Search

Purpose This study aimed to explore the correlations among heavy metals concentration, histologic subtypes and molecular characteristics in patients with non-small cell lung cancer (NSCLC). Methods In this study, an NGS panel of 82 tumor-associated genes was used to identify genomic alternations in 180 newly diagnosed patients with NSCLC. The concentrations of 18 heavy metals in the serum samples were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results A total of 243 somatic mutations of 25 mutant genes were identified in 115 of 148 patients with LUAD and 45 somatic mutations of 15 mutant genes were found in 24 of 32 patients with LUSC. The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were markedly different between patients with LUAD and LUSC. Moreover, patients with LUSC were significantly positively correlated with Ba, but not LUAD. Lastly, patients with EGFR mutations presented significant negative correlations with Cd and Sr, whereas patients with TP53 mutations showed a significant positive correlation with Pb. Conclusion The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were different between patients with LUAC and LUSC, and heavy metals (e.g., Ba, Pb, and Cd) may contribute to the tumorigenesis of NSCLC with different histological and molecular subtypes.

BACKGROUND AND PURPOSE Sleep disturbance and cognitive impairment are common and related in the elderly population worldwide. The aim of the present study was to explore the association between sleep disturbance and motoric cognitive risk (MCR) syndrome, which is characterized by subjective cognitive complaints and objective slow gait in older individuals without dementia or any mobility disability in the community-dwelling elderly Chinese population. METHODS We recruited 940 participants aged ≥65 years from November 2016 to March 2017 in the Ningbo Community Study on Aging (NCSA). Self-reported sleep duration and sleep-quality variables, comprehensive geriatric evaluation, as well as indicators for diagnosing MCR syndrome were evaluated in this cross-sectional study. RESULTS Multiple logistic regression analysis showed that a 1-SD increase in night (1.1 h) and 24-h sleep duration (1.3 h) was associated, respectively, with a 21% (95% confidence interval [CI], 1%-47%; p = 0.04) and 30% (95% CI, 3%-64%; p = 0.03) higher odds of having MCR syndrome. Considering sleep duration as a categorical variable, longer night-sleep duration (>8.5 h) was associated with MCR syndrome (OR, 2.03; p = 0.02) compared to shorter night-sleep duration (

Newborn screening (NBS) is an effective way for 3-step prevention of birth defects. The suitable technology and rational NBS screening diseases are critical for each country and area. High-throughput sequencing has shown high application potential in NBS. However, lack of sequencing strategy for monogenic inherited diseases NBS in China. In this study, we systematically evaluated the application efficiency of different sequencing approaches for NBS, and a gene-disease association list (NeoExome panel) for the Chinese population with 601 genes was designed based on the top rare disease list and databases. In the 1000 Genomes Project, 7.6% (23/301) were NGS positive. Among the 3249 neonates recruited, NGS positive rate was 12.0%. In the 200 conventional NBS (+) subgroup, 118 were NGS positive, with 76.3% (90/118) neonates harboring consistent results of conventional NBS and NGS; in the conventional NBS (-) subgroup, the NGS positive rate was 8.9% (271/3049). Our study designed a personal NBS targeted-sequencing NeoExome panel of monogenic inherited diseases for Chinese, which has shown acceptable performance.

Cardiovascular diseases (CVDs) are an important cause of death and disease worldwide. Because injured cardiac tissue cannot be repaired itself, it is urgent to develop other alternate therapies. Stem cells can be differentiated into cardiomyocytes, endothelial cells, and vascular smooth muscle cells for the treatment of CVDs. Therefore, cell therapy has recently been considered a viable treatment option that can significantly improve cardiac function. Nonetheless, implanted stem cells rarely survive in the recipient heart, suggesting that the benefits of stem cell therapy may involve other mechanisms. Exosomes derived from stem cells have a myocardial protection function after myocardial injury, and may be a promising and effective therapy for CVDs. Here, we discuss the application and mechanism of exosomes derived from stem cells in the diagnosis and treatment of CVDs and provide evidence for the application of exosomes in CVDs. Graphical Abstract.

Aims/Introduction Although increased reactive oxygen species (ROS) generation is a major mechanism leading to cardiac remodeling in diabetes mellitus, research into the effects of anti‐oxidation on diabetic cardiac remodeling remains scarce and controversial. Glucagon‐like peptide‐1 (GLP‐1) shows potential anti‐oxidative effects besides lowering blood glucose. The objective of this research was to investigate the effects of GLP‐1 on cardiac remodeling and the molecular mechanism involved in diabetes mellitus. Materials and Methods Streptozotocin‐induced diabetic rats received exenatide treatment for 3 months. Cardiac function, cardiac weight index and myocardial interstitial fibrosis were measured. Cardiomyocytes were cultured in high‐glucose medium with GLP‐1 treatment. The ROS production, apoptosis and the levels of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase protein expression in cardiomyocytes were analyzed. Results Experimental diabetes mellitus showed impaired cardiac diastolic function, increased brain natriuretic peptide expression and increased interstitial collagen deposition in the myocardium, which were ameliorated by exenatide treatment. Exenatide reduced myocardial ROS production and apoptosis in diabetes mellitus. Also, high glucose‐induced ROS generation and apoptosis in cardiomyocytes were inhibited by GLP‐1, as well as the levels of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase phosphorylation. Furthermore, GLP‐1 treatment upregulated adenosine monophosphate‐activated protein kinase activity in high‐glucose‐induced cardiomyocyte. Conclusions Glucagon‐like peptide‐1 protects the cardiomyocytes from oxidative stress and apoptosis in diabetes mellitus, which might contribute to the improvement of cardiac remodeling. The cardiac protection of GLP‐1 might be dependent on inhibition of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase, through an adenosine monophosphate‐activated protein kinase‐mediated pathway., Glucagon‐like peptide‐1 protects cardiomyocytes against oxidative stress, apoptosis and the resultant myocardial fibrosis in diabetes mellitus, which might contribute to the improvement of cardiac remodeling. The protective effects of glucagon‐like peptide‐1 are dependent on downstream inhibition of mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase, through an adenosine monophosphate‐activated protein kinase‐mediated pathway.

