Older adults 's hospitalizational costs and burden study in China--analysis from CHARLS data 2018.

Objective: The aging Chinese population is driving up health care costs, with hospitalizational accounting for a large portion of total health care costs. By 2012, hospitalization costs for people over 60 years of age exceeded outpatient costs, marking a change in the allocation of medical resources. Further research is needed on the factors influencing changes in hospitalizational costs and burden. This paper examines the costs and burden of hospitalization for older adults from a micro perspective, providing new evidence to explain how social, medical, family, personal, and geographic factors affect them. Methods: Utilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), a linear regression model was constructed to investigate the impact of various factors on the hospitalization costs and burden among the older adult in China. To ensure the heterogeneity of the results, the sample was divided into subgroups based on different regions for comparative analysis. Additionally, collinearity among the variables was examined. Results: The average hospitalization costs for the older adult are $1,199.24, with a burden score of 0.5. Residence, type of chronic diseases, region, family size, type of health service facility, received distance, smoke and alcoholic significantly affect the out-of-pocket expenses for older adult hospitalizations. In terms of the burden of hospitalization for the older adult, Residence, health insurance, education, type of chronic diseases, region, family size, ethnic, type of health service facility, received distance, smoke, alcoholic and pension significantly impact the hospitalization burden for the older adult. Conclusion: This paper provides a new perspective to explain the factors influencing hospitalizational costs and burden in China. The policy recommendations include expanding health insurance coverage and promoting commercial insurance to enhance the accessibility and financial security of healthcare services. Strengthening primary care is suggested to reduce the burden on hospitals and lower the overall cost of hospitalization. Policies aimed at addressing regional healthcare disparities are proposed, along with targeted support for vulnerable groups, including subsidies and culturally sensitive services.

Perspectives and needs for fertility preservation decision-making in childbearing-age patients with breast cancer: A qualitative study.

Objective: To explore the perspectives and needs related to fertility preservation decision-making in patients of childbearing age with breast cancer. Methods: Semistructured face-to-face interviews were conducted in a tertiary hospital in Baoding, China from July to October 2023. Purposive sampling was used to ensure the diversity of samples. The interview guide is based on the literature review and the discussions within the research team. A traditional content analysis approach was used for data analysis. Results: A total of 18 participants were interviewed. Three themes emerged from the data: conflicts between subjective desires and concerns, coexistence of objective benefits and challenges, and decision-making support needs. The conflicts between subjective desires and concerns included five sub-themes, the coexistence of objective benefits and challenges also included five sub-themes, and the decision-making support needs included two sub-themes. Conclusions: Patients faced a difficult trade-off between desires and concerns, benefits, and challenges regarding fertility preservation decisions, with numerous unmet needs. Healthcare professionals should prioritize patients' fertility desires, providing timely fertility preservation information and adequate counseling after a cancer diagnosis. This approach can help alleviate unnecessary concerns, facilitate satisfactory decision-making, and improve patients' quality of life.

A Supramolecular Fluorescent Sensor Array Composed of Conjugated Fluorophores and Cucurbit[7]uril for Bacterial Recognition.

Bacterial infections have emerged as a significant contributor to global mortality and morbidity rates. Herein, we introduce a dual fluorescence "turn-on" supramolecular sensor array composed of three assembled complexes (C1-C3), formed from three positively charged fluorophores (A1-A3) and one cucurbit[7]uril (CB[7]). The ability of this three-element array to simultaneously recognize 10 bacterial species within just 30 s was remarkable, boasting an impressive 100% accuracy. Additionally, the array excelled at distinguishing among various bacterial mixtures and enabled the quantitative detection of common bacterial strains. Notably, it has been skillfully applied to differentiate 10 bacterial samples in urine, achieving excellent differentiation and showcasing promising potential for medical diagnostic applications.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Association Between Socioeconomic Inequalities in Pain and All-Cause Mortality in the China Health and Retirement Longitudinal Study: Longitudinal Cohort Study.

