Compact In Situ Electrochemical NMR with Wireless and Anti-interference Strategy in Multiscenario Applications.

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

Diagnostic accuracy of eHealth literacy measurement tools in older adults: a systematic review.

BACKGROUND: In Canada, virtual health care rapidly expanded during the COVID-19 pandemic. There is substantial variability between older adults in terms of digital literacy skills, which precludes equitable participation of some older adults in virtual care. Little is known about how to measure older adults' electronic health (eHealth) literacy, which could help healthcare providers to support older adults in accessing virtual care. Our study objective was to examine the diagnostic accuracy of eHealth literacy tools in older adults. METHODS: We completed a systematic review examining the validity of eHealth literacy tools compared to a reference standard or another tool. We searched MEDLINE, EMBASE, CENTRAL/CDSR, PsycINFO and grey literature for articles published from inception until January 13, 2021. We included studies where the mean population age was at least 60 years old. Two reviewers independently completed article screening, data abstraction, and risk of bias assessment using the Quality Assessment for Diagnostic Accuracy Studies-2 tool. We implemented the PROGRESS-Plus framework to describe the reporting of social determinants of health. RESULTS: We identified 14,940 citations and included two studies. Included studies described three methods for assessing eHealth literacy: computer simulation, eHealth Literacy Scale (eHEALS), and Transactional Model of eHealth Literacy (TMeHL). eHEALS correlated moderately with participants' computer simulation performance (r = 0.34) and TMeHL correlated moderately to highly with eHEALS (r = 0.47-0.66). Using the PROGRESS-Plus framework, we identified shortcomings in the reporting of study participants' social determinants of health, including social capital and time-dependent relationships. CONCLUSIONS: We found two tools to support clinicians in identifying older adults' eHealth literacy. However, given the shortcomings highlighted in the validation of eHealth literacy tools in older adults, future primary research describing the diagnostic accuracy of tools for measuring eHealth literacy in this population and how social determinants of health impact the assessment of eHealth literacy is needed to strengthen tool implementation in clinical practice. PROTOCOL REGISTRATION: We registered our systematic review of the literature a priori with PROSPERO (CRD42021238365).

[Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress].

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1ß, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

The relationship between famine exposure during early life and ascending aorta dilatation in adults.

The relationship between exposure to famine in early life and the risk of ascending aorta dilatation (AAD) in adulthood is still unclear; therefore, we aimed to examine the association in the Chinese population. We investigated the data of 2598 adults who were born between 1952 and 1964 in Guangdong, China. All enrolled subjects were categorised into five groups: not exposed to famine, exposed during fetal period, and exposed during early, mid or late childhood. AAD was assessed by cardiac ultrasound. Multivariate logistic regression and interaction tests were performed to estimate the OR and CI on the association between famine exposure and AAD. There were 2598 (943 male, mean age 58·3 ± 3·68 years) participants were enrolled, and 270 (10·4 %) subjects with AAD. We found that famine exposure (OR = 2·266, 95 % CI 1·477, 3·477, P = 0·013) was associated with elevated AAD after adjusting for multiple confounders. In addition, compared with the non-exposed group, the adjusted OR for famine exposure during fetal period, early, mid or late childhood were 1·374 (95 % CI 0·794, 2·364, P = 0·251), 1·976 (95 % CI 1·243, 3·181, P = 0·004), 1·929 (95 % CI 1·237, 3·058, P = 0·004) and 2·227 (95 % CI 1·433, 3·524, P < 0·001), respectively. Subgroup analysis showed that the effect of famine exposure on the association with AAD was more pronounced in female, current smokers, people with BMI ≥ 24 kg/m2 and hypertensive patients. We observed that exposure to famine during early life was linked to AAD in adulthood.

Zonisamide alleviates cardiac hypertrophy in rats by increasing Hrd1 expression and inhibiting endoplasmic reticulum stress.

