Serine deficiency exacerbates psoriatic skin inflammation by regulating S-adenosyl methionine-dependent DNA methylation and NF-κB signalling activation in keratinocytes.

BACKGROUND: Serine metabolism is crucial for tumour oncogenesis and immune responses. S-adenosyl methionine (SAM), a methyl donor, is typically derived from serine-driven one-carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear. OBJECTIVES: To investigate the association between serine metabolism and psoriatic skin inflammation. METHODS: Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism-regulated psoriatic keratinocyte inflammation. An imiquimod (IMQ)-induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation. RESULTS: The expression of serine synthesis pathway enzymes, including the first rate-limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic-related signalling pathways, including the tumour necrosis factor-alpha (TNF-α) signalling pathway, interleukin (IL)-17 signalling pathway and NF-κB signalling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL-6 in keratinocytes with or without IL-17A, IL-22, IL-1α, oncostatin M and TNF-α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL-6 by inhibiting SAM-dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL-6 by increasing the activation of NF-κB via SAM inhibition. SAM treatment effectively alleviated IMQ-induced psoriasis-like skin inflammation in mice. CONCLUSIONS: Our study revealed the crucial role of PHGDH in antagonising psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.

Excess psoriasis and psoriatic arthritis mortality during the COVID-19 pandemic in the United States: A nationwide population-based study from 2010 to 2021.

BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.

Association between pulse pressure, systolic blood pressure and the risk of rapid decline of kidney function among general population without hypertension: results from the China health and retirement longitudinal study (CHARLS).

BACKGROUND: Association between blood pressure (BP) and kidney function among the middle and old aged general population without hypertension remains unclear. METHODS: Participants aged ≥ 45 years, with complete data in 2011 and 2015 interviews of the China Health and Retirement Longitudinal Study(CHARLS), and without pre-existing hypertension were included. Systolic BP (SBP) was categorized as low (< 120 mmHg), medium (120-129 mmHg), and high (120-139 mmHg). Diastolic BP (DBP) was categorized as low (< 60 mmHg), medium (60-74 mmHg), and high (75-89 mmHg). Pulse pressure (PP) was categorized as normal (< 60 mmHg) and high (≥ 60 mmHg). The outcome was defined as rapid decline of estimated glomerular filtration rate(eGFR, decline ≥ 4 ml/min/1.73 m2/year). BP combination was designed according to the category of SBP and PP. The association between BP components, types of BP combination, and the risk of rapid decline of eGFR was analyzed using multivariate logistic regression models, respectively. Age-stratified analyses were conducted. RESULTS: Of 4,534 participants included, 695(15.3%) individuals were recognized as having rapid decline of eGFR. High PP[odds ratio(OR) = 1.34, 95%confidence interval(CI) 1.02-1.75], low SBP (OR = 1.28, 95%CI 1.03-1.59), and high SBP (OR = 1.32, 95% CI 1.02-1.71) were significantly associated with the risk of eGFR decline. Low SBP were associated with 65% increment of the risk of eGFR decline among participants aged < 55 years. The combination of high SBP and high PP (OR = 1.79, 95% CI 1.27-2.54) and the combination of low SBP and high PP (OR = 3.07, 95% CI 1.24-7.58) were associated with the increased risk of eGFR decline among the middle and old aged general population. CONCLUSION: Single and combination of high PP and high SBP could be the risk indicators of eGFR decline among the middle and old aged general population.

The association between reduced kidney function and hearing loss: a cross-sectional study.

