Degradable Microneedle Patch with Photothermal-Promoted Bacteria-Infected Wound Healing and Microenvironment Remodeling.

Bacteria-infected wound healing is one of the most challenging issues in health management that is attracting worldwide concerns. Despite great achievements with antibiotics, emergence of antibiotic-resistance retarded the wound healing process and also led to severe outcomes. Exploration of novel antibiotics together with amelioration of wound healing efficacy is desirable. Herein, a degradable microneedle patch (AAZH@MNs) was fabricated through incorporating near-infrared light responsive photothermal agents for sustained bacteria killing and prevention of biofilm formation. In addition, the antibacterial microneedle patch could even remold the microenvironment of bacteria-infected wounds through an antibacterial effect, significantly facilitating the wound healing process.

The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. METHODS: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010-2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. RESULTS: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. CONCLUSIONS: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.

Coordination-Driven Self-Assembly of Iron Oxide Nanoparticles for Tumor Microenvironment-Responsive Magnetic Resonance Imaging.

Accurate diagnosis of diseases located in deep tissues is always challenging. The "always-on" probe often leads to false-positive signals due to nonspecific interaction of nanoprobes. Thus, stimuli-responsive nanoprobes are highly desirable, which, however, require complicated surface modification so as to achieve trigger-induced signal changes. Here pH-triggered switchable magnetic resonance imaging (MRI) nanoprobes were constructed by coordination-driven self-assembly of monodispersed iron oxide nanoparticles (MIONPs) with simple amino acid derivatives, which displayed typical T2-weighted MRI features, yet, were turned into T1-weighted MRI under slightly acidic conditions at the tumor site. The dynamic assembly and disassembly properties of MIONPs afford T2/T1 switchable contrast imaging, enabling selective "turn-on" signals at the tumor site with high specificity.

Prediction of Disease Genes Based on Stage-Specific Gene Regulatory Networks in Breast Cancer.

Breast cancer is one of the most common malignant tumors in women, which seriously endangers women's health. Great advances have been made over the last decades, however, most studies predict driver genes of breast cancer using biological experiments and/or computational methods, regardless of stage information. In this study, we propose a computational framework to predict the disease genes of breast cancer based on stage-specific gene regulatory networks. Firstly, we screen out differentially expressed genes and hypomethylated/hypermethylated genes by comparing tumor samples with corresponding normal samples. Secondly, we construct three stage-specific gene regulatory networks by integrating RNA-seq profiles and TF-target pairs, and apply WGCNA to detect modules from these networks. Subsequently, we perform network topological analysis and gene set enrichment analysis. Finally, the key genes of specific modules for each stage are screened as candidate disease genes. We obtain seven stage-specific modules, and identify 20, 12, and 22 key genes for three stages, respectively. Furthermore, 55%, 83%, and 64% of the genes are associated with breast cancer, for example E2F2, E2F8, TPX2, BUB1, and CKAP2L. So it may be of great importance for further verification by cancer experts.

Longitudinal Study of Brachial-Ankle Pulse Wave Velocity and Change in Estimated Glomerular Filtration Rate among Chinese Adults.

BACKGROUND AND OBJECTIVES: Studies on the association between arterial stiffness and kidney function have generated inconsistent results. Whether arterial stiffness is linked to decline in renal function warrants further study. This study aimed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and longitudinal change in estimated glomerular filtration rate (eGFR) among Chinese adults. METHODS: In this longitudinal study, 8,264 participants in a community-based cohort had baPWV measured in 2010-2011 and were followed in subsequent surveys through to 2016. During each survey visit, fasting blood samples were collected for serum creatinine and eGFR was calculated. Participants were divided into 5 groups (Q1-Q5) by baPWV quintile. The association between baPWV and longitudinal changes in eGFR was assessed using generalized estimating equation models. RESULTS: A total of 8,045 participants were included in the final analysis. The average age was 54 ± 12 years (age range 24-97 years), and mean eGFR was 93.0 ± 18.6 mL/min/1.73 m2. There was an inverse linear association between baseline baPWV and eGFR change rate (p < 0.001). Compared with Q1 (lowest) group, the mean differences and 95% CI in eGFR decrease rate among Q2-Q5 groups were -0.23 (-0.62, 0.16), -0.67 (-1.06, -0.28), -1.11 (-1.50, -0.72), and -1.30 (-1.69, -0.92) mL/min/1.73 m2 per year, respectively, after adjustment for age, gender, and other potential confounders (p trend < 0.0001). For each 100 cm/s increase in baPWV at baseline, the fully adjusted mean difference in eGFR decrease rate was -0.14 mL/min/1.73 m2 per year (95% CI -0.18, -0.10; p < 0.0001). Compared with participants with baPWV < 1,400 cm/s, the fully adjusted mean difference in eGFR decrease rate was -0.92 mL/min/1.73 m2 per year (95% CI -1.18, -0.66) for those with baPWV ≥ 1,400 cm/s (p < 0.0001). CONCLUSIONS: Participants with a higher baPWV at baseline had a greater decrease in eGFR over time. Future studies could examine the relationship between baPWV and decline in renal function in higher risk cohorts, and its potential role in targeting reno-protective interventions to those who may benefit from them most.

