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BackgroundSevere population ageing and weak long-term care support systems has spurred China’s pilot program for long-term care insurance (LTCI). This study aimed to provide references for optimizing long-term care insurance policies in Shandong Province by measuring the preferences of urban and rural older people for LTCI.MethodsBased on the discrete choice experiment, a questionnaire survey was conducted on urban and rural older people from Shandong Province. A mixed logit model was used for data analysis and the relative importance of attributes, willingness to pay, and preference heterogeneity based on residence type, number of children, chronic conditions, gender, education level and financial situation were further estimated.ResultsThe results showed that individual premium, reimbursement rate and whose provision of home-based care can be reimbursed had a significant effect on the LTCI preference of urban and rural older people in Shandong Province. Benefit package and government subsidy lost statistical significance in full sample but played a role in certain subgroups. There were also differences in preferences for individual premium among different groups of older people.ConclusionOptimizing the policy design of long-term care insurance based on the actual needs of the older adults can help increase the utility of them and promote the smooth implementation of long-term care insurance.

ObjectivesTo investigate the effects of age, period, and cohort on the trends of depression; and to examine the influence of these three temporal effects on residential disparities in depression.MethodsUsing data from the China Health and Retirement Longitudinal Study (CHARLS) during 2011 to 2020, involving 77,703 respondents aged 45 years old and above. The measurement of depressive symptoms was the score of 10-question version of the Center for Epidemiologic Studies Depression Scale (CES-D 10). The hierarchical age-period-cohort cross-classified random effects models were conducted to examine trends in depressive symptoms related to age, period and cohort.ResultsCES-D scores increased with age and slightly decreased at older age. The cohort trends mostly increased except for a downward trend among those born in 1950s. As for the period effect, CES-D scores decreased gradually from 2011 to 2013 followed by a upward trend. Rural residents were associated with higher level of depression than those live in urban area. These residence gaps in depression enlarged before the age of 80, and then narrowed. The urban–rural disparities in CES-D scores gradually diminished across cohorts, while the corresponding period-based change in urban–rural gaps was not significant.ConclusionWhen age, period, cohort factors are considered, the age effects on depression dominated, and the period and cohort variations were relatively small. The residence disparities in depression reduced with successive cohorts, more attention should be paid to the worsening depression condition of younger cohorts in urban areas.

Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R software, VOSviewer, and CiteSpace showed the interrelationships among literature, institutions, authors, and topic areas of focus. The publication rate and citations have grown exponentially over the past decade, with the US, China, and Germany as the major contributors. The University of Texas MD Anderson Cancer Center ranked highest in publications, while Memorial Sloan Kettering Cancer Center was most cited. Clusters of keywords revealed six hotspots: ‘Immunology’, ‘Check Point Inhibitors’, ‘Lung Cancer’, ‘Immunotherapy’, ‘Melanoma’, ‘Breast Cancer’, and ‘Microenvironment’. Melanoma, the most studied primary tumor with brain metastases offers promising immunotherapy advancements with generalizability and adaptability to other cancers. Our results outline the holistic overview of immunotherapy research for brain metastases, which pinpoints the forefront in the field, and directs researchers toward critical inquiries for enhanced mechanistic insight and improved clinical outcomes. Moreover, governmental and funding agencies will benefit from assigning financial resources to entities and regions with the greatest potential for combating brain metastases through immunotherapy.

Reward has been shown to influence selective attention, yet previous research has primarily focused on rewards associated with specific locations or features, with limited investigation into the impact of a reward object on object-based attention (OBA). Therefore, it remains unclear whether objects previously associated with rewards affect OBA. To address this issue, we conducted two experiments using a paradigm that combined a reward training phase with a modified two-rectangle paradigm. The results indicate that a reward object modulates both space-based attention (SBA) and OBA. When cues appear on a reward object, the effects of both SBA and OBA are amplified compared to when cues appear on a no-reward object. This finding supports the value-driven attentional capture (VDAC) theory, which suggests that a reward object gain enhanced saliency to capture attention, thereby providing a theoretical support for the treatment of conditions such as drug addiction.

Wintersweet (Chimonanthus praecox (L.) Link) is a commercial significance woody plant. As a rare winter-blooming plant, C. praecox is widely distributed and highly adaptable to various climates, especially low temperatures. In this study, we identified the COR413 plasma membrane gene CpCOR413PM1 in wintersweet. CpCOR413PM1 was expressed in all tissues of the plant, with the highest expression observed in the root and floral parts. Cultivation under 4 °C and with treatment of ABA led to the up-regulated expression of CpCOR413PM1. The expression of recombinant CpCOR413PM1 protein in Escherichia coli resulted in the tissues’ increased resilience to cold and drought stress. In vitro enzyme activity assays confirmed the protective impact of the CpCOR413PM1 protein on superoxide dismutase under low-temperature stress. Furthermore, the overexpression of CpCOR413PM1 in Arabidopsis thaliana resulted in increased cold and drought tolerance and ABA inhibited transgenic Arabidopsis seed germination. The CpCOR413PM1 gene promoter can influence expression of the GUS reporter gene under conditions of 4 °C, 42 °C and abscisic acid. Overall, our study demonstrates that CpCOR413PM1 plays a significate role in cold and drought stress. Our findings strengthen the knowledge of the molecular mechanisms underlying wintersweet’s tolerance to stress and lay the groundwork for the future investigation of the functions of the COR gene family.

