The COVID-19 Vaccines Evaluation Program: Implementation, Management, and Experiences, 2021-2023.

In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.

The efficacy of statins in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

BACKGROUND: A large body of research has investigated the use of statins in rheumatoid arthritis (RA); however, the therapeutic effects of statins remain uncertain. Thus, we designed a systematic review and meta-analysis to evaluate the role of statins in patients with RA. METHODS: Databases searched to detect clinical randomized controlled trials or clinical controlled trials on the interaction between statins and RA before January 2020 included PubMed, Web of Sciences, Embase, Cochrane Library, CNKI, Wan Fang Database. Efficacy was measured by Disease Activity Score in 28 Joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tenderness of the joint (TJ), swelling of the joint (SJ), and interleukin-6. The level of blood lipid was also evaluated. STATA 12.0 was used for the meta-analysis. The Cochrane method was used for quality assessment. Heterogeneity was considered to determine fixed effects or random effects models. RESULTS: Nineteen clinical trials with a total of 22,906 subjects were included in the meta-analysis. Sixteen studies reported a change in DAS28 after statin treatment. The pooled analysis showed that statins reduced DAS28 in RA patients. Change in ESR after statin treatment was reported in 9 studies. The summary analysis showed that statins lowered ESR in RA patients. Twelve studies reported a change in CRP after statin treatment. The results of the entire analysis showed that statins lowered CRP in RA patients. Seven studies reported a change in TJ after statin treatment. The combined analysis showed that statins reduced TJ at RA patients. Six studies reported changes in IL6 after statin therapy. The results showed that statins failed to reduce IL6 in RA patients. Seven studies reported changes in SJ after statin therapy, which showed that statins failed to reduce SJ in RA patients. We also found that statins can reduce blood lipid levels in RA patients. CONCLUSION: In conclusion, statins were able to reduce DAS28, ESR, CRP, TJ, and blood lipids. It indicated that stains can benefit patients with RA by inhibiting the expression of inflammatory factors and reducing the levels of lipids in the blood. Our study may offer a new perspective on the treatment of RA and provide research ideas for future larger multi-center clinical trials.

Extraction of soybean plant trait parameters based on SfM-MVS algorithm combined with GRNN.

Soybean is an important grain and oil crop worldwide and is rich in nutritional value. Phenotypic morphology plays an important role in the selection and breeding of excellent soybean varieties to achieve high yield. Nowadays, the mainstream manual phenotypic measurement has some problems such as strong subjectivity, high labor intensity and slow speed. To address the problems, a three-dimensional (3D) reconstruction method for soybean plants based on structure from motion (SFM) was proposed. First, the 3D point cloud of a soybean plant was reconstructed from multi-view images obtained by a smartphone based on the SFM algorithm. Second, low-pass filtering, Gaussian filtering, Ordinary Least Square (OLS) plane fitting, and Laplacian smoothing were used in fusion to automatically segment point cloud data, such as individual plants, stems, and leaves. Finally, Eleven morphological traits, such as plant height, minimum bounding box volume per plant, leaf projection area, leaf projection length and width, and leaf tilt information, were accurately and nondestructively measured by the proposed an algorithm for leaf phenotype measurement (LPM). Moreover, Support Vector Machine (SVM), Back Propagation Neural Network (BP), and Back Propagation Neural Network (GRNN) prediction models were established to predict and identify soybean plant varieties. The results indicated that, compared with the manual measurement, the root mean square error (RMSE) of plant height, leaf length, and leaf width were 0.9997, 0.2357, and 0.2666 cm, and the mean absolute percentage error (MAPE) were 2.7013%, 1.4706%, and 1.8669%, and the coefficients of determination (R2) were 0.9775, 0.9785, and 0.9487, respectively. The accuracy of predicting plant species according to the six leaf parameters was highest when using GRNN, reaching 0.9211, and the RMSE was 18.3263. Based on the phenotypic traits of plants, the differences between C3, 47-6 and W82 soybeans were analyzed genetically, and because C3 was an insect-resistant line, the trait parametes (minimum box volume per plant, number of leaves, minimum size of single leaf box, leaf projection area).The results show that the proposed method can effectively extract the 3D phenotypic structure information of soybean plants and leaves without loss which has the potential using ability in other plants with dense leaves.

Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10-15 g/L, and the quantitative limit reached 1.0 × 10-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Effectiveness of DTaP Against Pertussis in ≤2-Year-Old Children - Linyi Prefecture, Shandong Province, China, 2017-2019.