Transcatheter aortic valve replacement (TAVR) is a revolutionized treatment for severe aortic valve stenosis. Although new and improved TAVR devices are constantly being developed, cardiac conduction abnormalities post-TAVR requiring permanent pacemaker implantation (PPMI) still occur frequently. Previously, pre-existing right bundle branch block (RBBB) has been shown to be predictive of PPMI after TAVR, while occurrence of new left bundle branch block (LBBB) was associated with a higher rate of PPMI. However, less attention has been paid to the clinical values of new-onset RBBB post-TAVR. To our knowledge, this is the first report focus on the association of new-onset RBBB and PPMI after TAVR. Sometimes only changes in the right bundle branch can be detected, but the patient may have co-existing severe conduction block at this time, which caused adverse events including Adams-Stokes syndrome. New-onset RBBB post-TAVR may also have important clinical implications.

Transcatheter aortic valve replacement (TAVR) is a revolutionized treatment for severe aortic valve stenosis. Although new and improved TAVR devices are constantly being developed, cardiac conduction abnormalities post-TAVR requiring permanent pacemaker implantation (PPMI) still occur frequently1. Previously, pre-existing right bundle branch block (RBBB) has been shown to be predictive of PPMI after TAVR compared with patients without RBBB2, while occurrence of new left bundle branch block (LBBB) was associated with a higher rate of PPMI3. However, less attention has been paid to the clinical values of new onset non-LBBB conduction disturbances such as RBBB, left anterior fascicular block (LAFB) or atrioventricular block (AVB). To our knowledge, this is the first report focus on the association of new-onset non-LBBB and PPMI after TAVR. The study was approved by the Ethics Committee of HwaMei Hospital, University of Chinese Academy of Sciences. This article is protected by copyright. All rights reserved.

BackgroundIn the treatment of coronary heart disease, target vessel revascularization (TVR) has attracted increasing attention as an efficient means of percutaneous coronary intervention (PCI). The purpose of this study was to explore the association between stent diameter and TVR in patients undergoing PCI.MethodsThis was a secondary retrospective analysis involving patients with PCI with at least one stent implanted. Information was obtained from the Dryad Digital Repository. Multivariable logistic regression models, interaction analyses, subgroup analyses and piecewise linear regression models were used to evaluate the association between stent diameter and TVR.ResultsA total of 2522 patients were eventually enrolled in this study, of which 122 (4.8%) had undergone TVR. Significant positive associations were observed between stent diameter and TVR (continuous: odds ratio [OR] 0.485, 95% confidence interval [CI] 0.305–0.773, P = 0.002; categorical variable: T2 vs. T1, OR 0.541, 95% CI 0.348–0.843; T3 vs. T1, OR 0.520, 95% CI 0.334–0.809; P for trend = 0.005). The association remained stable in the fully adjusted model (continuous: OR 0.526, 95% CI 0.306–0.902, P = 0.020; categorical variable: T2 vs. T1, OR 0.510, 95% CI 0.310–0.839; T3 vs. T1, OR 0.585, 95% CI 0.352–0.973; P for trend = 0.042). Among the subgroups of differing clinical presentations, stent diameter was a powerful protective factor for TVR, especially in the delayed PCI group (P for interaction = 0.002). The association was highly consistent across all the other subgroups studied (all P for interaction > 0.05). In the piecewise linear regression model, the need for TVR decreased with an increase in stent diameter when this ranged between 2.5 and 2.9 mm (OR 0.01, 95% CI: 0.01–0.13, P ConclusionsA large stent diameter is a powerful protective factor for TVR in PCI patients, especially in the delayed PCI group. This “bigger-is-better” protective effect is remarkable in stents with diameter 2.5–2.9 mm.

FTIR absorption spectra indicate that H+ can easily enter the crystal structure and form OH– centers in Er:Yb:YCOB and O H bonds prefer to lie in the a-c plane. Within our current studied concentration level, crystal samples with higher OH– absorption coefficients demonstrate stronger fluorescence intensity and longer fluorescence lifetime at 1535 nm. As the stretching vibration energy of OH– group approximately corresponds to the energy gap between the 4I11/2 and 4I13/2 levels of Er3+, and thus, OH– ions can shorten the fluorescence lifetime of Er3+-4I11/2 level by the phonon-assisted cross-relaxation process between the Er3+ and OH– ions. Our current results confirm that a certain content of OH– ions can enhance the energy transfer process from Yb3+ to Er3+ and subsequently promote fluorescence output in 1.5–1.6 μm.