Anti-HER2 resistance causes treatment failure in HER2-positive breast cancers. Here the authors identify FGFR4 as one of the vulnerabilities of anti-HER2 resistant breast cancer and show that FGRR4 inhibition enhances sensitivity to anti-HER2 treatment in these resistant cells by triggering ferroptosis.

Abstract. Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.

The combination of photothermal therapy (PTT) and immune tumor therapy has emerged as a promising avenue for cancer treatment. However, the insufficient immune response caused by inefficient immunogenic cell death (ICD) inducers and thermal resistance, immunosuppression, and immune escape resulting from the hypoxic microenvironment of solid tumors severely limit its efficacy. Herein, we report an ultrasound and laser-promoted dual-gas nano-generator (calcium carbonate-polydopamine-manganese oxide nanoparticles, CPM NPs) for enhanced photothermal/immune tumor therapy through reprogramming tumor hypoxic microenvironment. In this system, CPM NPs undergo reactive decomposition in a moderately acidic tumor, resulting in the generation of calcium, manganese ions, carbon dioxide (CO2), and oxygen (O2). Calcium and manganese ions act as adjuvants that trigger an immune response. The cancer cell membrane rupture caused by sudden burst of bubbles (CO2 and O2) under ultrasound stimulation and the photothermal properties of PDA also contributed to the ICD effect. The generation of O2 alleviates tumor hypoxia and thus reduces hypoxia-induced heat resistance and immunosuppressive effects, thereby improving the therapeutic efficacy of combination PTT and immune therapy. The present study provides a novel approach for the fabrication of a safe and effective tumor treatment platform for future clinical applications.

Soil erosion disturbs not only the global carbon cycle, but it is a complex environmental problem. Revegetation could reduce carbon emission by controlling soil erosion and increase carbon sequestration and accumulation by fixing carbon in vegetation and soil. The Grain for Green Program (GFGP) of China is the largest ecological restoration program in the world closely related to land-use/land-cover change (LUCC). Systematically assessing the carbon sequestration benefit of GFGP is crucial for a better understanding of the effects of implementing GFGP and providing reasonable vegetation management. Therefore, we selected the hilly red soil region (HRSR) of southern China as a study area, which is one of the main ecologically vulnerable areas in China. We assessed the carbon sequestration in the GFGP area of the HRSR using the InVEST (Integrated Valuation of Environmental Services and Tradeoffs) model based on land-use/land-cover datasets during 2000–2015. Our results show that implementing GFGP is conducive to the enhancement of carbon sequestration services. Total carbon sequestration showed an increasing trend at a rate of 15.43% from 2000 to 2015. The most significant change mainly happened in Hunan Province with the shortest implementation time. The carbon sequestration of each carbon pool (namely aboveground biomass, belowground biomass, soil, and dead organic matter) also increased slightly. Additionally, for carbon sequestration, unused land converted to forest land is the most effective LUCC. This study can provide scientific support for the management and implementation of GFGP in the HRSR of China.

Abstract Background To estimate the cost -utility of imrecoxib compared with diclofenac, as well as the addition of a proton pump inhibitor to both two treatment strategies, for patients with osteoarthritis, from a Chinese healthcare perspective. Methods A Markov model was built. Costs of managing osteoarthritis and initial adverse events were collected from a Medical Database which collected information from 170 hospitals. Other parameters were obtained from the literature. Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events. Deterministic and probabilistic sensitivity analyses were performed. Results Imrecoxib was highly cost-effective than diclofenac (the ICER was $401.58 and $492.77 in patients at low and high gastrointestinal and cardiovascular risk, respectively). The addition of a proton pump inhibitor was more cost -effective compared with single drug for both treatment strategies. Findings remained robust to sensitivity analyses. 59.04% and 57.16% probability for the co-prescription of imrecoxib and a proton pump inhibitor to be the most cost-effective strategy in all patients considered using the cost-effectiveness threshold of $30,000. Conclusions The addition of a proton pump inhibitor to both imrecoxib and diclofenac was advised. Imrecoxib provides a valuable option for patients with osteoarthritis. Uncertainties existed in the model, and the suggestions can be adopted with caution.

Abstract To expand the application of tyrosol, a series of lipophilized tyrosol derivatives were synthesized via esterification of tyrosol with fatty acids of different chain lengths. The antiglycative activity of tyrosol esters so prepared was subsequently examined in the bovine serum albumin/glucose system. A quasi-parabolic shape was observed when the activity was plotted against alkyl chain length. Additionally, the anti-inflammatory effects of these derivatives were evaluated against methylglyoxal-induced inflammation in RAW264.7 cells. The same trend on anti-inflammatory activity was found as in the antiglycation study. The results showed that tyrosol esters with C12:0 and C14:0 were two most efficient ones among all the tested derivatives. Thus, some lipophilized tyrosol derivatives were stronger antiglycative and anti-inflammatory agents compared to the parent compound, tyrosol. Graphical abstract

