Growing old in China in socioeconomic and epidemiological context: systematic review of social care policy for older people.

BACKGROUND: From 2020 to 2050, China's population aged ≥65 years old is estimated to more than double from 172 million (12·0%) to 366 million (26·0%). Some 10 million have Alzheimer's disease and related dementias, to approach 40 million by 2050. Critically, the population is ageing fast while China is still a middle-income country. METHODS: Using official and population-level statistics, we summarise China's demographic and epidemiological trends relevant to ageing and health from 1970 to present, before examining key determinants of China's improving population health in a socioecological framework. We then explore how China is responding to the care needs of its older population by carrying out a systematic review to answer the question: 'what are the key policy challenges to China achieving an equitable nationwide long-term care system for older people?'. Databases were screened for records published between 1st June 2020 and 1st June 2022 in Mandarin Chinese or English, reflecting our focus on evidence published since introduction of China's second long-term care insurance pilot phase in 2020. RESULTS: Rapid economic development and improved access to education has led to widescale internal migration. Changing fertility policies and household structures also pose considerable challenges to the traditional family care model. To deal with increasing need, China has piloted 49 alternative long-term care insurance systems. Our findings from 42 studies (n = 16 in Mandarin) highlight significant challenges in the provision of quality and quantity of care which suits the preference of users, varying eligibility for long-term care insurance and an inequitable distribution of cost burden. Key recommendations include increasing salaries to attract and retain staff, introduction of mandatory financial contributions from employees and a unified standard of disability with regular assessment. Strengthening support for family caregivers and improving smart old age care capacity can also support preferences to age at home. CONCLUSIONS: China has yet to establish a sustainable funding mechanism, standardised eligibility criteria and a high-quality service delivery system. Its long-term care insurance pilot studies provide useful lessons for other middle-income countries facing similar challenges in terms of meeting the long-term care needs of their rapidly growing older populations.

Multi-Class Weed Recognition Using Hybrid CNN-SVM Classifier.

The Convolutional Neural Network (CNN) is one of the widely used deep learning models that offers the chance to boost farming productivity through autonomous inference of field conditions. In this paper, CNN is connected to a Support Vector Machine (SVM) to form a new model CNN-SVM; the CNN models chosen are ResNet-50 and VGG16 and the CNN-SVM models formed are ResNet-50-SVM and VGG16-SVM. The method consists of two parts: ResNet-50 and VGG16 for feature extraction and SVM for classification. This paper uses the public multi-class weeds dataset DeepWeeds for training and testing. The proposed ResNet-50-SVM and VGG16-SVM approaches achieved 97.6% and 95.9% recognition accuracies on the DeepWeeds dataset, respectively. The state-of-the-art networks (VGG16, ResNet-50, GoogLeNet, Densenet-121, and PSO-CNN) with the same dataset are accurate at 93.2%, 96.1%, 93.6%, 94.3%, and 96.9%, respectively. In comparison, the accuracy of the proposed methods has been improved by 1.5% and 2.7%, respectively. The proposed ResNet-50-SVM and the VGG16-SVM weed classification approaches are effective and can achieve high recognition accuracy.

Burden of caregivers who care for oldest-old parents with disability: A cross-sectional study.

OBJECTIVE: To describe the characteristics of oldest-old Chinese with disability and their adult-child caregivers, and the extent to which these characteristics were associated with caregiver burden. METHODS: The study was based on 168 pairs of disabled oldest-old adults and their adult-child caregivers, derived from the Chinese Longitudinal Healthy Longevity Survey. Descriptive analyses of care recipients' and caregivers' characteristics were conducted respectively, in reference to caregiver burden. Statistically significant characteristics identified in these bivariate analyses were then jointly evaluated in multiple linear regression models with caregiver burden as the outcome. RESULTS: Care recipients positive emotion status [(ß = -0.227 (-0.412, -0.042)], multiple chronic disease [(ß = 0.513 (0.081, 0.945)], and caregivers spent more caregiving time [(ß = 0.225 (0.061, 0.389)] were main factors associated with caregiver burden. CONCLUSION: Adult-children caregivers perceived heavier burden if care recipients had low positive emotions, had multiple chronic diseases, and caregivers spent more time caregiving.