BACKGROUND: The relationship between kidney function and hearing loss has long been recognized, but evidence of this association mostly comes from small observational studies or other populations. The aim of this study is to explore the association between reduced kidney function and hearing loss in a large population-based study among the middle-aged and elderly Chinese. METHODS: Data collected from the Chinese Health and Retirement Longitudinal Study (CHARLS) in 2015 were used for analysis. A cross-sectional study was conducted among 12,508 participants aged 45 years and older. Hearing loss, the outcome of this study, was defined according to interviewees' responses to three survey questions related to hearing in the CHARLS. Estimated glomerular filtration rate (eGFR) was employed to assess kidney function, and participants were classified into three categories based on eGFR: ≥90, 60-89 and < 60 mL/min/1.73 m2. Multivariable logistic regression was employed to adjust for potential confounders, including demographics, health-related behaviors, and cardiovascular risk factors. RESULTS: The overall prevalence of self-reported hearing loss in the study population was 23.6%. Compared with participants with eGFR ≥90 mL/min/1.73 m2, participants with eGFR of 60-89 mL/min/1.73 m2 (odds ratio [OR]: 1.11, 95% confidence interval [CI]: 1.00-1.23) and eGFR < 60 mL/min/1.73 m2 (OR: 1.25, 95% CI: 1.04-1.49) showed increased risk of hearing loss after adjusting for potential confounders. CONCLUSIONS: Reduced kidney function is independently associated with hearing loss. Testing for hearing should be included in the integrated management of patients with chronic kidney disease.

Venous Blood-Based Biomarkers in the China Health and Retirement Longitudinal Study: Rationale, Design, and Results From the 2015 Wave.

Blood biomarkers provide critical information about the health of older populations, especially in large developing countries where self-reports of health are often inaccurate due to lack of access to health care. However, it is very difficult to collect blood samples in representative population surveys in such countries. The China Health and Retirement Longitudinal Study (CHARLS), a nationally representative study of middle-aged and older Chinese, represents one of the first efforts to include blood biomarkers in a nationally representative survey of China. In the 2015 wave of CHARLS, 13,013 respondents located in 150 counties around China donated whole blood, which was assayed on a range of indicators. Here we describe the process of the sample collection, transportation, storage, and analysis and present basic statistics.

Validation of neuropsychological tests for the China Health and Retirement Longitudinal Study Harmonized Cognitive Assessment Protocol.

OBJECTIVE: To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS. METHODS: We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents' functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents' cognitive status independently. RESULTS: The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status. CONCLUSION: A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.

Incidence of infertility and risk factors of impaired fecundity among newly married couples in a Chinese population.

The aims of this study were to obtain the incidence of infertility, to examine the causes of infertility and to explore risk factors for impaired fecundity in a rural region of northern China using a prospective follow-up design. A total of 2151 newly married couples planning to become pregnant within the next 12 months were enrolled between 2009 and 2012 from two counties of Shanxi Province in northern China. Couples were followed up for at least 1 year or until a clinical pregnancy occurred. Information about clinical pregnancy was obtained. The 12-month and 24-month infertility rates were 13.6% (95% CI 11.9 to 15.3) and 8.5% (95% CI 6.7 to 10.3), respectively. About 63% of women became pregnant within 6 months of follow up, and 86% did so within 12 months of follow up. The main causes of female infertility were ovulation disorders, fallopian tube problems and polycystic ovary syndrome. The primary cause of male infertility was sperm quality problems. Couples who used coal as cooking fuel, women with a higher body mass index, women with long-term health problems, and men who had married at later ages were more likely to have delayed pregnancies.

Dietary folate intake levels in rural women immediately before pregnancy in Northern China.

BACKGROUND: The study aims to assess dietary folate levels and food sources in women immediately before pregnancy in a rural area of northern China associated with a high prevalence of neural tube defects. METHODS: Information was collected by face-to-face interviews with women who sought premarital healthcare and planned to become pregnant within the next 12 months from November 2009 through December 2012. Information regarding food consumption was obtained by means of 24-hr dietary recall. Folate values were assigned to foods according to the China Food Composition 2004. Factors associated with dietary folate intake were analyzed by multiple linear regression. RESULTS: Mean (± standard deviation) and median (interquartile range) daily folate intake levels were 114.3 ± 59.7 and 102.8 (69.3-146.8) µg/day, respectively. Over 99% of the subjects had an intake level below 320 µg/day, the estimated average requirement for nonpregnant women. Only 1% and 7% of the women consumed 75% and 50%, respectively, of the recommended daily folate intake of 400 µg for nonpregnant women. Over 80% of total folate consumption came from cereals, vegetables, and tubers, whereas fruit consumption was severely lacking. Underweight women, farmers, women enrolled during the winter, and women with access to fewer food types or daily meals were more likely to exhibit low folate intake levels. CONCLUSION: Dietary folate intake among study participants was far below the recommended intake level. Folic acid fortification of cereals is advised to raise folate intake in rural Chinese women planning to become pregnant.