Abstract Background Clinical guidelines recommend a stepped-escalation treatment strategy for type 2 diabetes (T2DM). Across multiple treatment strategies varying in efficacy and costs, no clinical or economic studies directly compared them. This study aims to estimate and compare the cost-effectiveness of 10 commonly used pharmacologic combination strategies for T2DM. Methods Based on Chinese guideline and practice, 10 three-stepwise add-on strategies were identified, which start with metformin, then switch to metformin plus one oral drug (i.e., sulfonylurea, thiazolidinedione, α-glucosidase inhibitor, glinide, or DPP-4 inhibitor) as second line, and finally switch to metformin plus one injection (i.e., insulin or GLP-1 receptor agonist) as third line. A cohort of 10,000 Chinese patients with newly diagnosed T2DM was established. From a healthcare system perspective, the Cardiff model was used to estimate the cost-effectiveness of the strategies, with clinical data sourced from a systematic review and indirect treatment comparison of 324 trials, costs from claims data of 1164 T2DM patients, and utilities from an EQ-5D study. Outcome measures include costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). Results Over 40-year simulation, the costs accumulated for a patient ranged from $7661 with strategy 1 to $14,273 with strategy 10, while the QALY gains ranged from 13.965 with strategy 1 to 14.117 with strategy 8. Strategy 7 was dominant over seven strategies (strategies 2~6, 9~10) with higher QALYs but lower costs. Additionally, at a willingness-to-pay threshold of $30,787/QALY (i.e., 3 times GDP/capita for China), strategy 7 was cost-effective compared with strategy 1 (ICER of strategy 7 vs. 1, $3371/QALY) and strategy 8 (ICER of strategy 8 vs. 7, $132,790/QALY). Ranking the strategies by ICERs and NMBs, strategy 7 provided the best value for money when compared to all other strategies, followed by strategies 5, 9, 8, 1, 3, 6, 10, 2, and 4. Scenario analyses showed that patients insist on pharmacologic treatments increased their QALYs (0.456~0.653) at an acceptable range of cost increase (ICERs, $1450/QALY~$12,360/QALY) or even at cost saving compared with those not receive treatments. Conclusions This study provides evidence-based references for diabetes management. Our findings can be used to design the essential drug formulary, infer clinical practice, and help the decision-maker design reimbursement policy.

Abstract Background This study aimed to examine the cost-effectiveness of one-time standard endoscopic screening with Lugol’s iodine staining for esophageal cancer (EC) in China. Methods A Markov decision analysis model with eleven states was built. Individuals aged 40 to 69 years were classified into six age groups in five-year intervals. Three different strategies were adopted for each cohort: (1) no screening; (2) one-time endoscopic screening with Lugol’s iodine staining with an annual follow-up for low-grade intraepithelial neoplasia (LGIN); and (3) one-time endoscopic screening with Lugol’s iodine staining without follow-up. Quality-adjusted life-years (QALYs) indicated the effectiveness of the model. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Sensitivity analysis was performed to assess the robustness of the model. Results One-time screening with follow-up was the undominated strategy for individuals aged 40–44 and 45–49 years, which saved USD 10,942.57 and USD 6611.73 per QALY gained compared to nonscreening strategy. For those aged 50–69 years, the nonscreening scenarios were undominated. One-time screening without follow-up was the extended dominated strategy. Compared to screening strategies without follow-up, all the screening strategies with follow-up were more cost-effective, with the ICER increasing from 299.57 USD/QALY for individuals aged 40–44 years to 1617.72 USD/QALY for individuals aged 65–69 years. Probabilistic sensitivity analysis (PSA) supported the results of the base case analysis. Conclusions One-time EC screening with follow-up targeting individuals aged 40–49 years was the most cost-effective strategy.

Abstract Background Empirical evidence that demonstrates the relationship between pelvic asymmetry and non-specific chronic low back pain (NCLBP) is currently lacking. Objective To establish the reliability of the Global Postural System (GPS) in assessing pelvic asymmetry and identify the association between pelvic asymmetry parameters and the occurrence of NCLBP in young adults. Design A cross-sectional, regression study. Methods People who were aged between 18 and 30 and were diagnosed with NCLBP were recruited. Healthy individuals who were matched for age, sex, and education level were recruited as controls. Global Postural System (GPS) was employed to assess pelvic asymmetry. Prior to exploring the association, the reliability of GPS was assessed by the ICC (2, k) for interrater reliability, ICC (3, k) for intra-rater reliability, standard error and minimal detectable difference. Bivariate correlation analysis and logistic regression analysis were used to determine the relationship between pelvic asymmetry and the occurrence of NCLBP. Results Twenty-eight healthy participants and 28 people with NCLBP were recruited. Moderate to excellent ICCs were observed for the inter-rater and intra-rater reliability of most postural parameters. The bivariate correlation analysis indicated that age, body mass index and pelvic asymmetry parameters were related to the occurrence of NCLBP. Pelvic angle asymmetry (odds ratio = 1.17), and asymmetry of the distance between the posterior superior iliac spine and the floor (odds ratio = 1.21) were associated with NCLBP. Limitations This study did not explore the causal relationship between pelvic asymmetry in the sagittal plane/pelvic asymmetry in the transverse plane and the occurrence of NCLBP. The interpretation of the results may not be generalized beyond the sample population. Conclusions The GPS is a reliable method to assess pelvic asymmetry in a clinical setting. Two pelvic parameters were associated with the presence of NLBP. Measurement of pelvic asymmetry may assist in the early identification of potential occurrence of NCLBP but further work is required.