Dual-Sensitive Charge-Conversional Polymeric Prodrug for Efficient Codelivery of Demethylcantharidin and Doxorubicin.

A tumor is a complicated system, and tumor cells are typically heterogeneous in many aspects. Polymeric drug delivery nanocarriers sensitive to a single type of biosignals may not release cargos effectively in all tumor cells, leading to low therapeutic efficacy. To address the challenges, here, we demonstrated a pH/reduction dual-sensitive charge-conversional polymeric prodrug strategy for efficient codelivery. Reduction-sensitive disulfide group and acid-labile anticancer drug (demethylcantharidin, DMC)-conjugated ß-carboxylic amide group were repeatedly and regularly introduced into copolymer chain simultaneously via facile CuAAC click polymerization. The obtained multifunctional polymeric prodrug P(DMC), mPEG-b-poly(disulfide-alt-demethylcantharidin)-b-mPEG was further utilized for DOX encapsulation. Under tumor tissue/cell microenvironments (pH 6.5 and 10 mM GSH), the DOX-loaded polymeric prodrug nanoparticles (P(DMC)@DOX NPs) performed surface negative-to-positive charge conversion and accelerated/sufficient release of DMC and DOX. The remarkably enhanced cellular internalization and cytotoxicity in vitro, especially against DOX-resistant SMMC-7721 cells, were demonstrated. P(DMC)@DOX NPs in vivo also exhibited higher tumor accumulation and improved antitumor efficiency compared to P(SA)@DOX NPs with one drug and without charge-conversion ability. The desired multifunctional polymeric prodrug strategy brings a new opportunity for cancer chemotherapy.

PRG4 represses the genesis and metastasis of osteosarcoma by inhibiting PDL1 expression.

BACKGROUND: Osteosarcoma is originated from skeletal system. Recombinant human proteoglycan 4 (rhPRG4) can inhibit cell proliferation and migration in multiple cancers. This research is designed to dig out the role and mechanism of PRG4 in osteosarcoma. METHODS: Human osteosarcoma cell lines, MG63 and 143B, were transfected with programmed death 1 (PD-L1) overexpression vectors and/or treated with 20, 50, and 100 µg/mL rhPRG4, followed by the determination of cell viability, colony formation, sphere formation, invasion, migration, apoptosis, and the expressions of matrix metalloproteinases (MMPs), PD-L1 and apoptosis-related proteins. Tumor-bearing mouse models were constructed by injection of 143B cells and treatment of anti-PD-L1 antibody and/or adenovirus PRG4 (AdPRG4). Tumor volume was monitored, and immunohistochemical location of Ki67 was performed. Expressions of MMPs, transforming growth factor-ß (TGF-ß), PD-L1, and epithelial mesenchymal transition (EMT)-related proteins were measured in tumors. RESULTS: RhPRG4 (20, 50, and 100 µg/mL) inhibited the viability, colony formation, sphere formation, invasion, migration, and the expressions of MMP2, MMP9 and Bcl2 in osteosarcoma cells, while promoting cell apoptosis as well as Bax and c-caspase3 expressions, at a dose-dependent manner; by contrast, PD-L1 overexpression reversed the above effects of 100 µg/mL rhPRG4. AdPRG4 or anti-PD-L1 antibody decreased tumor volume, number of pulmonary metastasis nodule, Ki67 location, and expressions of TGF-ß, PD-L1, MMP2, MMP9, Vimentin, and Snail, but increased E-cadherin expression in tumor cells. Moreover, anti-PD-L1 antibody and AdPRG4 together functioned more effectively than them alone in reducing tumor burden. CONCLUSION: PRG4 represses the genesis and metastasis of osteosarcoma via inhibiting PD-L1 expression, and AdPRG4 enhances the effectiveness of anti-PD-L1 therapy.

