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Frequent changes in economic policy pose challenges to normal business production and operations. However, little is known about the non-market strategies adopted by firms in emerging economies, such as China, in response to economic policy uncertainty. This study proposes that firms in China respond to high levels of economic policy uncertainty by increasing philanthropic donations and bribery. In addition, this study argues that private firms and state-owned firms implement different strategies to cope with economic policy uncertainty. Specifically, the study suggests that state-owned enterprises (SOEs) are more likely, than non-SOEs, to respond to economic policy uncertainty by increasing corporate philanthropy, and less likely to respond by increasing expenditure on bribes. This study obtained empirical evidence to support these views, based on an analysis of a dataset of 2,904 listed Chinese firms from 2008 to 2019. [ABSTRACT FROM AUTHOR]

With the proposal of the carbon neutrality target, China's attention to carbon emissions has been further enhanced. Effective prediction of future carbon emissions is important for the formulation of carbon neutralization target and action plans in the region. Many factors affecting carbon emissions, cause their development trends may be nonlinear. To forecast the carbon emissions of coal and natural gas in the industrial sector more accurately, a new MGM(1,m,N|γ) model considering nonlinear characteristics is proposed in this paper. The new model introduces power function γ as nonlinear parameter, and the γ value is solved by nonlinear constraint function. We further deduce the simulation and prediction formula and then apply the improved model to the carbon emission forecast. The comparisons show that the nonlinear parameters can modify the trend of sequences and improve the prediction accuracy, which verifies the validity of the model. Finally, according to the influencing factors and forecast results, this paper analyzes the causes of high carbon emissions and puts forward reasonable suggestions for China's carbon governance. [ABSTRACT FROM AUTHOR]

Obstructive hypertrophic cardiomyopathy (oHCM) is a subtype of HCM characterized by left ventricular outflow tract obstruction resulting from cardiac muscle hypertrophy and anatomic alterations in the mitral valve and apparatus. Mavacamten, a cardiac myosin inhibitor metabolized primarily by CYP2C19 in the liver, is the first and only targeted medication approved for the treatment of symptomatic New York Heart Association (NYHA) class II-III oHCM. Previous pharmacokinetic (PK) results of mavacamten in healthy Caucasian, Japanese, and Asian participants demonstrated that mavacamten exposure was affected by CYP2C19 metabolism status. This open-label, parallel-group, phase I trial aimed to determine the PK and safety of mavacamten in healthy Chinese participants with different CYP2C19 genotypes. The primary outcome was to define the PK of mavacamten in healthy Chinese participants; the secondary outcome was to examine safety and tolerability. After a single oral dose of 15 or 25 mg mavacamten in fasted healthy adult Chinese individuals, C max was reached within a median T max of 0.6-1.5 h, indicating rapid absorption. Inter-individual variability was moderate, and individuals carrying non-functional CYP2C19 alleles (*2/*2, *3/*3, or *2/*3) exhibited longer half-life and increased total exposure. After stratification of CYP2C19 genotypes, total mavacamten exposures were similar among different ethnic groups when compared with prior PK studies. No significant adverse events were observed in this study. Single oral administration of mavacamten at 15 mg was well tolerated across all CYP2C19 genotypes, and 25 mg dose was well tolerated in healthy participants with CYP2C19 genotypes UM/RM/NM. The PK profile of mavacamten in the healthy Chinese population was consistent with that in other healthy populations., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Vupanorsen is a GalNAc 3 -conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia., Objectives: The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG)., Methods: In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non-high-density lipoprotein cholesterol [non-HDL-C]), and safety were assessed., Results: Absorption of vupanorsen was rapid (median time to maximum concentration [T max ]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [C max ]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were - 59.7% and - 69.5% for ANGPTL3, - 41.9% and - 52.5% for TG, and - 23.2% and - 25.4% for non-HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study., Conclusions: This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted., Trial Registration: ClinicalTrials.gov identifier: NCT04916795., (© 2024. The Author(s).)