Ecological Restoration Programs (ERP) is an effective approach to increase carbon sequestration in terrestrial ecosystems to mitigate climate change, but it’s still controversial whether they are as important to carbon sequestration in areas with higher rainfall and accumulated temperature as they are in areas with low rainfall and accumulated temperature. In this study, we evaluated the influences of ERP on land use change (LUC) and carbon sequestration of terrestrial ecosystems in the red soil hilly region (RSHR) of China with higher rainfall and accumulated temperature. In view of the differences in LUC caused by ERP, the change point of ERP implementation was quantitatively determined in 2000 according to the characteristics of LUC, and divided the ERP implementation period into two stages: the early stage (1985–2000) and the mature stage (2000–2015). The Program Driving Force Model (PDFM) modified in this paper shows that ERP such as the Natural Forest Protection Program implemented in the mature stage has a greater driving effect on land use (+18%). Based on the three carbon pools (above-ground biomass, underground biomass, and soil organic carbon) of the ERP area in the forest land, cultivated land and grassland ecosystem, it is estimated that the total carbon storage of the terrestrial ecosystems generated in the period from 2000 to 2030 amounts to 1057.2 Tg, 65% of which is driven by ERP (691.6 Tg). Our estimates of future terrestrial ecosystem carbon sinks from ERP, reduces further uncertainty to our capacity to predict the future of terrestrial carbon uptake and losses and to China's projected carbon emissions peak in 2030. The quantitative assessment of the driving force of ERP on LUC provides a methodological reference for related researches. The practice of changing land use and increasing carbon sinks through ERP provides guidance for offsetting carbon dioxide emission when China's carbon dioxide emissions is expected to reach the peak by 2030, and striking sustainable development.

Patatin-like proteins (PLPs) have non-specific lipid acyl hydrolysis (LAH) activity, which can hydrolyze membrane lipids into fatty acids and lysophospholipids. The vital role of PLPs in plant growth and abiotic stress has been well documented. However, the function of PLPs in plant defense responses against pathogens is still poorly understood. Here, we isolated and identified a novel cotton (Gossypium hirsutum) PLP gene GhPLP2. The expression of GhPLP2 was induced upon treatment with Verticillium dahliae, the signaling molecules jasmonic acid (JA) and ethylene (ETH) in cotton plants. Subcellular localization revealed that GhPLP2 was localized to the plasma membrane. GhPLP2-silenced cotton plants were more susceptible to infection by V. dahliae, while the overexpression of GhPLP2 in Arabidopsis enhanced its resistance to V. dahliae, which was apparent as mild symptoms, and a decrease in the disease index and fungal biomass. The hypersensitive response, deposition of callose, and H2O2 accumulation triggered by V. dahliae elicitor were reduced in GhPLP2-silenced cotton plants. The overexpression of GhPLP2 in Arabidopsis resulted in the accumulation of linoleic acid (LA, 18:2) and α-linolenic acid (ALA, 18:3) and facilitated the biosynthesis of JA and JA-mediated defensive responses. GhPLP2 silencing in cotton plants consistently reduced the accumulation of linoleic acid (LA, 18:2) and α-linolenic acid (ALA, 18:3) and suppressed the biosynthesis of JA and the defensive responses mediated by JA. These results indicate that GhPLP2 is involved in the resistance of cotton to V. dahliae by maintaining fatty acid metabolism pools for JA biosynthesis and activating the JA signaling pathway.

Objectives: To investigate the effects of age, period, and cohort (APC) on trends in cognitive function among the Chinese elderly, and to explore how gender gaps in cognitive function change with age, period, and cohort.Methods: This study used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018, and included 90,432 participants aged above 65 years old. The measurement of cognitive function was the score of the Mini-Mental State Examination (MMSE). Cross-classified random-effect models were used to investigate age, period, and cohort trends in cognitive function.Results: Mini-Mental State Examination scores decreased with age at an increasing rate. While the cohort effect was nearly stable, the period effect demonstrated a downward trend from 1998 to 2002 followed by a nearly flat line. Females were associated with lower MMSE scores than males. When age increased, the gender gaps in MMSE scores further increased. The period-based gender gaps in MMSE scores diverged throughout the 20 years, while the cohort-based gender disparities in MMSE scores converged with successive cohorts.Conclusions: Age, period, and cohort had different and independent effects on cognitive function among the Chinese elderly. The effect of age was stronger than that of period and cohort. Gender disparities in cognitive function increased with age and period, and decreased with successive cohorts.