Antiepileptic drug zonisamide has been shown to be curative for Parkinson's disease (PD) through increasing HMG-CoA reductase degradation protein 1 (Hrd1) level and mitigating endoplasmic reticulum (ER) stress. Hrd1 is an ER-transmembrane E3 ubiquitin ligase, which is involved in cardiac dysfunction and cardiac hypertrophy in a mouse model of pressure overload. In this study, we investigated whether zonisamide alleviated cardiac hypertrophy in rats by increasing Hrd1 expression and inhibiting ER stress. The beneficial effects of zonisamide were assessed in two experimental models of cardiac hypertrophy: in rats subjected to abdominal aorta constriction (AAC) and treated with zonisamide (14, 28, 56 mg · kg-1 · d-1, i.g.) for 6 weeks as well as in neonatal rat cardiomyocytes (NRCMs) co-treated with Ang II (10 µM) and zonisamide (0.3 µM). Echocardiography analysis revealed that zonsiamide treatment significantly improved cardiac function in AAC rats. We found that zonsiamide treatment significantly attenuated cardiac hypertrophy and fibrosis, and suppressed apoptosis and ER stress in the hearts of AAC rats and in Ang II-treated NRCMs. Importantly, zonisamide markedly increased the expression of Hrd1 in the hearts of AAC rats and in Ang II-treated NRCMs. Furthermore, we demonstrated that zonisamide accelerated ER-associated protein degradation (ERAD) in Ang II-treated NRCMs; knockdown of Hrd1 abrogated the inhibitory effects of zonisamide on ER stress and cardiac hypertrophy. Taken together, our results demonstrate that zonisamide is effective in preserving heart structure and function in the experimental models of pathological cardiac hypertrophy. Zonisamide increases Hrd1 expression, thus preventing cardiac hypertrophy and improving the cardiac function of AAC rats.

Early-life exposure to the Chinese famine and risk of carotid intima-media thickness increased in adulthood.

BACKGROUND AND AIMS: Little was known about the effect of famine exposure on carotid intima-media thickness (cIMT). The present study aimed to explore the relationship in a Chinese population. METHODS AND RESULTS: Participants were divided into five groups: not exposed to famine, exposed to famine in fetal, early, mid or late childhood. Elevated cIMT was defined as a thickness of >0.9 mm measured by carotid ultrasound. Multivariate logistic regression was performed to calculate odds ratio (OR) and confidence interval (CI) between famine exposure and cIMT. A total of 2637 (970 male, mean age 59.1 ± 3.65 years) participants were recruited, and 491 (18.62%) of them had elevated cIMT. When compared with the non-exposure group, the fully adjusted ORs for increased cIMT for exposure in fetal, early, mid to late childhood were 1.321 (95%CI: 0.872, 1.994, P = 0.186), 1.713 (95% CI: 1.188, 2.483, P = 0.004), 2.359 (95% CI: 1.674, 3.357, P < 0.001) and 2.485 (95% CI: 1.773, 3.518, P < 0.001), respectively. Subgroup analyses showed that the exposure to famine did not interact with body mass index, gender, smoking status, hypertension and diabetes history on its effect on cIMT. CONCLUSION: Our findings indicated that early-life exposure to the Chinese famine might be associated with an increased risk of increased cIMT in adulthood.

The association of blood lipid parameters variability with ischemic stroke in hypertensive patients.

BACKGROUND AND AIMS: The relationship between lipid variability and stroke among patients with hypertension were inconclusive. We aimed to investigate the association of lipid variability with ischemic stroke in hypertensive patients. METHODS AND RESULTS: This retrospective cohort study included 4995 individuals with hypertension between 2013 and 2015, and recorded their status of ischemic stroke until the end of 2018. The variability in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using the standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM) and average absolute difference between successive values (ASV). Multivariate Cox proportional hazards models with hazard ratios (HRs) and 95% confidence interval (CI) were performed. There were 110 cases of ischemic stroke during a median follow up of 4.2 years. The multivariable adjusted HRs and 95% CIs comparing the highest versus the lowest quartiles of SD of TC, LDL-C, HDL-C and TG were 4.429 (95% CI: 2.292, 8.560), 2.140 (95% CI: 1.264, 3.621), 1.368 (95% CI: 0.793, 2.359) and 1.421 (95% CI: 0.800, 2.525), respectively. High variability in TC and LDL-C were associated with a higher risk for ischemic stroke. Similarly, the results were consistent when calculating variability of TC and LDL-C using CV, ASV and VIM, and in various subgroup analyses. CONCLUSION: Higher variability of TC and LDL-C associated with the risk of ischemic stroke among hypertensive patients. These findings suggest reducing variability of lipid parameters may decrease adverse outcomes.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality.

