Enhancing therapeutic efficacy in luminal androgen receptor triple-negative breast cancer: exploring chidamide and enzalutamide as a promising combination strategy.

Extensive exploration of the molecular subtypes of triple-negative breast cancer (TNBC) is critical for advancing precision medicine. Notably, the luminal androgen receptor (LAR) subtype has attracted attention for targeted treatment combining androgen receptor antagonists and CDK4/6 inhibitors. Unfortunately, this strategy has proven to be of limited efficacy, highlighting the need for further optimization. Using our center's comprehensive multiomics dataset (n = 465), we identified novel therapeutic targets and evaluated their efficacy through multiple models, including in vitro LAR cell lines, in vivo cell-derived allograft models and ex vivo patient-derived organoids. Moreover, we conducted flow cytometry and RNA-seq analysis to unveil potential mechanisms underlying the regulation of tumor progression by these therapeutic strategies. LAR breast cancer cells exhibited sensitivity to chidamide and enzalutamide individually, with a drug combination assay revealing their synergistic effect. Crucially, this synergistic effect was verified through in vivo allograft models and patient-derived organoids. Furthermore, transcriptomic analysis demonstrated that the combination therapeutic strategy could inhibit tumor progression by regulating metabolism and autophagy. This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

Kinetics of Nanobubbles in Tiny-Angle Twisted Bilayer Graphene.

Realization of high-quality van der Waals (vdWs) heterostructures by stacking two-dimensional (2D) layers requires atomically clean interfaces. Because of strong adhesion between the constituent layers, the vdWs forces could drive trapped contaminants together into submicron-size "bubbles", which leaves large interfacial areas atomically clean. Here, we study the kinetics of nanobubbles in tiny-angle twisted bilayer graphene (TBG) and our results reveal a substantial influence of the moiré superlattice on the motion of nanoscale interfacial substances. Our experiments indicate that the bubbles will mainly move along the triangular network of domain boundaries in the tiny-angle TBG when the sizes of the bubbles are comparable to that of an AA-stacking region. When the size of the bubble is smaller than that of an AA-stacking region, the bubble becomes motionless and is fixed in the AA-stacking region, because of its large out-of-plane corrugation.

Sasanquasaponin from Camellia oleifera Abel Exerts an Anti-Inflammatory Effect in RAW 264.7 Cells via Inhibition of the NF-κB/MAPK Signaling Pathways.

Sasanquasaponin (SQS), a secondary metabolite that is derived from Camellia seeds, reportedly possesses notable biological properties. However, the anti-inflammatory effects of SQS and its underlying mechanisms remain poorly explored. Herein, we aimed to investigate the anti-inflammatory properties of SQS against lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells, focusing on the nuclear factor-κB (NF-κB) and MAPK signaling pathways. SQS was isolated using a deep eutectic solvent and D101 macroporous adsorption resin and analyzed using high-performance liquid chromatography. The viability of LPS-stimulated RAW264.7 was assessed using the CCK-8 assay. The presence of reactive oxygen species (ROS) was evaluated using 2',7'-dichlorofluorescein-diacetate. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using reverse transcription-quantitative PCR and ELISA. Western blot was performed to analyze the protein expression of LPS-induced RAW264.7 cells. Herein, SQS exhibited anti-inflammatory activity: 30 µg/mL of SQS significantly reduced ROS generation, inhibited the LPS-induced expression of iNOS and COX-2, and attenuated the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. The anti-inflammatory activity was potentially mediated by inhibiting the phosphorylation of IκBα and p65 in the NF-κB signaling pathway and the phosphorylation of ERK and JNK in the MAPK signaling pathway. Accordingly, SQS could inhibit inflammation in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPK signaling pathways. This study demonstrated the potential application of SQS as an anti-inflammatory agent.

Wnt/ß-catenin signalling pathway in breast cancer cells and its effect on reversing tumour drug resistance by alkaloids extracted from traditional Chinese medicine.

Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/ß-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/ß-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.

eIF4A3 Promotes RNA Viruses' Replication by Inhibiting Innate Immune Responses.