Clinical features and long-term outcomes of diabetic kidney disease - A prospective cohort study from China.

BACKGROUND: Information regarding the clinical phenotypes of diabetic kidney disease (DKD) might guide better practice for clinicians. We aim to compare the clinical features and long-term outcomes of proteinuric and non-proteinuric phenotypes of DKD, based on a prospective cohort of Chinese population. METHODS: Altogether 8811 Chinese participants with diabetes were included. Kidney function decline was defined as estimated glomerular filtration rate <60 mL/min·1.73 m-2. The presence of proteinuria by urine dipstick test was further divided into micro-proteinuria (trace or 1+) and overt-proteinuria (≥2+). Participants were then stratified into 5 groups: no DKD, isolated kidney function decline, isolated micro-proteinuria, isolated overt-proteinuria, and proteinuria combined with kidney function decline. Outcomes include the first occurrence of composite cardiovascular events, end-stage renal disease (ESRD), and all-cause mortality. MAIN FINDINGS: After a median follow-up of 6.9 years, there were 646 composite cardiovascular events, 31 ESRD events, and 718 deaths. Isolated kidney function decline was only associated with the higher risk of ESRD (HRs 31.33 (95% CI 3.65-269.27)). Participants of overt-proteinuria and proteinuria combined with kidney function decline phenotypes were associated with increased risk of all predefined adverse outcomes. CONCLUSIONS: Proteinuric and non-proteinuric DKD phenotypes might follow different pathophysiological pathways, and result in heterogeneous clinical features and prognosis.

Relationship between the exposure to cumulative cardiovascular health behaviors and factors and chronic kidney disease-The Kailuan study.

It is unclear whether ideal cardiovascular health (CVH) behaviors and factors, particularly cumulative exposure to ideal CVH (cumCVH), is associated with chronic kidney disease (CKD). The aim of the study was to examine the effect of cumCVH on CKD using the data from the Kailuan study. The study included the 27,970 (21,199 males) of the Kailuan community (China). The participants were 19 to 98 years of age. They were followed in 2008-2009, 2010-2011, and 2012-2013 by the same medical staff that did the initial physical examinations in 2006-2007. Participants were censored on the visit reporting CKD. A CVH score was created based on the seven AHA health metrics. The cumCVH score was CVH1×timev1-v2+CVH2×timev2-v3+CVH3×timev3-v4. In the fully adjusted model, compared with the lowest quintile of cumCVH, individuals in the highest quintile had a 75% lower risk of CKD (95% confidence interval (CI): 66-82%). Every additional year lived with a 1-unit increase in ideal CVH was associated with an 11% (95% CI: 9-13%) reduction in the incidence of CKD. Furthermore, when we excluded each of the six metrics from the cumCVH score in turn, the association was unaffected after the exclusion of individual risk factors. Ideal CVH is associated with a reduced incidence of CKD. Measurements of cumCVH are more likely to reflect the lifetime risk of CKD and possibly of other health outcomes.

Sleep and CKD in Chinese Adults: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: To assess the association between self-reported sleep duration and quality and odds of having CKD in Chinese adults on the basis of a community study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional study, we included 11,040 Chinese adults who participated in an ongoing prospective study, the Kailuan cohort. Survey questionnaire items addressed insomnia, daytime sleepiness, snoring, and sleep duration during their 2012 interview. Overall sleep quality was evaluated by summarizing these four sleep parameters. Fasting blood samples and single random midstream morning urine samples were collected in 2012 and analyzed for serum creatinine and proteinuria. CKD was defined by eGFR<60 ml/min per 1.73 m2 or proteinuria >300 mg/dl. We also examined those at high or very high risk of having CKD, on the basis of the Kidney Disease Improving Global Outcomes recommendations. The association between sleep quality and CKD was assessed using logistic regression model. RESULTS: Worse overall sleep quality was associated with higher likelihood of being high or very high risk for CKD (multiadjusted odds ratio, 2.69; 95% confidence interval, 1.30 to 5.59 comparing two extreme categories; P trend <0.01), but not overall CKD (multiadjusted odds ratio, 1.58; 95% confidence interval, 0.89 to 2.80 comparing two extreme categories; P trend =0.46), after adjusting for potential confounders. Specifically, individuals with worse sleep quality were more likely to have proteinuria (multiadjusted odds ratio, 1.95; 95% confidence interval, 1.03 to 3.67 comparing two extreme categories; P trend =0.02), rather than lower eGFR level (multiadjusted mean eGFR levels were 96.4 and 93.6 ml/min per 1.73 m2 in the two extreme sleep categories, respectively; P trend =0.13). However, there was no statistically significant association between individual sleep parameters and CKD status. CONCLUSIONS: Worse overall sleep quality was associated with higher odds of being high or very high risk for CKD and proteinuria in Chinese adults.