The anomalous glasslike behavior of heat transfer in Er:Yb: YCa4O(BO3)3 crystal was explored by means of temperature dependence Raman scattering spectra and synchrotron radiation X-ray topography. Crystal samples were prepared by the Czochralski technique, and the corresponding thermal properties, including thermal expansion, specific heat and thermal conductivity were investigated. The temperature-dependent Raman scattering results indicate the frequencies of Raman peaks as a function of crystal temperature followed a linear dependency on crystal temperature with different slopes. Nevertheless, the temperature-dependent linewidths of different Raman peaks were inconsistent and complicated. The X-ray topography firstly revealed a core situated in the center of crystal. Surrounding the core, a number of other defects like striations and dislocations were observed. The existence of such defects can lead to phonon scattering, which will introduce complicated influence into heat transfer process. As a result, the anomalous behavior of heat transfer can be influenced by disordered structure and crystal defects.

Aging generally coincides with a gradual decline in mass and strength of muscles and bone mineral density (BMD). Sarcopenia is closely linked to osteoporosis in the elderly, which can lead to abnormal gait, balance disorders, and dysfunctions, as well as increase in the risks of falls, fractures, weakness, and death. MicroRNAs (miRNAs, miRs) are a kind of short and non-coding RNA molecules but can regulate posttranscriptional protein expression. However, we have known little about their participation in age-associated osteoporosis and sarcopenia. The current study aims to confirm those miRNAs as biomarkers for age-related reduction in muscular atrophy associated with human blood fractures. In our study, 10 fracture-risk-related miRNAs (miR-637, miR-148a-3p, miR-125b-5p, miR-124-3p, miR-122-5p, miR-100-5p, miR-93-5p, miR-21-5p, miR-23a-3p, and miR-24-3p) were analyzed. For the initial screening, we determined the abundance of fracture-risk-associated miRNAs by RT-PCR most frequently detected in enrolled 93 elderly with sarcopenia and non-sarcopenia, respectively. Statistically, the relative expression levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, while the levels of other miRNAs did not change significantly. Moreover, we showed that the levels of ASM/height2, handgrip strength, and 4-m velocity in the sarcopenia group were significantly lower than in the non-sarcopenia group. Whereafter, we expanded the sample for further detection and analysis and revealed that the levels of plasma miR-23a-3p, miR-93-5p, and miR-637 in the sarcopenia group were significantly lower than that in the non-sarcopenia group, which is consistent with the initial screening experiment. From our analysis, changes in levels of plasma miR-93-5p and miR-637 were dramatically related to ASM/height2. Furthermore, changes in miR-23a and miR-93-5p were significantly affected by ASM/height2 in female individuals, with no significant correlations between miRNAs changes and these diagnostic indexes in male individuals after adjusting sex. The study showed that plasma miRNAs changed in an aging-related sarcopenia manner and were associated with increased fracture risk. In aging patients, plasma miR-23a-3p, miR-93-5p, and miR-637 have the potential as biomarkers of sarcopenia, which can affect the development of physiological dysfunction and may be also used in the fracture risk assessment of these patients.

Background Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China. Results We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel. Conclusion This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.

Additional file 2. Table S2: Biochemical features of BKTD patients identified by NBS and SMS.

Additional file 1. Table S1: Biochemical, clinical, and molecular features of 29 Chinese patients with BKTD.

Background: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutations in ACAT1 that affects both isoleucine catabolism and ketolysis. Scant information is available regarding the incidence, newborn screening (NBS), and mutational spectrum in China.Methods: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published Chinese BKTD patients data.Results: Totally 16,088,190 newborns were screened and 14 were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. Twenty-nine patients were genetically diagnosed as BKTD and 12 patients were newly identified. Most patients showed typical blood acylcarnitine and urinary organic acid profiles. In particular, almost all patients (15/16, 94%) showed elevated C4OH levels. Eighteen patients presented acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of 9 patients were triggered by infections, diarrhea, and vaccination. About two thirds of patients have favorable outcomes, one showed developmental delay, while three had died. Twenty-seven distinct variants were identified in ACAT1, among which 5 were found to be novel.Conclusion: This study presented the largest series of BKTD cohort in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by adding C4OH to the current panel of C5OH and C5:1 markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in Chinese population were expanded with 5 newly identified variants.