Plasma folate levels in early to mid pregnancy after a nation-wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in China.

BACKGROUND: Folic acid supplementation is recommended for all women of child-bearing age to prevent neural tube defects (NTDs). A nation-wide folic acid supplementation program was implemented in rural areas of China since 2009; however, changes in plasma folate levels in pregnant women were unknown. METHODS: A cross-sectional survey was conducted in 2011 to 2012, with 1736 pregnant women enrolled, and results were compared with a previous survey in 2002 to 2004. A microbiological method was used to determine plasma folate levels. Preprogram and postprogram median plasma folate concentrations were compared while stratified by prevalence of NTDs and residence. RESULTS: In the high NTD prevalence population, plasma folate concentration increased to 33.4 (18.7, 58.4) nmol/L in the postprogram sample, which is 2.9 times of the preprogram. In the low NTD prevalence population, plasma folate increased to 67.9 (44.5, 101.9) nmol/L, which is 1.9 times of the preprogram. Gaps remained in plasma folate levels with respect to prevalence of NTDs and residence. Folic acid supplementation has a strong impact on plasma folate concentrations. Earlier supplementation (before the last menstrual period), increased supplementation frequency and more total days of supplementation were associated with a higher plasma folate concentration as demonstrated in both the high- and low-prevalence populations. CONCLUSION: Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy.

Changes in folic acid supplementation behaviour among women of reproductive age after the implementation of a massive supplementation programme in China.

OBJECTIVE: To examine changes in periconceptional folic acid supplementation behaviour among Chinese women of reproductive age after the implementation of a folic acid supplementation programme. DESIGN: Two cross-sectional surveys were conducted. SETTING: One survey was before (2002-2004) and the other was after (2011-2012) implementation of the programme, both were conducted in two areas of China with different prevalence of neural tube defects. Information on supplementation behaviours was collected in face-to-face interviews with women early in their pregnancy. SUBJECTS: A total of 1257 and 1736 pregnant women participated before and after the programme, respectively. RESULTS: The rate of periconceptional folic acid supplementation increased from 15 % to 85 % in the high-prevalence population and from 66 % to 92 % in the low-prevalence population. However, more than half of the women began taking the supplement after learning they were pregnant. The proportion of women who began taking folic acid before their last menstrual period decreased after the programme in rural areas with both a high and low prevalence of neural tube defects. CONCLUSIONS: Although periconceptional folic acid supplementation among Chinese women increased substantially after the programme, supplementation was often initiated too late to be effective in preventing neural tube defects. Educational and promotional campaigns should focus on how to increase the rate of folic acid supplementation before pregnancy.

Reactive oxygen species-responsive supramolecular deucravacitinib self-assembly polymer micelles alleviate psoriatic skin inflammation by reducing mitochondrial oxidative stress.