Abstract Background Antibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE (Enterococcus, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) organisms are the leading cause of healthcare-acquired infections worldwide. ABR in ESKAPE organisms is usually associated with significant higher morbidity, mortality, as well as economic burden. Directing attention towards the ESKAPE organisms can help us to better combat the wide challenge of ABR, especially multi-drug resistance (MDR). Objective This study aims to systematically review and evaluate the evidence of the economic consequences of ABR or MDR ESKAPE organisms compared with susceptible cases or control patients without infection/colonization in order to determine the impact of ABR on economic burden. Methods Both English-language databases and Chinese-language databases up to 16 January, 2019 were searched to identify relevant studies assessing the economic burden of ABR. Studies reported hospital costs (charges) or antibiotic cost during the entire hospitalization and during the period before/after culture among patients with ABR or MDR ESKAPE organisms were included. The costs were converted into 2015 United States Dollars. Disagreements were resolved by a third reviewer. Results Of 13,693 studies identified, 83 eligible studies were included in our review. The most studied organism was S. aureus, followed by Enterococcus, A. baumannii, E. coli, E. coli or/and K. pneumoniae, P. aeruginosa, and K. pneumoniae. There were 71 studies on total hospital cost or charge, 12 on antibiotic cost, 11 on hospital cost or charge after culture, 4 on ICU cost, 2 on hospital cost or charge before culture, and 2 on total direct and indirect cost. In general, ABR or MDR ESKAPE organisms are significantly associated with higher economic burden than those with susceptible organisms or those without infection or colonization. Nonetheless, there were no differences in a few studies between the two groups on total hospital cost or charge (16 studies), antibiotic cost (one study), hospital cost before culture (one study), hospital cost after culture (one study). Even, one reported that costs associated with MSSA infection were higher than the costs for similar MRSA cases. Conclusions ABR in ESKAPE organisms is not always, but usually, associated with significantly higher economic burden. The results without significant differences may lack statistical power to detect a significant association. In addition, study design which controls for severity of illness and same empirical antibiotic therapy in the two groups would be expected to bias the study towards a similar, even negative result. The review also highlights key areas where further research is needed.

Abstract Background The eastern and western regions of China are different in many ways such as socioeconomic characteristics and health resource distribution. This study aimed to explore the outpatient health-seeking behavior and compare the influencing factors of residents in Zhejiang and Qinghai Province, which represent the situation in eastern and western China. Thus, this research will provide evidence for health resource allocation and health reform. Methods A cross-sectional study was conducted on a sample selected from 1600 households in Zhejiang and Qinghai province between 2016 to 2017 by the multi-stage stratified cluster random sampling method. Among the 4231 residents aged 15 years or older in the sample, 566 who reported ill-health were selected for data analysis. Two-week outpatient visits and choice of health institutions were used to measure residents’ outpatient health-seeking behavior and assessed using Chi-square tests. The binary logistic regression was adopted to demonstrate the association between explanatory variables and outpatient visits. Results The study revealed that out of the people who reported ill-health, 58 individuals (50.97%) in Zhejiang and 106 (41.41%) in Qinghai went to health institutions to seek medical help (p 0.05). Among these respondents, Self-report severity was the common and significant factor related to their outpatient visits and it had a greater impact on outpatient visits in Zhejiang (4.18, CI 2.23–7.83, p

Abstract Background To estimate the potential gains in health-adjusted life expectancy (HALE) after hypothetical elimination of four non-communicable diseases (NCDs) among Chinese elderly from 1990 to 2016, including cardiovascular diseases (CVD), cancers, chronic respiratory diseases (CRD) and diabetes mellitus (DM). Methods Based on data from Global Burden of Disease 2016, we generated life table by gender using Sullivan method to calculate HALE. Disease-deleted method was used to calculate cause-elimination HALE, after hypothetical elimination of specific diseases. Results From 1990 to 2016, HALE increased for all age groups. After hypothetic eliminating the four main NCDs, potential gain in HALE by CVD, DM and cancers increased while by CRD decreased from 1990 to 2016 for both genders. Among four main NCDs, potential gain in HALE after eliminating CVD was largest and increased most for both genders. Although elimination of DM led to the smallest gain in HALE, the increasing speed of gain in HALE by DM was faster than that by CVD and cancers from 1990 to 2016. Conclusions This study highlights the potential gains in HALE of NCDs among Chinese elderly from 1990 to 2016. HALE of Chinese elderly could further increase from the reduction of NCDs. Control measures and targeted prevention should be carried out.

The trade-offs between ecological construction and urbanization changes in land-use, which can affect ecosystem services. This study aimed to analyze the trade-offs between urbanization and ecological construction through land-use change, and then to explore its impact on ecosystem services. We developed a coefficient for analyzing LUCC caused by ecological construction and urbanization. The spatio-temporal patterns of three ecosystem services (Water yield, Net primary production, Soil conservation) in the Xiangjiang River Basin (XRB) of China were identified and the trade-offs and synergies between ecosystem services explored at different spatial scales. The average trade-off coefficients between ecological construction and urbanization of upstream, midstream, downstream, and the whole basin were 0.20, −0.27, −0.46 and −0.37 respectively show that the LUCC was dominated by urbanization in the XRB from 2000 to 2015. However, ecological construction improved ecosystem services. The growth rates in NPP, soil conservation, and water yield were 10.88%, 2.23%, and 19.82%, respectively, between 2000 and 2015. We also confirmed three ecosystem services were spatially dominated by synergies (0

Background: Several biomarkers predict the efficacy of immunotherapy, which is essential for selecting patients who would potentially benefit. Discordant status of these biomarkers between primary tumours and paired metastases has been increasingly revealed. We aimed to comprehensively summarize the incidence of this phenomenon. Methods: Databases were searched to identify studies reporting primary-to-metastatic conversion of biomarkers, including programmed death ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), PD-L2, tumour-infiltrating lymphocyte (TIL), tumour mutational burden (TMB), and microsatellite instability (MSI). Findings: 56 studies with 2739 patients were included. The pooled discordance rate of PD-L1 was 22%. The percentage of PD-L1 changed from positive to negative was 41%, whereas that from negative to positive was 16%. The discordance rate for PD-1 and PD-L2 was 26% and 22%, respectively. TIL level was found with a discordance rate of 39%, and changes from high to low (50%) occurred more than that from low to high (16%). No significant difference in TMB was observed between two sites in most studies. MSI status discordance was found in 6% patients, with a percentage of 9% from MSI-high to microsatellite instable (MSS) and 0% from MSS to MSI-high. Interpretation: Our study demonstrates that PD-L1, PD-1, PD-L2, and TIL level had high frequency of discordance, while TMB and MSI status were less likely to change between primary tumours and paired metastases. Therefore, evaluating those frequently altered biomarkers of both primary and metastatic tumours is strongly recommended for precise clinical decision of immune checkpoint treatment. Fund: The National Natural Science Foundation of China (81872152).