Correlation between Carotid Intima-Media Thickness and Early-Stage Chronic Kidney Disease: Results from Asymptomatic Polyvascular Abnormalities in Community Study.

OBJECTIVE: Chronic kidney disease (CKD) might be a potential independent risk factor for increased carotid intima-media thickness (IMT). Our aim is to determine whether mild to moderate kidney dysfunction is associated with increased carotid IMT. METHODS: We employed 3629 subjects free from clinical cardiovascular diseases at the baseline visit of the Asymptomatic Polyvascular Abnormalities in Community Study. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration China equation. The mean of the maximal internal and common carotid IMT was measured by means of high-resolution B-mode ultrasound. Univariable linear regressions and multivariate logistic regressions were used to evaluate the independent association between kidney function and carotid IMT. RESULTS: In the unadjusted linear analysis, carotid IMT showed a significant negative correlation with eGFR in both male (r = -.346, P < .001) and female (r = -.253, P < .001) subjects. After adjustment for age, traditional vascular risk factors (smoking, diabetes, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and antihypertensive drug use), and nontraditional risk factors (C-reactive protein and homocysteine), the association remained significant. The odds ratio for increased IMT was 1.299 (95% confidence interval [CI], 1.062-1.588) in the group with an eGFR of 60-89 mL/minute/1.73 m(2) and 1.789 (95% CI, 1.203-2.660) in the group with an eGFR of 30-59 mL/minute/1.73 m(2). CONCLUSIONS: Increased IMT is associated with early-stage CKD. This association is independent of traditional and nontraditional cardiovascular risk factors. Early detection of kidney dysfunction is important to improve risk stratification of atherosclerotic disease.

Prehypertension and Chronic Kidney Disease in Chinese Population: Four-Year Follow-Up Study.

Hypertension is a well established cause of chronic kidney disease (CKD). However, the effect of prehypertension on risk of CKD is controversial. The aim of this study is to determine whether prehypertension increases the risk of CKD events in the Chinese population. We enrolled 20,034 with prehypertension and 12,351 with ideal blood pressure in this prospective study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min 1.73 m2. The new occurrences of CKD events were collected during follow-up. Cumulative survival and freedom for the occurrence of new CKD events was analyzed using the Kaplan-Meier approach. Multivariate Cox Regression was used to analyze the effect of prehypertension on CKD. The median follow-up time was 47 (interquartile range 44-51) months. 601 new onset CKD events occurred during the follow-up period. The cumulative incidence of new CKD events was higher in the prehypertensive population than that in the ideal blood pressure population (2.10% vs 1.46%, P = 0.0001). Multivariate Cox Regression showed that relative risks (RRs) for the new onset CKD events in the prehypertensive population were 1.69 (95% confidence intervals (CI): 1.41~2.04, P = 0.001) higher than those in the ideal blood pressure population. Similarly, the risks were 1.68 (95% CI: 1.33~2.13 P = 0.001) times higher in females and 2.14 (95% CI: 1.58~2.91 P = 0.001) times higher in males by adjustment for traditional CV risk factors. Our findings demonstrated prehypertension is an independent risk factor for the occurrence of new CKD events in the Chinese population.

[The prediction of high-sensitivity C reactive protein for peripheral arterial sclerosis in middle-aged population].

