Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity.

Innate immunity serves as the primary defense against viral and microbial infections in humans. The precise influence of cellular metabolites, especially fatty acids, on antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a key modulator of antiviral infections in human cells. Mechanistically, PA induces mitochondrial antiviral signaling protein (MAVS) palmitoylation, aggregation, and subsequent activation, thereby enhancing the innate immune response. The palmitoyl-transferase ZDHHC24 catalyzes MAVS palmitoylation, thereby boosting the TBK1-IRF3-interferon (IFN) pathway, particularly under conditions of PA stimulation or high-fat-diet-fed mouse models, leading to antiviral immune responses. Additionally, APT2 de-palmitoylates MAVS, thus inhibiting antiviral signaling, suggesting that its inhibitors, such as ML349, effectively reverse MAVS activation in response to antiviral infections. These findings underscore the critical role of PA in regulating antiviral innate immunity through MAVS palmitoylation and provide strategies for enhancing PA intake or targeting APT2 for combating viral infections.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-ß1 (TGF-ß1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.

Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.

Physiologically, FoxA1 plays a key role in liver differentiation and development, and pathologically exhibits an oncogenic role in prostate and breast cancers. However, its role and upstream regulation in liver tumorigenesis remain unclear. Here, we demonstrate that FoxA1 acts as a tumor suppressor in liver cancer. Using a CRISPR-based kinome screening approach, noncanonical inflammatory kinase IKBKE has been identified to inhibit FoxA1 transcriptional activity. Notably, IKBKE directly binds to and phosphorylates FoxA1 to reduce its complex formation and DNA interaction, leading to elevated hepatocellular malignancies. Nonphosphorylated mimic Foxa1 knock-in mice markedly delay liver tumorigenesis in hydrodynamic transfection murine models, while phospho-mimic Foxa1 knock-in phenocopy Foxa1 knockout mice to exhibit developmental defects and liver inflammation. Notably, Ikbke knockout delays diethylnitrosamine (DEN)-induced mouse liver tumor development. Together, our findings not only reveal FoxA1 as a bona fide substrate and negative nuclear effector of IKBKE in hepatocellular carcinioma (HCC) but also provide a promising strategy to target IKBEK for HCC therapy.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 knockout mice and Akt1C224S knock-in mice were employed. Human liver tissues from patients with NASH and HCC, hydrodynamic transfection mouse model, high-fat/high-cholesterol diet (HFHCD)-induced NASH/HCC mouse model and high-fat and methionine/choline-deficient diet (HFMCD)-induced NASH mouse model were also further explored for our mechanism studies. RESULTS: By screening a metabolite library, PA has been defined to activate AKT by promoting its palmitoyl modification, an essential step for growth factor-induced AKT activation. Biologically, a high-fat diet could promote AKT kinase activity, thereby promoting NASH and liver cancer. Mechanistically, palmitoyl binding anchors AKT to the cell membrane in a PIP3-independent manner, in part by preventing AKT from assembling into an inactive polymer. The palmitoyltransferases ZDHHC17/24 were characterised to palmitoylate AKT to exert oncogenic effects. Interestingly, the anti-obesity drug orlistat or specific penetrating peptides can effectively attenuate AKT palmitoylation and activation by restricting PA synthesis or repressing AKT modification, respectively, thereby antagonising liver tumorigenesis. CONCLUSIONS: Our findings elucidate a novel fine-tuned regulation of AKT by PA-ZDHHC17/24-mediated palmitoylation, and highlight tumour therapeutic strategies by taking PA-restricted diets, limiting PA synthesis, or directly targeting AKT palmitoylation.

AMPK phosphorylates and stabilises copper transporter 1 to synergise metformin and copper chelator for breast cancer therapy.