BACKGROUND: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR). OBJECTIVE: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults. METHODS: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality. RESULTS: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79). CONCLUSIONS: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.

Relationship between body mass index and ischaemic stroke in Chinese elderly hypertensive patients.

BACKGROUND: Despite obesity being a major risk factor for ischaemic stroke (IS), the association between body mass index (BMI) and IS in patients with hypertension remains uncertain. OBJECTIVE: To assess the association between BMI and IS among elderly hypertensive patients in China. METHODS AND RESULTS: We recruited 3500 hypertensive patients aged ≥60 between 1 January 2010 and 31 December 2011 in China and ascertained their stroke status until December 2016. Multivariate Cox regression was used to evaluate the association between BMI and IS with interaction tests for exposure and covariates. A total of 3315 subjects (mean age 71.41±7.20 years, 44.5% were men) were included for data analysis. During an average follow-up period of 5.5 years, there were 206 onset cases (6.21%) of IS. When BMI was treated as a continuous variable, it was positively associated with the incidence of new onset IS (HR=1.14; 95% CI: 1.05 to 1.34; p=0.005) after adjusting for potential confounders. Meanwhile, when BMI was treated as a categorical variable, the highest category (≥28 kg/m2) was strongly associated with an increased risk for IS compared with normal BMI category (18.5 to 24 kg/m2) (HR=1.36, 95% CI: 1.09 to 1.80; p<0.001) in the fully adjusted model. Subgroup and interaction analysis also demonstrated that BMI independently associated with IS among males, smokers, alcohol drinkers, diabetic patients, people with uncontrolled blood pressure, decreased estimated glomerular filtration rate and those aged ≥70 years. CONCLUSION: BMI was significantly associated with IS and was an independent risk of IS in Chinese elderly hypertensive patients.

Association between pulse pressure and ischaemic stroke in elderly patients with hypertension.

BACKGROUND: The association between pulse pressure (PP) and the risk of first ischaemic stroke (IS) is inconsistent. Therefore, we evaluated the association between PP and the risk of first IS among elderly hypertensive population in China. METHODS: This was a retrospective cohort study. Patients with hypertension and aged ≥60 years were recruited. Multivariate Cox regression was performed to evaluate the association between PP and the risk of IS. We further stratified the regression models into subgroups and test for interaction to assess whether the associations were modified by other covariates. RESULTS: A total of 3315 patients with hypertension (44.49% male; mean age 71.41±7.20 years) were included, and 206 cases of IS occurred with a median follow-up of 5.5 years. The results showed that per SD mm Hg increment in PP was associated with a 17% (95% CI 1.05 to 1.40, p=0.0172) increased risk of IS. Moreover, the HR of IS for the highest quartile of PP was 1.46 (95% CI 1.18 to 1.73, p=0.0011, p for trend <0.001) comparing with the lowest quartile of PP. Subgroup analysis showed that population aged ≥70 years, male, patients with smoking or drinking habit, diabetes at baseline, being overweight, with uncontrolled blood pressure or did not take antihypertensive drugs have a higher risk for IS. CONCLUSIONS: We found that PP was significantly associated with IS and was an independent risk factor for IS.

A dose-independent association of triglyceride levels with all-cause mortality among adults population.