BACKGROUND: Few studies focus on the equality of pain, and the relationship between pain and death is inconclusive. Investigating the distribution of pain and potential mortality risks is crucial for ameliorating painful conditions and devising targeted intervention measures. OBJECTIVE: Our study aimed to investigate the association between inequalities in pain and all-cause mortality in China. METHODS: Longitudinal cohort data from waves 1 and 2 of the China Health and Retirement Longitudinal Study (2011-2013) were used in this study. Pain was self-reported at baseline, and death information was obtained from the 2013 follow-up survey. The concentration index and its decomposition were used to explain the inequality of pain, and the association between pain and death was analyzed with a Cox proportional risk model. RESULTS: A total of 16,747 participants were included, with an average age of 59.57 (SD 9.82) years. The prevalence of pain was 32.54% (8196/16,747). Among participants with pain, the main pain type was moderate pain (1973/5426, 36.36%), and the common pain locations were the waist (3232/16,747, 19.3%), legs (2476/16,747, 14.78%) and head (2250/16,747, 13.44%). We found that the prevalence of pain was concentrated in participants with low economic status (concentration index -0.066, 95% CI -0.078 to -0.054). Educational level (36.49%), location (36.87%), and economic status (25.05%) contributed significantly to the inequality of pain. In addition, Cox regression showed that pain was associated with an increased risk of all-cause mortality (hazard ratio 1.30, 95% CI 1.06-1.61). CONCLUSIONS: The prevalence of pain in Chinese adults is concentrated among participants with low economic status, and pain increases the risk of all-cause death. Our results highlight the importance of socioeconomic factors in reducing deaths due to pain inequalities by implementing targeted interventions.

Effectiveness of hierarchical medical system and economic growth: based on China's urban vs. rural health perspectives.

Background: The hierarchical medical system is an important measure to promote equitable healthcare and sustain economic development. As the population's consumption level rises, the demand for healthcare services also increases. Based on urban and rural perspectives in China, this study aims to investigate the effectiveness of the hierarchical medical system and its relationship with economic development in China. Materials and methods: The study analyses panel data collected from Chinese government authorities, covering the period from 2009 to 2022. According to China's regional development policy, China is divided into the following regions: Eastern, Middle, Western, and Northeastern. Urban and rural component factors were downscaled using principal component analysis (PCA). The factor score formula combined with Urban-rural disparity rate (ΔD) were utilized to construct models for evaluating the effectiveness of the hierarchical medical system from an urban-rural perspective. A Vector Autoregression model is then constructed to analyze the dynamic relationship between the effects of the hierarchical medical system and economic growth, and to predict potential future changes. Results: Three principal factors were extracted. The contributions of the three principal factors were 38.132, 27.662, and 23.028%. In 2021, the hierarchical medical systems worked well in Henan (F = 47245.887), Shandong (F = 45999.640), and Guangdong (F = 42856.163). The Northeast (ΔDmax = 18.77%) and Eastern region (ΔDmax = 26.04%) had smaller disparities than the Middle (ΔDmax = 49.25%) and Western region (ΔDmax = 56.70%). Vector autoregression model reveals a long-term cointegration relationship between economic development and the healthcare burden for both urban and rural residents (ßurban = 3.09, ßrural = 3.66), as well as the number of individuals receiving health education (ß = -0.3492). Both the Granger causality test and impulse response analysis validate the existence of a substantial time lag between the impact of the hierarchical medical system and economic growth. Conclusion: Residents in urban areas are more affected by economic factors, while those in rural areas are more influenced by time considerations. The urban rural disparity in the hierarchical medical system is associated with the level of economic development of the region. When formulating policies for economically relevant hierarchical medical systems, it is important to consider the impact of longer lags.

Analysis of factors associated with depressive symptoms in stroke patients based on a national cross-sectional study.