BACKGROUND: Predominant roles of copper and its transporter, copper transporter 1 (CTR1), in tumorigenesis have been explored recently; however, the upstream regulation of CTR1 and combinational intervention of copper chelators in malignancies remain largely unclear. METHODS: CRISPR/Cas9-based kinome screening was used to identify the CTR1 upstream kinases. Immunofluorescence assays were utilised to detect CTR1 localisation. In vitro kinase assays and mass spectrometry were performed to detect CTR1 phosphorylation. Ubiquitination assays were performed to validate CTR1 stability. Colony formation, EdU labelling, Annexin V-FITC/PI-based apoptosis assays were carried out to detect the drug effect on cell growth and apoptosis. Xenografted mouse models were employed to investigate drug effects in vivo. RESULTS: We identify that CTR1 undergoes AMPK-mediated phosphorylation, which enhances CTR1 stabilisation and membrane translocation by affecting Nedd4l interaction, resulting in increased oncogenic roles in breast cancer. Importantly, activation of AMPK with its agonist metformin markedly enhances CTR1 levels, and leads to the combinational usage of AMPK agonists and copper chelators for breast cancer treatment. CONCLUSIONS: Our findings not only reveal the crosstalk between energy response and copper uptake via AMPK-mediated CTR1 phosphorylation and stability but also highlight the strategy to combat breast cancer by a combination of AMPK agonists and copper chelators. SIGNIFICANCE: The connection between energy response and copper homoeostasis is linked by AMPK phosphorylating and stabilising CTR1, which provides a promising strategy to combat breast cancer by combining AMPK agonists and copper chelators.

Gender-Specific Effect of Couple-Based Intervention on Behavioral and Psychological Outcomes of Older Adults with Type 2 Diabetes during the COVID-19 Partial Lockdown in Guangzhou, China.

This study aimed to evaluate the gender-specific effect of a couple-based intervention on the management behaviors and mental well-being of community-dwelling older adults with type 2 diabetes mellitus during the COVID-19 partial lockdown in Guangzhou. Out of 207 participants involved in a prior randomized controlled trial (Trial no. ChiCTR1900027137), 156 (75%) completed the COVID-19 survey. Gendered differences in management behaviors and depressive symptoms between the couple-based intervention group and the patient-only control group were compared by distance to the high-risk areas cross-sectionally and longitudinally using random intercept models. Cross-sectionally, female patients of the intervention group had more positive behavior change scores (ß = 1.53, p = 0.002) and fewer depressive symptoms (ß = −1.34, p = 0.02) than the control group. Over time, female patients lived closer to the high-risk areas (<5 km) and showed decreasing depressive symptoms (ß = −4.48, p = 0.008) in the intervention group vs. the control group. No statistically significant between-group difference was found for males. Females tended to benefit more from the coupled-based intervention than males did, particularly among these closer to the high-risk areas. Chronic disease management can be better sustained with active spousal engagement.

Expression of osteopontin and integrin αvß 3 receptor in retina of diabetic guinea pigs with high myopia.

INTRODUCTION: To investigate the effect of high myopia on the expression of retinal osteopontin (OPN) and integrin αVß 3 receptor in guinea pigs and determined the relationship between high myopia and diabetic retinopathy. METHODS: Ninety 3-week-old male guinea pigs were randomly divided into four groups that included normal control group (NOR，n=18), high myopia group (HM，n=24), diabetes group (DR，n=24), and diabetes with high myopia group (DR+HM，n=24). HM was induced by form deprivation (FDHM) in the right eye. The DR group was injected with 5% streptozotocin(STZ) 280 mg/kg intraperitoneally in the lower left abdomen of guinea pigs. The DRHM group was subjected to the same treatment as the HM and DR groups. Eighteen guinea pigs in each group were randomly selected to complete the experimental measurement. After enucleation of eyeballs, HE and immunohistochemical staining were performed to observe the retina morphology and count the positive rate of OPN and integrin αvß 3 receptor. RESULTS: Diabetic retinal changes were found in group DR and HM+DR. The degree of retinal change in group HM+DR was less than that in group DR. In the DR group, the morphology of retinal tissue was loose, the number of cells decreased, increased retinal microaneurysms, and a small amount of small artery embolism and venous thrombosis were observed. Although the retinal structure in the HM+DR group also became thinner, looser, and disordered, only a small number of microaneurysms were observed compared with the diabetic group. Immunohistochemical staining showed that the expression of OPN and integrin αvß 3 receptors in the diabetic groups (DR, HM+DR) was significantly higher than in the HM and NOR groups. The positive expression rates of OPN and integrin αvß 3 receptors in group HM+DR were significantly lower than those in group DR (P < 0.05). CONCLUSION: The expression of OPN and integrin αvß 3 receptor in the retina of diabetic guinea pigs with high myopia was lower than that of diabetic models, which may be due to the influence of high myopia on neovascularization in DR.