Viral infection activates the type I interferons (IFNs) and cellular antiviral responses. Eukaryotic initiation factor 4A-III (eIF4A3) has been shown to promote influenza A virus (IAV) replication by promoting viral mRNA splicing and spliced mRNA nuclear export. Here, we identified eIF4A3 as a negative regulator of virus-triggered type I IFN induction. Our study found that eIF4A3 promoted multiple RNA viruses' replication by binding to IFN regulatory factor 3 (IRF3) and impaired the interaction between tank-binding kinase 1 (TBK1) and IRF3, leading to attenuation of the phosphorylation of IRF3 by TBK1, the formation of IRF3 dimer, and the nuclear translocation of IRF3. This impaired its biological functions in the nucleus, which blocked IRF3 binding to interferon-stimulated response element (ISRE) and the interaction of IRF3 and CBP/p300, resulting in inhibiting the transcription of IFN-ß and downstream IFN-stimulated genes (ISGs), thereby impairing innate antiviral immune responses against RNA viruses. These findings reveal a previously unknown function of eIF4A3 in host innate immunity and establish a mechanistic link between eIF4A3 and IRF3 activation that expands potential therapeutic strategies for viral infectious diseases. IMPORTANCE Production of type I IFN is pivotal for the cellular antiviral immunity. Virus infection leads to the activation of transcription factor IRF3 and subsequent production of type I IFN to eliminate viral infection. Thus, the regulation of IRF3 activity is an important way to affect type I IFN production. IRF3 activation requires phosphorylation, dimerization, and nuclear translocation. Here, we first reported that eIF4A3, a member of DEAD box family, served as a negative regulator of antiviral innate immune responses by inhibiting IRF3 activation. Mechanistically, eIF4A3 binds to IRF3 to impair the recruitment of IRF3 by TBK1, which is independent of eIF4A3 ATP binding, ATPase, and RNA helicase activities. Our study delineates a common mechanism of eIF4A3 promoting replication of different RNA viruses and provides important insights into the negative regulation of host antiviral innate immune responses against virus infections.

Design and Evaluation of Tretinoin Fatty Acid Vesicles for the Topical Treatment of Psoriasis.

The goal of the current study was to explore the potential benefits of Tretinoin (Tre) fatty acid vesicles (Tre-FAV) as a prospective antipsoriatic topical delivery system. This promising system can counteract the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Tre-loaded fatty acid vesicles were successfully developed and entirely characterised. The selected formulation was investigated for in vitro release, ex vivo skin retention and psoriasis efficacy studies. The characterisation results of Tre-FAV showed it has a globular shape with a particle size of 126.37 ± 1.290 nm (0.188 ± 0.019 PDI). The entrapment efficiency and zeta potential were discovered to be 84.26 ± 0.816% and -28.9 ± 1.92 mV, respectively. Encapsulation of the drug in the fatty acid vesicles was also strengthened by differential scanning calorimetric and powder FTIR diffraction studies. In vitro release results showed that Tre-FAV significantly increased skin absorption and retention in comparison to the Tre solution. The topical application of Tre-FAV to a mouse model confirmed that it has superior in vivo antipsoriatic properties in terms of well-demarcated papules, erythema and reduced epidermal thickness in comparison to other treatments. The weight of the spleen and the levels of the cytokines IL-17 and IL-6 decreased after treatment. In conclusion, FAV dramatically increased the water solubility and skin permeability of Tre and its anti-psoriasis activity.

Retinoic acid exerts sexually dimorphic effects on muscle energy metabolism and function.

The retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and reduces adiposity. Skeletal muscle contributes to preventing adiposity, by consuming nearly half the energy of a typical human. We report sexually dimorphic differences in energy metabolism and muscle function in Rdh10+/- mice. Relative to wild-type (WT) controls, Rdh10+/- males fed a high-fat diet decrease reliance on fatty-acid oxidation and experience glucose intolerance and insulin resistance. Running endurance decreases 40%. Rdh10+/- females fed this diet increase fatty acid oxidation and experience neither glucose intolerance nor insulin resistance. Running endurance increases 220%. We therefore assessed RA function in the mixed-fiber type gastrocnemius muscles (GM), which contribute to running, rather than standing, and are similar to human GM. RA levels in Rdh10+/- male GM decrease 38% relative to WT. Rdh10+/- male GM increase expression of Myog and reduce Eif6 mRNAs, which reduce and enhance running endurance, respectively. Cox5A, complex IV activity, and ATP decrease. Increased centralized nuclei reveal existence of muscle malady and/or repair in GM fibers. Comparatively, RA in Rdh10+/- female GM decreases by less than half the male decrease, from a more modest decrease in Rdh10 and an increase in the estrogen-induced retinol dehydrogenase Dhrs9. Myog mRNA decreases. Cox5A, complex IV activity, and ATP increase. Centralized GM nuclei do not increase. We conclude that Rdh10/RA affects whole body energy use and insulin resistance partially through sexual dimorphic effects on skeletal muscle gene expression, structure, and mitochondria activity.