In recent years, hemorrhagic fever with renal syndrome (HFRS) incidence has been becoming a severe public health problem again due to its significant increase in Shaanxi Province, China. Baoji, located in the Guanzhong Plain in the central part of Shaanxi Province, has been severely affected by HFRS since its first emergence in 1955. To better understand the epidemiology of orthohantaviruses infection in humans and the causative agents carried by the rodents, the long-term incidence patterns were analyzed and a molecular epidemiological investigation of orthohantaviruses infection in humans and rodents was performed. During 1984-2019, 13,042 HFRS cases were registered in Baoji, including 275 death cases. Except the first high prevalence of HFRS in 1988-1993, another two epidemic peaks were observed in 1998-2003 and 2012, respectively, although vaccination project was started since 1996. During the same period, HFRS cases in Baoji mainly were recorded in winter suggesting they may be caused by Hantaan orthohantavirus (HTNV), while a small peak of HFRS was also found in summer with unknown reason. Nucleotide identity and phylogenetic analyses demonstrated that a novel clade of HTNV sequences recovered from HFRS cases were closely related to those from rodents, including species close contact with humans, suggesting a direct viral transmission from rodents to humans and the important role in the HTNV transmission the nontraditional rodent hosts may play. Moreover, two distant related Dabieshan orthohantavirus (DBSV) lineages were also identified in Niviventer niviventer in this area demonstrating its considerable genetic diversity. Our data indicated that continual spillover of HTNV from rodents to humans, contributing to the high prevalence of HFRS in humans in Baoji.

Abstract Background China has made great achievements in health insurance coverage and healthcare financing; however, the rate of catastrophic health expenditure (CHE) was 13.0% in China in 2008, which is higher than that in some other countries. There remain some differences in life-style, national customs, medical conditions, and health consciousness in different provinces in China. This study aimed to compare the rates of households with CHE, further to explore the different performance of factors influencing CHE between Zhejiang and Qinghai province, China. Methods Data were derived from the household surveys conducted in Zhejiang and Qinghai. Sampling on multi-stage stratified cluster random method was adopted. Household with CHE occurs when the out-of-pocket payment for health care equals to or exceeds 40% of a household’s income. Univariate and multivariate logistic regression analyses were used to identify the performance of factors of CHE. Results A total of 1598 households were included in this study, including 995 in Zhejiang and 603 in Qinghai. The average rates of CHE in Zhejiang and Qinghai were 9.6 and 30.5%, respectively. We found that economic status of households and households headed by an employed person are the protective factors for CHE; and number of members with chronic diseases and number of inpatients in household are the risk factors for CHE in the two provinces. Besides, poor/low-insured households in Zhejiang; and households having outpatients and households headed by a minority person in Qinghai are more likely to experience the risk of CHE. Conclusions This study highlights the importance of improving economic development, expanding employment, and adjusting policies to make greater efforts to protect chronic diseases patients, outpatients, and inpatients, further to reduce the risk of CHE. The Chinese government should pay more attention to the actual conditions in different provinces, further to make policy decisions according to the local knowledge.

Abstract Background Equity is the core of primary care. The issue of equity in health has become urgent, and China has attached increasing attention to it. With rapid economic development and great changes in medical insurance policy, the pattern of equity in health has changed tremendously. The reform of healthcare in Zhejiang Province is at the forefront in China, and studies on Zhejiang Province are of great significance to the entire country. This paper aimed to measure health equity from the perspectives of health needs and health-seeking behavior and to provide suggestions for the next policy formulations, with respect to timeliness. Methods The investigator’s household survey was conducted in August 2016. A sample of 1000 households, which included2807 individuals in Zhejiang, China, was obtained with the multi-stage stratified cluster sampling method. Descriptive analysis and chi-square tests were adopted in the analysis. The value of the concentration index was used to measure the equity. Results This study found that the poor have more urgent health needs and poorer health situations than the rich. Through studies on health-seeking behavior, the utilization of outpatient services was almost equitable, while the utilization of hospitalization showed a pro-rich inequity (i.e., the rich use more services). Individuals with employer-based medical insurance used more outpatient services than those with rural and urban medical insurance. More people in the poorer income groups did not use inpatient services due to financial difficulties. Conclusions Absolute medical prices and medical insurance may explain the equity in the utilization of outpatient services and the inequity in the utilization of hospitalization. In view of the pro-rich inequity of hospitalization, more financial protection should be provided for the poor.