Geographical variation in dementia prevalence across China: a geospatial analysis.

Background: Dementia poses great health and social challenges in China. Dementia prevalence may vary across geographic areas, while comparable estimations on provincial level is lacking. This study aims to estimate dementia prevalence by provinces across China, taking into account risk factors of individual level and potential spatial correlation of provinces. Methods: In this study, 17,176 adults aged 50 years or older were included from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS 2018), covering 28 provinces, autonomous regions and municipalities. To improve provincial representativeness, we constructed provincial survey weights based on China 7th census (2020). The prevalence of dementia and 95% Bayesian credible intervals (BCIs) were estimated using a Bayesian conditional autoregressive (CAR) model with spatially varying coefficients of covariates. Findings: The weighted prevalence of dementia at provincial level in China in 2018 ranged from 2.62% (95%BCI: 1.70%, 3.91%) to 13.53% (95%BCI: 8.82%, 20.93%). High dementia prevalence was concentrated in North China, with a prominent high-high cluster, while provinces of low prevalence were concentrated on East and South China, characterized by a low-low cluster. Ordered by the median estimation of prevalence, the top 10% of provinces, include Xinjiang, Jilin, and Beijing. Meanwhile, Fujian, Zhejiang, and Guangdong rank among the last. The association between dementia prevalence and drinking, smoking, social isolation, physical inactivity, hearing impairment, hypertension, and diabetes exhibits provincial variation. Interpretation: Our study identifies a geospatial disparity in dementia prevalence and risk factor effects across China's provinces, with high-high and low-low clusters in some northern and southern provinces, respectively. The findings emphasize the need for targeted strategies, such as addressing hypertension and hearing impairment, in specific regions for more effective dementia prevention and treatment. Funding: National Science Foundation of China/the Economic and Social Research Council, UK Research and Innovation joint call: Understanding and Addressing Health and Social Challenges for Ageing in the UK and China. UK-China Health And Social Challenges Ageing Project (UKCHASCAP): present and future burden of dementia, and policy responses (grant number 72061137003, ES/T014377/1).

Visually evaluating drug efficacy in living cells using COF-based fluorescent nanoprobe via CHA amplified detection of miRNA and simultaneous apoptosis imaging.

BACKGROUNDS: Cancer is a highly fatal disease which is close relative of miRNA aberrant expression and apoptosis disorders. Elucidation of the therapeutic efficacy through investigating the changes in miRNA and apoptosis holds immense importance in advancing the development of miRNA-based precision therapy. However, it remains a challenge as how to visually evaluate the efficacy during protocol optimization of miRNA-based anticancer drugs at the cellular level. Therefore, exploring effective and noninvasive methods for real-time monitoring of therapeutic efficacy in living cells is of great significance. RESULTS: Herein, we reported a novel fluorescent nanoprobe COF-H1/H2-Peptide for visually evaluating drug efficacy in living cells through amplified imaging of low-abundant miRNA-221 with catalytic hairpin assembly (CHA) circle amplification, as well as simultaneous caspase-3 imaging. With strong stability and good biocompatibility, this newly fabricated amplified nanoprobe showed high sensitivity and specificity for the detection of miRNA-221 and caspase-3, and the limit of detection (LOD) of miRNA-221 was as low as 2.79 pM. The fluorescent imaging results showed that this amplified nanoprobe could not only detect caspase-3 in living cells, but also effectively detect low levels of miRNA-221 with increasing anticancer drug concentration and treatment time. The smart nanoprobe had effective performance for optimizing miRNA-based drug treatment schedules by dual-color fluorescence imaging. SIGNIFICANCE: This nanoprobe combined CHA amplified detection of intracellular miRNA-221 and synchronous apoptosis imaging, with excellent sensitivity for the detection of cellular low-level miRNA, enabling the realization of real-time assessment of the efficacy of miRNA-based therapy in living cells. This work presents a promising approach for revealing the regulatory mechanisms between miRNAs and apoptosis in cancer occurrence, development, and treatment.