Post-stroke depression is commonly experienced by stroke survivors and has a significant negative impact on the physical, cognitive, and social functioning of those affected. This study aims to investigate the prevalence of depressive symptoms and their associated factors in Chinese stroke patients. Research samples were selected from the China Health and Retirement Longitudinal Study 2018 survey. Depression was evaluated using the 10-item Center for Epidemiological Studies Depression Scale, with a score ≥ 10 defined as depression. Univariate and multivariable analyses were performed to examine the associations of depressive symptoms with demographics, family relationships, health status, and lifestyle. A total of 963 stroke patients were included and 57.8% of them had depressive symptoms. Depressive symptoms were significantly associated with female sex (OR 1.762, 95% CI 1.235-2.514), lower education level (non-formal education: OR 2.148, 95% CI 1.235-3.737, primary to secondary school education: OR 1.964, 95% CI 1.272-3.033), dissatisfaction with spouse (OR 1.912, 95% CI 1.075-3.401), dissatisfaction with life (OR 1.779, 95% CI 1.080-2.931), dissatisfaction with health (OR 1.592, 95% CI 1.138-2.226), pain (OR 1.392, 95% CI 1.005-1.928) and abnormal sleep (OR 1.557, 95% CI 1.126-2.152). The findings suggest the need for regular depression screening and evaluation after a stroke, and that a well-functioning support system, effective health management, and lifestyle modifications could potentially improve the mental state of stroke patients.

Electronic structure and optical properties of In- and Vacancy-doped 6H-SiC: a first-principles study.

PURPOSES: The paper aims to investigative the cacuses and impacts of In- and Vacancy-doped to 6H-SiC, expecting that improving optical properties of materials. Design-Using the first-principles calculations, we discuss the electronic structure and optical properties of different doped 6H-SiC systems. FINDINGS: The results show that In-doped 6H-SiC becomes a direct bandgap p-type semiconductor and the energy bandgap is reduced from the intrinsic 2.059 to 1.515 eV. We demonstrate the stability of the systems through the formation energy analysis, meanwhile identify their physical origins and discuss applications of all structures in electronic devices within optical analysis. Find the energy beginning values of the VSi-doped and VC-doped systems' optical absorption spectrums and extend to 0.4 2 eV and 0.11 eV respectively compared with the original 3.23 eV. In the visible light region, the reflectivity images of the VC/VSi and (In, VSi)-codoped systems rise obviously. CONCLUSIONS: The optical properties of all doping systems were analyzed to be improved compared with the intrinsic, all above mentioned provide a theoretical basis for the fabrication of spintronic and optical devices.

How provider payment methods affect health expenditure of depressive patients? Empirical study from national claims data in China from 2013 to 2017.

BACKGROUND: This study aimed to investigate the associations between provider payment methods and expenditure of depressive patients, stratified by service types and hospital levels. METHODS: We used a 5 % random sample of urban claims data in China (2013-2017), collected by China Health Insurance Research Association. Provider payment methods (fee-for-services, global budget, capitation, case-based and per-diem payments) were the explanatory variables. A generalized linear model was fitted for the associations between provider payment methods and expenditure. All analyses were adjusted for patient"cioeconomic and health-related characteristics. RESULTS: In total, 64,615 depressive patient visits were included, 59,459 for outpatients and 5156 for inpatients. Female patients accounted for 63.00 %. The total and out-of-pocket (OOP) expenditure significantly differentiated by provider payments. Among outpatient services, when comparing with fee-for-services, capitation payment was associated with substantial marginal reduction in total and OOP expenditure (-$34.18, -$9.71) in primary institutes, yet increases ($27.26, $24.11) in secondary hospitals. Similarly, global budget was associated with lower total and OOP expenditure (-$13.51, -$1.61) in secondary hospitals, while higher total and OOP expenditure ($7.43, $32.27) in tertiary hospitals than fee-for-services. For inpatients, total and OOP expenditures under per-diem (-$857.65, -$283.48) and case-based payments (-$997.93, -$137.56) were remarkably smaller than those under fee-for-services in primary and secondary hospitals, respectively. Besides, case-base payment was only linked with the largest reduction in OOP expense (-$239.39) in inpatient services of tertiary hospitals. LIMITATION: Only urban claims data was included in this study, and investigations for rural population still warrant. And updated data are needed for future studies. CONCLUSIONS: There were varying correlations between provider payment methods and expenditure, which differed by service types and hospital levels. These findings provided empirical evidence for optimizing the mixed payment methods for depression in China.

Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway.

Lead (Pb), as a heavy metal that is easily exposed in daily life, can cause damage to various systems of body. Apoptosis is an autonomous cell death process regulated by genes in order to maintain the stability of internal environment, which plays an important role in the development of nervous system. RB binding protein 4 (RBBP4) is one of the core histone binding subunits and is closely related to the apoptosis process of nervous system cells. However, it is not known whether RBBP4 can regulate neuronal apoptosis in lead-exposed environments. We exposed PC12 cells to 0 µM (control group), 1 µM, and 100 µM PbAc for 24 h to obtain cell samples. The female rats ingested drinking water containing 0, 0.5 g/L, and 2.0 g/L PbAc from the first day of pregnancy to three weeks after delivery to obtain hippocampal tissue samples from mammary rats. The results of TUNEL showed that lead exposure promoted the onset of apoptosis in cells and hippocampus. The mRNA and protein levels of the apoptosis-related protein Survivin were significantly reduced in the lead-exposed group compared to the control group. In addition, we found that lead exposure reduces the mRNA and protein levels of RBBP4 in PC12 cells and hippocampus, and increases the mRNA and protein levels of NFκB p65. Moreover, inhibiting NFκB p65 can reverse the decrease in RBBP4 expression in the lead exposure model. Overexpression of RBBP4 increased Survivin expression and reduced apoptosis induced by lead exposure. This suggests that lead exposure induces apoptosis through the NFκB p65/RBBP4/Survivin signaling pathway.

Cucurbitacin C suppresses the progression of pancreatic ductal adenocarcinoma via inhibition of the cGMP-PKG-VASP axis.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating diseases; it has a considerably poor prognosis and may become the second most lethal malignancy in the next 10 years. Chemotherapeutic resistance is common in PDAC; thus, it is necessary to exploit effective alternative drugs. In recent years, traditional folk medicines and their extracts have shown great potential in cancer treatment. The seed of Lagenaria siceraria (Molina) Standl. is a traditional medicine in Asia. Because of its analgesic effects and ability to reduce swelling, it is often used as an adjuvant treatment for abdominal tumors. Cucurbitacin compounds are extracts abundant in Lagenaria siceraria (Molina) Standl. Here, we found that cucurbitacin C (CuC), a member of the cucurbitacin family, has apparent anti-PDAC therapeutic properties. CuC decreased the viability and suppressed the proliferation of PDAC cells in a time- and dose-dependent manner. Further studies revealed that CuC inhibited cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT). In addition, G2/M arrest was induced, and the apoptotic pathway was activated. Transcriptomic and bioinformatic analyses showed that CuC inhibited the cGMP-PKG-VASP axis, increasing the content of cGMP to restore tumor characteristics. The antitumor activity of CuC in vivo was verified through animal experiments, and no obvious side effects were observed. Overall, our study indicates a candidate therapeutic compound for PDAC that is worthy of further development.

Risk of antiangiogenic adverse events in metastatic colorectal cancer patients receiving aflibercept in combination with chemotherapy: A meta-analysis.