Introduction: The new topical formula is urgent needed to meet clinical needs for majority mild patients with psoriasis. Deucravacitinib exerts outstanding anti-psoriatic capacity as an oral TYK2 inhibitor; however, single therapy is insufficient to target the complicated psoriatic skin, including excessive reactive oxygen species (ROS) and persistent inflammation. To address this need, engineered smart nano-therapeutics hold potential for the topical delivery of deucravacitinib. Methods: hydrophobic Deucravacitinib was loaded into polyethylene glycol block-polypropylene sulphide (PEG-b-PPS) for transdermal delivery in the treatment of psoriasis. The oxidative stress model of HaCaT psoriasis was established by TNF-α and IL-17A in vitro. JC-1 assay, DCFH-DA staining and mtDNA copy number were utilized to assess mitochondrial function. 0.75% Carbopol®934 was incorporated into SPMs to produce hydrogels and Rhb was labeled to monitor penetration by Immunofluorescence. In vivo, we established IMQ-induced psoriatic model to evaluate therapeutic effect of Car@Deu@PEPS. Results: Deu@PEPS exerted anti-psoriatic effects by restoring mitochondrial DNA copy number and mitochondrial membrane potential in HaCaT. In vivo, Car@Deu@PEPS supramolecular micelle hydrogels had longer retention time in the dermis in the IMQ-induced ROS microenvironment. Topical application of Car@Deu@PEPS significantly restored the normal epidermal architecture of psoriatic skin with abrogation of splenomegaly in the IMQ-induced psoriatic dermatitis model. Car@Deu@PEPS inhibited STAT3 signaling cascade with a corresponding decrease in the levels of the differentiation and proliferative markers Keratin 17 and Cyclin D1, respectively. Meanwhile, Car@Deu@PEPS alleviated IMQ-induced ROS generation and subsequent NLRP3 inflammasome-mediated pyroptosis. Conclusion: Deu@PEPS exerts prominent anti-inflammatory and anti-oxidative effects, which may offers a more patient-acceptable therapy with fewer adverse effects compared with oral deucravacitinib.

Identification of Chemokines-Related miRNAs as Potential Biomarkers in Psoriasis Based on Integrated Bioinformatics Analysis.

BACKGROUND: Psoriasis is an immune-mediated skin disorder caused by the proliferation of keratinocytes. Although psoriasis is generally diagnosed based on clinical manifestations, sensitive biomarkers are needed to help diagnose psoriasis early with atypical presentations. MicroRNAs play a functional role in the development of psoriasis, and they are stable and suitable as biomarkers in psoriasis. MATERIAL AND METHODS: The GSE50790 and GSE53552 datasets from the Gene Expression Omnibus (GEO) database were used to identify Differentially Expressed Genes (DEGs) between the control group and the lesional group. DEGs were processed for enrichment analysis to explore the functions, and a Protein-Protein Interaction (PPI) network was constructed to obtain gene clusters. The signalling pathway associated with gene cluster 1 was processed to further identify related genes. Hub genes were obtained through the intersection of cluster 1 and the related genes. Hub genes were used to predict the miRNAs through a gene-miRNA interaction network. The relative expression of miRNAs was measured by qRT-PCR to identify the suitability of miRNAs as biomarkers. RESULTS: Bioinformatics analysis revealed that the chemokine signalling pathway is involved in the development of psoriasis. Five related miRNAs were mined from the datasets, and qRT-PCR showed that hsa-miR-612 (p=0.0015), hsa-miR-3194-5p (p=0.0078) and hsa-miR-4316 (p<0.0001) may be potential biomarkers in psoriasis.

Inhibition of Serum- and Glucocorticoid-Regulated Protein Kinase-1 Aggravates Imiquimod-Induced Psoriatic Dermatitis and Enhances Proinflammatory Cytokine Expression through the NF-kB Pathway.

Although the anti-inflammatory effect of serum- and glucocorticoid-regulated protein kinase 1 (SGK1) has been established in other diseases, the possible regulatory role of SGK1 in psoriasis and the underlying molecular mechanisms remain largely unknown. In this study, we found that SGK1 expression was decreased in macrophages from patients with psoriasis. Moreover, a specific pharmacological SGK1 inhibitor, EMD638683, significantly enhanced imiquimod-mediated toll-like receptor 7/8 activity and proinflammatory cytokine production in RAW264.7 cells, and this result was confirmed by Sgk1 small interfering RNA. Further mechanistic data showed that SGK1 inhibition increased the phosphorylation of Bruton's agammaglobulinemia tyrosine kinase; moreover, Bruton's agammaglobulinemia tyrosine kinase inhibition abrogated the proinflammatory effects of the SGK1 inhibitor on toll-like receptor 7/8 activation, thereby validating that SGK1 inhibition enhances the toll-like receptor 7/8 pathway by increasing Bruton's agammaglobulinemia tyrosine kinase phosphorylation. In addition, our in vivo results showed that SGK1 inhibition significantly increased the secretion of proinflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and the infiltration of T helper 17 cells in an imiquimod-induced psoriasis mouse model. Altogether, these results show that SGK1 plays a critical role in the pathogenesis of psoriasis by modulating inflammatory responses in skin lesions, indicating that SGK1‒Bruton's agammaglobulinemia tyrosine kinase signaling could be a novel therapeutic target for the control of psoriasis.