Beyond controlling cell size: functional analyses of S6K in tumorigenesis.

As a substrate and major effector of the mammalian target of rapamycin complex 1 (mTORC1), the biological functions of ribosomal protein S6 kinase (S6K) have been canonically assigned for cell size control by facilitating mRNA transcription, splicing, and protein synthesis. However, accumulating evidence implies that diverse stimuli and upstream regulators modulate S6K kinase activity, leading to the activation of a plethora of downstream substrates for distinct pathobiological functions. Beyond controlling cell size, S6K simultaneously plays crucial roles in directing cell apoptosis, metabolism, and feedback regulation of its upstream signals. Thus, we comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for S6K and shed light on S6K as a potential therapeutic target for cancers.

S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions.

Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Mechanistically, S6K1-mediated phosphorylation of PDK1 augments its interaction with 14-3-3 adaptor protein and homo-dimerization, subsequently dissociating PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP3) and retarding its interaction with AKT. Pathologically, tumor patient-associated PDK1 mutations, either attenuating S6K1-mediated PDK1 phosphorylation or impairing PDK1 interaction with 14-3-3, result in elevated AKT kinase activity and oncogenic functions. Taken together, our findings not only unravel a delicate feedback regulation of AKT signaling via S6K1-mediated PDK1 phosphorylation, but also highlight the potential strategy to combat mutant PDK1-driven cancers.

IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis.

IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis. Biologically, ectopic expression of IKBKE accelerates, whereas depletion of IKBKE attenuates breast cancer invasiveness and migration in vitro and tumor metastasis in vivo. Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase ß-TRCP1-mediated Snail degradation, resulting in breast cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast cancer therapies.

Copper Promotes Tumorigenesis by Activating the PDK1-AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner.

Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3-phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis. Blocking the copper transporter 1 (CTR1)-copper axis by either depleting CTR1 or through the use of copper chelators diminishes the AKT signaling and reduces tumorigenesis. In support of an oncogenic role for CTR1, the authors find that CTR1 is abnormally elevated in breast cancer, and is subjected by NEDD4 like E3 ubiquitin protein ligase (Nedd4l)-mediated negative regulation through ubiquitination and subsequent degradation. Accordingly, Nedd4l displays a tumor suppressive function by suppressing the CTR1-AKT signaling. Thus, the findings identify a novel regulatory crosstalk between the Nedd4l-CTR1-copper axis and the PDK1-AKT oncogenic signaling, and highlight the therapeutic relevance of targeting the CTR1-copper node for the treatment of hyperactive AKT-driven cancers.

Development and Implementation of Couple-Based Collaborative Management Model of Type 2 Diabetes Mellitus for Community-Dwelling Chinese Older Adults: A Pilot Randomized Trial.