BACKGROUND: Aflibercept has been approved for the treatment of metastatic colorectal cancer for more than a decade, but its antiangiogenesis adverse effect profile during treatment remains unclear. This study is conducted to systematically review the risk of antiangiogenic adverse events in patients with metastatic colorectal cancer receiving aflibercept plus chemotherapy. METHODS: We searched databases, including PubMed, Embase and the Cochrane Library up to September 9, 2021. Relevant randomized controlled trials (RCTs) and single-arm studies were included in the review. Statistical analyses were performed using R to calculate the summary incidence rate of antiangiogenic-related adverse events, odds ratios and 95% CIs. Heterogeneity among the included studies was assessed by subgroup analysis. Publication bias analysis and sensitivity analysis were performed to confirm the reliability of the results. RESULTS: A total of 2889 patients from 10 studies met the inclusion criteria. The quality of the included studies was evaluated as qualified for further quantitative synthesis. In part of single-arm studies, the occurrence rates were 44.2% (95%CI, 39.7-48.7%) for hypertension, 31.3% (95% CI, 19.3-43.3%) for proteinuria, 27.3% (95%CI, 21.2-33.4%) for epistaxis, 22.5% (95%CI, 7.8-37.3%) for hemorrhage events, 8.0% (95%CI, 2.0-14 .0%) for venous thromboembolic event in all grades and 22.6% (95%CI, 19.1-26.2%) for grade III/IV hypertension, 7.4% (95%CI, 6.2-8.5%) for grade III/IV proteinuria. In part of RCT, compared to its counterpart, aflibercept containing arm was associated with the increased incidence rate in hypertension (OR:6.30, 95%CI: 3.49-11.36), proteinuria (OR:4.12, 95%CI: 1.25-13.61), epistaxis (OR:3.71, 95%CI: 2.84-4.85), III/IV hypertension (OR:7.20, 95%CI: 5.23-9.92), III/IV proteinuria (OR:5.13, 95%CI: 3.13-8.41). The funnel plot, Begg test and Egger test were carried out on the primary endpoints, III/IV hypertension rate and III/IV proteinuria rate, the result of which detected no obvious publication bias. No significant difference was observed in subgroup analysis in the primary endpoint between the subgroups stratified by treatment line (firstline or non-firstline), chemotherapy regime (FOLFIRI or others) and study design (RCTs or single-arm trials). CONCLUSION: The available evidence suggests that using aflibercept is associated with an increased risk of antiangiogenic adverse events compared with controls. Further studies are needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept in its approved indications remains justified. However, the results of this study should be interpreted with caution, as some of the evidence comes from single-arm clinical trials.

The synergistic effect of residues 32T and 550L in the PA protein of H5 subtype avian influenza virus contributes to viral pathogenicity in mice.

The avian influenza virus (AIV) PA protein contributes to viral replication and pathogenicity; however, its interaction with innate immunity is not well understood. Here, we report that the H5 subtype AIV PA protein strongly suppresses host antiviral defense by interacting with and degrading a key protein in interferon (IFN) signaling, Janus kinase 1 (JAK1). Specifically, the AIV PA protein catalyzes the K48-linked polyubiquitination and degradation of JAK1 at lysine residue 249. Importantly, the AIV PA protein harboring 32T/550L degrades both avian and mammalian JAK1, while the AIV PA protein with residues 32M/550I degrades avian JAK1 only. Furthermore, the residues 32T/550L in PA protein confer optimum polymerase activity and AIV growth in mammalian cells. Notably, the replication and virulence of the AIV PA T32M/L550I mutant are attenuated in infected mice. Collectively, these data reveal an interference role for H5 subtype AIV PA protein in host innate immunity, which can be targeted for the development of specific and effective anti-influenza therapeutics.

Rational design of heterointerface between MoO2 and N-doped carbon with tunable electromagnetic interference shielding capacity.