How dyadic appraisal moderate the association between dyadic coping and diabetes management efficacy.

To explore the moderating role of dyadic appraisal in the association between dyadic coping and diabetes management efficacy. Two hundred seventy six middle-aged and older couple pairs with one spouse who had diabetes were recruited from 14 community healthcare centers across Guangzhou. The moderating role of dyadic appraisal was investigated using the actor-partner interdependence moderation model. When both couples considered diabetes to be a shared condition, statistically-significant associations were found between patients' negative (ß = -22.7, p = 0.008) and neutral behaviors (ß = 13.6, p = 0.017), plus spouses' positive behaviors (ß = 22.8, p = 0.009) on their own diabetes management efficacy, respectively (i.e. actor effects); as well as between spouses' positive (ß = 16.8, p = 0.028), negative (ß = -28.5, p < 0.001), and neutral behaviors (ß = 16.9, p = 0.006) on patient's diabetes management efficacy (i.e. partner effects). Dyadic appraisal moderates the association between dyadic coping and diabetes management efficacy.

Dementia incidence trend in England and Wales, 2002-19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing.

BACKGROUND: Dementia incidence declined in many high-income countries in the 2000s, but evidence on the post-2010 trend is scarce. We aimed to analyse the temporal trend in England and Wales between 2002 and 2019, considering bias and non-linearity. METHODS: Population-based panel data representing adults aged 50 years and older from the English Longitudinal Study of Ageing were linked to the mortality register across wave 1 (2002-03) to wave 9 (2018-19) (90 073 person observations). Standard criteria based on cognitive and functional impairment were used to ascertain incident dementia. Crude incidence rates were determined in seven overlapping initially dementia-free subcohorts each followed up for 4 years (ie, 2002-06, 2004-08, 2006-10, 2008-12, 2010-14, 2012-16, and 2014-18). We examined the temporal trend of dementia incidence according to age, sex, and educational attainment. We estimated the trend of dementia incidence adjusted by age and sex with Cox proportional hazards and multistate models. Restricted cubic splines allowed for potential non-linearity in the time trend. A Markov model was used to project future dementia burden considering the estimated incidence trend. FINDINGS: Incidence rate standardised by age and sex declined from 2002 to 2010 (from 10·7 to 8·6 per 1000 person-years), then increased from 2010 to 2019 (from 8·6 to 11·3 per 1000 person-years). Adjusting for age and sex, and accounting for missing dementia cases due to death, estimated dementia incidence declined by 28·8% from 2002 to 2008 (incidence rate ratio 0·71, 95% CI 0·58-0·88), and increased by 25·2% from 2008 to 2016 (1·25, 1·03-1·54). The group with lower educational attainment had a smaller decline in dementia incidence from 2002 to 2008 and a greater increase after 2008. If the upward incidence trend continued, there would be 1·7 million (1·62-1·75) dementia cases in England and Wales by 2040, 70% more than previously forecast. INTERPRETATION: Dementia incidence might no longer be declining in England and Wales. If the upward trend since 2008 continues, along with population ageing, the burden on health and social care will be large. FUNDING: UK Economic and Social Research Council.

NIR and Reduction Dual-Sensitive Polymeric Prodrug Nanoparticles for Bioimaging and Combined Chemo-Phototherapy.

The combination of chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) based on a single nanosystem is highly desirable for cancer treatment. In this study, we developed a versatile Pt(IV) prodrug-based nanodrug, PVPt@Cy NPs, to realize synchronous chemotherapy, PDT and PTT and integrate cancer treatment with bioimaging. To construct PVPt@Cy NPs, the amphiphilic Pt(IV)-based polymeric prodrug PVPt was synthesized by a facile one-pot coupling reaction, and then it was used to encapsulate an optotheranostic agent (HOCyOH, Cy) via hydrophobic interaction-induced self-assembly. These NPs would disaggregate under acidic, reductive conditions and NIR irradiation, which are accompanied by photothermal conversion and reactive oxygen species (ROS) generation. Moreover, the PVPt@Cy NPs exhibited an enhanced in vitro anticancer efficiency with 808-nm light irradiation. Furthermore, the PVPt@Cy NPs showed strong NIR fluorescence and photothermal imaging in H22 tumor-bearing mice, allowing the detection of the tumor site and monitoring of the drug biodistribution. Therefore, PVPt@Cy NPs displayed an enormous potential in combined chemo-phototherapy.