BACKGROUND AND PURPOSE A recently proposed pre-dementia syndrome, motoric cognitive risk (MCR) syndrome, is characterized by cognitive complaints and slow gait, and increases the risk of dementia and mortality. The aim of the present study was to explore the prevalence of and factors associated with MCR syndrome in elderly community-dwelling Chinese subjects. METHODS The Ningbo Community Study on Aging recruited 953 Chinese community-dwelling participants aged ≥ 65 years from November 2016 to March 2017. Handgrip, Five-Times-Sit-to-Stand (FTSS) test time and body composition, as well as comprehensive geriatric evaluation, were measured as potentially independent factors associated with MCR syndrome. RESULTS The prevalence of MCR syndrome was 12.8% in men and 12.6% in women, and high prevalence of MCR syndrome was not associated with age or sex. Multiple logistic regression analysis by sex showed that a 1-SD increase in FTSS test time in males and females was associated with 45% (95% confidence intervals, 19-76; P

sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is a major cause of morbidity and mortality in elders. Current diagnostic criteria of sarcopenia have not been agreed internationally, and the clinical diagnostic biomarkers for sarcopenia have not been identified. Circulating miRNAs (miRNAs, miRs) have recently been characterized as novel biomarkers for sarcopenia. However, the change of circulating miRNAs in response to sarcopenia are still not fully understood. Here, we enrolled a total of 93 elderly patients clinically diagnosed with sarcopenia and matching 93 non-sarcopenia elderly in this study. Specifically, levels of candidate circulating miRNAs which were involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were detected in these two groups. In small-sample screening experiments, plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels were significantly down-regulated in sarcopenia compared to those who non-sarcopenia. In contrast, miR-1, mir-133a, miR-133b, miR-21, miR-146a, miR-126, miR-221, and miR-20a were not changed significantly. Subsequently, we expanded the sample size to further detection and verification, and found that plasma miR-155, miR-208b, miR-222, miR-210, miR-328, and miR-499 levels in the sarcopenia group were significantly reduced compared to the non-sarcoma group, which is consistent with the results of the small-sample screening experiment. In addition, we showed that ASM/Height2, handgrip strength, knee extension and 4-meter velocity in sarcopenia group were significantly lower than those in non-sarcopenia group. Here we correlated the decrease of miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 in sarcopenia group and non-sarcopenia group with diagnostic indexes of sarcopenia (ASM/Height2, Handgrip strength and 4-meter velocity) after adjusting sex. The results showed that miR-208b and miR-155 changes were significantly correlated with handgrip strength in woman, miR-208b, miR-499, and miR-222 changes were significantly correlated with ASM/Height2 in man, while other miRNAs changes did not show a strong correlation with these diagnostic indexes. In conclusion, plasma miR-208b, miR-499, miR-155, miR-222, miR-328, and miR-210 decrease in response to sarcopenia in the elderly. Although further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of sarcopenia, present findings set the stage for defining circulating miRNAs as biomarkers and suggesting their physiological roles in elderly with sarcopenia.

Electroacupuncture (EA) therapy has widely been accepted as a useful therapeutic technique with low risk in the clinical setting for prevention from cardiac disease. However, the physiological mechanism under which this protective effect works remains unclear. The present study investigated the effects of EA pretreatment on myocardial ischaemia/reperfusion (MI/R) injury in mice and its possible signalling pathway. Mice were randomly divided into Sham, MI/R, EA + MI/R, EA(−) + MI/R, and AM630 + EA + MI/R groups. We reported that EA pretreatment significantly ameliorated MI/R injury, evidenced by increased cardiac function, reduced infarct size, and decreased apoptosis. This was associated with a reduction of oxidative stress in the infarcted myocardium, which was through CB2. The CB2 expression was up-regulated in the heart after EA pretreatment, as well as heart tissue content of N -arach-idonoylethanolamine-anandamide and 2-arachidonylglycerol. Furthermore, the expression of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in the left ventricular myocardial tissue was decreased in the MI/R group, whereas increased in the EA pretreatment group. Administration of AM630 before EA pretreatment did not improve cardiac function and inhibit oxidative stress. Preinjection of AM630 or AMPK inhibitor compound C could partially decrease the expression of EA pretreatment-mediated AMPK or PGC-1α. Pretreatment with EA increased the production of endocannabinoid, which elicited protective effects against MI/R injury through CB2 activation. The mechanism of this effect was related to the activation of AMPK/PGC-1α pathway, followed by an inhibition of oxidative stress.

Accumulating evidence suggests that maternal obesity increases the risk of their offspring developing noncommunicable diseases later in life, but the potential mechanisms, especially those resulting in abnormal respiratory conditions, are not thoroughly understood. Here, we used maternal high-fat diet (HFD) feeding during premating, pregnancy, and lactation to investigate the effect of maternal HFD on offspring lung development. Offspring birth weight and body weight and composition were measured. Serum leptin levels were measured by ELISA. Hematoxylin-eosin (H&E) and Masson's staining were used in paraffin-embedded lung sections. Levels of transfer growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry and western blot, respectively. Maternal HFD feeding during pregnancy and lactation lead to higher birth weight, final body weight, fat accumulation and hyperleptinemia in offspring. Maternal HFD feeding aggravated lung inflammatory response in the offspring, resulting in inflammatory cell infiltration and collagen deposition potentially via the enhanced expression of TGF-β and α-SMA in the offspring.

