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Objective Cognitive frailty (CF) is associated with adverse health outcomes, but different CF models have been proposed in the literature. We explored whether cognitive impairment (CoI) assessed by the Revised Hasegawa dementia scale (HDS-R) and physical frailty (PF) assessed by the modified Frailty Phenotype can be combined to predict risks of adverse outcomes in elderly Chinese subjects. Methods The data collected in the Rugao Longevity and Aging Study were used. PF was assessed by the modified Frailty phenotype. CoI was defined as the lowest 20% of the HDS-R score. CF was defined as the co-existence of physical frailty and CoI, excluding those with severe CoI(HDR-S ≤ 10). The date and cause of death were acquired from the Death registry of Rugao's Civil Affairs Bureau. Disability was measured using the activities of daily living (ADL) scale. Results The prevalence of CF was 2.9% at baseline. During 3-year follow-up, 130 (8.1%) of the 1607 elderly subjects died. The highest mortality risk was observed among subjects with CF (hazard ratio [HR] = 2.94, 95% confidence interval [CI] = 1.28-6.78). Fully adjusted survival plots showed that CF was associated with the highest risk for 3-year mortality. The incidence of ADL disability was 6.0% after 3 years. Compared with the robust and non-CoI elderly, CF was associated with a 10.48-fold (95% CI 2.98-36.80) higher risk of ADL disability. Conclusions The CF model defined as a combination of HDS-R and Frail Phenotypes showed predictive validity for all-cause death and new-onset ADL disability 3 years later.

The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome (HFRS) epidemic area, while HFRS prevalence has decreased in most epidemic areas in China. Little information is available regarding the leading fine-scale influencing factors in this highly HFRS-concentrated area and the roles of natural environmental and socioeconomic factors. To investigate this, two regions in the Guanzhong Plain, that is, the Chang'an District and Hu County, with similar geographical environments, different levels of economic development, and high epidemic prevalence, were chosen as representative areas of the HFRS epidemic.Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors, including meteorological, natural environmental, and socioeconomic factors, from 2014 to 2016.More than 95% of the HFRS cases in the study area were located in the northern plains, which has an altitude of less than 800 m, with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic. In the northern plains, precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic, with contribution rates of 60.7% and 28.0%, respectively. By comparing the influencing factors of the northern plains of Chang'an District and Hu County, we found that precipitation and the normalized difference vegetation index (NDVI) dominated the HFRS epidemic in the relatively developed Chang'an District, while land-use type, temperature, precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County.Topography was the primary key factor for HFRS prevalence in the Chang'an District and Hu County, and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains. Compared with the influencing factors of the relatively developed Chang'an District, the developing Hu County was more affected by socioeconomic factors. When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas, it is crucial to consider the local economic development state and combine natural environmental factors, including the meteorological environment and vegetation coverage.

Chronic granulomatous disease (CGD) is the most common phagocyte defect disease. Here, we describe 114 CGD patients in our center and report a rare female infant with XL-CGD to provide a better understanding of diagnosis, treatment, and prenatal diagnosis of CGD. Patients were diagnosed by DHR-1,2,3 flow cytometry assays and gene analysis. X chromosome inactivation analysis and gp91phox protein test were used for a female infant with XL-CGD. XL-CGD accounts for the majority of cases in China and results in higher susceptibility to some infections than AR-CGD. The DHR assay can help diagnose CGD quickly, and atypical results should be combined with clinical manifestations, genetic analysis, and regular follow-up. For prenatal diagnosis, both gDNA and cDNA genotypes of amniotic fluid cells should be identified, and cord blood DHR assays should be performed to identify female XL-CGD patients.

Objective Waardenburg syndrome type 2 (WS2) is an autosomal dominant syndrome, characterized by bright blue eyes, hearing loss, and depigmented patches of hair and skin. It exhibits high phenotypic and genetic heterogeneity. We explored the molecular etiology in a Chinese family with WS2. Methods We recruited a three-generation family with three affected members. Medical history was obtained from all family members who underwent detailed physical examinations and audiology tests. Genomic DNA was extracted from peripheral blood of each individual, and 139 candidate genes associated with hearing loss were sequenced using Illumina HiSeq 2000 (Illumina Inc., San Diego, CA, USA) and verified by Sanger sequencing. Results Genetic evaluation revealed a novel nonsense heterozygous variant, NM_006941.4: c.342G>A (p.Trp114Ter) in exon 2 of the SOX10 gene in the three affected patients; no unaffected family member carried the variation. We did not detect the variation in 500 Chinese individuals with normal hearing or in 122 unrelated Chinese families with hearing loss, suggesting that it was specific to our patients. Conclusions We identified a novel heterozygous nonsense variation in a family with syndromic hearing loss and WS2. Our findings expand the pathogenic spectrum and strengthen the clinical diagnostic role of SOX10 in patients with WS2.

