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ObjectiveTo understand the medication preference of type 2 diabetes mellitus (T2DM) patients with different insurance coverages, and to provide reference for improving the patient-centered clinical treatment decision.MethodsThis study used Discrete Choice Experiment (DCE) to elicit preferences of T2DM patients with different insurance coverages in China. A multistage stratified cluster-sampling procedure for data collection and a total of 1,409 valid respondent were conducted.ResultsSeven attributes have significant influence on the preference of T2DM patients with Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI) (p

Abstract Background Health Technology Assessment (HTA) in China has recently expanded from purely academic research to include policy or decision-oriented practice, especially after HTA evidence was used to update the National Reimbursement Drug List for the first time in 2017. This study aims to identify the progress and challenges of HTA development from 2016 to 2021 and inform policies and decisions to promote further HTA development in China. Methods We conducted a cross-sectional web-based survey with policy makers, researchers and industry-providers in China in 2016 and 2021 respectively. The ‘Mapping of HTA Instrument’, was utilized to assess the HTA development across eight domains: Institutionalization, Identification, Priority setting, Assessment, Appraisal, Reporting, Dissemination of findings and conclusions, and Implementation in policy and practice. To reduce the influence of confounders and compare the mapping outcomes between the 2016 and 2021 groups, we conducted 1:1 Propensity Score Matching (PSM). Univariate analysis was conducted to compare the differences between the two groups. The overall results were further compared with those of a mapping study that included ten countries. Results In total, 212 and 255 respondents completed the survey in 2016 and 2021, respectively. The total score of the HTA development level in China in 2021 was higher than that in 2016 before PSM (89.38 versus 83.96). Following PSM, 183 respondents from the 2016 and 2021 groups were matched. Overall, the mean scores for most indicators in the Institutionalization domain and Dissemination domain in 2021 were higher than those in 2016 (P

Background Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. Methods and Results We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P

The rapidly growing field of cannabinoid research is gaining recognition for its impact in neuropsychopharmacology and mood regulation. However, prenyltransferase (NphB) (a key enzyme in cannabinoid precursor synthesis) still needs significant improvement in order to be usable in large-scale industrial applications due to low activity and limited product range. By rational design and high-throughput screening, NphB’s catalytic efficiency and product diversity have been markedly enhanced, enabling direct production of a range of cannabinoids, without the need for traditional enzymatic conversions, thus broadening the production scope of cannabinoids, including cannabigerol (CBG), cannabigerolic acid (CBGA), cannabigerovarin (CBGV), and cannabigerovarinic acid (CBGVA). Notably, the W3 mutant achieved a 10.6-fold increase in CBG yield and exhibited a 10.3- and 20.8-fold enhancement in catalytic efficiency for CBGA and CBGV production, respectively. The W4 mutant also displayed an 9.3-fold increase in CBGVA activity. Molecular dynamics simulations revealed that strategic reconfiguration of the active site’s hydrogen bonding network, disulfide bond formation, and enhanced hydrophobic interactions are pivotal for the improved synthetic efficiency of these NphB mutants. Our findings advance the understanding of enzyme optimization for cannabinoid synthesis and lay a foundation for the industrial-scale production of these valuable compounds.

Based on daily precipitation data of 123 national stations in Shandong province from 1961 to 2021, ERA5 monthly reanalysis data and NOAA sea surface temperature data, the causes of the positive precipitation anomaly in Shandong in autumn 2021 were analyzed. The results showed that there was a "two ridges and one trough" double-resistance circulation pattern over mid-high latitudes at the geopotential height of 500 hPa. The long-wave trough in the west of Lake Baikal was deepened and strengthened, which was conducive to the southward and eastward transmission of cold air from the west road to affect Shandong. The Western Pacific Subtropical High had larger area and stronger intensity than usual, with the ridge point to the west and the ridge line to the north, which transported sufficient warm and wet air from the periphery northward to the Huanghuai area and provided sufficient water vapor for Shandong. The intersection of cold air and warm and wet air flow in the Huanghuai area leaded to abnormally more precipitation. Further analysis showed that under the synergistic influence of the cold water state in the equatorial Middle Eastern Pacific and the warm sea surface temperature phase in the Indian Ocean, the Western Pacific Subtropical High was stronger, more westerly and northerly, thus providing favorable water vapor conditions for the transport of warm and wet air. The stronger and northerly Western Pacific Subtropical High anomaly, the warm SST anomaly over the east coast of South America and the north Pacific Ocean, and the cold SST anomaly over the central equatorial Pacific Ocean were the main reasons for the positive precipitation anomaly in Shandong in September of 2021.