Cannabinoid receptor type 2 (CB2) activation is recently reported to promote proliferation of some types of resident stem cells (e.g., hematopoietic stem/progenitor cell or neural progenitor cell). Resident cardiac progenitor cell (CPC) activation and proliferation are crucial for endogenous cardiac regeneration and cardiac repair after myocardial infarction (MI). This study aims to explore the role and possible mechanisms of CB2 receptor activation in enhancing myocardial repair. Our results revealed that CB2 receptor agonist AM1241 can significantly increase CPCs by c-kit and Runx1 staining in ischemic myocardium as well as improve cardiomyocyte proliferation. AM1241 also decreased serum levels of MDA, TNF-α and IL-6 after MI. In addition, AM1241 can ameliorate left ventricular ejection fraction and fractional shortening, and reduce fibrosis. Moreover, AM1241 treatment markedly increased p-Akt and HO-1 expression, and promoted Nrf-2 nuclear translocation. However, PI3K inhibitor wortmannin eliminated these cardioprotective roles of AM1241. In conclusion, AM1241 could induce myocardial regeneration and improve cardiac function, which might be associated with PI3K/Akt/Nrf2 signaling pathway activation. Our findings may provide a promising strategy for cardiac endogenous regeneration after MI.

BRIP1 (BRCA1-interacting protein 1), a DNA-dependent ATPase and a DNA helicase, is critical for BRCA-associated DNA damage repair functions, and may be involved in the development of cervical cancer. Genetic markers in different regions of the BRIP1 gene have a plausible role in modulating the risk of cervical cancer. In this study, we evaluate the association between the BRIP1 variations and the risk of cervix cancer. We examined the potential association between cervical cancer and eighteen single nucleotide polymorphisms (SNPs, rs2048718, rs16945692, rs4968451, rs6504074, rs4988344, rs8077088, rs10515211, rs9897121, rs9906313, rs2159450, rs4986764, rs11871785, rs4986763, rs11079454, rs7213430, rs34289250, rs4988345 and rs12937080) of the BRIP1 gene using the MassARRAY system. The participants enrolled in this study included 298 patients with cervical cancer and 286 healthy women as the healthy controls from a Chinese Han population. The results showed that rs16945692 (intron 1), rs4968451 (intron 4), rs4986764 (exon 18) and rs7213430 (3'UTR) were significantly associated with cervical cancer (P0.05). Furthermore, strong linkage disequilibrium (LD) was observed in three blocks (D'0.9), and significantly more T-A-C-A haplotypes (block 1) (P=0.001) were found in the patients with cervical cancer. Significantly higher frequencies of C-A-T haplotypes (block 2) (P=0.018) and A-A haplotypes (block 3) (P=0.009) were detected in the healthy controls than in the patients with cervical cancer, suggesting that they may show protective effects against cervical cancer. These findings point to a role for the BRIP1 gene polymorphisms in cervical cancer in a Chinese Han population, and may be informative for future genetic or biological studies on cervical cancer.

Aims Apelin, an endogenous cytokine, has a number of biological effects on the cardiovascular system, including a cardioprotective effect and calcium modulation. Because the intracellular calcium abnormality is considered to play an important role in cardiac dysfunction induced by ischaemia–reperfusion (I/R), the aim of this study was to examine the effects of apelin-13 on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. Methods and results Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of apelin-13 and inhibitors of some survival kinases. We found that depressed cardiac performance induced by I/R was attenuated by apelin-13. Furthermore, apelin-13 depressed oxidative stress during I/R. SR function depressed during I/R was partly reversed by apelin-13. SR oxidative modification levels were increased in I/R and reversed by apelin. Inhibitors of phosphatidylinositol-3-kinase and protein kinase C abolished the effects of apelin. Apelin-13 maintained the Ca2+ transient against I/R in cardiomyocytes. Conclusion Apelin protects SR function and cardiac performance during I/R by attenuating oxidation of sarco(endo)plasmic reticulum Ca2+-ATPase and RyR.

Impaired cardiac microvascular function contributes to cardiovascular complications in diabetes. Glucagon-like peptide-1 (GLP-1) exhibits potential cardioprotective properties in addition to its glucose-lowering effect. This study was designed to evaluate the impact of GLP-1 on cardiac microvascular injury in diabetes and the underlying mechanism involved. Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received a 12-week treatment of vildagliptin (dipeptidyl peptidase-4 inhibitor) or exenatide (GLP-1 analog). Experimental diabetes attenuated cardiac function, glucose uptake, and microvascular barrier function, which were significantly improved by vildagliptin or exenatide treatment. Cardiac microvascular endothelial cells (CMECs) were isolated and cultured in normal or high glucose medium with or without GLP-1. GLP-1 decreased high-glucose–induced reactive oxygen species production and apoptotic index, as well as the levels of NADPH oxidase such as p47phox and gp91phox. Furthermore, cAMP/PKA (cAMP-dependent protein kinase activity) was increased and Rho-expression was decreased in high-glucose–induced CMECs after GLP-1 treatment. In conclusion, GLP-1 could protect the cardiac microvessels against oxidative stress, apoptosis, and the resultant microvascular barrier dysfunction in diabetes, which may contribute to the improvement of cardiac function and cardiac glucose metabolism in diabetes. The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-mediated pathway.