BACKGROUND: The relationship between triglyceride (TG) level and the mortality risk of all-cause and cardiovascular disease is not entirely consistent among adults. METHODS: The present analysis included adult participants from National Health and Nutrition Examination Surveys (NHANES) between the periods 1999-2014. The levels of TG were categorized into < 150, 150-199, 200-250 and ≥ 250 mg/dL respectively. Multivariate Cox regression analysis, stratified analysis and generalized additive model were conducted to reveal the correlation between TG and mortality risk. Results were presented in hazard ratio (HRs) and 95% confidence intervals (CIs). RESULTS: There were 18,781 (9130 males, mean age was 45.64 years) participants being included in the analysis. The average follow-up period was 8.25 years, where 1992 (10.61%) cases of all-cause and 421 (2.24%) cardiovascular death have occurred. In the multivariate Cox model, every 1 mg/dL raise in TG has significantly associated with all-cause mortality (HR: 1.08, 95% CI: 1.02, 1.15) but not cardiovascular mortality (HR: 1.10, 95% CI: 0.97, 1.24). When using TG <  150 mg/dL as reference, TG ≥ 250 mg/dL associated with death from all-cause (HR = 1.34, 95% CI: 1.12, 1.60; P = 0.0016 but not cardiovascular death (HR = 1.26, 95% CI: 0.85, 1.88; P = 0.2517). According to smoothing spline plots, the risk of all-cause was the lowest when TG was approximately 135 mg/dL. CONCLUSION: TG might have a dose-independent association with all-cause mortality among adults in United States.

Association of pulse pressure with all-cause mortality in young adults.

BACKGROUND: Pulse blood pressure was significantly associated with all-cause mortality in middle-aged and elderly populations, but less evidence was known in young adults. OBJECTIVE: To assess the association of pulse pressure (PP) with all-cause mortality in young adults. METHODS: This cohort from the 1999-2006 National Health and Nutrition Examination Survey included adults aged 18-40 years. All included participants were followed up until the date of death or 31 December 2015. PP was categorised into three groups: <50, 50~60, ≥60 mm Hg. Cox proportional hazards models and subgroup analysis were performed to estimate the adjusted HRs and 95% CIs for all-cause mortality. RESULTS: After applying the exclusion criteria, 8356 participants (median age 26.63±7.01 years, 4598 women (55.03%)) were included, of which 265 (3.17%) have died during a median follow-up duration of 152.96±30.45 months. When treating PP as a continuous variable, multivariate Cox analysis showed that PP was an independent risk factor for all-cause mortality (HR 1.94, 95% CI 1.02 to 3.69; p=0.0422). When using PP<50 mm Hg as referent, from the 50~60 mm Hg to the ≥60 mm Hg group, the risks of all-cause mortality for participants with PP ranging 50-60 mm Hg or ≥60 mm Hg were 0.93 (95% CI 0.42 to 2.04) and 1.15 (95% CI 0.32 to 4.07) (P for tend was 0.959). Subgroup analysis showed that PP (HR 2.00, 95% CI 1.05 to 3.82; p=0.0360) was associated with all-cause mortality among non-hypertensive participants. CONCLUSION: Among young adults, higher PP was significantly associated with an increased risk of all-cause mortality, particularly among those without hypertension.

Association of mean arterial pressure with all-cause and cardiovascular mortality in young adults.

BACKGROUND: Mean arterial pressure (MAP) is a predictor of all-cause and cardiovascular disease (CVD) mortality in middle-aged population and elderly, but less evidence has been shown in young adults. OBJECTIVES: We examined the associations of MAP with all-cause and CVD mortality in young adults aged between 18 and 40 years. METHODS: Data were from the National Health and Nutrition Examination Survey (1999-2006) and participants were followed up to 31 December 2015. MAP was categorised by quartiles. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were performed to estimate the association between MAP, all-cause and CVD mortality. RESULTS: There were a total of 8356 (4598 women (55.03%)) participants with the mean age of 26.63±7.01 years, of which 265 (3.17%) and 10 (0.12%) cases of all-cause and cardiovascular mortality occurred during a median follow-up duration of 152.96±30.45 months, respectively. There was no significant difference in the survival rate by MAP quartiles (p=0.058). When MAP was treated as a continuous variable, the multivariable adjusted HRs for all-cause and CVD mortality were 1.00 (95% CI 0.96 to 1.04; p=0.910) and 0.94 (95% CI 0.77 to 1.14; p=0.529), respectively. When using the lowest quartile (Q1) as referent, the adjusted HRs for all-cause mortality from Q2 to Q4 were 1.16 (95% CI 0.56 to 2.42), 1.06 (95% CI 0.48 to 2.32) and 0.91 (95% CI 0.37 to 2.24; p for tend was 0.749) after adjusting for potential confounders. CONCLUSION: There was no significant association of MAP with all-cause and CVD mortality in young adults with a relatively short follow-up time.