Ethnopharmacological relevance: Aging is related to many factors, such as genes, oxidative damage, metabolic abnormalities, immune regulation and sex hormones. This article reviews the pharmacological mechanism of Epimedium on slow aging from six aspects: gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, the regulation of sex hormone, and clinical efficacy.Aim of the studyThrough literature review, to discover the potential pharmacological mechanism of Epimedium for slow aging. Materials and methods: We reviewed the literature on the applications of Epimedium in multiple systems and the potential underlying mechanisms with systematic and comprehensive illustrations. The review includes the following aspects: gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, the regulation of sex hormone, clinical efficacy and safety. Results: The slow aging active components of Epimedium may be flavonoids, such as Epimedins A, B, C and icariin The slow aging effect of Epimedium may be related to gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, and the regulation of sex hormone. No severe adverse reaction has been reported. Conclusions: Epimedium has potential slow aging effect and been widely used in the clinic for aging-related diseases in the real world in China; however, large-scale studies are still needed.

Abstract Purpose To assess the reporting quality of published economic evaluations of the negotiated oncology drugs listed for China’s 2020 National Reimbursement Drug List (NRDL). Methods A comprehensive search was conducted to identify economic evaluation studies of negotiated oncology drugs listed in China’s 2020 NRDL using the PubMed/MEDLINE, Embase, Web of Science, CNKI, SinoMed, and WanFang Database up to March 31, 2021. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist scored the reporting quality between 0 and 100. A linear regression analysis was employed to examine the influence of various characteristics on the reporting quality scores. Results Eighty papers were included in the study, with the majority published during the past decade. Furthermore, more than half of the articles (57.5%, or 46 out of 80) were written in English. The average CHEERS score was 74.63 ± 12.75 and ranged from 43.48 to 93.75. The most inadequately reported items included choice of model, characterization of heterogeneity, and discussion, as well as currency, price date and conversion. Higher scores were associated with articles published from 2019 to 2021 and English publications. Conclusion The economic evaluation studies of negotiated oncology drugs listed in 2020 NRDL had moderate reporting quality. The Chinese economic evaluation publications could improve the reporting quality if the CHEERS checklist is consistently implemented. Also, the Chinese journals maybe explore introducing a reporting standard for economic evaluations.

Uterine leiomyomas cause heavy menstrual bleeding, anemia, and pregnancy loss in millions of women worldwide. Driver mutations in the transcriptional mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% of leiomyomas that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 in mutant MED12 (mut-MED12) versus WT-MED12 leiomyomas. Integration of cistromic and transcriptomics data identified tryptophan 2,3-dioxygenase (TDO2) as the top mut-MED12 target gene that was significantly upregulated in mut-MED12 leiomyomas when compared with adjacent myometrium and WT-MED12 leiomyomas. TDO2 catalyzes the conversion of tryptophan to kynurenine, an aryl hydrocarbon receptor (AHR) ligand that we confirmed to be significantly elevated in mut-MED12 leiomyomas. Treatment of primary mut-MED12 leiomyoma cells with tryptophan or kynurenine stimulated AHR nuclear translocation, increased proliferation, inhibited apoptosis, and induced AHR-target gene expression, whereas blocking the TDO2/kynurenine/AHR pathway by siRNA or pharmacological treatment abolished these effects. Progesterone receptors regulated the expression of AHR and its target genes. In vivo, TDO2 expression positively correlated with the expression of genes crucial for leiomyoma growth. In summary, activation of the TDO2/kynurenine/AHR pathway selectively in mut-MED12 leiomyomas promoted tumor growth and may inform the future development of targeted treatments and precision medicine.

Background: Traditional Chinese Medicine (TCM), integrating patient preferences into decision-making process, has been widely used in the multimodality therapy of lung cancer. This study aimed to estimate patient preferences for treatment and shared decision-making (SDM) modes concerning inpatient TCM treatment of lung cancer in Shanghai in order to provide a basis for clinical decision-making process on TCM therapy for lung cancer. Methods: This study was conducted among patients (n = 347) from nine tertiary hospitals in Shanghai by discrete-choice experiment (DCE) survey and Shared Decision-Making Questionnaire-patient version (SDM-Q-9) survey. The DCE was developed with the inclusion of the most relevant attributes at appropriate levels for the TCM treatment of lung cancer. The empirical data analyses of patients were performed using mixed logit models. Additionally, subgroup analysis was conducted. Results: In total, 347 respondents completed the questionnaire. All attributes’ coefficients were statistically significant for patients’ preferences. Patients showed strong preferences for increasing disease control rate, relieving nausea and vomiting, reducing the risk of side effects, and were concerned about monthly out-of-pocket costs. Subgroup analysis indicated that patients with a lower SDM-Q-9 score and those who were satisfied with medical services emphasized more importance of higher disease control rate. Furthermore, most of the patients (90.20%) self-reported a high willingness to use SDM during the decision-making process. Conclusion: In Shanghai, patients mainly preferred SDM and considered disease control rate as the most essential attribute in the TCM treatment of lung cancer. The study findings could underscore the importance of considering patients’ preferences and promote SDM.