Exploring highly efficient electromagnetic interference (EMI) shielding filler is urgently desired for next-generation wireless communication and integrated electronics. In this regard, a series of heterogeneous MoO2/N-doped carbon (MoO2/NC) nanorods with tunable conductivity have been successfully synthesized by regulating the pyrolysis temperature within 600, 700 and 800 °C. Profiting from the rational design of heterointerface and low-dimensional structure, the MoO2/NC powder achieves stronger EMI shielding capacity with the incremental temperature. It is found that the MoO2/NC-800 nanorods exhibit the optimal average EMI shielding effectiveness (SE) of 57.2 dB at a thickness of ∼0.3 mm in the X band. Meanwhile, the corresponding shielding mechanisms of MoO2/NC nanorods are also elaborately explained. More interestingly, the increase of sintering temperature makes an obvious effect on absorption loss but has little influence on reflection loss, demonstrating that adjusting the pyrolysis temperature is an effective strategy to strengthen the electromagnetic energy dissipation.

How working-age population education and health of older people shape the burden of population aging: A comparative study of Macau, Hong Kong, and Singapore.

Macau, Hong Kong and Singapore are all facing increasing population aging. Those aged 65 and over make up the old-age population. The working-age population refers to the population aged 15 to 64. Conventionally, the burden of population aging is measured by the Old-Age Dependency Ratio, which is the ratio of the old-age population to the working-age population. As life expectancy rises, depending exclusively on age to calculate the burden of aging hinders the development of effective anti-aging strategies. The working-age population's education and the elderly's health affect the aging burden's support and generator, respectively. Including them in the calculation gives us a fuller view of the burden of aging. Objective: To compare the population aging burden in Macau, Hong Kong, and Singapore by including working-age population education and elderly health. Methods: The overall, working-age and old-age population and proportion, as well as the Old-Age Dependency Ratio of Macau, Hong Kong, and Singapore, were collected from the World Bank database. The life expectancy at 65 was extracted from the 2022 World Population Prospect. The tertiary education rate of the working-age population and the self-rated health status of the old-age population were retrieved from governments' statistical reports. We then calculated the Education-Health Adjusted Old-Age Dependency Ratio, a set of four equations showing the support of the working-age population on the old-age population, where OADRh_t and OADRuh_t represent the burden of healthy and unhealthy old-age population on the working-age population with tertiary education; similarly, OADRh_nt and OADRuh_nt indicate the burden placed on the working-age population without tertiary education by healthy and unhealthy old-age population. Lastly, for comparison with the conventional Old-Age Dependency Ratio, we generated the Weighted Education-Health Adjusted Old-Age Dependency Ratio. Results: Hong Kong has the greatest old-age population proportion and Old-Age Dependency Ratio, yet its growth rates are moderate and stable, ranging from 0 to 4% and 0 to 6%, respectively. Macau and Singapore experienced sharper changes in old-age population proportion and the Old-Age Dependency Ratio, with Macau's Old-Age Dependency Ratio varying between -2.66 and 8.50% and Singapore's ranging from -1.53 to 9.70%. Three cities showed different patterns in four Education-Health Adjusted Old-Age Dependency Ratio indicators. In Macau, the OADRh_nt and OADRuh_nt increased by 0.4 and 6.2, while the OADRh_t and OADRuh_t decreased by 13.5 and 15.3 from 2004 to 2016. In Hong Kong, only the OADRuh_t fell by 9.4, and the other three increased from 2003 to 2015. In Singapore, the OADRh_nt and OADRh_t increased by 3.8 and 1.0, while OADRuh_nt and OADRuh_t decreased by 1.2 and 3.9 from 2007 to 2011. The Weighted Education-Health Adjusted Old-Age Dependency Ratios are all smaller than the conventional Old-Age Dependency Ratio in the three regions, particularly in Singapore. The Weighted Education-Health Adjusted Old-Age Dependency Ratio of Singapore was reduced by 9.5 to 30.5% compared with the conventional Old-Age Dependency Ratio, that of Hong Kong reduced by 6.2 to 22.5%, and that of Macau reduced by 4.4 to 16.1%. Conclusion: This is the first study to compare the aging burden in Macau, Hong Kong, and Singapore in connection to working-age population education and elderly health. With the new assessment, the burden of population aging in three regions has been reduced, showing that improving the education of the working-age population and maintaining older people's wellbeing can assist authorities to deal with population aging, especially in Macau and Hong Kong.