Effective treatment for acute lung injury (ALI) is in high demand. Lung-targeted ternary nanoparticles containing anti-intercellular adhesion molecule-1 (ICAM-1) antibody-conjugated simvastatin-loaded nanostructured lipid carrier (ICAM/NLC), protamine (Pro), and angiopoietin-1 (Ang-1) gene (ICAM-NLC/Pro/Ang) were developed for ALI therapy. The ternary nanoparticles with different weight ratios of ICAM-NLC to Ang-1 gene were prepared via charge interaction. The anti-ICAM-1 antibody-conjugated ternary nanoparticles exhibited higher cellular uptake and transfection efficiency (from 26.7% to 30.9%) in human vascular endothelial cell line EAhy926 than the non-targeted control. The largest size of ICAM-NLC/Pro/Ang (357.1 nm) was employed for further study, which significantly up-regulated in vitro and in vivo Ang-1 protein expression. In vivo i.v. administration of ICAM-NLC/Pro/Ang (357.1 nm) significantly attenuated pulmonary TNF-α and IL-6 levels, inflammatory cell infiltration, and led to positive histological improvements in lipopolysaccharide-induced ALI mice. Collectively, the ICAM-NLC/Pro/Ang that co-delivered simvastatin and Ang-1 gene may represent a potential treatment modality for ALI.

Objective To expose the spectrum and frequency of GJB2, GJB3, SLC26A4 and MT-RNR1 in northwest China and to investigate the underlying causative genes in patients without common mutations. Methods We analyzed the mutation screening results of GJB2, GJB3, SLC26A4 and MT-RNR1 in 398 unrelated severe-to-profound probands with bilateral, symmetrical sensorineural hearing loss. Subsequently, we selected 10 probands with a significant family history of inherited hearing loss (HL) that did not have the above four common gene mutations to perform next-generation sequencing (NGS) of 139 known deafness genes, followed by co-segregation analysis of all available family members. Results Among the 398 patients, 69 (17.34%) had the biallelic GJB2 gene mutations, and the most common mutations were c.235delC, c.109G>A and c.299_300delAT, with allele frequencies of 12.31%, 3.38% and 3.89%, respectively. A total of 63 (15.83%) cases with biallelic SLC26A4 mutations were detected, and the most common pathogenic alleles were c.919-2A>G, c.2168A>G and c.1174A>T, with allele frequencies of 9.17%, 2.26% and 0.88%, respectively. Mitochondrial gene mutations were detected in 9 (2.26%) patients, with 5 cases of mitochondrial DNA (mtDNA) m.1555A>G mutation and 4 cases of mtDNA m.1095T>C mutation. In 10 probands with a clear family history of HL, NGS showed two novel pathogenic variants in 2 families, including c.4129C>T/c.3268C>T in LOXHD1, c.334G>A/c.2968G>T in CDH23. Sanger sequencing confirmed that these variants segregated with the HL in each family. Conclusions Our results showed that GJB2 and SLC26A4 were the two major HL-causing genes in northwest China. The most common mutation alleles in GJB2 were c.235delC, c.109G>A and c.299_300delAT, and those in SLC26A4 were c.919-2A>G, c.2168A>G and c.1174A>T. In addition, both genes and their loci can be used as the first selection of deafness gene screening. Additionally, for patients who did not have mutations of these common genes, NGS provided an efficient diagnosis for increasing known deafness genes.

Depression has been associated with chronic kidney disease (CKD). However, few studies have examined whether such association exist in average older individuals with mild to moderate reduced kidney function. This study investigated the association between reduced estimated glomerular filtration rate (eGFR) and depressive symptoms in Chinese older population. Data was obtained from the Rugao Longevity and Ageing Study conducted in Jiangsu, China. Cockcroft-Gault (CG) equation was used to calculate eGFR. Depressive symptoms were defined by using Chinese version of 15-item Geriatric Depression Scale (GDS-15). The prevalence of depressive symptoms was 9.9% among 1749 elderly participants aged 70-84 years. Many elderly had a mild to moderate reduced renal function (84.3%, 57.1% in stage2 CKD and 27.2% in stage3 CKD, respectively). The overall GDS-15 score showed an upward trend with decreasing of eGFR (p 0.05). Furthermore, a moderate decline of eGFR (in stage3 CKD) was significantly associated with increased risk of depressive symptoms even after adjusting for confounders (OR = 1.71, 95%CI 1.05-2.77, P = 0.03). Elder had no depressive symptoms if their eGFR was normal or mildly reduced. Our results suggest that a moderate decrease of eGFR (stage3 CKD) was independently associated with depressive symptoms in general Chinese elderly.

Objective: To develop a physical- cognitive scale for assessment of frailty and compare the clinical features between the new scale and the conventional Fried criteria. Methods: 1757 individuals aged 70-84 were analyzed. Participants reporting three or more Fried phenotypes were grouped as frail patients (FP) whereas others as non-frail (NF). A score of Hasegawa's dementia scale (HDS-R) higher than 21.5 were classified as non-cognitive impairment group (NCI) group. By combining the cognitive and frailty criteria, participants manifesting three or more positive components out of the six were categorized into the Physical-cognitive frailty group (Pc-F) while others into non- Pc-F (Pc-NF). Results: Of all the participants, 46.7% (820) were males and 53.3% (937) were females. The mean age was 75.33 ± 3.90. 10.1% (178/1757) were evaluated as FP patients. The prevalence of CI was 53.2%; CI was much higher in the frail group (77.0%) than in the non-frail group (50.5%). Based on the new Pc-F scale, 163 out of 1579 NF participants were identified as Pc-F, and the prevalence of Pc-F reached 19.4% (341/1757). In the Pc-F group, there are more females, patients of advanced age, diabetes, stroke, CHD, CKD, metabolic syndrome, and high hs-CRP. Within the Pc-F group, patients with CI showed a higher incidence of exhaustion, low activity, weakness, and slowness than those without CI. Conclusions: Our study revealed a significantly worse status in frail participants with CI than without. Our new scale shows a stronger correlation between frailty and complications than the classic phenotype.

Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily. With particle size increasing from 143.7 nm to 337.8 nm, SV/NLCs showed increasing drug-encapsulated efficiency from 66.70% to 91.04%. Although larger SV/NLCs exhibited slower in vitro cellular uptake by human vascular endothelial cell line EAhy926 at initial stage, while in vivo distribution demonstrated higher pulmonary accumulation of the larger ones. Thus, the largest size SV/NLCs (337.8 nm) were conjugated with intercellular adhesion molecule 1 (ICAM-1) antibody (anti-ICAM/SV/NLCs) for lung-targeted study. The anti-ICAM/SV/NLCs exhibited ideal lung-targeted characteristic in lipopolysaccharide-induced ALI mice. In vivo i.v. administration of anti-ICAM/SV/NLCs attenuated TNF-α, IL-6 and inflammatory cells infiltration more effectively than free SV or non-targeted SV/NLCs after 48-h administration. Significant histological improvements by anti-ICAM/SV/NLCs were further revealed by H&E stain. Therefore, ICAM-1 antibody-conjugated NLCs may represent a potential lung-targeted DDS contributing to ALI therapy by statins.

This study investigated whether sleep duration and quality were related to life satisfaction (LS) among older Chinese adults and whether depression mediated those relationships. Cross-sectional data from the aging arm of the Rugao Longevity and Aging Study were used. Sleep duration, sleep quality, depression, LS and covariates were analyzed using logistic regressions. To assess the potential mediation of depression on the association between sleep duration and quality and LS, Aroian tests were used. Of 1756 older Chinese adults aged 70-84 years, 90.7% of the men and 83.3% of the women reported being satisfied with their lives. After adjusting for covariates, older adults who slept ≤6h per night were more likely to suffer from life dissatisfaction compared with those who slept 7-8h (OR=2.67, 95% CI 1.86-3.79), and individuals who slept poorly were almost 2 times (OR=2.91, 95% CI 2.16-3.91) more likely to have life dissatisfaction. The Aroian tests confirmed that these relationships were partially mediated by depression (p

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.

Rheumatoid arthritis (RA) patients have suffered from the current drug therapeutic regimen because of its high toxicity and the absence of bone regeneration for existing erosion, seriously affecting the quality of life. Herein, a sialic acid-dextran-octadecanoic acid (SA-Dex-OA) conjugate was synthesized to form micelles with a 55.06 μg mL−1 critical micelle concentration. The obtained micelles can encapsulate a disease-modifying anti-rheumatic drug, methotrexate (MTX), with 4.28% (w/w) drug content, featuring sustained drug release behavior over 48 h. In vitro and in vivo studies showed that SA-Dex-OA micelles significantly improved accumulation and transportation through a combination of SA and E-selectin receptors in inflamed cells and arthritic paws highly expressing E-selectin. MTX-loaded SA-Dex-OA micelles not only significantly inhibited the inflammatory response, but also diminished the adverse effects of MTX, as reflected by the reduced alanine aminotransferase, aspartate aminotransferase, creatinine, and urea nitrogen levels. Most importantly, the bone mineral density in rats treated with MTX-loaded SA-Dex-OA micelles was significantly higher as compared to in those treated with free MTX and Dex-OA/MTX micelles (increasing from 391.4 to 417.4 to 492.7 mg cc−1), benefiting from the effects of endogenous sialic acid in promoting MC3T3-E1 cell differentiation and mineralization. It is anticipated that SA-based micelles with bone repair activities have great potential for RA treatment and other metabolic bone diseases with serious bone erosion.

Objectives Studies have showed the associations between different definitions of metabolic syndrome (MetS) and risk of ischemic stroke were inconsistent. In this study, we compared associations of different MetS definitions with ischemic stroke in Chinese elderly population. Methods A total of 1713 individuals aged 70–84 years from Rugao Longevity and Ageing Study were analyzed. The MetS was defined by four different criteria: Chinese Adult Dyslipidemia Prevention Guide, International Diabetes Federation (IDF), Updated ATPIII (Updated ATPIII) by American heart association/American heart, lung and blood institute (AHA/NHLBI), and Joint Interim Statement(JIS) recommended by IDF and the American heart association/American national institutes of health/American heart, lung and blood institute (AHA/NIH/NHLBI). Results Prevalence of MetS in the whole population was 24.0% (Chinese guide), 32.5% (IDF), 38.8% (Updated ATPIII) and 24.0% (JIS) and in stroke population was 27.1% (Chinese guide), 41.1% (IDF), 48.8% (Updated ATPIII) and 27.1% (JIS), respectively. The agreement between definitions was highest in Updated ATPIII vs. IDF (kappa = 0.863). It showed that only definitions of IDF (OR 1.55, 95%CI 1.04–2.31, p = 0.031) and Updated ATPIII (OR 1.64, 95%CI 1.11–2.42, p = 0.013) were independently associated with risk of ischemic stroke in multivariable logistic regression analysis. The risk of ischemic stroke increased with the increasing of numbers of Mets components in Updated ATPIII (p Conclusion In this population, Updated ATPIII criteria was a more suitable definition of Mets than definitions of Chinese guide, IDF and JIS for screening high-risk individuals of ischemic stroke, and the additive effects of Mets components might play a greater role than its composition alone in ischemic stroke.