BackgroundHemophilia A is a chronic condition that requires meticulous treatment and management. Patient preferences for prophylactic treatment can substantially influence adherence, outcomes, and quality of life, yet these preferences remain underexplored, particularly in China. ObjectiveThis study aimed to investigate the preferences for prophylactic treatment among Chinese adult patients with hemophilia A without inhibitors, considering clinical effectiveness, side effects, dosing mode, and dosing frequency. MethodsA discrete choice experiment was used to elicit patient preferences for prophylactic treatment of hemophilia. The study was conducted across 7 provinces in China with socioeconomic and geographical diversity. Subgroup analysis was performed according to education level, geographic location, and treatment type, alongside the exploration of benefit-risk trade-offs. ResultsA total of 113 patients completed the discrete choice experiment questionnaire, and we included 102 responses for analysis based on predetermined exclusion criteria. The study found that patients prioritized reducing annual bleeding times and avoiding the risk of developing inhibitors over treatment process attributes. Subgroup analysis revealed that lower-educated patients and those from rural areas attached more importance to the dosing mode, likely due to barriers to self-administration. Patients demonstrated a clear understanding of benefit-risk trade-offs, exhibiting a willingness to accept an increased risk of developing inhibitors for improved clinical outcomes. ConclusionsThis study provides valuable insights into the preferences of patients with hemophilia A for prophylactic treatment in China. Understanding these preferences can enhance shared decision-making between patients and clinicians, fostering personalized prophylactic treatment plans that may optimize adherence and improve clinical outcomes.

Bacterial infections pose a significant risk to human health. Magnolol, derived from Magnolia officinalis, exhibits potent antibacterial properties. Synthetic biology offers a promising approach to manufacture such natural compounds. However, the plant-based biosynthesis of magnolol remains obscure, and the lack of identification of critical genes hampers its synthetic production. In this study, we have proposed a one-step conversion of magnolol from chavicol using laccase. After leveraging 20 transcriptomes from diverse parts of M. officinalis, transcripts were assembled, enriching genome annotation. Upon integrating this dataset with current genomic information, we could identify 30 laccase enzymes. From two potential gene clusters associated with magnolol production, highly expressed genes were subjected to functional analysis. In vitro experiments confirmed MoLAC14 as a pivotal enzyme in magnolol synthesis. Improvements in the thermal stability of MoLAC14 were achieved through selective mutations, where E345P, G377P, H347F, E346C, and E346F notably enhanced stability. By conducting alanine scanning, the essential residues in MoLAC14 were identified, and the L532A mutation further boosted magnolol production to an unprecedented level of 148.83 mg/L. Our findings not only elucidated the key enzymes for chavicol to magnolol conversion, but also laid the groundwork for synthetic biology-driven magnolol production, thereby providing valuable insights into M. officinalis biology and comparative plant science.

Trilobatin (TBL) is a key sweet compound from the traditional Chinese sweet tea plant (Rubus suavissimus S. Lee). Because of its intense sweetness, superior taste profile, and minimal caloric value, it serves as an exemplary natural dihydrochalcone sweetener. It also has various health benefits, including anti-inflammatory and glucose-lowering effects. It is primarily produced through botanical extraction, which impedes its scalability and cost-effectiveness. In a novel biotechnological approach, phloretin is used as a precursor that is transformed into TBL by the glycosyltransferase enzyme ph-4′-OGT. However, this enzyme’s low catalytic efficiency and by-product formation limit the large-scale synthesis of TBL. In our study, the enzyme Mdph-4′-OGT was used to screen 17 sequences across species for TBL synthesis, of which seven exhibited catalytic activity. Notably, PT577 exhibited an unparalleled 97.3% conversion yield within 3 h. We then optimized the reaction conditions of PT577, attaining a peak TBL bioproduction of 163.3 mg/L. By employing virtual screening, we identified 25 mutation sites for PT577, thereby creating mutant strains that reduced by-products by up to 50%. This research enhances the enzymatic precision for TBL biosynthesis and offers a robust foundation for its industrial-scale production, with broader implications for the engineering and in silico analysis of glycosyltransferases.