The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling.

Influenza A virus (IAV) polymerase protein PB2 has been shown to partially inhibit the host immune response by blocking the induction of interferons (IFNs). However, the IAV PB2 protein that regulates the downstream signaling pathway of IFNs is not well characterized. Here, we report that IAV PB2 protein reduces cellular sensitivity to IFNs, suppressing the activation of STAT1/STAT2 and ISGs. Furthermore, IAV PB2 protein targets mammalian JAK1 at lysine 859 and 860 for ubiquitination and degradation. Notably, the H5 subtype of highly pathogenic avian influenza virus with I283M/K526R mutations on PB2 increases the ability to degrade mammalian JAK1 and exhibits higher replicate efficiency in mammalian (but not avian) cells and mouse lung tissues, and causes greater mortality in infected mice. Altogether, these data describe a negative regulatory mechanism involving PB2-JAK1 and provide insights into an evasion strategy from host antiviral immunity employed by IAV.

Efficacy, safety, and cost-effectiveness analysis of aflibercept in metastatic colorectal cancer: A rapid health technology assessment.

Background: Metastatic colorectal cancer (mCRC) imposes a heavy tumor burden worldwide due to limited availability of therapeutic drugs. Aflibercept, a kind of recombinant protein of the anti-vascular endothelial growth factor (VEGF) family, has been approved in clinical application among mCRC patients since 2012. A comprehensive analysis of the efficacy, safety, and cost-effectiveness of aflibercept in mCRC treatment is necessary. Objective: To evaluate the efficacy, safety, and cost-effectiveness of aflibercept for the treatment of mCRC in order to provide a decision-making reference for the selection of targeted drugs for second-line treatment of mCRC in Hong Kong, Macao, and Taiwan regions of China and the selection of new drugs for medical institutions in these regions. Methods: A systematic retrieve on databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu, as well as relevant websites and databases of health technology assessment including the National Institute of Health and Clinical Optimization, Centre for Evaluation and Communication at the University of York, and the Canadian Agency for Medicines and Health Technology, was conducted. The literature was screened according to the inclusion and exclusion criteria, and data were extracted and analyzed by two authors, while the quality of the literature was assessed. Results: Finally, we included two HTA reports, 11 systematic reviews/meta-analyses, and two cost-effectiveness studies in the rapid health technology assessment. For mCRC patients receiving second-line treatment, aflibercept combined with FOLFIRI significantly increased progression-free survival (PFS) and overall survival (OS) and the objective response rate (ORR) also improved, compared with folinic acid + fluorouracil + irinotecan (FOLFIRI). In terms of safety, mCRC patients who received aflibercept combined with FOLFIRI therapy had a higher incidence of grade 3-4 adverse events than those who received FOLFIRI alone, including anti-VEGF-related adverse events (hypertension, hemorrhagic events, and proteinuria) and chemotherapy-related adverse events (diarrhea, weakness, stomatitis, hand-foot syndrome, neutropenia, and thrombocytopenia). In terms of cost-effectiveness, two economic studies conducted in the United Kingdom and Japan, respectively, found that compared with FOLFIRI, aflibercept combined with FOLFIRI had no cost-effectiveness advantage in mCRC patients receiving second-line treatment. Conclusion: Compared with FOLFIRI treatment, aflibercept combined with FOLFIRI for the second-line treatment of mCRC patients has better efficacy, worse safety, and is not cost-effective. More high-quality clinical studies are required for further exploration of aflibercept's clinical value. Medical institutions in Hong Kong, Macao, and Taiwan regions of China should be cautious when using or introducing aflibercept plus FOLFIRI as a mCRC treatment.

Linderalactone Suppresses Pancreatic Cancer Development In Vitro and In Vivo via Negatively Regulating PI3K/AKT Signaling Pathway.

Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo. The results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.