Background: To mobilize family's positive involvement in improving and sustaining self-management activities of older adults with diabetes, we developed a couple-based collaborative management model (CCMM) for community-dwelling older Chinese. Methods: The model was developed stepwise through applying theoretical models, interviewing older couples and community healthcare workers, as well as incorporating expert reviews. A 3-month pilot study was conducted to test the model's feasibility and its treatment effects by linear regression on 18 pairs of older couples aged 60 years+, who were equally divided into a couple-based intervention arm and a patient-only control arm. Results: The developed CCMM covered four theory-driven intervention modules: dyadic assessment, dyadic education, dyadic behavior-change training, and dyadic monitoring. Each module was delivered by community healthcare workers and targeted at older couples as the management units. Based on interviews with older couples and healthcare workers, 4 weekly education and training group sessions and 2-month weekly behavior change booster calls were designed to address older adults' main management barriers. These modules and session contents were evaluated as essential and relevant by the expert panel. Furthermore, the CCMM showed good feasibility and acceptability in the pilot, with non-significant yet more positive changes in physiological outcomes of diabetic participants and couples' well-being and exercise levels of these in the intervention arm than their controlled counterparts. Conclusion: We systematically developed a couple-based collaborative management model of diabetes, which was well-received by healthcare practitioners and highly feasible among older Chinese couples living in the community. The model's treatment effects need to be verified in fully powered randomized controlled trials. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=42964, identifier: ChiCTR1900027137.

Dyadic appraisal and coping with illness among older Chinese adults with type 2 diabetes mellitus: a qualitative study.

INTRODUCTION: Diabetes management permeates patients' daily routines and interacts with their living context. Less is known about how older Chinese couples view their supportive roles and the allocation of the management responsibility between them. OBJECTIVES: To explore dyadic appraisal, coping and the barriers to diabetes management shared by older Chinese couples. METHODS: A qualitative study of older couples where at least one partner had type 2 diabetes mellitus was implemented in four communities of Guangzhou, China. Four focus groups containing 11 couples, and ten in-depth interviews with individual couples were conducted sequentially. All of the data were coded with Nvivo 11 using thematic analysis. RESULTS: The majority of the older couples interviewed appraised diabetes as a shared problem, taking part in monitoring and altering each other's health status and behaviour. Limited knowledge and a lack of accurate information about diabetes negatively impacted the patients' self-management and their spouse's ability to support them. A female dominated-care pattern was evident that female spouses, regardless of their health status, were actively involved in or fully responsible for managing their husband's health. Older couples' management practices were also shaped by family responsibilities and their living environment. CONCLUSIONS: Our study provides first-hand evidence of older Chinese couples' daily interactions and the main barriers to diabetes management. It is vital to provide health education directly to older couples to empower them to access adequate mutual support when managing chronic diseases.

Couple-based collaborative management model of type 2 diabetes mellitus for community-dwelling older adults in China: protocol for a hybrid type 1 randomized controlled trial.

BACKGROUND: China's limited health care resources cannot meet the needs of chronic disease treatment and management of its rapid growing ageing population. The improvement and maintenance of patient's self-management is essential to disease management. Given disease management mainly occurs in the context of family, this study proposes to validate a Couple-based Collaborative Management Model of chronic diseases that integrates health professionals and family supporters; such as to empower the couples with disease management knowledge and skills, and to improve the couples' health and quality of life. METHODS: The proposed study will validate a couple-based collaborative management model of Type 2 Diabetes Mellitus (T2DM) in a community-based multicenter, two-arm, randomized controlled trial of block design in Guangzhou, China. Specifically, 194 T2DM patients aged ≥55 and their partners recruited from community health care centers will be randomized at the patient level for each center at a 1:1 ratio into the couple-based intervention arm and the individual-based control arm. For the intervention arm, both the patients and their spouses will receive four-weekly structured group education & training sessions and 2 months of weekly tailored behavior change boosters; while these interventions will be only provided to the patients in the control group. Behavior change incentives will be targeted at the couples or only at the patient respectively. Treatment effects on patients' hemoglobin, spouses' quality of life, alongside couples' behavior outcomes will be compared between arms. Study implementation will be evaluated considering its Reach, Effectiveness, Adoption, Implementation and Maintenance following the RE-AIM framework. DISCUSSION: This study will generate a model of effective collaboration between community health professionals and patients' family, which will shield light on chronic disease management strategy for the increasing ageing population. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027137, Registered 1st Nov. 2019.

Functionally analyzing the important roles of hepatocyte nuclear factor 3 (FoxA) in tumorigenesis.