Objective This study aimed to investigate the preferences regarding risks, benefits and other treatment attributes of patients with type 2 diabetes mellitus (T2DM) in China when selecting a second-line anti-hyperglycaemic medicine.Methods A discrete choice experiment with hypothetical anti-hyperglycaemic medication profiles was performed using a face-to-face survey administered to patients with T2DM. The medication profile was described using seven attributes: treatment efficacy, hypoglycaemia risk, cardiovascular benefits, gastrointestinal (GI) adverse events, weight change, mode of administration and out-of-pocket cost. Participants chose between medication profiles by comparing attributes. Data were analysed using a mixed logit model with marginal willingness to pay (mWTP) and maximum acceptable risk (MAR) calculated. The preference heterogeneity within the sample was explored using a latent class model (LCM).Results A total of 3327 respondents from five major geographical regions completed the survey. Treatment efficacy, hypoglycaemia risk, cardiovascular benefits and GI adverse events were major concerns among the seven attributes measured. Weight change and mode of administration were of lesser concern. Regarding mWTP, respondents would pay ¥236.1 (US$36.6) for an anti-hyperglycaemic medication with an efficacy of 2.5% points reduction in HbA1c, while they were willing to accept a weight gain of 3 kg only if they received a compensation of ¥56.7 (US$8.8). Respondents were willing to accept a relatively large increase in hypoglycaemia risk (MAR=15.9%) to improve treatment efficacy from intermediate (1.0% points) to high (1.5% points). LCM identified the following four unobserved subgroups: trypanophobia, cardiovascular-benefits-focused, safety-focused and efficacy-focused and cost-sensitive.Conclusion Patients with T2DM prioritised free out-of-pocket costs, highest efficacy, no hypoglycaemia risk and cardiovascular benefits over weight change and mode of administration. There exists great preference heterogeneity among patients, which should be taken into account in healthcare decision-making processes.

Abstract Background Given the demands for public health and infectious disease management skills during COVID-19, a shortage of the public health workforce, particularly with skills and competencies in epidemiology and biostatistics, has emerged at the Centers for Disease Controls (CDCs) in China. This study aims to investigate the employment preferences of doctoral students majoring in epidemiology and biostatistics, to inform policy-makers and future employers to address recruitment and retention requirements at CDCs across China. Methods A convenience sampling approach for recruitment, and an online discrete choice experiment (DCE) survey instrument to elicit future employee profiles, and self-report of their employment and aspirational preferences during October 20 and November 12, 2020. Attributes included monthly income, employment location, housing benefits, children’s education opportunities, working environment, career promotion speed and bianzhi (formally established post). Results A total of 106 doctoral epidemiology and biostatistics students from 28 universities completed the online survey. Monthly income, employment location and bianzhi was of highest concern in the seven attributes measured, though all attributes were statistically significant and presented in the expected direction, demonstrating preference heterogeneity. Work environment was of least concern. For the subgroup analysis, employment located in a first-tier city was more likely to lead to a higher utility value for PhD students who were women, married, from an urban area and had a high annual family income. Unsurprisingly, when compared to single students, married students were willing to forgo more for good educational opportunities for their children. The simulation results suggest that, given our base case, increasing only monthly income from 10,000 ($ 1449.1) to 25,000 CNY ($ 3622.7) the probability of choosing the job in the third-tier city would increase from 18.1 to 53.8% (i.e., the location choice is changed). Conclusion Monthly income and employment location were the preferred attributes across the cohort, with other attributes then clearly ranked and delineated. A wider use of DCEs could inform both recruitment and retention of a public health workforce, especially for CDCs in third-tier cities where resource constraints preclude all the strategies discussed here.

Aspartokinase (AK) is synergistically suppressed by Thr and Lys in the Corynebacterium metabolic pathway. Site-directed mutations can significantly improve AK inhibition. Our previous studies confirmed that sites 379 and 380 were important sites affecting enzyme activity, so we further screen the double mutants with excellent enzymatic properties from sites 379 and 380, and discuss the difference of enzyme activity between the double mutants and single mutants. Here, a double mutant, T379L/A380 M, with improved enzyme activity (2.74-fold) was obtained. Enzymatic property experiments showed that the optimum temperature of T379L/A380 M increased from 26 °C (recombinant Escherichia coli; WT-AK) to 45 °C and that the optimal pH decreased from 8.0 (WT-AK) to 7.5. Further, the half-life decreased from 4.5 to 3.32 h. These enzymatic properties were better than other mutant strains. Inhibition was diminished with low concentrations of Lys, and Lys + Thr presented an activating role. Subsequently, the reasons for the improved AK enzyme activity were illustrated with microscale thermophoresis (MST) experiments and molecular dynamic (MD) simulation by measuring ligand affinity and AK conformational changes. MST showed that the affinity between T379L/A380 M and Lys decreased, but the affinity between T379L/A380 M and Asp increased, promoting T379L/A380 M enzyme activity. MD experiments showed that T379L/A380 M enhanced the Asp-ATP affinity and catalyzed the transfer of residues S192 and D193 to Asp, promoting T379L/A380 M enzyme activity. However, the mutation did not cause fluctuations in the substrate Asp and ATP pockets. This might be why the enzyme activity was inferior to that of the single mutants (T379L and A380 M).