What is already known about this topic?: Vaccine effectiveness (VE) is positively correlated with the number of administered co-purified diphtheria, tetanus, and acellular pertussis vaccine (DTaP) doses. A matched case-control study conducted in Zhongshan City revealed that the co-purified DTaP VE against pertussis-related illnesses in children aged 4-11 months was 42% for one dose, 88% for two doses, and 95% for three doses, respectively. What is added by this report?: The results of this study contribute to the current body of research. We found that the VE of co-purified DTaP against pertussis-related illness and hospitalization increased substantially, ranging from 24%-26% after one dose to 86%-87% after four doses. What are the implications for public health practice?: The results of this study underscore the significance of prompt and comprehensive immunization using co-purified DTaP to decrease the incidence of pertussis. Additionally, these findings offer evidence supporting the modification of China's pertussis vaccination approach.

Data-driven engineering framework with AI algorithm of Ginkgo Folium tablets manufacturing.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate Cpk integrated Bootstrap-t. The Cpk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

The Influence of Small Biomolecules, Salts and Buffers on the Molecular Recognition of Amide Naphthotube in Aqueous Solutions.

We found the binding affinities of amide naphthotube to neutral organic molecules in water are not influenced by most of small biomolecules, inorganic salts, and PBS and Tris buffers but are reduced in HEPES buffer through competitive binding. Nevertheless, salts do change the binding affinities of amide naphthotube to charged molecules through a screening effect.

Exploring the protective mechanism of baicalin in treatment of atherosclerosis using endothelial cells deregulation model and network pharmacology.

BACKGROUND: Baicalin is a generally available flavonoid with potent biological activity. The present study aimed to assess the underlying mechanism of baicalin in treatment of atherosclerosis (AS) with the help of network pharmacology, molecular docking and experimental validation. METHODS: The target genes of baicalin and AS were identified from public databases, and the overlapping results were considered to be baicalin-AS targets. Core target genes of baicalin were obtained through the PPI network and validated by a clinical microarray dataset (GSE132651). Human aortic endothelial cells (HAECs) were treated with Lipopolysaccharide (LPS) to construct an endothelial injury model. The expression of NOX4 was examined by real-time qPCR and western blot. Flow cytometry was used to detect intracellular levels of reactive oxygen species (ROS). Furthermore, HAECs were transfected with NOX4-specific siRNA and then co-stimulated with baicalin and LPS to investigate whether NOX4 was involved in the anti-oxidative stress effects of baicalin. RESULTS: In this study, baicalin had 45 biological targets against AS. Functional enrichment analysis demonstrated that most targets were involved in oxidative stress. Using the CytoHubba plug-in, we obtained the top 10 genes in the PPI network ranked by the EPC algorithm. Molecular docking and microarray dataset validation indicated that NOX4 may be an essential target of baicalin, and its expression was significantly suppressed in AS samples compared to controls. In endothelial injury model, intervention of HAECs with baicalin increased the expression levels of NOX4 and NOS3 (eNOS), and decreased LPS-induced ROS generation. After inhibition of NOX4, the anti-ROS-generating effect of baicalin was abolished. CONCLUSION: Collectively, we combined network pharmacology and endothelial injury models to investigate the anti-AS mechanism of baicalin. The results demonstrate that baicalin may exert anti-oxidative stress effects by targeting NOX4, providing new mechanisms and insights to baicalin for the treatment of AS.

Molecular recognition and spectral tuning of organic dyes in water by amide naphthotubes.

Molecular recognition and spectral tuning of 13 organic dyes were achieved in water by amide naphthotubes. The association affinity to a styryl derivative is up to 4.5 × 107 M-1, which is the highest among all the known hosts. In addition, great fluorescence enhancement was observed for styryl derivatives. This would lay a basis for the potential analysis application.

Stabilization of Imines and Hemiaminals in Water by an Endo-Functionalized Container Molecule.

Stabilizing water-sensitive reaction intermediates is challenging but desirable for guiding reactions to desired products in water. Herein, we report that labile imine and hemiaminal functional groups can be stabilized inside a synthetic container compound, a water-soluble naphthotube. The naphthotube features a primary amine group anchored in a cavity with both hydrogen bonding sites and hydrophobic surfaces. Aldehydes in bulk aqueous solution are trapped in the cavity by the amine to form hemiaminals stabilized through hydrogen bonding and hydrophobic effects. Dehydration of the hemiaminal to the imine is favored by the release of water from the hydrophobic microenvironment. Both the hemiaminals and imines can be detected at room temperature by NMR spectroscopy and mass spectrometry.