Chronic granulomatous disease (CGD) is an inherited disorder, with phagocytes failing to produce antimicrobial superoxide due to deficient NADPH oxidase activity. Mutations in the gene encoding CYBB are responsible for the majority of the CGD cases. To date, there have been no reports on large samples of children with CGD in China. Therefore, in this study, we described the clinical and molecular features of 38 suspected CGD patients from 36 unrelated Chinese families. Clinical diagnosis was performed using dihydrorhodamine assays detected by flow cytometry. Molecular analysis was used to identify underlying CGD-causative genes. The mean age of onset in our 38 patients was 3.4 months, while the mean age at diagnosis was 31.7 months. Apart from recurrent pneumonia and abscesses, tuberculosis (TB) and Bacille Calmette-Guerin (BCG) infections were notable features in our cohort. Overall, 17 cases died and patient 1 did not participate in the follow-up period . In total, we identified 29 different CYBB gene mutations in 31 patients. We found NCF1 and CYBA mutations in 3 and 2 patients, respectively. In addition, we identified 31 carriers and prenatally diagnosed 4 CGD and 4 healthy fetuses. The results of our study demonstrate that children with BCG infections or recurrent TB infections should have immune function screening tests performed. Moreover, newborns with family histories of primary immunodeficiency diseases should avoid of BCG vaccination. Molecular analysis is an important tool for identifying patients, carriers, and high-risk CGD fetuses.

Aims This study sought to explore right (RV) and left ventricular (LV) mechanics and ventricular–ventricular interaction in adolescents and young adults late after percutaneous balloon pulmonary valvoplasty (PBPV) for valvar pulmonary stenosis (PS). Methods and results Potential late effects of PS despite PBPV on cardiac mechanics have not been well defined. Thirty-one patients aged 20.2 ± 7.6 years were studied at 18 ± 6 years after PBPV. Ventricular myocardial deformation was determined using speckle tracking echocardiography, while RV and LV volumes and ejection fraction as well as LV systolic dyssynchrony index were assessed by three-dimensional echocardiography. The results were compared with those of 30 controls. Pulmonary regurgitation, mostly trivial to mild, was present in 90% (28/31) of patients. Compared with controls, patients had significantly greater RV end-diastolic ( P < 0.001), RV end-systolic ( P < 0.001), and LV end-systolic ( P = 0.04) volumes as well as lower LV ejection fraction ( P < 0.001). For deformation, patients had significantly reduced RV longitudinal systolic strain ( P = 0.004), decreased LV circumferential systolic strain ( P < 0.001), and strain rate ( P = 0.001) as well as greater LV mechanical dyssynchrony ( P < 0.001). In patients, RV end-diastolic and end-systolic volumes correlated with LV circumferential strain ( r = −0.47, P = 0.008 and r = −0.36, P = 0.049, respectively) and dyssynchrony ( r = 0.53, P = 0.002 and r = 0.49, P = 0.005, respectively). Patients who had PBPV at age ≤1 year had ventricular deformation indices similar to those who had interventions beyond 1 year. Conclusion Impaired RV and LV mechanics and adverse ventricular–ventricular interaction occur in adolescents and young adults late after balloon valvoplasty for isolated valvar PS.

In an attempt to improve therapeutic efficacy of dexamethasone (DXM)-loaded solid lipid nanoparticles (NPs) for renal ischemia-reperfusion injury (IRI)-induced acute renal injury (AKI), sialic acid (SA) is used as a ligand to target the inflamed vascular endothelium. DXM-loaded SA-conjugated polyethylene glycol (PEG)ylated NPs (SA-NPs) are prepared via solvent diffusion method and show the good colloidal stability. SA-NPs reduce apoptotic human umbilical vein endothelial cells (HUVECs) via downregulating oxidative stress-induced Bax, upregulating Bcl-xL, and inhibiting Caspase-3 and Caspase-9 activation. Cellular uptake results suggest SA-NPs can be specifically internalized by the inflamed vascular endothelial cells (H2O2-pretreated HUVECs), and the mechanism is associated with the specific binding between SA and E-selectin receptor expressed on the inflamed vascular endothelial cells. Bio-distribution results further demonstrated the enhanced renal accumulation of DXM is achieved in AKI mice treated with SA-NPs, and its content is 2.70- and 5.88-fold higher than those treated with DXM and NPs at 6 h after intravenous administration, respectively. Pharmacodynamic studies demonstrate SA-NPs effectively ameliorate renal functions in AKI mice, as reflected by improved blood biochemical indexes, histopathological changes, oxidative stress levels and pro-inflammatory cytokines. Moreover, SA-NPs cause little negative effects on lymphocyte count and bone mineral density while DXM leads to severe osteoporosis. It is concluded that SA-NPs provide an efficient and targeted delivery of DXM for ischemia-reperfusion-induced injury-induced AKI, with improved therapeutic outcomes and reduced adverse effects.