BackgroundChina is the only country in the world that has not included the Haemophilus influenzae type b (Hib) vaccine in its National Immunization Program, making it more difficult to eliminate Hib-related diseases through Hib vaccination. It is necessary to study parental preferences for Hib vaccination to optimize vaccine promotion strategies in China.ObjectiveThis study aimed to investigate Chinese parental preference for five attributes of Hib vaccination, i.e., the place of origin, effectiveness, adverse event, doctors' recommendation, and the price of full vaccination when making a decision to vaccinate their children under 2 years old.MethodsA cross-sectional survey was conducted in two cities in Zhejiang Province from November to December in 2020 using a discrete choice experiment (DCE). A mixed logit model was used to estimate participating parents' preference for Hib vaccination attributes included in the DCE. Subgroup analysis and probability analysis were also conducted to capture the heterogeneity and trade-off of parental preference for Hib vaccination.ResultsData from 6,168 observations were included in the analyses. Parents of children are, on average, more likely to voice a positive preference for Hib vaccination. Such attributes of Hib vaccination as effectiveness and doctor's recommendation have a significant positive influence on parents' preference for Hib vaccination, while imported vaccines, adverse events, and the price of full vaccination have a significant negative influence on parents' preference. Parents with different demographic characteristics also existed heterogeneities in preference for Hib vaccination. Parents will make a trade-off on price if the Hib vaccine has a good performance on effectiveness and safety.ConclusionThe study found that, regardless of the place of origin of the Hib vaccine, parents with children under 2 years old prefer to compromise on price if the vaccine has a better effectiveness and safety profile. A proactive recommendation from doctors would strengthen their willingness for Hib vaccination. These findings help aid the development of communication strategies with parents for Hib vaccination in China.

Abstract Background Pharmacists are a crucial part of the health workforce and play an important role in achieving universal health coverage. In China, pharmaceutical human resources are in short supply, and the distribution is unequal. This study aimed to identify the key job characteristics that influence the job preferences of undergraduate pharmacy students and to elicit the relative importance of different job characteristics to shed light on future policy interventions. Methods A discrete choice experiment was conducted to assess the job preferences of undergraduate pharmacy students from 6 provinces in mainland China. A face-to-face interview was used to collect data. Conditional logit and mixed logit models were used to analyse data, and the final model was chosen according to the model fit statistics. A series of policy simulations was also conducted. Results In total, 581 respondents completed the questionnaire, and 500 respondents who passed the internal consistency test were analysed. All attributes were statistically significant except for open management. Monthly income and work location were most important to respondents, followed by work unit (which refers to the nature of the workplace) and years to promotion. There was preference heterogeneity among respondents, e.g., male students preferred open management, and female students preferred jobs in public institutions. Furthermore, students with an urban background or from a single-child family placed higher value on a job in the city compared to their counterparts. Conclusion The heterogeneity of attributes showed the complexity of job preferences. Both monetary and nonmonetary job characteristics significantly influenced the job preferences of pharmacy students in China. A more effective policy intervention to attract graduates to work in rural areas should consider both incentives on the job itself and the background of pharmacy school graduates.

Climate change is the main cause of frequent extreme weather and natural disasters. Therefore, effective climate adaptation strategies for urban rail transit (URT) should be adopted to cope with extreme precipitation events (EPEs). This study proposes a decision-making model based on climate change for drainage renovation, which consists of an optimal renovation sequence model and an optimal investment timing model. This study analyzes the inundation risk of each station and its node importance in the URT network and then uses a multi-attribute decision analysis (MADA) to determine the optimal renovation sequence. This study also uses a real options pricing approach to calculate the value of an option in order to defer the renovation project and determine the optimal investment timing. Then, the Beijing Urban Rail Transit (BURT) is taken as an example to conduct an empirical analysis of the proposed model. Considering the uncertainty of climate change and the complexity of the URT network, the model can obtain the optimal renovation sequence and the investment timing of each station, which is expected to provide a decision-making tool for urban governments to formulate an optimal plan that strengthens the prevention of flooding disasters.

Fine grained Mg–7Gd–5Y–1.2Nd–0.5Zr alloy was investigated by dynamic compression tests using a Split Hopkinson Pressure Bar under the strain rates in the range 1000–2000 s − 1 and the temperature range 293–573 K along the normal direction. The microstructure was measured by optical microscopy, electron back-scattering diffraction, transmission electron microscopy and X-ray diffractometry. The results showed that Mg–7Gd–5Y–1.2Nd–0.5Zr alloy had the positive strain rate strengthening effect and thermal softening effect at high temperature. The solid solution of Gd and Y atoms in Mg–7Gd–5Y–1.2Nd–0.5Zr alloy reduced the asymmetry of α-Mg crystals and changed the critical shear stress of various deformation mechanisms. The main deformation mechanisms were prismatic slip and pyramidal 〈a〉 slip, {102} tension twinning, and dynamic recrystallization caused by local deformation such as particle-stimulated nucleation.