Association of COVID-19 Vaccination and Clinical Severity of Patients Infected with Delta or Omicron Variants - China, May 21, 2021-February 28, 2022.

What is already known about this topic?: Compared with the international mRNA and adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines, there is less real-world research data about breakthrough cases in people vaccinated with China-made COVID-19 vaccines. Analyses of clinical outcomes of breakthrough cases will be an important supplement to the clinical trial efficacy and observational effectiveness data of China-made COVID-19 vaccines. What is added by this report?: COVID-19 vaccine age-eligible individuals (≥3 years old) who received full primary series and a booster dose of China-made COVID-19 vaccines had good protection from pneumonia caused by Delta variant infection. There was only one serious Delta case in children (unvaccinated), but among adults 18 years and older, there was good protection from serious illness with primary vaccination and booster vaccination. Among people ≥60 years, full vaccination and booster vaccination were associated with protection from pneumonia and risk of serious COVID-19 caused by Omicron variant infection. There were few serious Omicron cases. What are the implications for public health practice?: Everyone 3 years and older without contraindications should be fully vaccinated against COVID-19; schedule-eligible adults should receive booster doses. The pace of booster dose administration, especially among the elderly, should be accelerated.

Impact of public health insurance coverage of novel anticancer medication on medical expenditure and patient affordability in a provincial medical centre of China: a propensity score-matching analysis with the quasi-experimental design.

INTRODUCTION: Little is known about the impact of the government's efforts in having novel anticancer medicines covered by the public health insurance system in China. This study targeted the above policy implemented in Fujian province in 2017, analysed the policy impact on the medical expenditure of cancer treatment and patient affordability based on the clinical data of Fujian provincial medical centre. METHODS: The study included 253 human epidermal growth factor receptor 2-positive patients with breast cancer who completed at least one course of trastuzumab treatment extracted from the hospital health information system of the provincial medical centre of Fujian. We adopted the propensity score-matching method to mimic a quasi-experimental design to estimate the impact of the public health insurance coverage policy on all the indicated patients with a before-after comparison of the total breast cancer-associated direct medical expenditures for a standard course of treatment or maintenance treatment and the proportionate patient out-of-pocket (OOP) expenditure based on the real clinical data. RESULTS: We found evidence of an association between the public health insurance coverage of novel breast cancer medication and the reductions of the medical expenditure by US$18661.02 (95% CI 13 836.57 to 28 201.45), and the proportionate patient OOP expenditure by 24% (95% CI0.20 to 0.27). The medical expenditure and the proportionate patient OOP expenditure might be generally reduced. CONCLUSIONS: The coverage of innovative antibreast cancer medicines by the public health insurance was found to be associated with a reduction of the medical expenditure and share of patient OOP expenditure for cancer treatment of the indicated patients. Patients with lower ability-to-pay did not benefit well from the coverage policy. To maximise the welfare of the public health insurance coverage of novel anticancer medication, the study called for strengthened health insurance benefit packages of the rural patient and the patient enrolled in the urban and rural resident health insurance programme, who might have lower ability-to-pay and need more support from the public security system.

Single-cell RNA-seq reveals altered NK cell subsets and reduced levels of cytotoxic molecules in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune disease with unknown aetiology. To unravel the mechanisms mediating AS pathogenesis, we profiled peripheral blood mononuclear cells (PBMCs) from AS patients and healthy subjects using 10X single-cell RNA sequencing. The frequencies of immune cell subsets were evaluated by flow cytometry. NK cells were purified from PBMCs using isolation kit and were examined for gene expression by RT-qPCR. Plasma levels of cytolytic molecules were examined by enzyme-linked immunosorbent assay. Compared to healthy controls, AS patients showed a significant decrease in total NK cells as well as CD56dim NK subset, whereas CD56bright NK cells were increased. Additionally, impaired expression of cytotoxic genes in NK cells of AS patients was observed by bioinformatics algorithm and verified by RT-qPCR and flow cytometry. Consistent with changes in transcriptomics, we found decreased plasma levels of granzymes, but not granulysin, in AS patients. Furthermore, Pearson correlation analysis revealed a negative correlation between plasma GZMB levels and disease activity (r = -0.5275, p = 0.0358). No correlation was observed between plasma cytolytic molecules and biochemical indexes (ESR and CRP). Our findings uncover altered NK cell subsets and cytotoxic profiles in peripheral circulation of AS patients at single-cell resolution.