Aims: To determine the effects of percutaneous coronary intervention (PCI) on cardiac perfusion, cardiac function, and quality of life in patients with chronic total occlusion (CTO) lesion in left anterior descending (LAD) coronary artery. Methods and Results: Patients (n=99) with CTO lesion in the LAD coronary artery who had successfully undergone PCI were divided into three groups based on the SPECT/CTCA fusion imaging: (a) no severe cardiac perfusion defects (n=9); (b) reversible cardiac perfusion defects (n=40); or (c) fixed cardiac perfusion defects (n=50). No statistical difference of perfusion abnormality was observed at 6 months and 1 year after PCI in group (a). In group (b), SPECT/CTCA fusion imaging demonstrated that cardiac perfusion abnormality was significantly decreased 6 month and 1 year after PCI. Left ventricular ejection fraction (LVEF) increased significantly at 6 months and 1 year follow up. Quality of life improved at 6 months and 1 year after PCI procedure. Moreover, patients in group (c) also benefited from PCI therapy: a decrease in cardiac perfusion abnormality, an increase in LVEF, and an improvement in quality of life. PCI of coronary arteries in addition to LAD did not significantly affect cardiac function and quality of life improvement in each group. Conclusions: PCI exerts functional and clinical benefits in patients with CTO lesion in LAD coronary artery, particularly in patients with reversible cardiac perfusion defects. SPECT/CTCA fusion imaging may serve as a useful tool to evaluate the outcomes of patients with CTO lesion in LAD coronary artery.

Aims: To determine the effects of percutaneous coronary intervention (PCI) on cardiac perfusion, cardiac function, and quality of life in patients with chronic total occlusion (CTO) lesion in left anterior descending (LAD) coronary artery.Methods and Results: Patients (n=99) with CTO lesion in the LAD coronary artery who had successfully undergone PCI were divided into three groups based on the SPECT/CTCA fusion imaging: (a) no severe cardiac perfusion defects (n=9); (b) reversible cardiac perfusion defects (n=40); or (c) fixed cardiac perfusion defects (n=50). No statistical difference of perfusion abnormality was observed at 6 months and 1 year after PCI in group (a). In group (b), SPECT/CTCA fusion imaging demonstrated that cardiac perfusion abnormality was significantly decreased 6 month and 1 year after PCI. Left ventricular ejection fraction (LVEF) increased significantly at 6 months and 1 year follow up. Quality of life improved at 6 months and 1 year after PCI procedure. Moreover, patients in group (c) also benefited from PCI therapy: a decrease in cardiac perfusion abnormality, an increase in LVEF, and an improvement in quality of life. PCI of coronary arteries in addition to LAD did not significantly affect cardiac function and quality of life improvement in each group.Conclusions: PCI exerts functional and clinical benefits in patients with CTO lesion in LAD coronary artery, particularly in patients with reversible cardiac perfusion defects. SPECT/CTCA fusion imaging may serve as a useful tool to evaluate the outcomes of patients with CTO lesion in LAD coronary artery.

Ghrelin is thought to directly exert a protective effect on the cardiovascular system, specifically by promoting vascular endothelial cell function. Our study demonstrates the ability of ghrelin to promote rat CMEC (cardiac microvascular endothelial cell) proliferation, migration and NO (nitric oxide) secretion. CMECs were isolated from left ventricle of adult male Sprague-Dawley rat by enzyme digestion and maintained in endothelial cell medium. Dil-ac-LDL (1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein) intake assays were used to identify CMECs. Cells were split into five groups and treated with varying concentrations of ghrelin as follows: one control non-treated group; three ghrelin dosage groups (1×10-9, 1×10-8, 1×10-7 mol/l) and one ghrelin+PI3K inhibitor group (1×10-7 mol/l ghrelin+20 μmol/l LY294002). After 24 h treatment, cell proliferation capability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and Western blot for PCNA (proliferating cell nuclear antigen) protein expression. Migration of CMECs was detected by transwell assays, and NO secretion of CMECs was measured via nitrate reduction. Protein expression of AKT and phosphorylated AKT in CMECs was measured by Western blot after exposure to various concentrations of ghrelin and the PI3K inhibitor LY294002. Our results indicate that ghrelin significantly enhanced cell growth at concentrations of 10-8 mol/l (0.271±0.041 compared with 0.199±0.021, P = 0.03) and 10-7 mol/l (0.296±0.039 compared with 0.199±0.021, P

The coniform bottom device was designed and used in the rapid growth process of KDP crystal. A seed support rack was also designed to be used in rapid growth of KDP crystal to avoid spontaneous nucleation on the interface of seed crystal and rack. The KDP crystals were fast grown at the growth rate of up to 25 mm/day. The optical scatter centers in KDP crystals were observed and their transmissions of different parts were measured. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background Evidence suggests that activation of κ-opioid receptor (KOR) by U50,488H exhibits potential cardiovascular protective properties. However, the effects of U50,488H on vascular dysfunction in diabetes mellitus (DM) are still not clear. The present study was designed to investigate the effects of U50,488H on vascular dysfunction in diabetic rats and explore the underlying mechanisms involved. Methods Rats were randomly divided into control, DM, DM + vehicle, DM + U50,488H and DM + nor-binaltorphimine (nor-BNI) groups. Streptozotocin injection was used to induce DM. Weight, blood glucose, blood pressure and plasma insulin for each group were measured. Arterial functions were assessed with isolated vessels mounted for isometric tension recordings. Angiotensin II (ANG II), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and IL-8 levels were measured by ELISA, and endothelial nitric oxide synthase (eNOS) phosphorylation and NF-κB p65 translocation were measured by Western blot. Results Activation of KOR by U50,488H reduced the enhanced contractility of aortas to KCl and noradrenaline and increased acetylcholine-induced vascular relaxation, which could also protect the aortal ultrastructure in DM. U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment. Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment. Conclusions Our study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

Three experiments about KDP crystal were designed to analyze the relationship between the thin surface-layer growth mechanism and formation of solution inclusions. It is found that asymmetrical hydrodynamics condition and imperfect crystallographic shape can induce generation of a thin surface layer. The morphology of the thin layer is observed under microscopy and SEM, revealing that the thin surface layer was composed of many thinner layers. At the same time, the growth mechanism of thin surface layers was also found in the rapid growth of ADP crystal.