The objective of this study is to evaluate the pattern of bone mineral density (BMD) in native Jiaxing women, and to investigate their awareness of osteoporosis. A total of 538 native Jiaxing women aged 40 to 60 years were recruited from January 2022 to December 2023 when they had routine examinations in the physical examination center of Jiaxing Maternal and Child Health Hospital. The Chinese version of Osteoporosis Prevention and Cognition Tool was used to evaluate participants' cognitive level of osteoporosis. BMD of participants' lumbar spine (L1-L4) and left hip (Neck/Troch/Ward) was measured by dual-energy X-ray absorptiometry. The mean total score of the awareness about osteoporosis (general knowledge, complications, and prevention) was 22.08 ± 2.74, which was suboptimal. The higher the education level, the higher the score of awareness (P < .01). Medical staff had the highest awareness rate of osteoporosis and the farmer had the lowest. Lumber spine and hip BMD of all sites was significantly decreased with increasing age (P < .001). Premenopausal women had higher BMD than postmenopausal women at all lumbar spine and hip sites (P < .01). The overall frequency of osteoporosis was 10.8% in the lumbar spine, 8.6% in the total hip, and 17.7% in either site. Osteoporosis and osteopenia are highly prevalent among native Jiaxing women but their awareness of osteoporosis is inadequate. To reduce the prevalence of osteoporosis, especially among the unemployed, we should carry out effective health education through multimedia to raise their awareness of osteoporosis. In addition, menopausal hormone therapy should also be considered in menopausal women., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: 9MW1411 is a humanised monoclonal antibody against Staphylococcus aureus alpha-toxin. The safety, pharmacokinetics (PK) and immunogenicity of 9MW1411 should be characterised in humans before further clinical development., Methods: A single-centre, randomised, double-blind, placebo-controlled phase I clinical study was conducted in humans for the first time. A total of 42 healthy Chinese subjects were randomised to receive a single ascending dose of 9MW1411 (200, 600, 1500, 3000 or 5000 mg) or placebo. Safety, PK parameters and anti-drug antibody (ADA) were analysed. Monte Carlo simulations (MCS) were performed to predict the probability of target attainment (PTA) after single dose IV administration of 1500, 3000 and 5000 mg of 9MW1411., Results: Thirty-four subjects received 9MW1411, completed the study and were included in data analysis. Five cases of drug-related AEs occurred in four subjects. All the adverse events (AEs) were mild or moderate. The C max , AUC 0-t and AUC 0-∞ of 9MW1411 increased with dose after IV administration of 200 to 5000 mg 9MW1411. The mean C max increased from 85.40 ± 5.43 to 2082.11 ± 343.10 µg/mL and AUC 0-∞ from 29,511.68 ± 5550.91 to 729,985.49 ± 124,932.18 h·µg/mL. The elimination half-life (T 1/2 ) was 19-23 days. 9MW1411 ADA was positive in three subjects. MCS indicated that a single dose of 3000 or 5000 mg 9MW1411 could achieve PTA > 90% for S. aureus., Conclusions: 9MW1411 has shown a good safety profile in healthy Chinese subjects after a single dose up to 5000 mg. A single dose of 3000 mg 9MW1411 is appropriate for use in subsequent studies., (Copyright © 2023. Published by Elsevier Ltd.)