Transcriptional factors (TFs) play a central role in governing gene expression under physiological conditions including the processes of embryonic development, metabolic homeostasis and response to extracellular stimuli. Conceivably, the aberrant dysregulations of TFs would dominantly result in various human disorders including tumorigenesis, diabetes and neurodegenerative diseases. Serving as the most evolutionarily reserved TFs, Fox family TFs have been explored to exert distinct biological functions in neoplastic development, by manipulating diverse gene expression. Recently, among the Fox family members, the pilot roles of FoxAs attract more attention due to their functions as both pioneer factor and transcriptional factor in human tumorigenesis, particularly in the sex-dimorphism tumors. Therefore, the pathological roles of FoxAs in tumorigenesis have been well-explored in modulating inflammation, immune response and metabolic homeostasis. In this review, we comprehensively summarize the impressive progression of FoxA functional annotation, clinical relevance, upstream regulators and downstream effectors, as well as valuable animal models, and highlight the potential strategies to target FoxAs for cancer therapies.

Laxative Effects of Yangyin Tongmi Capsule on a Model of Diphenoxylate-Induced Constipation in Mice.

Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is used in the treatment of constipation, while the underlying mechanisms remain unknown. Herein, this work attempted to prove the effects of YTC on constipation treatment and its possible mechanisms. KM mice were randomly divided into four groups (n = 10/group) and treated with double distilled water (Control), diphenoxylate (Model: 10 mg/kg), or diphenoxylate plus low-dose YTC (L-YTC: 0.6 g/kg) or high-dose YTC (H-YTC: 1.2 g/kg). The data indicated that YTC can significantly shorten the discharge time of the first black stool, improve intestinal propulsion rate, and increase the water content and quantity of feces in mice. ELISA suggested that YTC regulate the content of intestinal hormones and neurotransmitters, such as motilin (MTL), gastrin (GT), somatostatin (SST), substance P (SP), acetylcholine (Ach), and nitric oxide (NO). The expression levels of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) in the colon were examined by immunohistochemistry. In the meantime, the expression levels of P2X2, C-kit, and stem cell factor (SCF) in the colon were examined by western blot analysis. The results of this study suggest that YTC has mitigative effects on diphenoxylate-induced constipation by regulating the content of intestinal hormones and neurotransmitters and regulating the expression of related proteins in the colon.

20(S)-Protopanaxadiol Inhibits Angiotensin II-Induced Epithelial- Mesenchymal Transition by Downregulating SIRT1.

20(S)-Protopanaxadiol (PPD) is one of the major active metabolites in ginseng saponin. Our previous studies revealed a broad spectrum of antitumor effects of PPD. Angiotensin II (Ang II), the biologically active peptide of the renin-angiotensin system (RAS), plays a critical role in the metastasis of various cancers. However, its role in the anti-metastatic effects of PPD is not clearly understood. In this study, we investigated the inhibitory effect of PPD on Ang II-induced epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells, and the potential molecular mechanisms of suppression of NSCLC migration and metastasis by PPD. Treatment of A549 cells with Ang II increased metastases in an experimental model of cancer metastasis in vivo. PPD effectively prevented Ang II-induced EMT, as indicated by upregulation of E-cadherin and downregulation of vimentin. Additionally, Ang II upregulated the class III deacetylase sirtuin 1 (SIRT1) expression in EMT progression, while downregulation of SIRT1 was involved in suppression of Ang II-induced EMT by PPD. Moreover, the inhibitory effect of PPD was reversed by SIRT1 upregulation, and PPD demonstrated synergy with an SIRT1 inhibitor on Ang II-induced EMT. Taken together, our data reveal the mechanism of the anti-metastatic effects of PPD on Ang II-induced EMT and indicate that PPD can be used as an effective anti-tumor treatment.

Examining income-related inequality in health literacy and health-information seeking among urban population in China.