Research on the insurance of swimming crab temperature and salinity index insurance based on Copula function.

Under climate change, the sea surface temperature and salinity change greatly, which poses a considerable threat to sustainable food security. Sea surface temperature and salinity (SST/SSS) are selected to examine the annual output of swimming crab in 24 cities along the eastern China. The Copula-based function was used to construct the probability distribution model of the swimming crab yield with SST and SSS. The pure premium rate of the swimming crab production in these 24 cities are also examined. The results show that 1) There is significant positive correlations between the yield of swimming crab with temperature and salinity over the study area. The only exception is that the correlation between yield of swimming crab and salinity is not significant in the south of study area. 2) The span of the pure insurance premium rate of swimming crab in 24 cities increases rapidly with the increase of the protection level, the maximum span up to 2.04%, and the minimum span is only 1.6%. 3) The distribution of the swimming crab insurance premium rate is various in space. The insurance premium rate of 8 cities in the south of Taizhou is low with the highest premium rate at 5.6%. The insurance premium rate of 16 cities in north of Taizhou is relatively high with the rate between 6%-22%. The research can provide a theoretical basis for the pricing of insurance products for swimming crab in 24 cities in the typical aquaculture areas in eastern China.

A multifunctional platinum(IV) and cyanine dye-based polyprodrug for trimodal imaging-guided chemo-phototherapy.

Imaging-guided chemo-phototherapy based on a single nanoplatform has a great significance to improve the efficiency of cancer therapy and diagnosis. However, high drug content, no burst release and real-time tracking of nanodrugs are the three main challenges for this kind of multifunctional nanotheranostics. In this work, we developed an innovative theranostic nanoplatform based on a Pt(IV) prodrug and a near-infrared (NIR) photosensitizer. A Pt(IV) prodrug and a cyanine dye (HOCyOH, Cy) were copolymerized and incorporated into the main chain of a polyprodrug (PCPP), which self-assembled into nanoparticles (NPs) with ∼27.61% Cy loading and ∼9.37% Pt loading, respectively. PCPP NPs enabled reduction-triggered backbone cleavage of polyprodrugs and bioactive Pt(II) release; Cy could be activated under 808 nm laser irradiation to produce local hyperthermia and reactive oxygen species (ROS) for phototherapy. Moreover, PCPP NPs with extremely high Cy and Pt heavy metal contents in the backbone of the polyprodrug could directly track the nanodrugs themselves via near-infrared fluorescence (NIRF) imaging, photothermal imaging, and computed tomography (CT) imaging in vitro and in vivo. As revealed by trimodal imaging, PCPP NPs were found to exhibit excellent tumor accumulation and antitumor efficiency after intravenous injection into H22-tumor-bearing mice. The dual-drug backboned polyprodrug nanoplatform exhibited great potential for bioimaging and combined chemo-phototherapy.

Is there a common latent cognitive construct for dementia estimation across two Chinese cohorts?