J-shaped association between serum uric acid and acute coronary syndrome in patients with essential hypertension.

BACKGROUND: The prognostic value of serum uric acid (SUA) for incident acute coronary syndrome (ACS) in hypertensive subjects is uncertain. Therefore, the present study examined the association between SUA and incident ACS in a large cohort of Chinese hypertensive adults. METHODS: This was a retrospective cohort study, which enrolled 5473 Chinese community-dwelling hypertensive patients from 1 January 2012 to 31 December 2012. Study outcomes were ACS events, and patients were followed until 31 December 2016. Cox regression analyses were conducted to determine adjusted HRs and 95% CIs for baseline SUA tertiles (low, middle and high group) and for men and women separately. RESULTS: A total of 5473 participants were included in the analysis (median follow-up was 4.5 years). Participants were divided into tertiles based on SUA levels. During follow-up, 9 (0.49%), 14 (0.77%) and 25 (1.37%) patients developed ACS in the lowest, middle and highest tertiles, respectively. When compared with the lowest tertile of SUA, the highest tertile of SUA was associated with ACS risk in all subjects and in men and women separately (HR: 2.62, 95% CI 1.14 to 7.01, p=0.0233; 2.15, 95% CI 1.08 to 6.04, p=0.021, and 3.49, 95% CI 1.25 to 7.74, p=0.017, respectively). CONCLUSIONS: Higher SUA levels were independently associated with an elevated risk of ACS incidence. The relationship between SUA levels and ACS in hypertensive patients was J-shaped.

Relationship between serum uric acid level and all-cause and cardiovascular mortality in population with obesity.

BACKGROUND: We aimed to investigate the association between serum uric acid (SUA) and all-cause or cardiovascular mortality among participants with obesity. METHOD: All participants were included from the 1999 to 2014 National Health and Nutrition Examination Survey with follow-up mortality assessment through 31 December 2015. Cox proportional hazards models were built to estimate adjusted HRs and 95% CIs for mortality according to baseline uric acid in quartiles. Obesity was defined as body mass index ≥30 (kg/m2). Generalised additive model (GAM) and two-piecewise linear regression models were performed to explore any non-linearity in associations. RESULTS: There were 12 637 adults with obesity eligible for analysis. There were 999 (7.91%) all-cause and 147 (1.16%) cardiovascular mortality occurred during the mean follow-up of 98.11 months. Comparing with the lowest quartile of SUA, the highest SUA group did not have significant association with all-cause (HR 1.08, 95% CI 0.76 to 1.52) and cardiovascular mortality (HR 1.63, 95% CI 0.58 to 4.53) after adjusting for various confounding factors. GAM and two-piecewise linear regression model demonstrated a non-linearly relationship between SUA and all-cause mortality, and the corresponding cut-off point was 6.5 mg/dL. However, there is no significant relationship between uric acid and cardiovascular death on both sides of the cut-off value of 6.1 mg/dL. CONCLUSIONS: SUA showed a J-shaped relationship with all-cause mortality, but no significant with cardiovascular mortality in adults with obesity.

Relationship between triglyceride levels and ischaemic stroke in elderly hypertensive patients.