The aim of this study is to determine the expression and roles of miR-346 in nasopharyngeal carcinoma (NPC). We showed that miR-346 was upregulated in NPC tissues compared with adjacent non-tumorous nasopharyngeal tissues. Inhibition of miR-346 significantly attenuated the migration and invasion of NPC cells. Luciferase reporter assay showed that miR-346 targeted the 3'-untranslated region (3'-UTR) of breast cancer metastasis suppressor 1 (BRMS1). Overexpression of miR-346 suppressed the endogenous expression of BRMS1 in NPC cells. There was a significant negative correlation between miR-346 and BRMS1 protein expression in NPC tissues (r = -0.372, P = 0.008). Rescue experiments demonstrated that overexpression of BRMS1 lacking the 3'-UTR impaired the invasiveness of NPC cells transfected with miR-346 mimic. Taken together, miR-346 shows the ability to promote the migration and invasion of nasopharyngeal cancer cells via targeting BRMS1 and represents a potential therapeutic target for NPC.

Background The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. Methods Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2*

Recently, a genome-wide association study reported an association between two single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important candidate locus in the prevalence of ischemic stroke. We performed a hospital based genetic association study in Chinese Han subjects to investigate the relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924 control subjects and conducted the association between these tSNPs and ischemic stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene significantly associated with ischemic stroke (both genotype and allelic p = 0.0001). The minor A allele increased the risk of ischemic stroke with a per-allele OR of 1.37 for the additive genetic model in univariate analysis (p = 0.0001). The significance remained after adjustment for the covariates of age, gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes. Therefore, we report a new genetic variant, rs10849373, located in the first intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han subjects. Further genetic association and functional studies are required to search the causal functional variant in linkage disequilibrium with this polymorphism.

Background/Aims: Post-stroke complications may influence prognosis, and may even become potentially life-threatening. The aim of this prospective study was to examine the frequency and timing of medical complications during the acute stage of critical ischemic stroke in patients treated in a neurological intensive care unit. Methods: Seventy acute ischemic stroke patients in a critical condition with morbid changes in organs other than the brain or with severe complications were admitted to a neurological intensive care unit and followed up with assessments of 15 specified complications during the first 2 weeks on days 2, 4, 7, and 14. Results: The most common complications within 2 weeks of onset were chest infection (90%), fever (64%), hypoalbuminemia (56%), arrhythmia (46%), irritable ulcer (44%), gastrointestinal dysfunction (39%), progression or recurrence of stroke (33%), and urinary tract infection (30%). The incidence of progression or recurrence of stroke and urinary tract infection peaked at day 2, and the incidence of arrhythmia, fever, chest infection, irritable ulcer, gastrointestinal dysfunction, and malnutrition peaked from 1 to 2 weeks. Conclusion: Progression or recurrence of stroke, fever, and chest infection are common complications in the acute stage of critical ischemic stroke.

Both activities of daily living (ADL) and some blood biomarkers (such as albumin) have been associated with mortality in very elderly people, but scarce data is available on the predictive performance of them in isolation or in combination, which is important for clinicians in decision making. Here, based on prospective mortality data over a 6-year follow-up period from 433 long-lived individuals (LLIs) aged 95+ years in the Rugao longevity cohort, we aimed to evaluate Cox proportional hazard ratios (HRs) and discriminative power (ROC curve) of 14 biomarkers and ADL for all-cause mortality. We found that six biomarkers (total triglyceride, albumin, low-density lipoprotein cholesterol, platelet count, lymphocyte count, and neutrophil count) were associated with mortality with a p

a Heart Center, Beijing Chaoyang Hospital, Institute of Cardiovascular Disease, Capital University of Medical Sciences, Beijing 100020, China b Department of Cardiology, Tangshan Gongren Hospital, Hebei Medical University, Tangshan, 063000, Hebei province, China c Department of Neurology, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020, China d State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China e Institute of epidemiology, School of public health, Fudan University, Shanghai, China f CMC Institute of Health Sciences, Taizhou 225300, Jiangsu Province, China