SIRT3 alleviates imiquimod-induced psoriatic dermatitis through deacetylation of XBP1s and modulation of TLR7/8 inducing IL-23 production in macrophages.

Current evidence suggests that IL-23, IL-6, and TNF-α play pivotal roles in the pathogenesis of psoriasis. Although it has been established that Sirtuin 3 (SIRT3) mediates the inflammatory process, the underlying mechanisms remain largely unclear. Herein, we substantiated that the inhibition or deletion of SIRT3 increased the acetylation level of spliced form of X-box binding protein 1 (XPB1s), enhancing its transcriptional activity and IL-23a production. Pharmacologically inhibition of XBP1s with MKC8866 downregulated the expression of inflammatory cytokines in SIRT3-inhibited or Sirt3-KO BMDMs stimulated by IMQ. Inhibition or knockdown of SIRT3 could exacerbate psoriasis-like skin inflammation in an imiquimod-induced psoriasis-like mouse model. Besides, a decrease in SIRT3 expression was observed in the macrophages of psoriasis patients, which increased the expression and acetylation level of XBP1s. Overall, we provide compelling evidence of the crucial role of SIRT3 in the IL-23 axis in psoriatic inflammation and novel molecular insights into the anti-inflammatory effects of SIRT3.

Determinants of COVID-19 vaccination status and hesitancy among older adults in China.

Vaccination is the primary defense against severe acute respiratory syndrome coronavirus 2, especially among older adults and those with chronic conditions. Using a nationally representative sample of 12,900 participants from the fifth wave (2021-2022) of the China Health and Retirement Longitudinal Study (CHARLS), we examined the coronavirus disease 2019 (COVID-19) vaccination status and the determinants of vaccination hesitancy in Chinese adults aged 52 and older. By July/August 2022, 92.3% of the Chinese population aged 60 years and older had received at least one COVID-19 vaccination, 88.6% had completed the primary series and 72.4% had received a booster. Those aged 80 years and older had lower vaccination rates, with 71.9% and 46.7% completing the primary series and booster shots, respectively. These statistics represent the situation before China ended the Zero-COVID policy in November 2022 because vaccination stagnated between July/August and November 2022. Multivariate regression analysis revealed that belonging to the oldest age groups (individuals aged 70 years and older and especially those aged 80 years and older) as well as being female and unmarried, residing in urban areas, being functionally dependent and having chronic conditions meant that these individuals were less likely to receive COVID-19 vaccines. Our regression analysis results were corroborated by self-reported reasons for nonvaccination. Vaccination hesitancy probably contributed to excessive mortality among vulnerable populations after China ceased its Zero-COVID policy. Our study provides important lessons on how to balance containment efforts with vaccination and treatment measures, as well as highlighting the need to clarify the side effects and contraindications of vaccines early on.