Abstract Background Language barriers were reported to affect timely access to health care and outcome. The aim of this study was to investigate the effect of language disparity on quality benchmarks of acute ischemic stroke therapy. Methods Consecutive patients with acute ischemic stroke at the University of California Irvine Medical Center from 2013 to 2016 were studied. Patients were categorized into 3 groups according to their preferred language: English, Spanish, and other languages. Quality benchmarks and outcomes of the 3 language groups were analyzed. Results Of the 928 admissions, 69.7% patients recorded English as preferred language, as compared to 17.3% Spanish and 13.0% other languages. There was no significant difference in the rate of receiving intravenous thrombolysis (24.3, 22.1 and 21.0%), last-known-well to door time, door-to-imaging time, door-to-needle time, and hospital length of stay among the 3 language groups. In univariate analysis, the other languages group had lower chance of favorable outcomes than the English-speaking group (26.3% vs 40.4, p

Abstract Background Preliminary evaluations have found that family doctor contract services (FDCSs) have significantly controlled medical expenses, better managed chronic diseases, and increased patient satisfaction and service compliance. In 2016, China proposed the establishment of a family doctor system to carry out contract services, but studies have found the uptake and utilization of these services to be limited. This study aimed to investigate rural residents’ preferences for FDCSs from the perspective of the Chinese public. Methods A discrete choice experiment (DCE) was performed to elicit the preferences for FDCSs among rural residents in China. Attributes and levels were established based on a literature review and qualitative methods. Five attributes, i.e., cost, medicine availability, the reimbursement rate, family doctor competence, and family doctor attitude, were evaluated using a mixed logit model. Results A total of 609 residents were included in the main DCE analysis. The respondents valued the high competence (coefficient 2.44, [SE 0.13]) and the good attitude (coefficient 1.42, [SE 0.09]) of family doctors the most. Cost was negatively valued (coefficient − 0.01, [SE 0.01]), as expected. Preference heterogeneity analysis was conducted after adjusting the interaction terms, and we found that rural residents with higher educational attainment prefer a good attitude more than their counterparts with lower educational attainment. The estimated willingness to pay (WTP) for “high” relative to “low” competence was 441.13 RMB/year, and the WTP for a provider with a “good” attitude relative to a “poor” attitude was 255.77 RMB/year. Conclusion The present study suggests that strengthening and improving the quality of primary health care, including the competence and attitudes of family doctors, should be prioritized to increase the uptake of FDCSs. The contract service package, including the annual cost, the insurance reimbursement rate and individualized services, should be redesigned to be congruent with residents having different health statuses and their stated preferences.

The purpose of this study was to investigate how the subjective impression of English speech would change when pause duration at punctuation marks was varied. Two listening experiments were performed in which written English speech segments were rated on a variety of evaluation items by both native-English speakers and non-native speakers (native-Chinese speakers and native-Japanese speakers). The ratings were then subjected to factor analysis. In the first experiment, the pauses in three segments were made into the same durations, from 0.075 to 4.8 s. Participants rated the segments on 23 evaluation items on a rating scale from 1 to 10. A varimax rotation after PCA (principal component analysis) led to two factors that were related to speech style. These two factors could be interpreted as representing speech naturalness and speech rate. Speech segments with a pause duration of 0.6 s received the highest naturalness evaluation, while perceived speech rate decreased as the physical pause duration increased, without any changes in utterance segments. In the second experiment, a full-factorial design of pause durations (0.15, 0.3, 0.6, 1.2, and 2.4 s) within and between sentences, i.e., for commas and for periods, was implemented in two speech segments. The original speech segments and speech segments without any pauses were also included as control conditions. From ratings on 12 evaluation items, similar to Experiment 1, two factors representing speech naturalness and speech rate were obtained. The results showed again that the perceived speech rate decreased with an increase only in pause duration. As for speech naturalness, the highest evaluations occurred when pause durations were 0.6 s within sentences, and either 0.6 or 1.2 s between sentences. This recommends fixing all pause durations to 0.6 s as a practical way to train non-native speakers to make their spoken English appear more natural.

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months.Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days.Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions.Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

Objective: To estimate patient preferences for second-line antihyperglycemic medications in China.Methods: A face to face survey with the best-worst scaling (BWS) choices was administered in patients with diagnosed type 2 diabetes mellitus (T2DM). Study participants were asked to indicate which attribute they valued most and which attribute they valued least in 11 choice sets, each of which consisted of five alternatives out of 11 antihyperglycemic medication-specific attributes (treatment efficacy, weight change, hypoglycemic events, gastrointestinal side effects, cardiovascular health, urinary tract infection and genital infection side effects, edema, mode of administration, bone fracture, dosing frequency and out-of-pocket cost). A counting approach, a conditional logit model, and K-means clustering were used to estimate the relative importance of items and preference heterogeneity.Results: A total of 362 participants were included with a mean age of 63.6 (standard deviation: 11.8) years. There were 56.4% of participants were women, and 56.3% being diagnosed with diabetes for at least 5 years. Efficacy, cardiovascular health and hypoglycemic events were valued most, while dosing frequency, mode of administration and bone fracture were valued least. The K-means clustering further showed preference heterogeneity in out-of-pocket cost across the participants.Conclusion: Our study suggests that treatment efficacy, cardiovascular health and hypoglycemic events are valued most by Chinese patients with T2DM when selecting second-line antihyperglycemic medications. The study improves the understanding of patients’ preferences for second-line antihyperglycemic medications in China.