Pterostilbene is a natural stilbene compound found in blueberries. It has been found to show anticancer, anti-inflammatory and anti-oxidative effects. However, little is known about its relationship with AGEs-induced oxidative stress and inflammation. In this study, we examined the inhibitory effect of pterostilbene on AGEs-induced damage using RAW264.7 cells. Pterostilbene was found to significantly suppress ROS production, mRNA expression of NADPH oxidase, and carbonyl levels of proteins and AOPP, which are related to oxidative stress. In addition, pterostilbene significantly reduced gene expression of inflammatory mediators, including TNF-α, IL-1β and IL-6. Further analysis showed that pterostilbene inhibited AGEs-induced RAGE up-regulation, but showed no effect on CD36. Moreover, it reduced NF-κB phosphorylation and MAPKs activation, including p38 and ERK1/2 induced by AGEs. Thus our results indicated that pterostilbene might act as a promising agent to alleviate AGEs-induced oxidative stress and inflammation via RAGE/MAPK/NF-κB pathway.

In China, doctor-patient relationships (D-P relationships) are cited frequently and attracted international attention. This study assesses whether the D-P relationship experienced by the Chinese is associated with ethnicity, hospital hierarchies, and socioeconomic factors. In a national cross-sectional survey, multi-stage random sampling was adopted to assess regional and socio-economic differences between year 2016 and year 2017. Each area surveyed consisted of about 250 randomly chosen households, and valid results were obtained from 4,173 adults aged 16–99. When provided a choice of eight types of D-P relationship, for doctors in primary care institutions, 63.8% of ethnic minorities indicated having a friend-type relationship with their physicians, with 23.3% having a trading/reciprocal relationship. Han Chinese, however, predicts the opposite relationship between doctors from different hierarchy and the types of D-P relationship. For physicians working in hospitals, this difference in relationship was more pronounced, where 52.9% of ethnic minorities indicated having a friend-type relationship with their physicians, and 30.1% indicated the presence of a trading/reciprocal relationship. For Han Chinese, however, 53.3% indicated having a reciprocal relationship with their doctor. Overall, the prevalence of friendly D-P relationships was correlated with ethnic minorities, lower levels of education, and lower incomes. Ethnic minorities are most likely to perceive their physicians as friends, while Han Chinese are more likely to perceive a trading relationship with their physicians. The primary contribution of this research is the finding that D-P relationships differ for Han Chinese and other ethnic minorities.

Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic inflammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinflammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specific lipid mediators with anti-inflammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2), reflecting cytosolic phospholipase A2 α activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-inflammatory PGE2 potently induced macrophage migration while different FFAs and PGD2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE2 with inflammation suppressive properties plays a significant role in mediating ATM accumulation during lipolysis.

The incidence of obesity, caused by an imbalance between energy intake and expenditure, has dramatically risen in recent years. Obesity is becoming a worldwide burden to public health. In many epidemic studies a lower prevalence of obesity-related diseases is observed in seafood-consuming population, suggesting a beneficial role of marine foods against obesity. It is believed that some functional ingredients in marine foods account for their anti-obesity effect. In this review, the cause and mechanism of obesity are first discussed in order to better understand how functional compounds can alleviate obesity. In addition, a series of anti-obesity components derived from marine origin, especially edible sources, are summarised, including lipids, polysaccharides, phlorotannins, carotenoids and others, with an emphasis on their efficacy and mechanism of action. Due to their anti-obesity effect, these marine-derived compounds might be excellent sources in the development of functional food against obesity.

Objectives This study was performed to describe the health status of Chinese oldest-old individuals aged ≥80 years from 1998 to 2014 and explore differences in their health status based on demographic characteristics and socioeconomic status. Methods Data were obtained from the seven waves of the Chinese Longitudinal Healthy Longevity Survey. The Mini Mental State Examination, Katz Index of Independence in Activities of Daily Living, and chair stand test were used to examine cognitive and physical function. Logistic regression was used to evaluate the changes in health outcomes. Results Regression results showed increasing cognitive impairment trends and decreasing disability trends, indicating that the oldest-old individuals had worse body function in more recent years. Older people and women had a weaker health status. Rural elders had better physical performance but worse cognitive function. Participants with an education had better overall functioning. Individuals with severe disability had the shortest survival time among the study population. Conclusions From 1998 to 2014, the health status of oldest-old individuals was relatively stable in China. These findings indicate the need for specific and continuing attention to the oldest-old population to improve their health condition.

Antibiotic resistance (ABR) is one of the biggest threats to global health, especially in China. This study aims to analyze the published literature on the clinical and economic impact of ABR or multi-drug resistant (MDR) bacteria compared to susceptible bacteria or non-infection, in mainland China. English and Chinese databases were searched to identify relevant studies evaluating mortality, hospital stay, and hospital costs of ABR. A meta-analysis of mortality was performed using a random effects model. The costs were converted into 2015 United States (US) dollars. Of 13,693 studies identified, 44 eligible studies were included. Twenty-nine investigated the impact of ABR on hospital mortality, 37 were focused on hospital stay, and 21 on hospital costs. Patients with ABR were associated with a greater risk of overall mortality compared to those with susceptibility or those without infection (odds ratio: 2.67 and 3.29, 95% confidence interval: 2.18−3.26 and 1.71−6.33, p < 0.001 and p < 0.001, respectively). The extra mean total hospital stay and total hospital cost were reported, ranging from 3 to 46 days, and from US$238 to US$16,496, respectively. Our study indicates that ABR is associated with significantly higher mortality. Moreover, ABR is not always, but usually, associated with significantly longer hospital stay and higher hospital costs.