Tunable Sample-Wide Electronic Kagome Lattice in Low-Angle Twisted Bilayer Graphene.

Overlaying two graphene layers with a small twist angle θ can create a moiré superlattice to realize exotic phenomena that are entirely absent in a graphene monolayer. A representative example is the predicted formation of localized pseudo-Landau levels (PLLs) with kagome lattice in tiny-angle twisted bilayer graphene (TBG) with θ<0.3° when the graphene layers are subjected to different electrostatic potentials. However, this was shown only for the model of rigidly rotated TBG, which is not realized in reality due to an interfacial structural reconstruction. It is believed that the interfacial structural reconstruction strongly inhibits the formation of the PLLs. Here, we systematically study electronic properties of the TBG with 0.075°≤θ<1.2° and demonstrate, unexpectedly, that the PLLs are quite robust for all the studied TBG. The structural reconstruction suppresses the formation of the emergent kagome lattice in the tiny-angle TBG. However, for the TBG around the magic angle, the sample-wide electronic kagome lattices with tunable lattice constants are directly imaged by using a scanning tunneling microscope. Our observations open a new direction to explore exotic correlated phases in moiré systems.

Does social capital buffer or exacerbate mental health inequality? Evidence from the China Family Panel Study (CFPS).

BACKGROUND: Health inequality, including physical and mental health inequality, is an important issue. What role social capital plays in mental health inequality is still ambiguous, especially in developing countries. The aim of this study is to explore the relationship between social capital and mental health inequality in China. METHOD: Both family-level and community-/village-level social capitals are included in our analysis. Data is mainly extracted from the China Family Panel Studies in 2018, and lagged term of social capital in CFPS 2016 was used to link with other variables in 2018. Depressive symptoms and subjective well-being are set as indicators of mental health. A series of OLS regression models were conducted to estimate the effects of social capital on mental health and mental health inequality. RESULTS: Higher levels of social capital and income are related to a lower level of depressive symptoms and a higher level of subjective well-being. The positive coefficient of interaction term of family-level social capital and income level in the urban area indicates that the inhibiting effect of social capital on depressive symptoms is pro-poor. The negative coefficient of interaction term of village-level social capital and income level in the rural area suggests that the promoting effect of social capital on subjective well-being is pro-poor, too. CONCLUSION: The results show that severe mental health inequality exists in China; family-level social capital can buffer depressive symptom inequality, and village-level social capital can buffer SWB inequality. Although the amount of social capital of the poor is less than the rich, the poor can better use social capital to improve their mental health. Our study advocates enhancing social participation and communication for the poor to reduce mental health inequality.

Transportin-3 Facilitates Uncoating of Influenza A Virus.

Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV-host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease.

Oscillations of the Spacing between van Hove Singularities Induced by sub-Ångstrom Fluctuations of Interlayer Spacing in Graphene Superlattices.

Physical properties of two-dimensional van der Waals (vdWs) structures depend sensitively on both stacking orders and interlayer interactions. Yet, in most cases studied to date, the interlayer interaction is considered to be a "static" property of the vdWs structures. Here we demonstrate that applying a scanning tunneling microscopy (STM) tip pulse on twisted bilayer graphene (TBG) can induce sub-Ångstrom fluctuations of the interlayer separation in the TBG, which are equivalent to dynamic vertical external pressure of about 10 GPa on the TBG. The sub-Ångstrom fluctuations of the interlayer separation result in large oscillations of the energy separations between two van Hove singularities (VHSs) in the TBG. The period of the oscillations of the VHSs spacing is extremely long, about 500-1000 sec, attributing to tip-induced local stress in the atomic-thick TBG. Our result provides an efficient method to tune and measure the physical properties of the vdWs structures dynamically.