Objective: Left atrial (LA) dilatation and heart failure are independent risk factors for ischemic stroke. The goal of this study is to evaluate the association between LA dilatation and reduced left ventricular ejection fraction (EF) with cardioembolic stroke.Methods: Four hundred fifty-three patients with ischemic stroke admitted to the University of California, Irvine between 2016 and 2017 were included based on the following criteria: age >18 and availability of echocardiogram. Stroke was categorized into cardioembolic and non-cardioembolic. EF was categorized into normal: 52–72% (male), 54–74% (female), mildly abnormal: 41–51% (male), 41–53% (female), moderately abnormal: 30–40%, and severely abnormal:

Hot tearing susceptibility (HTS) of Mg–2Zn–(3 + 0.5x)Y–xAl (x = 0, 2 and 3 at%) alloys is predicted by using modified Clyne–Davies’ model (CSC*). The solidification path, solidification characteristic temperatures and dendritic coherency solid fraction have been studied by double-thermocouple thermal analysis. The solidification contraction stress vs. temperature (and time) curves are measured by using a “T” type hot tearing permanent-mold. The results reveal that the CSC* prediction values are in good agreement with the experimental results. Moreover, Al2Y phase acts as the heterogeneous nucleation core of α-Mg and significantly influences the grain size. It has been observed that minimum grain size, optimal dendritic coherency and minimum HTS are exhibited by Mg–2Zn–(3 + 0.5x)Y–xAl alloy (x = 2). Furthermore, when Al content was increased to 3 at%, Al2Y phase exhibited a peritectic reaction and transformed into a mixed structure of Al2Y and Al + Al3Y phases, which increased the HTS of the alloy due to reduced fine-grained Al2Y content. Keywords: Mg–Zn–Y–Al alloys, Hot tearing susceptibility (HTS), Solidification path, Clyne–Davies’ model (CSC*), Dendritic coherency

Abstract Background Shortage and mal-distribution of nursing human resources is an intractable problem in China. There is an urgent need to explore the job preferences of undergraduate nursing students. The main aim of this study is to investigate the stated preferences of nursing students when choosing a job. Methods A discrete choice experiment (DCE) was conducted to assess job preferences of the final year undergraduate nursing students from four medical universities/colleges in Shandong Province, China. Job attributes include location, monthly income, bianzhi (which refers to the established posts and can be loosely regarded as state administrative staffing), career development and training opportunity, work environment and working strength. Mixed logit models were used to analyze the DCE data. Results A total of 445 undergraduate nursing students were included in the main DCE analysis. They demonstrated higher preference for a job with higher monthly income, and the probability of choosing a rural job would increase to 92.8% if monthly income increased from RMB 2000 (US$ 296) to RMB 8000 (US$ 1183). They expressed higher stated preferences for a job which required light working strength and with excellent work environment over other non-economic attributes. Among all attributes, location was the least important attribute. Subgroup analysis showed that students who came from city or county and whose family income was more than RMB 50 000 (US$ 7396) were significantly willing to pay more monthly income for a job in city. Conclusions This study confirmed that economic and non-economic factors both affected the job choices of the students. These results may be more effective for policymakers to perfect the employment policies and design strategies to attract more nursing students taking jobs in rural areas.

Background and Purpose: Our aim was to investigate the frequency of dehydration at admission and associations with in-hospital mortality in patients with intracerebral hemorrhage (ICH).Methods: Data of consecutive patients with ICH between August 2015 and July 2019 from the China Stroke Center Alliance (CSCA) registry were analyzed. The patients were stratified based on the blood urea nitrogen (BUN) to creatinine (CR) ratio (BUN/CR) on admission into dehydrated (BUN/CR ≥ 15) or non-dehydrated (BUN/CR < 15) groups. Data were analyzed with multivariate logistic regression models to investigate admission dehydration status and the risks of death at hospital.Results: A total number of 84,043 patients with ICH were included in the study. The median age of patients on admission was 63.0 years, and 37.5% of them were women. Based on the baseline BUN/CR, 59,153 (70.4%) patients were classified into dehydration group. Patients with admission dehydration (BUN/CR ≥ 15) had 13% lower risks of in-hospital mortality than those without dehydration (BUN/CR < 15, adjusted OR = 0.87, 95%CI 0.78–0.96). In patients aged