Carbon emission is a common concern of the international community and effectively predicting its future trend is necessary for emission reduction planning. Considering that the change trend of carbon emissions is unstable, more attention should be paid to the correction effect of new information on the development trend. Therefore, based on the traditional MGM(1,m) model, this paper introduces the new information priority operator λ and nonlinear parameter γ to strengthen the role of new information, further constructs three comparison models of MGM(1,m|λ), MGM(1,m|γ) and MGM(1,m|λ,γ).Then we apply the new model to the carbon emission prediction of different regions (cities, countries and continents) and different trends (fluctuating, rising and declining). The results illustrate that the new model has higher prediction accuracy, and adding dynamic parameters is a scientific and practical method to improve the forecasting ability of the grey forecasting model. Finally, we analyze the current situation and future development trend of carbon emissions, and put forward reasonable suggestions., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study aimed to build a population pharmacokinetic (PopPK) model for contezolid tablet (MRX-I) in healthy subjects and adults with complicated skin and soft-tissue infections (cSSTIs) to further evaluate the efficacy and safety of contezolid and recommend the optimal dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) analysis. PopPK analysis was performed using a nonlinear mixed-effects model (NONMEM) to examine the effects of age, body weight, sex, liver and renal functions, albumin, food, dosage strength, and subject type on the PK parameters of contezolid. PK/PD analysis was combined with the MIC of contezolid, clinical/microbiological efficacy, and nonclinical study data. Adverse events (AEs) and study drug-related AEs reported were summarized to examine the relationship between contezolid exposure level and safety measures. A two-compartment model was built. An exponential model was used to describe the interindividual variation. A proportional model was used to describe the intraindividual variation of PK parameters. Good clinical and microbiological efficacy are expected for the infections caused by S. aureus when contezolid is administered at 600 mg or 800 mg every 12 h (q12h). The area under the concentration-time curve from 0 to 24 h at steady state and maximum concentration of drug in serum at steady state of contezolid did not show significant association with the incidence of any AE. The dosing regimen of contezolid at 800 mg q12h administered postprandially for 7 to 14 days is expected to achieve satisfactory clinical and microbiological efficacy in cSSTIs, which is slightly better than that of 600 mg contezolid. This administration has been added to the prescribing information of contezolid tablets.

While video games are one of the most common online entertainment activities, Internet gaming disorder (IGD) in adolescents is a critical issue that has become a widely raised public concern. This one-year longitudinal study examined the reciprocal associations between shyness, depression, and IGD symptoms in a sample of Chinese adolescents. A fully cross-lagged panel design was used, in which shyness, depression, and IGD symptoms were assessed at two time points with an interval of one year (T1 and T2). A total of 1,047 junior high school students (504 boys; 543 girls; mean age = 12.45 years) participated in the study. Cross-lagged analysis results indicated a significant positive correlation between shyness, depression, and IGD symptoms, as well as a dynamic and bidirectional relationship between them. Specifically, T1 shyness positively predicted T2 depression symptoms (β = 0.167, p < 0.001), T1 depression symptoms positively predicted T2 shyness (β = 0.141, p < 0.01), and T1 IGD symptoms positively predicted T2 depression symptoms (β = 0.073, p < 0.05). In addition to these findings, gender differences were identified in shyness (T1 and T2), IGD symptoms (T1 and T2), and depression symptoms (T2). The results also indicated that shyness and symptoms of depression could significantly positively predict each other over time, and IGD symptoms could significantly predict depression symptoms. However, depression symptoms could not significantly predict IGD symptoms over the one-year study period, and there was no significant two-way prediction between shyness and IGD symptoms. Thus, this study reveals possible reciprocal associations between shyness, depression, and IGD symptoms in Chinese adolescents and provides insights and suggestions for reducing online gaming addiction among adolescents from the perspective of shyness and depression., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The objectives of this phase I study are to assess the safety, tolerability, and pharmacokinetics (PKs) of RO7049389 in healthy Chinese volunteers (HVs) and evaluate potential ethnic differences in the safety and PKs using data from this study and the first-in-human study (in which most of the HVs were non-Asian). HVs randomly received a single dose of 200-600 mg of RO7049389 or a placebo in a single ascending dose (n = 28) or multiple doses of 200-400 mg of RO7049389 or a placebo in multiple ascending doses (n = 24). Safety and tolerability were monitored throughout the study. Serial blood samples were collected for PK analysis. RO7049389 was safe and well-tolerated in the HVs. The time to maximum concentration ranged from 1.5 to 3.0 h, and terminal half-life ranged from 3.66 to 14.6 h. A single dose of 200-600 mg and multiple doses of 200-400 mg exhibited nonlinear PKs. In general, the safety profiles were comparable between non-Asian and Asian HVs, but the plasma exposure of RO7049389 in Chinese HVs was higher than that in non-Asian HVs. The data generated from this study will provide guidance for future clinical studies on RO7049389 in Chinese/Asian patients with hepatitis B virus., (© 2021 Roche R&D Center China Ltd. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)