The benefits of an integrated social medical insurance for health services utilization in rural China: evidence from the China health and retirement longitudinal study.

BACKGROUND: Improving health equity is a fundamental goal for establishing social health insurance. This article evaluated the benefits of the Integration of Social Medical Insurance (ISMI) policy for health services utilization in rural China. METHODS: Using the China Health and Retirement Longitudinal study (2011‒2018), we estimated the changes in rates and equity in health services utilization by a generalized linear mixed model, concentration curves, concentration indices, and a horizontal inequity index before and after the introduction of the ISMI policy. RESULTS: For the changes in rates, the generalized linear mixed model showed that the rate of inpatient health services utilization (IHSU) nearly doubled after the introduction of the ISMI policy (8.78 % vs. 16.58 %), while the rate of outpatient health services utilization (OHSU) decreased (20.25 % vs. 16.35 %) after the implementation of the policy. For the changes in inequity, the concentration index of OHSU decreased significantly from - 0.0636 (95 % CL: -0.0846, - 0.0430) before the policy to - 0.0457 (95 % CL: -0.0684, - 0.0229) after it. In addition, the horizontal inequity index decreased from - 0.0284 before the implementation of the policy to - 0.0171 after it, indicating that the inequity of OHSU was further reduced. The concentration index of IHSU increased significantly from - 0.0532 (95 % CL: -0.0868, - 0.0196) before the policy was implemented to - 0.1105 (95 % CL: -0.1333, - 0.0876) afterwards; the horizontal inequity index of IHSU increased from - 0.0066 before policy implementation to - 0.0595 afterwards, indicating that more low-income participants utilized inpatient services after the policy came into effect. CONCLUSIONS: The ISMI policy had a positive effect on improving the rate of IHSU but not on the rate of OHSU. This is in line with this policy's original intention of focusing on inpatient service rather than outpatients to achieve its principal goal of preventing catastrophic health expenditure. The ISMI policy had a positive effect on reducing the inequity in OHSU but a negative effect on the decrease in inequity in IHSU. Further research is needed to verify this change. This research on the effects of integration policy implementation may be useful to policy makers and has important policy implications for other developing countries facing similar challenges on the road to universal health coverage.

The effects of family physician-contracted service on health-related quality of life and equity in health in China.

BACKGROUND: Family physician-contracted service (FPCs) has been recently implemented in Chinese primary care settings. This study was aimed at measuring the effects of FPCs on residents' health-related quality of life (HRQoL) and equity in health among the Chinese population. METHODS: The study data was drawn from the 2018 household health survey (Shaanxi Province, China) using multistage, stratified cluster random sampling. We measured HRQoL using EQ-5D-3L based on the Chinese-specific time trade-off values set. Coarsened exact matching (CEM) technique was used to control for confounding factors between residents with and without a contracted family physician. The concentration index (C) was calculated to measure equity in health. RESULTS: Individuals with a contracted family physician had significantly higher HRQoL than those without, after data matching (0.9355 vs. 0.8995; P <  0.001). Additionally, the inequity in HRQoL among respondents with a contracted family physician was significantly lower than those without a contracted family physician (Cs of EQ-5D utility score: 0.0084 vs. 0.0263; p <  0.001). CONCLUSIONS: This study highlights the positive effects of FPCs on HRQoL and socioeconomic-related equity in HRQoL. Future efforts should prioritize the economically and educationally disadvantaged groups, the expansion of service coverage, and the competency of family physician teams to further enhance health outcome and equity in health.

Trends in equity of inpatient health service utilization for the middle-aged and elderly in China: based on longitudinal data from 2011 to 2018.