To analyze the association between hypertension and tobacco exposure Luoping county of Yunnan province and estimate the direct cost attributable to hypertension .Using Probability proportional to size (PPS) sampling method, 5000 rural residents aged over 18 years were selected from 12 townships in Luoping county, Yunnan province in April 2011, from which 4611 subjects completed the survey. Self-designed questionnaires were used to collect general information, smoking status, costs for outpatient consultation, inpatient, treatment, medication, travel, accommodation and extra-nutrition caused by hypertension as well as the information of health-related behavior. Their height, weight, waist circumference, hip circumference and blood pressure were measured. The direct economic burden of hypertension was calculated. Chi-square (χ(2)) test was used to compare gender differences of hypertension prevalence, smoking and passive smoking. And t test was used to compare the differences of direct economic burden of hypertension among different gender, smoking and passive smoking status. Multivariable logistic regression model was used to analyze the influence factors of hypertension.Among the 4611 subjects, the age was (46.90 ± 16.74) years old. Male accounted for 49.8% (2294/4611) and female 50.2% (2317/4611) . The smoking rate was higher in males (75.7% (1736/2294)) than in females(1.6% (38/2317)) (χ(2) = 2669.21, P0.01). The passive smoking rate was lower in males (10.0% (230/2294)) than in females (46.2% (1070/2317)) (χ(2) = 744.27, P0.05). Non-tobacco exposure rate in males (14.3% (328/1537)) was lower than in females (52.2% (1209/1537)) (χ(2) = 744.37, P0.05) . The risk of hypertension in smokers and passive smokers were higher than those without tobacco exposure, OR (95%CI) was 1.41 (1.15-1.71) (P0.05) and 1.31 (1.07-1.63) (P0.05) respectively. The per capita direct cost of hypertension was (3444.09 ± 3067.83) Yuan. Of this, tobacco exposure (4552.46 ± 3189.05) Yuan was higher than non-tobacco exposure (1907.71 ± 1383.94) Yuan (t = -3.81, P0.05) . Moreover, smokers were (6951.71 ± 3422.87) Yuan higher than passive smokers (3128.09 ± 2083.17) Yuan (t = 3.19, P0.05) and males (5827.39 ± 3240.50) Yuan were higher than females (2633.03 ± 2569.01) Yuan (t = 3.22, P0.05) . The total direct costs of hypertension attributable to smoking and SHS was 41 million and 38 million, respectively.Both smoking and SHS had significant impact on prevalence and economic burden of hypertension in Luoping county. Implementing effective strategies to control tobacco exposure is useful to reduce the economic burden of hypertension in the study region.

Background The clinical relevance of evaluating right ventricular (RV) myocardial deformation in congenital heart disease is increasingly recognized. The aim of this study was to explore, using three-dimensional (3D) speckle-tracking echocardiography, RV mechanics in terms of 3D global area strain and mechanical dyssynchrony in adults with repaired tetralogy of Fallot. Methods Twenty patients (12 men) aged 24.7 ± 8.6 years and 22 age-matched controls (11 men) were studied. Global RV peak area strain and area strain–derived systolic dyssynchrony index (SDI) were determined using 3D speckle-tracking echocardiography. RV end-diastolic volume and end-systolic volume, ejection fraction (EF), and pulmonary regurgitation fraction were measured in patients using cardiac magnetic resonance. Results Coefficients of variation for intraobserver and interobserver measurements of RV global area strain were 6.1% and 7.9%, respectively, and those for SDI were 7.6% and 10.1%, respectively. Compared with controls, patients had significantly lower global area strain ( P = .005) and greater SDI ( P = .008). The prevalence of RV mechanical dyssynchrony (SDI > control mean + 2 SDs) in patients was 30%. In patients, global area strain correlated inversely with SDI ( r = −0.42, P = .04), RV end-diastolic volume ( r = −0.48, P = .032), and RV end-systolic volume ( r = −0.48, P = .031) and positively with EF ( r = −0.51, P = .02), while RV SDI correlated positively with RV end-systolic volume ( r = 0.55, P = .012), pulmonary regurgitation fraction ( r = 0.54, P = .031), and QRS duration ( r = 0.51, P = .022) and negatively with RV EF ( r = −0.62, P = .004). Multivariate analysis showed that RV EF (β = 0.22, P = .048) was a significant correlate of global area strain in patients. Conclusions In adults after tetralogy of Fallot repair, 3D RV deformation is impaired in association with RV dyssynchrony, volume overloading, and reduced EF.

To explore the characteristics of cognitive impairment in patients with leukoaraiosis (LA).Forty-six LA patients and 38 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between September 2010 and March 2011. All participants underwent the neuropsychological tests recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards (NINDS/CSN). The were divided into 3 different groups (mild, moderate and severe) according to the Fazekas scale. The differences of neuropsychological performances were compared among 3 groups.The LA patients were associated with comprehensive cognitive function deficits, including MMSE (24.4 ± 3.2 vs 28.3 ± 1.2), MoCA (20.4 ± 3.0 vs 26.2 ± 0.8), digital span forward (5.7 ± 0.9 vs 6.8 ± 1.0), digital span backward (3.5 ± 0.7 vs 4.1 ± 0.7), Stroop-B (69 ± 13 vs 43 ± 5), Stroop-C (141 ± 42 vs 65 ± 10), trail making test-A (73 ± 15 vs 31 ± 7), trail making test-B (126 ± 18 vs 82 ± 6) and digit symbol test (25 ± 6 vs 37 ± 5, P0.05). However, there was no difference in the performance of verbal fluency (12.7 ± 2.5 vs 13.4 ± 2.5, P0.05). Correlation analysis showed that the severity of LA had a negative correlation with the performance of MoCA (r = -0.601, P = 0.002).The LA patients are closely correlated with cognitive impairments of attention, memory, executive function and information processing speed. It may be attributed to the frontal-subcortical circuitry dysfunction.