NIR robustness model of variable selection investigation of critical quality attributes coupled with different simulate noises by prediction capability and reproducibility.

variable selection is critical to select characteristic variables of critical quality attributes to improve model performance and interpret the identified variables in multivariate calibration. However, classical variable selection methods were developed and optimized by the prediction error. It is rare for the robustness evaluation of variable selection methods. In this study, the robustness of four different variable selection methods was investigated by adding different types of simulate noises to validation set and calibration and validation sets, respectively. The reproducibility as well as root mean squared error of prediction (RMSEP) were used together as common measure in assessing the robustness of different variable selection methods. The robustness of four variable selection methods method was investigated using two near infrared (NIR) datasets including open-source dataset of corn and Chinese herbal medicine (CHM) dataset. The result illustrated that variable importance in projection (VIP) was substantially more robust to additive noise, with smaller RMSEP value and high reproducibility. This provides a novel strategy for the reliability evaluation of variable selection methods in NIR model of critical quality attributes.

Tanyu Tongzhi Formula Delays Atherosclerotic Plaque Progression by Promoting Alternative Macrophage Activation via PPARγ and AKT/ERK Signal Pathway in ApoE Knock-Out Mice.

We previously demonstrated that the Tanyu Tongzhi Formula (TTF) significantly alleviated the clinical symptoms of patients with coronary heart disease and lowered serum lipid and inflammatory factor levels in patients with coronary heart disease and atherosclerosis model rats. However, the mechanism underlying TTF remains unknown. In this study, we examined the effect of TTF on atherosclerotic plaques in ApoE-/- mice and underlying mechanisms involved in macrophage polarization. Sixty male ApoE-/- mice were randomly divided into four groups. Mice in the control group were fed a regular diet, whereas experimental mice were fed a high-fat diet and received either saline (HFD group) or TTF at concentrations of 0.60 (TTF-L group) or 2.25 g/ml (TTF-H group) by daily oral gavage for 16 weeks. In the TTF-L and TTF-H groups, the levels of serum cholesterol, triglyceride, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were decreased, lipid content was significantly decreased, and percentage area of collagen/lipid increased in atherosclerotic plaque compared to in the HFD group. Moreover, we found TTF promoted the expression of alternative macrophage markers (Fizz1, Arg1, and Mrc) and suppressed the expression of M1 macrophage markers (TNF-α, IL-1ß, and IL-6) by regulating peroxisome proliferator-activated receptor γ (PPARγ) expression and AKT/extracellular signal-regulated kinase (ERK) activation. We further investigated whether alternative macrophage was reduced when PPARγ was inhibited or the AKT/ERK signaling pathway was activated. TTF delayed atherosclerotic plaque progression by promoting alternative macrophage activation through increasing PPARγ expression and inhibiting AKT/ERK phosphorylation, providing a theoretical basis for its clinical application.

Development of MIF/IL-1ß biosensors for discovery of critical quality attributes and potential allergic rhinitis targets from clinical real-world data by intelligent algorithm coupled with in vitro and vivo mechanism validation.

There are still huge challenges from clinical real-world data to accurate targets and critical quality attributes (CQAs) for effective treatment of allergic rhinitis (AR). Here, we present a novel integrated strategy that biosensors and intelligent algorithms were used to angle AR targets and CQAs from clinical real world. Firstly, bagging and boosting partial least squares discrimination analysis (PLS-DA) and Monte-Carlo sampling were proposed to screen accurate AR targets. Macrophage migration inhibitory factor (MIF) and Interleukin-1beta (IL-1ß) potential targets were obtained based on large-scale analysis of one thousand proteins and in-depth precise screening of seventy proteins. Furthermore, high electron mobility transistor (HEMT) biosensors were fabricated and successfully modified by MIF and IL-1ß potential targets with a low detection concentration as 1 pM and quantitative range from 1 pM to 10 nM. Surprisingly, through MIF/IL-1ß biosensors, we angled 5-O-methylvisammioside, amygdalin, and cimicifugoside three CQAs. The strong interaction was discovered among three CQAs and MIF/IL-1ß biosensors with almost all KD up to 10-11 M. Finally, interaction among three CQAs and MIF/IL-1ß biosensors were evaluated by in vitro and vivo experiments. In this paper, two critical potential targets and three effective CQAs for AR treatment were discovered and validated by biosensor and advanced algorithms. It provides a superior integrated idea for angling critical targets and CQAs from clinical real-world data by biosensors and informatics.