BACKGROUND: Health literacy and health-information seeking behaviour (HISB) play vital roles in health outcome improvements. This study examines the extent of income-related inequality in health literacy and health-information seeking as well as the contributions of the main socioeconomic determinants in China. METHODS: We analysed representative data of participants aged over 18 years as well as older adults from the Guangzhou Community Health Survey. A concentration index (CI) was used to quantify the degree of income-related inequity in health literacy and health-information seeking. Probit regression models were employed to decompose the CI into the contributions to each factor. RESULTS: Results showed a significant pro-rich distribution of adequate health literacy (CI: 0.0602, P < 0.001; horizontal index [HI]: 0.0562, P < 0.001) and HISB from healthcare professionals (CI: 0.105, P < 0.001; HI: 0.0965, P < 0.001). The pro-rich distribution of health literacy was mainly attributable to education background (contribution: 54.76%), whereas income inequalities contributed most to the pro-rich distribution of health-information seeking among an urban population (contribution: 62.53%). CONCLUSION: Public interventions in China to reduce inequality in health literacy and HISBs among the urban population, coupled with easily accessible information sources on health, warrant further attention from policymakers.

The Risk of Hypertension Doubles Every 10 Years in China: Age, Period, and Birth Cohort Effects on the Prevalence of Hypertension From 2004 to 2013.

BACKGROUND: Hypertension is a growing problem worldwide and can often result in a variety of negative health outcomes. The aim of this study was to assess the effects of age at diagnosis, calendar period, and birth cohort on the change in the prevalence rate of hypertension in Guangzhou from 2004 to 2013. METHODS: We used data from the Guangzhou Community Health Survey, a population-based study designed by the National Health and Family Planning Commission of the PRC every 5 years. A total of 27,299, 23,467, and 18,362 participants aged 15-79 years completed the survey in 2004, 2009, and 2013, respectively. RESULTS: Age effects increased slowly before the age of 42 years but increased rapidly after the age of 42 years, peaking at 79 years. Cohort effects grew slowly before the end of the 1960s but grew quickly after the end of the 1960s. The risk of suffering from hypertension among people born in 1962, 1972, 1982, and 1992 was 1.39, 2.68, 5.55, and 11.53 times, respectively, than that of people born in 1952. The period effects increased 25% from 2004 to 2009 and later declined 27% from 2009 to 2013 in the entire population. There was no gender difference in age effects and period effects, but strong cohort effects on hypertension were observed among males compared with females. CONCLUSIONS: For Chinese individuals, the later one is born, the higher the risk is of suffering from hypertension. Strong cohort effects for hypertension were observed among males compared with females, indicating that males are more easily affected by hypertension based on the change in birth cohort.

Trends and Associated Factors of Hypertension among Residents Aged ≥15 Years in Guangzhou, China, 2004-2013.

BACKGROUND: We aimed to describe the trends and associated factors of hypertension among residents aged ≥15 yr in Guangzhou, China. METHODS: Three standardized cross-sectional health surveys were conducted in 2004, 2009 and 2013 using a multi-stage cluster sampling method, and a total of 69128 qualified participants were included in the study. The data were obtained through physical health examination and questionnaire survey. RESULTS: The age-standardised prevalence of hypertension increased from 12.5% to 16.0% between 2004 and 2009 and declined from 16.0% to 14.0% between 2009 and 2013, and crude prevalence respectively was 14.6%, 19.1% and 18.8% in 2004, 2009 and 2013. The proportion of optimal blood pressure dropped from 51.1% to 33.2%, high-normal blood pressure increased from 20.1% to 28.9%, grade 1 hypertension and grade 2 or 3 hypertension increased from 11.5% to 13.6% and 3.9% to 5.8% between 2004 and 2013. The average age was significantly increased (P<0.001) from 42.8 to 47.5 yr, and the average body mass index slightly increased (P<0.001) from 22.4 to 23.0. Logistic regression analysis shows that higher age, male, higher body mass index, smoking and drinking alcohol were potential risk factors for hypertension. CONCLUSION: Both crude and age-standardized prevalence of hypertension were initially increased, but subsequently decreased in Guangzhou during 2004-2013. The optimal blood pressure population decreased significantly while the high-normal blood pressure population increased substantially during the survey period.