BACKGROUND: The aim of this study was to assess the trends in equity of receiving inpatient health service utilization (IHSU) in China over the period 2011-2018. METHODS: Longitudinal data obtained from China Health and Retirement Longitudinal Studies were used to determine trends in receiving IHSU. Concentration curves, concentration indices, and horizontal inequity indices were applied to evaluate the trends in equity of IHSU. RESULTS: This study showed that the annual rate of IHSU gradually increased from 7.99% in 2011 to 18.63% in 2018. Logistic regression shows that the rates of annual IHSU in 2018 were nearly 3 times (OR = 2.86, 95%CL: 2.57, 3.19) higher for rural respondents and 2.5 times (OR = 2.49, 95%CL: 1.99, 3.11) higher for urban respondents than the rates in 2011 after adjusting for other variables. Concentration curves both in urban and rural respondents lay above the line of equality from 2011 to 2018. The concentration index remained negative and increased significantly from - 0.0147 (95% CL: - 0.0506, 0.0211) to - 0.0676 (95% CL: - 0.0894, - 0.458), the adjusted concentration index kept the same tendency. The horizontal inequity index was positive in 2011 but became negative from 2013 to 2018, evidencing a pro-low-economic inequity trend. CONCLUSIONS: We find that the inequity of IHSU for the middle-aged and elderly increased over the past 10 years, becoming more focused on the lower-economic population. Economic status, lifestyle factors were the main contributors to the pro-low-economic inequity. Health policies to allocate resources and services are needed to satisfy the needs of the middle-aged and elderly.

Gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren.

BACKGROUND: Caring for grandchildren is regarded as one of the principle roles of middle- and old-aged adults, especially among rural Chinese grandparents. This study aims to examine the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren, based on the gender differences in grandparental role engagement and the theories of role strain and role enhancement. METHODS: A total of 4833 rural citizens with one or more grandchildren were selected from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015. Grandchild care was measured by continuous variable (duration) and categorical variable (no care, low intensity, moderate intensity, high intensity). Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). We used coarsened exact matching (CEM) to balance the covariates of caregivers and non-caregivers. Following CEM, 1975 non-caregivers and 2212 caregivers were identified (N = 4187). Multilevel linear regression was employed to examine the gender differences in depressive symptoms. We also tested for the moderating role of gender on the association between grandchild care and depressive symptoms. RESULTS: Grandmothers were more likely to provide grandchild care (54.42% vs 51.43%) at high intensity (61.46% vs 51.01%), with longer duration (39.24 h vs 33.15 h) than that given by grandfathers. Grandmothers suffered more from depressive symptoms than grandfathers, and such gap increased when grandparents were involved in high-intensity care. Grandmothers providing grandchild care, particularly at moderate intensity, were associated with fewer depressive symptoms (Coef. = - 0.087, 95%CI: - 0.163, - 0.010; Coef. = - 0.291, 95%CI: - 0.435, - 0.147), compared with non-caregivers. Grandmothers giving moderate intensity of grandchild care were also associated with fewer depressive symptoms (Coef. = - 0.171, 95% CI: - 0.313, - 0.029), compared with those with low-intensity care. However, such associations were not significant among grandfathers. CONCLUSIONS: Our findings highlight the gender differences in depressive symptoms of rural Chinese grandparents caring for grandchildren. Grandparents should be encouraged to engage in grandchild care, but at moderate intensity. The health status of middle- and old-aged adults, particularly females, should be monitored closely. Humanistic care, preventive care and curative treatment strategies focusing on such populations should be developed and refined.

Comparison of inequity in health-related quality of life among unemployed and employed individuals in China.

BACKGROUND: In China, achieving health equity has been regarded as a key issue for health reform and development in the current context. It is well known that unemployment has a negative effect on health. However, few studies have addressed the association between unemployment and inequity in health-related quality of life (HRQOL). This study aims to compare the inequality and inequity in HRQOL between the unemployed and employed in China. METHODS: The material regarding this study was derived from the Chinese National Health Services Survey of Shaanxi Province for 2013. We controlled for confounding factors by utilizing the coarsened exact matching method. Finally, 7524 employed individuals and 283 unemployed individuals who were 15 to 64 years old in urban areas were included in this study. We used HRQOL as the outcome variable, which was evaluated by using the Chinese version of EQ-5D-3L. The health concentration index, decomposition analysis based on the Tobit model, and the horizontal inequity index were employed to compute the socioeconomic-related equity between the unemployed and employed and the contribution of various factors. RESULTS: After matching, unemployed people tended to have poorer EQ-5D utility scores than employed people. There were statistically pro-rich inequalities in HRQOL among both employed and unemployed people, and the pro-rich health inequity of unemployed people was substantially higher than that of employed people. Economic status, age, education, smoking and health insurance were the factors influencing inequality in HRQOL between employed and unemployed individuals. Education status and basic health insurance have reduced the pro-rich inequity in HRQOL for unemployed people. CONCLUSION: It is suggested that unemployment intensifies inequality and inequity in HRQOL. According to policymakers, basic health insurance is still a critical health policy for improving health equity for the unemployed. Intervention initiatives aiming to tackle long-term unemployment through active labour market programmes, narrow economic gaps, improve educational equity and promote the health status of the unemployed should be considered by the government to achieve health equity.