BACKGROUND: Although hyperlipidaemia was a well-known risk factor for ischaemic stroke, the association between triglyceride and first ischaemic stroke remains uncertain. OBJECTIVES: The present study attempted to explore the relationship between triglyceride and first ischaemic stroke in a Chinese community elderly patients with hypertension. METHODS AND RESULTS: This was a retrospective cohort study. We enrolled 3249 consecutive elderly patients with hypertension from a community in China between January 2010 and December 2011. Patients were divided into four groups based on the quartiles of triglyceride. Multivariate Cox regression analysis, subgroup and interaction test were performed to evaluate the relationship between triglyceride and first ischaemic stroke. There were a total of 3249 participants including 1455 male and 1794 female, with a mean age of 71.36±7.18 years. At an average follow-up of 5.5 years, 205 patients were identified to have first ischaemic stroke. After adjustment for potential confounders, using the lowest quartiles of triglyceride as the reference, multivariable HR (95% CI) for first ischaemic stroke increased in parallel with the quartiles of triglyceride (HRs were 1.56 (95% CI 1.07 to 2.51), 1.74 (95% CI 1.07 to 2.84) and 1.85 (95% CI 1.05 to 2.89)) from the second to the fourth quartiles, respectively (p=0.002 for trend). Subgroup and interaction analysis showed that there was no interactive effect on triglyceride and first ischaemic stroke. CONCLUSION: Triglyceride was an independent risk factor for first ischaemic stroke among Chinese elderly patients with hypertension.

Relationship between diastolic blood pressure and the first ischaemic stroke in elderly patients with hypertension.

BACKGROUND: It is uncertain how diastolic blood pressure (DBP) may associate with ischaemic stroke in elder patients with hypertension. We aimed to explore this relationship in a Chinese community. METHODS: A total of 3315 participants aged ≥60 years with essential hypertension were enrolled between January 2010 and December 2011, and being followed up until 31 December 2016. DBP levels were categorised into five groups (<60, 60-70, 70-80, 80-90 and ≥90 mm Hg), using 70-80 mm Hg as referent. We performed Cox regression analysis and subgroup analyses to evaluate the relationship between DBP and the incidence of ischaemic stroke. RESULTS: Among the 3315 participants, 44.49% were men and they were 71.4 years old on average. During a median follow-up period of 5.5 years, there were 206 onset cases of ischaemic stroke. The HRs for the first ischaemic stroke in the fully adjusted model were 1.32 (95% CI 0.73 to 2.40) for DBP <70 mm Hg, 1.50 (95% CI 1.13 to 2.73) for DBP between 80 and 89.9 mm Hg and 2.31 (95% CI 1.14 to 4.68) for DBP ≥90 mm Hg compared with DBP between 70 and 79.9 mm Hg (p=0.020 for trend). Subgroup and interaction analysis showed no significant findings. CONCLUSIONS: DBP had a non-linear association with the risk of ischaemic stroke among Chinese elderly patients with hypertension. DBP between 70 and 80 mm Hg may be an appropriate indicator for a lower stroke risk.

The correlation of circulating miR-29b and inflammatory markers with albuminuria in hypertensive patients.

AIMS: Circulating miR-29b and inflammatory process play a vital role in hypertension and hypertensive nephropathy. The aim of the present study was to investigate the association of circulating miR-29b and inflammatory markers with albuminuria and assess the predictive value of circulating miR-29b for albuminuria in essential hypertension. METHODS: This cross-sectional study was continuously enrolled 150 subjects and were divided into three groups based on random urinary albumin/creatinine ratio (UACR, mg/g), the patients with ACR<30 mg/g were classified as normal albuminuria, the values of 30< ACR<300 was defined as micro-albuminuria while the group with ACR over 300 mg/g are macro-albuminuria. Circulating miR-29b was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Multivariate logistic regression and area under the ROC curve (AUC) were used. RESULTS: We found miR-29b, C-reactive protein, and transforming growth factor-ß1 (TGF-ß1) in macro-albuminuria group were significantly higher than those in the micro-albuminuria and normal albuminuria group. The level of miR-29b was positively associated with TGF-ß1, C-reactive protein, and UACR, while negatively related to glomerular filtration rate. Circulating miR-29b was a significant independent determinant factor for albuminuria. CONCLUSION: Our results provided a clinical evidence of a positive association between circulating miR-29b, inflammatory markers, and UACR, and implied miR-29b was a significant independent determinant factor for albuminuria.