OBJECTIVE: To explore the predictive value of high-sensitivity C reactive protein (hsCRP) in middle-aged population during the peripheral arteriosclerosis. METHODS: Random sampling method was used in the study. In 2006-2007 Kailuan Group health examination of 101,510 employees, using stratified random sampling method to select 5,852 as observational cohort included, in the final with a standard queue 5,440 in December 2009. This study selected to participate in the 2012-2013 health examination cohort as the research object, in accordance with the inclusion criteria ultimately selected survey 3,978, select the epidemiological investigation, physical examination, laboratory testing data analysis. Of the 3 978 subjects, 2,282 were male and 1,696 were female, and the baseline age was (53.80±11.14) years. According to the baseline hsCRP quartile level was divided into four groups for comparison of baseline data, using multiple linear regression analysis between hsCRP and brachial-ankle pulse wave velocity (baPWV). Area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the prediction of hsCRP levels in peripheral arteriosclerosis. RESULTS: With increase of hsCRP levels, the survey of baseline levels of baPWV showed increasing trend, (1,445.49±300.55), (1,494.46±307.94), (1,547.67±320.34), (1,621.32±342.53) cm/s, respectively. Multiple linear regression results showed that age, by logarithmic transformation of hsCRP (lghsCRP) level, systolic blood pressure and fasting blood glucose for each additional unit, baPWV levels were increased 266.47, 58.00, 5.02, 39.79 cm/s (P<0.001), and BMI for each additional unit, baPWV level decreased 9.52 cm/s (P=0.030). The prediction of hsCRP in peripheral artery showed that lghsCRP level of AUC to 0.59 (95% CI: 0.57-0.61), lower than the age and systolic blood pressure predicted value AUC (95% CI) of 0.69 (0.67-0.71), 0.75 (0.73-0.77), respectively. CONCLUSION: The hsCRP level could not predict the peripheral arteriosclerosis alone, and the combined age and systolic blood pressure level could have better predictive value.

Ideal cardiovascular health behaviors and factors and high sensitivity C-reactive protein: the Kailuan cross-sectional study in Chinese.

BACKGROUND: High sensitivity C-reactive protein (hs-CRP) is an inflammatory marker associated with increased cardiovascular disease risk. Health-related behaviors and factors decrease the risk of cardiovascular disease events, but the association between ideal cardiovascular health behaviors and hs-CRP is not clear. This study evaluated the relationship between the number of ideal cardiovascular health metrics and hs-CRP levels. METHODS: We conducted a cross-sectional study from 2006 to 2007 that included 93,967 healthy subjects and 7869 diabetic patients. hs-CRP was measured by high-sensitivity nephelometry. Multivariate logistic regression was performed to analyze the association between the number of ideal cardiovascular health metrics and hs-CRP levels in the general population and in non-diabetic and diabetic subjects. RESULTS: We found that hs-CRP levels decreased as the number of ideal cardiovascular health metrics increased in the general population, different genders, non-diabetic and diabetic subgroups. After adjusting for traditional risk factors, logistic regression analyses revealed that the risk of hs-CRP >3 mg/L in the general population with 6-7 ideal cardiovascular health metrics was 0.39 times lower than in those with 0-1 ideal metrics. Similarly, the risks were 0.39 times lower than in those with 0-1 ideal metrics in non-diabetic population. The risk of hs-CRP >3 mg/L in the diabetic population with 4-6 ideal cardiovascular health metrics was 0.45 times lower than those with 0-1 ideal metrics. CONCLUSIONS: Our findings demonstrate an inverse relationship between the number of ideal health metrics and hs-CRP in the general population, and similar relationships were observed for different gender, non-diabetic and diabetic subgroups.

Association of ideal cardiovascular metrics and serum high-sensitivity C-reactive protein in hypertensive population.

UNLABELLED: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of cardiovascular disease. However, ideal cardiovascular health indicates lower risk of cardiovascular disease. This study aimed to investigate the effect of ideal cardiovascular health behaviors and health factors on hs-CRP levels among a hypertensive population. From 2006 to 2007, a cross-sectional study was conducted to survey 41,476 hypertensive subjects among the employees of Kailuan Corporation. Data from unified questionnaires and blood biochemical examinations were collected. The effects of ideal cardiovascular health behaviors and health factors on hs-CRP levels were evaluated through multivariate logistic regression analysis. A negative correlation was observed between hs-CRP levels and the number of ideal cardiovascular health metrics. The mean hs-CRP levels of subjects with zero to one, two, three, and four to six ideal cardiovascular health metrics were 1.11, 0.96, 0.90, and 0.80 mg/L, respectively (P<0.01). Multivariate logistic regression analysis revealed that after adjustment for sex, age, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and other risk factors, the risks for subjects with two, three, and four to six ideal health metrics with serum hs-CRP >3 mg/L were lower than those with zero to one ideal health metrics, with corresponding odd ratios of 0.86 (95%CI: 0.79-0.93, P<0.01), 0.76 (95%CI: 0.69-0.83, P<0.01), and 0.68 (95%CI: 0.64-0.75, P<0.01), respectively. This finding suggests that ideal cardiovascular health behaviors and health factors were related to decreased hs-CRP levels in a hypertensive population. CLINICAL TRIAL REGISTRATION: UNIQUE IDENTIFIER: ChiCTR-TNC-11001489.