In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11–2.05, p = 0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30–3.37, p = 0.002) and 1.63 (95%CI 1.06–2.51, p = 0.026), respectively. In gene–environmental interaction analysis, elevation of ischemic stroke risk was observed among AG + GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51–5.41), 4.30(2.38–7.77), and 13.97(7.78–25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.

article i nfo Common pathogenic mechanisms may be involved in the prevalence of ischemic stroke and coronary heart disease. Recently, genome-wide association (GWA) studies identified a chromosome region (9p21) that confers the risk of coronary heart disease. In a hospital-based case-control study conducted in Chinese Hans, we tested the hypothesis that the methylthioadenosine phosphorylase (MTAP) gene on chromosome region 9p21 is involved in the aetiology of ischemic stroke using a tagging single nucleotide polymorphism (tSNP) strategy. We observed significant association of rs10118757 in the MTAP gene with ischemic stroke. The G allele of rs10118757 was associated with an increased risk of stroke, with a per-allele OR of 1.31(95% CI,1.04- 1.65, p=0.025). The association remains after controlling for confounding factors including age, gender, body mass index, smoking, alcohol drinking, hypertension, diabetes, and hyperlipidaemia (OR=1.38, 95 CI, 1.02-1.88, p=0.039). In addition, the GA+GG genotype of rs10118757 was associated with the increased risk of an undetermined subtype of ischemic stroke (OR=2.14, 95 CI, 1.35-3.38, p=0.001). Further, we also observed the combined effects of rs10118757 with alcohol drinking and hypertension, which increased the risk of ischemic stroke. Our observations support the hypothesis that the MTAP gene may be involved in the prevalence of ischemic stroke in Chinese Hans.

To investigate the expression of peroxisome proliferators-activated receptor gamma (PPARgamma) in trophoblast and relation between PPARgamma ligands and trophoblast invasion.We examined the expression of PPARgamma by immunohistochemistry, immunocytochemistry and real time quantitative PCR. We next examined, using the cytotrophoblast culture model, the biological role of PPARgamma ligands in vitro.PPARgamma was mainly localized in the nuclei of villous cytotrophoblast and extravillous cytotrophoblast of cell islands and cell columns. In villous tissue and cultured trophoblast from early first trimester, the level of expression of PPARgamma mRNA and protein was 36.0 +/- 5.1, 13.4 +/- 3.1 and 1.35 +/- 0.08, 1.13 +/- 0.11; from late first trimester it was 23.3 +/- 5.5, 6.1 +/- 1.3 and 1.17 +/- 0.03, 0.86 +/- 0.05, and the expression of PPARgamma was obviously decreased (P0.05). Our studies showed that both natural and synthetic PPARgamma agonists inhibited cytotrophoblast invasion in a concentration-dependent manner. In trophoblast from early and late first trimester, while 15-d-PGJ(2) at concentrations 1 and 10 micromol/L, troglitazone at a concentration 10 micromol/L, invasion index was 0.57 +/- 0.03, 0.43 +/- 0.02, 0.50 +/- 0.06 and 0.69 +/- 0.02, 0.59 +/- 0.03, 0.66 +/- 0.05. The effect on inhibition of trophoblast was significant compared with control (P0.05). Conversely, PPARgamma antagonists promoted cytotrophoblast invasion. Furthermore the PPARgamma antagonist abolished inhibitory effect of the PPARgamma agonists partially. PPARgamma ligands had a significant effect on cytotrophoblast from early first trimester more than cytotrophoblast from late first trimester (P0.05).PPARgamma plays an important role in the modulation of trophoblast invasion. Consequently, one can hypothesize that abnormal increases in the production of PPARgamma agonist ligands in placenta can alter trophoblast invasion and generate human pregnancy diseases such as preeclampsia.

BACKGROUND: Enhanced apoptosis of cytotrophoblasts in early pregnancy is associated with high risk of intrauterine growth retardation and preeclampsia, which are two common pregnant complications. Its etiological factors remain unclear. Cytotrophoblasts share some traits with innate immune cells and may show response to lipopolysaccharide. This study was conducted to demonstrate whether lipopolysaccharide has apoptosis-inducing effects on cytotrophoblast and the role of innate immune reaction in this process. METHODS: Cytotrophoblasts were isolated from early pregnant villous tissues and cultured with serum-free medium. Subsequently, cytotrophoblasts were treated with lipopolysaccharide at the concentrations of 0 (control), 25, 50, 100 and 200 ng/ml for 24 hours. Apoptosis of cytotrophoblasts was determined by light microscopy, Hoechst 33258 DNA staining with a fluorescent microscope, transmission electron microscope and annexin V-fluorescein isothiocyanate-conjugated/propidium iodide (PI) staining with flow cytometry. Then expression of caspase-3 was detected by Western blot. Confocal immunofluorescence technique was used to detect tumor necrosis factor alpha expression in cytotrophoblasts. The levels of tumor necrosis factor alpha in the culture medium were detected by enzyme-linked immunosorbent assay. RESULTS: Under light, fluorescence microscope and transmission electron microscope, characteristic alternations of apoptosis in cytotrophoblasts were observed after lipopolysaccharide treatment. Flow cytometry results showed that lipopolysaccharide significantly increased apoptosis indexes of cytotrophoblasts. Significant statistical differences were found in the above groups (P = 0.01). The mean relative densities of bands corresponding to caspase-3 were significantly increased in groups treated with lipopolysaccharide, as compared with the normal control (P < 0.001). Tumor necrosis factor a expression was found to increase in cytotrophoblasts by confocal immunofluorescence technique and in culture medium by enzyme-linked immunosorbent assay after lipopolysaccharide treatment. A positive correlation was found between tumor necrosis factor a expression and apoptosis indexes of cytotrophoblasts (r = 0.747, P < 0.001). CONCLUSION: Apoptosis of cytotrophoblasts could be induced by lipopolysaccharide, in which innate immune reaction is the important mechanism.

