analysis, education level, registered residence, pre-retirement occupation and family income are more obvious for the elderly to support medical care and health. It is necessary to increase investment in elderly activity centers, actively carry out activities.

FCNet: Stereo 3D Object Detection with Feature Correlation Networks.

Deep-learning techniques have significantly improved object detection performance, especially with binocular images in 3D scenarios. To supervise the depth information in stereo 3D object detection, reconstructing the 3D dense depth of LiDAR point clouds causes higher computational costs and lower inference speed. After exploring the intrinsic relationship between the implicit depth information and semantic texture features of the binocular images, we propose an efficient and accurate 3D object detection algorithm, FCNet, in stereo images. First, we construct a multi-scale cost-volume containing implicit depth information using the normalized dot-product by generating multi-scale feature maps from the input stereo images. Secondly, the variant attention model enhances its global and local description, and the sparse region monitors the depth loss deep regression. Thirdly, for balancing the channel information preservation of the re-fused left-right feature maps and computational burden, a reweighting strategy is employed to enhance the feature correlation in merging the last-layer features of binocular images. Extensive experiment results on the challenging KITTI benchmark demonstrate that the proposed algorithm achieves better performance, including a lower computational cost and higher inference speed in 3D object detection.

Impact of Perceived Skillset and Organizational Traits on Digital Wellbeing of Teachers: Mediating Role of Resilience.

Given the current unstable and unpredictable circumstances, especially due to the COVID-19 education system has evolved, requiring frequently distinct skills, and coping behavior. This study intended to empirically test the impact of perceived skillset and organizational traits on teachers' digital wellbeing with the mediating role of three levels of resilience. To serve the cause, non-probability convenience sampling was chosen, and data was gathered through an online survey from 336 on-duty teachers in the education sector of Pakistan. The results of the study have been drawn by using the PLS-SEM partial least squares structural equation modeling technique through the Smart-PLS software 3.0 version. The findings show that perceived skillset had a positive and significant impact on digital wellbeing and organizational traits had an insignificant effect on digital wellbeing. Moreover, results indicate that organizational resilience and employee resilience positively mediate the relationship between perceived skillset and organizational traits on digital wellbeing. Similarly, findings illustrate that team resilience positively mediates the relationship between perceived skillset and digital wellbeing. Furthermore, results show that team resilience negatively and insignificantly mediates the relationship between organizational traits and digital wellbeing. Lastly, discussion, theoretical and practical implications were also discussed in this research article.

Does digital finance improve the green investment of Chinese listed heavily polluting companies? The perspective of corporate financialization.

While now appears appropriate to assert that digital finance can relieve firms' financing constraints, the picture of whether it can improve enterprises' green investment is much less clear. Using 2011-2019 data for Chinese listed heavily polluting (HP) enterprises, we examine the effects of digital finance on corporate green investment. Results show that digital finance impedes HP firms' green investments, and this finding is robust to various tests, including the instrumental variable approach, exogenous shock, and alternative measures of variables. Additional tests reveal that digital finance increases firms' financial investment, which crowds out green investment. Also, this inhibitory impact varies with firms' geographical location, industry characteristics, and the implementation of the new Environmental Protection Law. The findings of this study provide new perspectives on digital finance by identifying its negative impact on the corporate green environment. We also propose corresponding policy recommendations, including strengthening the regulation and guidance of digital finance development, reducing monopolies in the financial sector, and formulating differentiated environmental policies.

Residual Learning and Multi-Path Feature Fusion-Based Channel Estimation for Millimeter-Wave Massive MIMO System.

Channel estimation is a challenging task in a millimeter-wave (mm Wave) massive multiple-input multiple-output (MIMO) system. The existing deep learning scheme, which learns the mapping from the input to the target channel, has great difficulty in estimating the exact channel state information (CSI). In this paper, we consider the quantized received measurements as a low-resolution image, and we adopt the deep learning-based image super-resolution technique to reconstruct the mm Wave channel. Specifically, we exploit a state-of-the-art channel estimation framework based on residual learning and multi-path feature fusion (RL-MFF-Net). Firstly, residual learning makes the channel estimator focus on learning high-frequency residual information between the quantized received measurements and the mm Wave channel, while abundant low-frequency information is bypassed through skip connections. Moreover, to address the estimator's gradient dispersion problem, a dense connection is added to the residual blocks to ensure the maximum information flow between the layers. Furthermore, the underlying mm Wave channel local features extracted from different residual blocks are preserved by multi-path feature fusion. The simulation results demonstrate that the proposed scheme outperforms traditional methods as well as existing deep learning methods, especially in the low signal-to-noise-ration (SNR) region.

SIDT1 plays a key role in type I IFN responses to nucleic acids in plasmacytoid dendritic cells and mediates the pathogenesis of an imiquimod-induced psoriasis model.