Psychometric Properties of the Fertility Intention Scale among Patients with Breast Cancer of Childbearing Age in Mainland China.

Objective: There are no valid assessment instruments assessing fertility intention among breast cancer survivors in mainland China. Therefore, this study aims to examine the psychometric properties of the Taiwanese version of the Fertility Intention Scale (FIS) among female patients with breast cancer of childbearing age in mainland China. Methods: Two hundred and sixty-four female patients with breast cancer of childbearing age were recruited from two tertiary hospitals in Tianjin and Baoding, of which 32 patients completed the survey twice. Confirmatory factor analysis was adopted to assess construct validity. Correlations between the Reproductive Concerns After Cancer scale and FIS scores were calculated using Spearman correlation for convergent validity. The known-group validity of the FIS was verified using Mann-Whitney U test to compare the FIS scores between patients with or without the intention to conceive. Moreover, reliabilities were examined using Cronbach's alpha and intra-class correlation coefficient. Results: Confirmatory factor analysis showed a good model fit to previous factor structures (χ2/df = 3.19, root mean square error of approximation = 0.091, comparative fitting index = 0.980, Tucker-Lewis index = 0.975), and no FIS item was dropped. The FIS scores were weak negatively correlated with the Reproductive Concerns After Cancer scale scores (r = -0.172, P < 0.01). The convergent validity of FIS was not satisfactory. Differences were noted between patients with or without the intention to conceive (50.62 ± 6.35 vs. 45.98 ± 7.19, P < 0.01). The FIS showed acceptable known-group validity. The internal consistency (Cronbach's α = 0.824) and the test-retest reliability (r = 0.863, P < 0.01) of the FIS were also acceptable. Conclusions: Overall, the FIS provides a comprehensive evaluation of the fertility intention among patients with breast cancer of childbearing age in mainland China. However, the convergent validity was not satisfactory; thus, further revision and validation may be required in the future.

A multi-omics analysis for the prediction of neurocognitive disorders risk among the elderly in Macao.

BACKGROUND: Due to the increasing ageing population, neurocognitive disorders (NCDs) have been a global public health issue, and its prevention and early diagnosis are crucial. Our previous study demonstrated that there is a significant correlation between specific populations and NCDs, but the biological characteristics of the vulnerable group predispose to NCDs are unclear. The purpose of this study is to investigate the predictors for the vulnerable group by a multi-omics analysis. METHODS: Multi-omics approaches, including metagenomics, metabolomic and proteomic, were used to detect gut microbiota, faecal metabolites and urine exosome of 8 normal controls and 13 vulnerable elders after a rigorous screening of 400 elders in Macao. The multi-omics data were analysed using R and Bioconductor. The two-sided Wilcoxon's rank-sum test, Kruskal-Wallis rank sum test and the linear discriminant analysis effective size were applied to investigate characterized features. Moreover, a 2-year follow-up was conducted to evaluate cognitive function change of the elderly. RESULTS: Compared with the control elders, the metagenomics of gut microbiota showed that Ruminococcus gnavus, Lachnospira eligens, Escherichia coli and Desulfovibrio piger were increased significantly in the vulnerable group. Carboxylates, like alpha-ketoglutaric acid and d-saccharic acid, and levels of vitamins had obvious differences in the faecal metabolites. There was a distinct decrease in the expression of eukaryotic translation initiation factor 2 subunit 1 (eIF2α) and amine oxidase A (MAO-A) according to the proteomic results of the urine exosomes. Moreover, the compound annual growth rate of neurocognitive scores was notably decreased in vulnerable elders. CONCLUSIONS: The multi-omics characteristics of disturbed glyoxylate and dicarboxylate metabolism (bacteria), vitamin digestion and absorption and tricarboxylic acid cycle in vulnerable elders can serve as predictors of NCDs risk among the elderly of Macao. Intervention with them may be effective therapeutic approaches for NCDs, and the underlying mechanisms merit further exploration.