The present study examined the effect of Lactobacillus plantarum ATCC14917 fermentation on the chemical composition and antioxidant activity of apple juice. Apple juice was fermented and examined of its antioxidant activity using chemical models and cellular antioxidant assay. Furthermore, the chemical composition of fermented apple juice was characterized by LC-MS/MS. Lactobacillus plantarum ATCC14917 fermentation showed an increase in DPPH and ABTS radical scavenging activity as well as cellular antioxidant activity of apple juice. However, fermentation decreased the total phenolic and flavonoid content. Subsequent LC-MS/MS analysis of the phenolic profile indicated that the content of 5-O-caffeoylquinic acid (5-CQA), quercetin, and phloretin with strong antioxidant activity was increased significantly after fermentation. The modified phenolic composition may contribute to the increased antioxidant activity of fermented apple juice. Our findings showed that Lactobacillus plantarum ATCC14917 fermentation may be an efficient way to enhance the bioavailability of phenolic compounds and to protect cells from oxidative stress.

This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone.Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime.SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses.SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.

Recently, there is a growing interest in fortifying food products with flavonoids to enhance health benefits. Naringenin, naringin, hesperetin, and dihydromyricetin are four typical flavonoids constituting a natural part of our diet. In the present work, they were fortified into a chia oil cookie model to evaluate their thermal stability during baking as well as their impact on antioxidant capacity and toxicant formation. Among them dihydromyricetin was the most unstable one (only 36.1% of which was left after baking at 180 °C for 20 min) and led to a loss of brightness in cookie. However, the antioxidant capacity of cookie fortified with dihydromyricetin was significantly enhanced compared with untreated cookie; on the other hand, dihydromyricetin showed the strongest effect to attenuate lipid and protein oxidation as well as decrease the level of fluorescent advanced glycation endproducts and carboxymethyl lysine in cookie model. Overall, among the four selected flavonoids, dihydromyricetin might be the most promising functional bakery additive enhancing the antioxidant capacity while decreasing the formation of toxicants.

Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Besides, 4′MR significantly decreased oxidative stress, demonstrated by levels of ROS production, protein carbonyl and advanced oxidation protein product via down-regulation of NADPH oxidase. Further analysis showed that 4′MR attenuated the RAGE overexpression induced by MGO-BSA. It also blocked the downstream signal of AGE-RAGE, particularly, MAPKs including p38 and JNK, and subsequently reduced NF-κB activation. Additionally, 4′MR significantly abated the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome including NLRP3 and cleaved caspase-1 and reduced the secretion of mature IL-1β. Taken together, our results suggest that the anti-inflammatory effect of 4′MR is mainly through suppressing RAGE-mediated MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. 4′MR could be a novel therapeutic agent for inflammation-related diseases.

Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA expression. Moreover, both of them inhibited LPS-induced mRNA expression of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and IL-1β, and tumor necrosis factor α (TNF-α), and attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 phosphorylation. In addition, 4MR but not Pte inhibited LPS-induced the activator protein (AP)-1 pathway in RAW 264.7 macrophages. Further study suggested that Pte had an inhibitory effect on extracellular regulated protein kinases (ERK) and p38 activation, but not on c-Jun N-terminal kinase (JNK), while 4MR had an inhibitory effect on JNK and p38 activation, but not on ERK. Taken together, our data suggested that Pte induced anti-inflammatory activity by blocking mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, while 4MR showed anti-inflammatory activity through suppression of MAPK, AP-1, and NF-κB signaling pathways in LPS-treated RAW 264.7 macrophages.

The inhibitory effect of rifampicin on the amyloid formation of hen egg white lysozyme was assessed with both Thioflavin T (ThT) fluorescence assay and Fourier transform infrared (FTIR) difference spectroscopy. We reveal that ThT fluorescence assay gives a false positive result due to rifampicin interference, while FTIR difference spectroscopy provides a reliable assessment. With FTIR, we show that rifampicin only has marginally inhibitory effect. We then propose that FTIR difference spectroscopy can potentially be a convenient method for inhibitor screening in amyloid study.

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation. [ABSTRACT FROM AUTHOR]

This present work investigated the influence of black rice anthocyanins as antioxidants on the oxidation stability of oil. Malonic acid, succinic acid and succinic anhydride were grafted on black rice anthocyanins through acylation method to improve their antioxidant activity in oil. The results from fourier transform infrared spectroscopy (FTIR) showed new absorption peaks near 1744 cm-1 and 1514 cm-1, which implied that malonic acid, succinic acid and succinic anhydride grafted on the -OH of glucoside and rutinoside through esterification reaction and resulted that the polarity of these were reduced. Total content of anthocyanin (TAC) decreased to 166. 3 mg/g, 163.7 mg/g and 150.2 mg/g, respectively after modification with succinic acid, malonic acid and succinic anhydride. Compared with native anthocyanins, the acylation of black rice anthocyanins partially reduced its antioxidant activity. In addition, DPPH clearance of molecular modified anthocyanins decreased to 62.6% (San-An). As revealed in the oil stability through the determination of primary oxidation products (PV) and secondary oxidation products (p-AV), Sa-An, Ma-An and San-An showed stronger antioxidant activity in Schaal oven accelerated oxidation test during 12 days than native black rice anthocyanin in both corn oil and flaxseed oil. Molecular modified black rice anthocyanins are expected to be used as colorants, antioxidants, etc. in oil-rich food. [ABSTRACT FROM AUTHOR]