Whether high government subsidies reduce the healthcare provision of township healthcare centers in rural China.

BACKGROUND: China's government launched a large-scale healthcare reform from 2009. One of the main targets of this round reform was to improve the primary health care system. Major reforms for primary healthcare institutions include increasing government investment. However, there are insufficient empirical studies based on large sample to catch long-term effect of increased government subsidy and lack of sufficient incentives on township healthcare centers (THCs), therefore, this study aims to provide additional empirical evidence on the concern by conducting an empirical analysis of THCs in Shaanxi province in China. METHODS: We collected nine years (2009 to 2017) data of THCs from the Health Finance Annual Report System (HFARS) that was acquired from the Health Commission of Shaanxi Province. We applied two-way fixed effect model and continue difference-in-difference (DID) model to estimate the effect of percentage of government subsidy on medical provision. RESULTS: A clear jump of the average percentage of government subsidy to total revenue of THCs can be found in Shaanxi province in 2011, and the average percentage has been more than 60% after 2011. Continue DID models indicate every 1% percentage of government subsidy to total revenue increase after 2011 resulted in a decrease of 1.1 to 3.5% in THCs healthcare provision (1.9% in medical revenue, 1.2% in outpatient visit, 3.5% in total occupy beds of inpatient, 1.1% in surgery revenue, 2.1% in sickbed utilization rate). The results show that the THCs with high government subsidy reduce the number of medical services after 2011. CONCLUSIONS: We think that it is no doubt that the government should take more responsibility for the financing of primary healthcare institutions, the problem is when government plays a central role in the financing and delivery of primary health care services, more effective incentives should be developed.

Rural and urban differences in patient experience in China: a coarsened exact matching study from the perspective of residents.

BACKGROUND: Patient experience is a key measure widely used to evaluate quality of healthcare, yet there is little discussion about it in China using national survey data. This study aimed to explore rural and urban differences in patient experience in China. METHODS: Data regarding this study were drawn from Chinese General Social Survey (CGSS) 2015, with a sample size of 9604. Patient experience was measured by the evaluation on healthcare services. Coarsened exact matching (CEM) method was used to balance covariates between the rural and urban respondents. Three thousand three hundred seventy-two participants finally comprised the matched cohort, including 1592 rural residents and 1780 urban residents. Rural and urban differences in patient experience were tested by ordinary least-squares regression and ordered logistic regression. RESULTS: The mean (SD) score of patient experience for rural and urban residents was 72.35(17.32) and 69.45(17.00), respectively. Urban residents reported worse patient experience than rural counterparts (Crude analysis: Coef. = - 2.897, 95%CI: - 4.434, - 1.361; OR = 0.706, 95%CI: 0.595, 0.838; Multivariate analysis: Coef. = - 3.040, 95%CI: - 4.473, - 1.607; OR = 0.675, 95%CI: 0.569, 0.801). Older (Coef. = 2.029, 95%CI: 0.338, 3.719) and healthier (Coef. = 2.287, 95%CI: 0.729, 3.845; OR = 1.217, 95%CI: 1.008, 1.469) rural residents living in western area (Coef. = 2.098, 95%CI: 0.464, 3.732; OR = 1.276, 95%CI: 1.044, 1.560) with higher social status (Coef. = 1.158, 95%CI: 0.756, 1.561; OR = 1.145, 95%CI: 1.090, 1.204), evaluation on adequacy (Coef. = 7.018, 95%CI: 5.045, 8.992; OR = 2.163, 95%CI: 1.719, 2.721), distribution (Coef. = 4.464, 95%CI: 2.471, 6.456; OR = 1.658, 95%CI: 1.312, 2.096) and accessibility (Coef. = 2.995, 95%CI: 0.963, 5.026; OR = 1.525, 95%CI: 1.217, 1.911) of healthcare resources had better patient experience. In addition, urban peers with lower education (OR = 0.763, 95%CI: 0.625, 0.931) and higher family economic status (Coef. = 2.990, 95%CI: 0.959, 5.021; OR = 1.371, 95%CI: 1.090,1.723) reported better patient experience. CONCLUSIONS: Differences in patient experience for rural and urban residents were observed in this study. It is necessary to not only encourage residents to form a habit of seeking healthcare services in local primary healthcare institutions first and then go to large hospitals in urban areas when necessary, but also endeavor to reduce the disparity of healthcare resources between rural and urban areas by improving quality and capacity of rural healthcare institutions and primary healthcare system of China.