To investigate effects of peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands on cytotrophoblast invasion and its influence on matrix metalloproteinase (MMP)-2 and MMP-9 activities on cytotrophoblast cells.Samples of fresh placental trophoblast tissue were obtained from the pregnant women in first trimester. Cytotrophoblasts were isolated, cultured, and added with PPARgamma. Immunocytochemistry and inverted microscopy were used to examine the protein expression of PPARgamma in the cytotrophoblasts. Isolated cytotrophoblasts were inoculated in the Transwell chamber The natural stimulatory ligand of PPARgamma15-deoxy-delta (12, 14)-prostaglandin J2 (15d-PGJ2) and synthesized stimulatory ligand of PPARgamma troglitazone (TGZ) of the concentrations of 0, 1, and 10 micromol/L respectively were added respectively to examine the invasion ability of the cytotrophoblasts. Immunofluorochemistry and confocal technique and RT-PCR were used to examine the expression of MMP-2 and MMP-9.PPARgamma protein expression was detectable in the cytotrophoblasts, mainly in the nuclei. The invasion indexes of the cytotrophoblasts stimulated by 15d-PGJ2 and TGZ of different concentrations were significant lowered in a concentration-dependent manner, the effect of 15d-PGJ2 being stronger than that of TGZ (P0.05). After stimulated by 15d-PGJ2 and TGZ of different concentrations the mRNA expression and protein expression of MMP-9 and MMP-2 in the cytotrophoblasts were all inhibited significantly (all P0.05).PPARgamma plays an important role in the modulation of trophoblast invasion, and PPARgamma ligands can inhibit the trophoblast invasion through downregulating MMP-2 and MMP-9 expressions.

To investigate the dynamic changes of heart rate variability (HRV) in acute cerebral vascular disease, in order to make a criterion for evaluating cerebral function, and establish an assessment for risk stratification after acute stroke.All 35 patients who suffered from cerebral vascular disease in the distribution of the carotid artery system were studied from 1 to 7 days following the stroke. HRV analysis with 24-hour Holter tapes was performed every day or every other day continuously for 5 days. According to GCS, the patients were divided into two groups. Critical cerebral vascular disease (CCVD): a state of severe cerebral dysfunction with the Glasgow coma scale (GCS) value between 3 and 8. Non-critical cerebral vascular disease (nCCVD): a state of slightly cerebral dysfunction with the GCS value between 9 and 15.Of the 35 patients, 17 were classified to CCVD, 18 to nCCVD. The CCVD patients had significantly decreased HRV, especially the standard deviation of all R-R intervals (SDNN) and total frequency (TF). The 24-hour heart rate variability graph lost its circadian variation showing a low and plain curve during the whole day. There was a significant correlation between the decrease of HRV and bad prognosis. The borderline of HRV for prognosis was: SDNNor=60 ms, TFor=1 500 ms(2)/Hz, high frequency (HF)or=600 ms(2)/Hz, low frequency (LF)or=1000 ms(2)/Hz. Dynamic observation proved that if the components of HRV reached this standard, it always indicated bad outcome. On the contrary, if those components increased continuously and were higher than those of the above, it was always indicative of good outcome. These changes always advanced GCS. Prognosis had a high correlate with TF, LF, HF and GCS. Logistic regression showed that only TF, HF and GCS were the main factors affecting the prognosis. The accurate rate of death predication was 88.89 percent; the accurate rate of survival was 82.14 percent. It was much better than the traditional GCS.HRV decreases significantly in CCVD and loses its circadian variation. Dynamic observation of HRV offers a good marker for monitoring cerebral function and the progress of disease. HRV could be considered as an objective, non-traumatic and sensitive indicator of the cerebral function and prognosis.

Background Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures, which may affect atrial and ventricular filling. The aim of this study was to test the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, atriopulmonary connection (APC) and extracardiac conduit, which have distinctly different systemic venous hemodynamics. Methods This was a cross-sectional, case-control study of 28 Fontan patients (13 with APC, 15 with extracardiac conduit) aged 19.8 ± 6.5 years and 26 healthy controls. Atrial and systemic ventricular myocardial deformation was determined using speckle-tracking echocardiography, while ventricular volumes and systolic dyssynchrony index were assessed using three-dimensional echocardiography. Results Compared with controls, patients had significantly lower values of global ventricular longitudinal, circumferential, and radial systolic strain in all three directions, reduced systolic and early diastolic strain rates (SRs) in more than one dimension, lower ejection fractions, and worse ventricular dyssynchrony. For atrial deformation, patients had lower global and positive strain and conduit and reservoir SRs and delayed electromechanical coupling. Among patients, those with APC had significantly lower ventricular longitudinal strain and early diastolic SRs, worse ventricular dyssynchrony, and reduced atrial positive and negative strain and conduit and active contractile SRs. Atrial global strain ( r = 0.60, P = .001) and conduit SR ( r = 0.49, P = .008) correlated positively with systemic ventricular early diastolic SR. Conclusions Atrial and ventricular mechanics are impaired in patients after Fontan-type operation, which is worse with APC than extracardiac conduit.