Abstract Background DNA methylation of CpG dinucleotides is an essential epigenetic modification that plays a key role in transcription. Widely used DNA enrichment-based methods offer high coverage for measuring methylated CpG dinucleotides, with the lowest cost per CpG covered genome-wide. However, these methods measure the DNA enrichment of methyl-CpG binding, and thus do not provide information on absolute methylation levels. Further, the enrichment is influenced by various confounding factors in addition to methylation status, for example, CpG density. Computational models that can accurately derive absolute methylation levels from DNA enrichment data are needed. Results We developed “MeDEStrand,” a method that uses a sigmoid function to estimate and correct the CpG bias from enrichment results to infer absolute DNA methylation levels. Unlike previous methods, which estimate CpG bias based on reads mapped at the same genomic loci, MeDEStrand processes the reads for the positive and negative DNA strands separately. We compared the performance of MeDEStrand to that of three other state-of-the-art methods “MEDIPS,” “BayMeth,” and “QSEA” on four independent datasets generated using immortalized cell lines (GM12878 and K562) and human primary cells (foreskin fibroblasts and mammary epithelial cells). Based on the comparison of the inferred absolute methylation levels from MeDIP-seq data and the corresponding reduced-representation bisulfite sequencing data from each method, MeDEStrand showed the best performance at high resolution of 25, 50, and 100 base pairs. Conclusions The MeDEStrand tool can be used to infer whole-genome absolute DNA methylation levels at the same cost of enrichment-based methods with adequate accuracy and resolution. R package MeDEStrand and its tutorial is freely available for download at https://github.com/jxu1234/MeDEStrand.git.

BACKGROUND:There is a deficiency of healthcare administrators in China as compared with other countries; furthermore, the distribution is unequal. To inform an effective policy intervention, it is crucial to understand healthcare administration students' career decision-making. This study aims to investigate the undergraduate students' stated preferences when choosing a job. METHODS:A discrete choice experiment (DCE) was conducted among a population-based multistage sample of 668 final year undergraduate healthcare administration students during April to June 2017 in eight universities of China to elicit their job preferences. Attributes include location, monthly income, bianzhi (which refers to the established posts and can be loosely regarded as state administrative staffing), training and career development opportunity, working environment and workload. Conditional and mixed logit models were used to analyze the relative importance of job attributes. RESULTS:All six attributes were statistically significant with the expected sign and demonstrated the existence of preference heterogeneity. Monthly income, workload and working environment were of most concern to healthcare administration students when deciding their future. Among the presented attributes bianzhi was of the least concern. Sub-group analysis showed that students who have an urban background and/or with higher annual family incomes were willing to pay more for working in the city. In addition, students from western and middle universities valued bianzhi higher than students from eastern universities. CONCLUSIONS:This is the first study focusing on the career decision-making of Chinese healthcare administration students at a critical career decision-making point. Both monetary and non-monetary interventions could be considered by policy-makers to attract students to work in health institutions, especially in rural and remote health institutions in China. There exists preference heterogeneity on healthcare administration students' job preferences, which should also be taken into account in developing more effective policy incentive packages.

Mg−7Gd−5Y−0.5Zr alloy has excellent mechanical properties but poor hot tearing resistance. The latter makes it difficult to cast billets, which limits the size of subsequently processed parts. Therefore, the hot tearing susceptibility of Mg−7Gd−5Y−xZn−0.5Zr (x = 0, 3, 5, 7 wt%) alloys was studied. It was found that Zn can significantly reduce hot tearing susceptibility of Mg−7Gd−5Y−0.5Zr alloy, which almost linearly decreased with Zn content. When Zn content was 3 wt%, 5 wt% and 7 wt%, hot tearing susceptibility will be reduced by 27%, 83% and 100%, respectively. It was further revealed that the solid solubility of Gd and Y in α-Mg decreased with the increase of Zn content, and the nucleation temperature decreased accordingly, which resulted in the increase of nucleation rate and the refinement of final grains. On the macro level, it showed that the dendrite coherency temperature decreased, the solidification shrinkage stress of α-Mg slowed down, and the residual liquid channel became shorter and hot tearing susceptibility decreased. It was also found that with the increase of Zn content, the content of Zn, Gd and Y enriched on the grain boundary increased, the content of residual liquid phase between dendrites increased after α-Mg crystallization, and the solidified precipitated second phase also changed from Mg5RE phase to long-period stacking ordered phase + W-phase (a little), long-period stacking ordered phase + W-phase (much) and finally to W-phase only. The feeding effect of sufficient intergranular residual liquid on the shrinkage of α-Mg dendrite and the bridging effect of the precipitated phase at the grain boundary (especially long-period stacking ordered phase which is coherent with the parent phase) also led to the decrease of hot tearing susceptibility.