To evaluate the association between gene variations in BRIP1 (BRCA1-interacting protein 1) and the risk of cervical cancer, we examined eight single nucleotide polymorphisms (SNPs: rs2048718, rs12937080, rs4988344, rs6504074, rs4988345, rs4986764, rs4986763, and rs11079454) in the BRIP1 gene in cervical tissue from a Chinese population using the MassARRAY system. The participants enrolled included 454 cervical cancer patients and 562 healthy controls. Quantitative real-time reverse transcription PCR (qRT-PCR) was performed to examine the potential correlation between functional BRIP1 SNP genotypes and mRNA levels in cervical cancer tissues. Our results first showed that rs4986764, located in exon 18 in the BRIP1 gene, was significantly associated with cervical cancer (χ(2)=11.191, P=0.001, odds ratio (OR)=1.384, 95% confidence interval (CI)=1.144-1.675). Another significant association was observed for rs4986763 located in exon 20 in BRIP1 (χ(2)=4.988, P=0.026, OR=1.241, 95% CI=1.027-1.500). Strong linkage disequilibrium was observed in the rs11079454-rs4986763-rs4986764 SNP block (D'>0.9). The frequencies of haplotype T-T-T are higher in controls than in these patients (P=2.01E-5). Moreover, cervical cancer tissues with a homozygous C/C genotype for rs4986764 had the lowest level of BRIP1, which was 2.8 and 2.9-fold lower than the C/T heterozygote and the T/T homozygote, respectively. These findings indicate a role for BRIP1 gene variations in cervical cancer and may be informative for future genetic or biological studies on cervical cancer.

P2P e-commerce becomes one of most important e-business models. The paper about e-commerce activities has focused on the trust risk increasingly. To solve identity trust problem in e-commerce transactions, the idea of threshold cryptography is introduced and a distributed digital signature scheme based on the P2P e-commerce is designed in this paper. The threshold program having the trust node and enhancing safty based on the Elliptic Curve digital signature is provided in P2P environment, which uses elliptic encryption technology and safe Elliptic Curves, combining with the threshold system, verifiable secret sharing and proactive secret sharing system. The trust node is responsible for producing the key, the sub-key and distributing sub-key. Then it revokes the key immediately to ensure key security. The threshold signature scheme based on elliptic encryption technology for solving the risks of P2P e-commerce, which architecture of authority is built by trust degree nodes.

Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs. In contrast, ghrelin pretreatment significantly improved proliferation and NO secretion, and inhibited cell apoptosis and secretion of cytokines in HCY-induced CMECs. In addition, Western blot assay showed that NF-κB (nuclear factor κB) and cleaved-caspase 3 expression were elevated, and PCNA (proliferating cell nuclear antigen) and eNOS (endothelial nitric oxide synthase) expression were decreased after treatment with HCY, which was significantly reversed by pretreatment with ghrelin. The data suggest that ghrelin inhibits HCY-induced CMEC dysfunction and inflammatory response, probably mediated by inhibition of NF-κB activation.

BackgroundObesity is a risk factor for the development of certain respiratory diseases, and neonatal overfeeding results in an early onset of obesity in adulthood. However, the influence of neonatal overfeeding on respiratory diseases has rarely been studied. Therefore, this paper is aimed at investigating the effect of neonatal overfeeding on airway responsiveness and inflammation.Methodology/principal findingsThe neonatal overfeeding was induced by reducing litter size to three pups per litter (small litter, SL) in contrast to the normal litter size with ten pups per litter (NL) on postnatal day 3 (P3) in male ICR mice. On P21, mice were weaned to standard chow diet. Airway responsiveness to methacholine was measured either on P21 or P150. Total and classified inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted, lung inflammatory cells were evaluated through staining with hematoxylin & eosin and F4/80 immunohistochemistry; lung fibrosis was evaluated through staining with Masson and α-SAM immunohistochemistry. Leptin levels in serum were measured by RIA; TNF-α levels in serum and BALF were quantified by ELISA; mRNA levels of TNF-α, CTGF and TGF-β1 in lung tissues were measured using real-time PCR. Mice from SL exhibited accelerated body weight gain, impaired glucose tolerance and hyperleptinemia. Enhanced airway responsiveness to methacholine was observed in SL mice on P150, but not on P21. Pulmonary inflammation was evident in SL mice on P150, as reflected by inflammatory cells especially macrophages around bronchi and interstitium. BALF and serum TNF-α levels and lung TNF-α mRNA expression were significantly increased in SL mice on P150. More collagen accumulated surrounding the bronchi on P150; lung mRNA levels of TGF-β1 and CTGF were also increased on P150.ConclusionIn addition to inducing a variety of metabolic defects, neonatal overfeeding enhanced lung inflammation, which may lead to airway remodeling and airway hyperresponsiveness in adulthood.