BACKGROUND: Type I IFN (IFN-I) is a family of cytokines involved in the pathogenesis of autoimmune and autoinflammatory diseases such as psoriasis. SIDT1 is an ER-resident protein expressed in the lymphoid lineage, and involved in anti-viral IFN-I responses in vivo, through an unclear mechanism. Herein we have dissected the role of SIDT1 in the natural IFN-producing cells, the plasmacytoid dendritic cells (pDC). METHODS: The function of SIDT1 in pDC was determined by silencing its expression in human primary pDC and GEN2.2 cell line. SIDT1 role in vivo was assessed using the imiquimod-induced psoriasis model in the SIDT1-deficient mice (sidt1-/-). FINDINGS: Silencing of SIDT1 in GEN2.2 led to a blockade of the IFN-I response after stimulation of TLR7 and TLR9, without affecting the pro-inflammatory responses or upregulation of maturation markers. We found that SIDT1 migrates from the ER to the endosomal and lysosomal compartments together with TLR9 after CpG stimulation, participating in the access of the TLR9-CpG complex to lysosome-related vesicles, and therefore mediating the activation of TBK1 and the nuclear migration of IRF7, but not of NF-κB. sidt1-/- mice showed a significant decrease in severity parameters of the imiquimod-induced acute psoriasis-like model, associated with a decrease in the production of IFN-I and IFN-dependent chemokines. INTERPRETATION: Our findings indicate that SIDT1 is at the cross-road between the IFN-I and the proinflammatory pathways and constitutes a promising drug target for psoriasis and other diseases mediated by IFN-I responses. FUNDING: This work was supported by the Consejería de Salud y Familias de la Junta de Andalucía (PIER_S1149 and C2_S0050) and Instituto de Salud Carlos III (PI18/00082 and PI21/01151), partly supported by European FEDER funds, and prior funding to MEAR from the Alliance for Lupus Research and the Swedish Research Council.

THRAP3 depletion reduces PPARγ mRNA and anti-inflammatory action in 3T3-L1 adipocytes.

Peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator of adipocytes and the cellular target of thiazolidinedione (TZD) drugs. Suppression of pro-inflammatory actions, including pro-inflammatory gene expression and lipolysis in adipocytes, contributes to PPARγ-mediated anti-diabetic effects of TZDs. However, adverse side effects largely limited the clinical use of TZDs, despite their potent insulin-sensitizing effects. Therefore, it is important to understand how PPARγ is regulated. Thyroid hormone receptor-associated protein 3 (THRAP3) was previously reported to promote diabetic gene expression by acting as a transcriptional coregulator of PPARγ in adipocytes. Therefore, we tested if THRAP3 modulated anti-inflammatory functions of PPARγ in 3T3-L1 adipocytes. THRAP3 depletion increased basal and tumor necrosis factor α (TNFα)-induced lipolysis, pro-inflammatory gene expression, and phosphorylation of extracellular signal-regulated kinases (ERKs), suggesting elevated pro-inflammatory response after THRAP3 depletion in adipocytes. Moreover, TZD-mediated suppression of TNFα-induced lipolysis, pro-inflammatory gene expression, and ERK phosphorylation was attenuated or alleviated after THRAP3 depletion. Interestingly, the mRNA and protein levels of PPARγ were greatly reduced in THRAP3-depleted adipocytes. Actinomycin D treatment revealed that the stability of PPARγ mRNA was greatly reduced by THRAP3 depletion in adipocytes. Thus, in addition to modulating PPARγ function, THRAP3 may directly regulate the transcript of PPARγ in differentiated adipocytes.

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

Can environmental information disclosure promote the high-quality development of enterprises? The mediating effect of intellectual capital.

The Chinese government has given a high priority to economic high-quality development (HQD) in recent years. This study empirically examines whether environmental information disclosure (EID) can promote corporate HQD using a sample of 302 Chinese listed companies from 2012 to 2018. The results show that EID has a positive impact on firms' HQD and intellectual capital plays a mediating role in this relationship. The results remain robust and valid after a series of endogenous and robustness tests. This study significantly contributes to the existing EID literature by exploring the integrated effect of EID on corporate HQD through constructing a comprehensive indicator to measure corporate HQD, which includes economic performance, environmental performance, and social performance. The findings of our study also add impetus for enterprises to improve their EID.

Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity.

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.

Association Between Selenium Level in Blood and Glycolipid Metabolism in Residents of Enshi Prefecture, China.

The present study aimed to detect selenium (Se) levels in the blood of Enshi Prefecture residents in China and investigate the relationship between blood Se levels and glucose or lipid metabolism disorder. A cross-sectional study was conducted, and 1876 subjects were selected through cluster random sampling from Enshi Prefecture using a questionnaire survey, physical examinations, and biochemical blood tests. The mean blood Se level in the overall population was 0.128 ± 0.178 µg/mL. Se exhibits a "U"-shaped curve on the serum fasting plasma glucose (FPG) of the total samples, that is, when the blood Se is more than 0.131 µg/mL or less than 0.062 µg/mL, the FPG increases significantly. A significant negative correlation was demonstrated between the FPG levels of the 4-17-year-old age group and different blood Se levels (P < 0.001). No significant correlation was demonstrated between the serum triglyceride (TG) and blood Se levels. However, a positive correlation was demonstrated between blood Se and serum total cholesterol (TC) levels and the incidence of high cholesterol in the total population (P < 0.001). The odds ratio and related 95% confidence interval for the incidence of high cholesterol between the highest (≥ 0.133 µg/mL) and lowest blood Se (< 0.064 µg/mL) levels was 2.64 and 1.48-4.79, respectively. The results of this study are very important for the safety scope and risk-benefit assessment of Se in the human; however, further investigation with a larger sample size is required.