Molecular Imaging of Brown Adipose Tissue Mass.

Brown adipose tissue (BAT), a uniquely thermogenic tissue that plays an important role in metabolism and energy expenditure, has recently become a revived target in the fight against metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Different from white adipose tissue (WAT), the brown adipocytes have distinctive features including multilocular lipid droplets, a large number of mitochondria, and a high expression of uncoupling protein-1 (UCP-1), as well as abundant capillarity. These histologic characteristics provide an opportunity to differentiate BAT from WAT using imaging modalities, such as PET/CT, SPECT/CT, MRI, NIRF and Ultrasound. However, most of the reported imaging methods were BAT activation dependent, and the imaging signals could be affected by many factors, including environmental temperatures and the states of the sympathetic nervous system. Accurate BAT mass detection methods that are independent of temperature and hormone levels have the capacity to track the development and changes of BAT throughout the lifetime of mammals, and such methods could be very useful for the investigation of potential BAT-related therapies. In this review, we focus on molecular imaging modalities that can detect and quantify BAT mass. In addition, their detection mechanism and limitations will be discussed as well.

How government health insurance coverage of novel anti-cancer medicines benefited patients in China - a retrospective analysis of hospital clinical data.

BACKGROUND: China started to cover novel medicines for the treatment of major cancers, such as trastuzumab for breast cancer by the government health insurance programs since 2016. Limited data have been published on the use of cancer medications and little is known about how government health insurance coverage of novel anti-cancer medicines benefited patients in the real world. This study aimed to generate evidence to inform the health security authorities to optimize the government health insurance coverage of novel anti-cancer medicines as a more inclusive and equal policy, through which each of the needed patient can get access to the novel anti-cancer medicines regardless of the ability to pay. METHODS: The study targeted one of the government health insurance newly covered novel medicines for breast cancer and the breast cancer patients. The analyses were based on the data collected from one tertiary public hospital in Fujian province of China. We conducted interrupted time series analysis with a segmented regression model and multivariate analyses with a binary logistic regression model to analyze the impact of the government health insurance coverage on medicines utilization and the determinants of patient's medication choice. RESULTS: The average proportion of patients who initiated medication with novel medicines increased from 37.4% before the government health insurance coverage to 69.2% afterwards. Such an increase was observed in all patient sub-groups. The monthly proportion of patients who initiated medication with novel medicines increased sharply by 18.3 % (95 %CI,10.4-34.0 %, p = 0.01) in September 2017, the afterwards trend continuously increased (95 %CI,1.03-3.60, p = 0.02). The critical determinants of patient's medication choice were mostly connected with the patient's health insurance benefits packages. CONCLUSIONS: The government health insurance coverage of novel anti-breast-cancer medicines benefited the patients generally. The utilization of novel medicines such as trastuzumab continuously increased. The insurance coverage benefited well the patients in the high-risk age groups. However, rural patients, patients enrolled in the "resident program", and patients from low-income residential areas and non-local patients benefited less from this policy. Improving the benefits package of the low-income patients and the "resident program" beneficiary would be of considerable significance for a more inclusive and equal health insurance coverage of novel anti-cancer medicines.

Training non-native vowel perception: In quiet or noise.

Noise makes speech perception much more challenging for non-native listeners than for native listeners. Training for non-native speech perception is usually implemented in quiet. It remains unclear if background noise may benefit or hamper non-native speech perception learning. In this study, 51 Chinese-native listeners were randomly assigned into three groups, including vowel training in quiet (TIQ), vowel training in noise (TIN), and watching videos in English as an active control. Vowel identification was assessed before (T1), right after (T2), and three months after training (T3) in quiet and various noise conditions. Results indicated that compared with the video watching group, the TIN group improved vowel identification in both quiet and noise significantly more at T2 and at T3. In contrast, the TIQ group improved significantly more in quiet and also in non-speech noise conditions at T2, but the improvement did not hold at T3. Moreover, compared to the TIQ group, the TIN group showed significantly less informational masking at both T2 and T3 and less energetic masking at T3. These results suggest that L2 speech training in background noise may improve non-native vowel perception more effectively than TIQ background only. The implications for non-native speech perception learning are discussed.