Introduction: It is valuable to identify common latent cognitive constructs for dementia prevalence estimation across Chinese aging cohorts. Methods: Based on cognitive measures of 12015 Chinese Longitudinal Healthy Longevity Survey (CLHLS; 13 items) and 6623 China Health and Retirement Longitudinal Study (CHARLS; 9 items) participants aged 65 to 99 in 2018, confirmatory factor analysis was applied to identify latent cognitive constructs, and to estimate dementia prevalence compared to Mini-Mental State Examination (MMSE) and nationwide estimates of the literature. Results: A common three-factor cognitive construct of orientation, memory, and executive function and language was found for both cohorts with adequate model fits. Crude dementia prevalence estimated by factor scores was similar to MMSE in CLHLS, and was more reliable in CHARLS. Age-standardized dementia estimates of CLHLS were lower than CHARLS among those aged 70+, which were close to the nationwide prevalence reported by the COAST study and Global Burden of Disease. Discussion: We verified common three-factor cognitive constructs for both cohorts, providing an approach to estimate dementia prevalence at the national level. Highlights: Common three-factor cognitive constructs were identified in Chinese Longitudinal Healthy Longevity Survey (CLHLS) and China Health and Retirement Longitudinal Study (CHARLS).Crude dementia estimates using factor scores were reliable in both cohorts.Estimates of CHARLS were close to current evidence, but higher than that of CLHLS.

Exosomes loaded with programmed death ligand-1 promote tumor growth by immunosuppression in osteosarcoma.

Osteosarcoma (OS) is a malignant tumor commonly observed in adolescents, who experience relapse and metastasis (30% of the total cases). Its progression is attributed to immune escape mediated by immune checkpoints. However, the intercellular connection between tumor cells and T cells remain unclear. This study was conducted to explore the effects of PD-L1-loaded exosomes on the tumor growth of OS. The exosomes were extracted from cells and tissues through ultracentrifugation. IFN-γ production was determined to evaluate the activity of Jurkat cells. The in vivo growth of OS cells was examined using a C3H xenograft model in mice, tumor volumes were monitored, and the proportion of CD3 + T cells in tumor tissues was detected. Results revealed that PD-L1 was significantly upregulated in the OS cell lines. MG63 and Saos-2 cells were the most abundant in PD-L1, so they were selected as investigation targets. PD-L1 was found to be also highly expressed in the exosomes isolated from MG63 and Saos-2 cells. The exosomes elicited significant inhibitory effects on IFN-γ secretion in Jurkat cells, which were abolished by the PD-L1 antibody or siRNAs. The in vivo growth of C3H cells was significantly facilitated by the overexpression of mPD-L1 or by the administration of mPD-L1-overloaded exosomes. The infiltration of CD3 + T cells was also decreased. The exosomes extracted from clinical PD-L1-positive OS tissues showed a promising inhibitory property against activated T cells. Therefore, PD-L1-loaded exosomes extracted from OS cells aggravated OS progression by suppressing T cell activities.

pH and Reduction Dual-Responsive Bi-Drugs Conjugated Dextran Assemblies for Combination Chemotherapy and In Vitro Evaluation.

Polymeric prodrugs, synthesized by conjugating chemotherapeutic agents to functional polymers, have been extensively investigated and employed for safer and more efficacious cancer therapy. By rational design, a pH and reduction dual-sensitive dextran-di-drugs conjugate (oDex-g-Pt+DOX) was synthesized by the covalent conjugation of Pt (IV) prodrug and doxorubicin (DOX) to an oxidized dextran (oDex). Pt (IV) prodrug and DOX were linked by the versatile efficient esterification reactions and Schiff base reaction, respectively. oDex-g-Pt+DOX could self-assemble into nanoparticles with an average diameter at around 180 nm. The acidic and reductive (GSH) environment induced degradation and drug release behavior of the resulting nanoparticles (oDex-g-Pt+DOX NPs) were systematically investigated by optical experiment, DLS analysis, TEM measurement, and in vitro drugs release experiment. Effective cellular uptake of the oDex-g-Pt+DOX NPs was identified by the human cervical carcinoma HeLa cells via confocal laser scanning microscopy. Furthermore, oDex-g-Pt+DOX NPs displayed a comparable antiproliferative activity than the simple combination of free cisplatin and DOX (Cis+DOX) as the extension of time. More importantly, oDex-g-Pt+DOX NPs exhibited remarkable reversal ability of tumor resistance compared to the cisplatin in cisplatin-resistant lung carcinoma A549 cells. Take advantage of the acidic and reductive microenvironment of tumors, this smart polymer-dual-drugs conjugate could serve as a promising and effective nanomedicine for combination chemotherapy.