Income-related inequality in distribution of health human resource among districts of Pakistan.

BACKGROUND: Solving inequality of health human resource (HHR) is one of the motives of Pakistan health policies, however, there is still exists a massive quantity of HHR inequality in almost every district of Pakistan. The main goal of this research is to scrutinize the disparity in allocation of human health resources among 114 regions of Pakistan from the year 2012 to 2016 and to expose the foundations and aspects of HHR inequality. METHODS: The data regarding this research has been obtained from Pakistan Statistical Bureau from the year 2012 to 2016. The statistics had also been collected from United Nation Development Program (UNDP) Pakistan 2017, Pakistan economic surveys, Ministry of finance Islamabad, Pakistan, Pakistan Social and Living standards Measurement (PSLM) Surveys from 2012 to 2016. The information incorporates district wise; the number of specialists and medical caretakers those are doctors and nurses, number of hospitals, number of beds, number of dispensaries, number of beds in dispensaries, urbanization, total estimated GNI per capita, infant mortality rate, geographical area, and population size. The concentration index is used to compute the extent of disparity in allocation of human health resources and decomposition analysis is also carried out to enumerate the contribution of each variable towards total inequality. Furthermore, the horizontal concentration was used to measure the participation of the need variable. RESULTS: 7. The consequent Concentration Indexes (CI) of the doctors and nurses for the year 2016 are 0.60 (95% CI= 0.42, 0.78) and 0.67 (95% CI= 0.42, 0.92) respectively. Decomposition of the concentration indexes exposed that the monetary status accounts are the leading percentage contributor in doctors disparity (77.5, 44.9, 30.6, - 11.6% and 13%) and population size (- 20.7,-10.5%, 4.6, 49.8, 19.7%). Furthermore, the monetary status formulates the superior contribution HHR disparity from nurses inequality (104.5, 75.1, 59.2, - 54.3%, - 40.1%), and population size (- 53.7, - 53.6%, - 36.3, 83.8, 65.3%). Moreover, after the identification of the need variable the Horizontal Concentration Index (HCI) values of doctors from the year 2012 to 2016 are 0.62, 0.64, 0.63, 0.62 and 0.61 and HCI of the nurses are 0.69, 0.70, 0.69, 0.68 and 0.67. CONCLUSION: The pro-rich disparity in allocation of HHR has been scrutinized from the year 2012 to 2016 among 114 districts of Pakistan. The hard concern of HHR disparity should be concentrated by the complete procedures from a multidisciplinary approach.

CMAS and ST3GAL4 Play an Important Role in the Adsorption of Influenza Virus by Affecting the Synthesis of Sialic Acid Receptors.

Influenza A viruses (IAVs) initiate infection by attaching Hemagglutinin (HA) on the viral envelope to sialic acid (SA) receptors on the cell surface. Importantly, HA of human IAVs has a higher affinity for α-2,6-linked SA receptors, and avian strains prefer α-2,3-linked SA receptors, whereas swine strains have a strong affinity for both SA receptors. Host gene CMAS and ST3GAL4 were found to be essential for IAV attachment and entry. Loss of CMAS and ST3GAL4 hindered the synthesis of sialic acid receptors, which in turn prevented the adsorption of IAV. Further, the knockout of CMAS had an effect on the adsorption of swine, avian and human IAVs. However, ST3GAL4 knockout prevented the adsorption of swine and avian IAV and the impact on avian IAV was more distinct, whereas it had no effect on the adsorption of human IAV. Collectively, our findings demonstrate that knocking out CMAS and ST3GAL4 negatively regulated IAV replication by inhibiting the synthesis of SA receptors, which also provides new insights into the production of gene-edited animals in the future.