Nowcasting and forecasting the care needs of the older population in China: analysis of data from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: An ageing population coupled with an increase in morbidity places a considerable burden on health and social care systems. The aim of our study was to estimate the trends in functional dependency and project future care needs for older people in China. METHODS: We analysed data from the China Health and Retirement Longitudinal Study, a nationally representative survey of a cohort of Chinese people (aged ≥45 years) from 150 counties or districts and 450 villages or urban communities across 28 provinces, who were selected by use of multistage stratified probability-proportionate-to-size sampling. The baseline survey was conducted in 2011 and follow-up surveys were conducted in 2013, 2015, 2018, and 2020. We excluded people younger than 60 years or people who had missing variables on dependency in the five follow-up interviews. Three dependency levels were determined on the basis of activities of daily living (ADLs) and instrumental activities of daily living (IADLs): any ADL items (level 1 dependency); any ADL items or difficulty cooking, shopping, or taking medications (level 2 dependency); and difficulty in any ADL or IADL items (level 3 dependency). The dependency rates were extrapolated to derive the number of people older than 60 years with dependency in China from 2011 to 2020. We used a regression model to project future changes and forecast the size of the older population with dependency between 2021 and 2030. FINDINGS: A total of 89 031 individuals across five waves completed the surveys, of whom 46 619 were eligible for inclusion. The prevalence of level 1 dependency among older Chinese adults declined from 11·7% (95% CI 10·6-12·8) in 2011 to 8·1% (7·5-8·7) in 2020. Level 2 and level 3 dependency also declined. The total number of older people requiring care in 2020 was 20·61 million (95% CI 19·01-22·20) with level 1 dependency, 36·33 million (34·27-38·40) with level 2 dependency, and 45·30 million (43·02-47·59) with level 3 dependency. Improved education, housing, and access to health care was associated with 41·84% of the decline in level 3 dependency prevalence between 2011 and 2020. By 2030, the projected dependency rates could decline to 8·04% for level 1 dependency, 13·28% for level 2 dependency, and 16·05% for level 3 dependency. Nonetheless, the cohort size will grow, resulting in more older Chinese people who need care (29·71 million [27·07-32·36] in level 1, 49·07 million [45·98-52·16] in level 2, and 59·32 million [55·94-62·70] in level 3) in 2030. By 2030, we estimate that 14·02 million more older Chinese people will need care than in 2020. INTERPRETATION: Rapid ageing of the population could offset the decline in dependency and result in a substantial increase in the population with complex care needs. Promoting healthy ageing and investing in an age-friendly environment are important in reducing care burdens in China. FUNDING: National Institute on Aging, Natural Science Foundation of China, China Medical Board. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

COVID-19 non-vaccination among older adults in China: a nationwide survey based on the China Health and Retirement Longitudinal Study (CHARLS).

China has a lower rate of vaccination among older adults and those who have chronic conditions and functional disabilities. As China has recently ended the zero-COVID policy, understanding the factors behind low vaccination rates among these vulnerable populations can inform immediate policy priorities to save lives for China and offer lessons for the world at large. We used the fifth wave (2021-22) of the China Health and Retirement Longitudinal Study (CHARLS), which represented mainland Chinese 45 and older. Vaccination status was updated in the summer of 2022, reflecting the current situation because very few additional vaccinations were administered afterward. For those who were unvaccinated, self-reported reasons were recorded. Using regression analysis, we investigated the determinants of non-vaccination, including demographics, functional status, and chronic conditions. In addition, two-thirds of the respondents had their vaccination status recorded twice in 2021 and 2022, allowing us to examine changes in vaccination rates in the recent year, zeroing in on the effects of the government's most recent vaccination campaign. Finally, we corroborated the regression results using self-reported reasons for non-vaccination in both years. A total of 12900 participants were included in the analysis. By the summer of 2022, the weighted COVID-19 vaccination rate among older Chinese people (≥60 years old) was 92.3%, with 88.8% having completed the primary series and 72.7% having received boosters. Only 72.0% of the oldest-old (≥80 years old) had completed the primary series, and 47.1% had had boosters. Regression analysis showed that participants who were older, female, unmarried, registered with urban Hukou residence, functionally dependent, and comorbid with chronic conditions were less likely to receive COVID-19 vaccines. A significant increase in vaccination rates among ethnic minorities, older adults, rural residents, and those with chronic conditions and functional dependency was observed in the year after the winter of 2021 when the government started to push for universal vaccination. The self-reported reasons for non-vaccination in 2022 were contraindications (48%), advanced ages/frailty/health conditions (21%), problems in accessing vaccines (18%), concerns about side effects or efficacy (9%), and having never heard of COVID-19 vaccine (6%). Nevertheless, as China has ended the zero-COVID policy, many older people, especially the oldest and those with chronic conditions and disabilities, have not yet been fully vaccinated with the primary series or booster doses, exposing them to the danger of infection. Therefore, health authorities should immediately abandon the previous practice of refusing to vaccinate those with chronic conditions, change people's mistaken perceptions of contraindications and side effects, and improve access to vaccines. Most importantly, China should strengthen public trust in vaccines by making information transparent regarding the vaccine's protection rates and side effects.