Objectives The aim of this study was to investigate the ability of CB2 agonist AM1241 to promote murine infarcted myocardium repair by activating resident endogenous cardiac stem/progenitor cells (CSC/CPCs) and possible mechanisms. Methods Acute myocardial infarction (AMI) was induced in mice by ligation of left descending artery. Mice were randomised into following groups with n = 10 each: (1) Sham group, (2) MI group, (3) MI + AM1241 group, (4) MI + AM1241 + AM630 (CB2 receptor antagonist). Then, AM1241(10mg/kg) was intraperitoneal injected into mice for seven consecutive days. Three days post-operation, cardiomyocyte survival and apoptosis was determined by Ki67 and TUNEL staining respectively. The levels of LDH, TNF-α and IL-6 were examined with ELISA assay. The express-ion of CSC/CPCs markers c-kit and Runx1 in infarction border zones (IBZs) of myocardium were evaluated with immohistopathology 7 days later. The mice cardiac function evaluation was performed by echocardiography 3, 7, 14 and 28 days postoperation respectively. Myocardium fibrosis was detected with Masson’s trichrome stain 4 weeks later. The expression of ERK, Keap-1, Nrf2 and heme oxygenase (HO-1) and superoxide dismutase (Cu/Zn-SOD) were performed by Western blot analysis. Results In contrast to sham group, AM1241 could significantly increase c-kit and Runx1 positive CSC/CPCs number [Runx 1 positive cells: (3.32 + 0.25)% vs. (1.14 + 0.13)%, p p p p p p p In contrast to sham group, AM1241 could significantly increase c-kit and Runx1 positive CSC/CPCs number [Runx 1 positive cells: (3.32 + 0.25)% vs. (1.14 + 0.13)%, p p p p p p p Conclusions AM1241 could better adverse oxidative stress and inflammation milieu after AMI, benefit CSC/CPCs activation, induce myocardial regeneration, and improve cardiac function, which might be associated with ERK/Nrf 2/ARE signaling pathway activation.

Objectives Electroacupuncture (EA) therapy has been widely accepted as a useful therapeutic technique with low or no risk in the clinical prevention from cardiac disease. However, the physiological mechanism underlying this protective effect remains unclear. The current study investigates the effects of EA pretreatment on myocardial ischaemia/reperfusion (MI/R) injury in mice and its possible signalling pathway. Methods Up to 100 C57BL/6 mice were randomly divided into Sham, MI/R, EA + MI/R, EA (-) + MI/R, and AM630 + EA + MI/R groups (n = 20, each group). The mice in EA + MI/R and AM630 + EA + MI/R groups received EA pretreatment for 30 min before MI/R. Five minutes before EA pretreatment, mice received intraperitoneal injection of the cannabinoid receptor type 2 (CB2) selective inhibitor AM630 (20 mg/kg) or vehicle. Left anterior descending coronary artery ligature in mice was performed for 30 min, and the myocardium was reperfused for 3 h after knot release (for apoptosis, oxidative stress, and CB2 expression) or 24 h (for cardiac function and infarct size determination). Results EA pretreatment significantly ameliorated MI/R-induced myocardial injury, evidenced by increased cardiac function, reduced infarct size, and decreased apoptosis in mice. This was associated with a reduction of oxidative stress in the infarcted myocardium, which was through CB2. Administration of AM630 before EA pretreatment didn’t improve cardiac function and inhibit oxidative stress. The expression of CB2 was up-regulated in hearts after EA pretreatment, as well as content of N-arach-idonoylethanolamine-anandamide (AEA) and 2-arachidonylglycerol (2-AG) in heart tissue. Furthermore, the expression of AMPK and PGC-1α in the left ventricular myocardial tissue was decreased in MI/R group, while increased in EA pretreatment group. Preinjection of CB2 inhibitor AM630 could partially decreased the EA pretreatment-mediated AMPK or PGC-1α expression. Conclusions Pretreatment with EA increases the production of endocannabinoid, which elicits protective effects against MI/R injury through CB2 activation. The mechanism of this effect is related to the activation of AMPK/PGC-1α pathways, followed by an inhibition of oxidative stress. These results suggest a novel mechanism of EA pretreatment-induced protective effects on MI/R.

Objectives Glucagon-like peptide-1 (GLP-1) was a hormone predominately synthesised and secreted by intestinal L-cells. Pharmacological modulation of the GLP-1 had emerged as an important treatment target for diabetes mellitus. In addition to its glucose lowering properties, GLP-1 was found to have multiple cardioprotective effects. Impaired cardiac microvascular function is thought to contribute greatly to the diabetes cardiovascular disease. Yet the effects of GLP-1 on cardiac microvessels remained unclear, this study was aim to investigate the protective effects of GLP-1 on cardiac microvessels injury and the underlying regulatory mechanism in diabetes mellitus. Methods Streptozocin (STZ)-induced diabetic rats (n=45) were randomised to 12 weeks of treatment with vehicle, LAF237 (DPP-IV inhibitor, 1 mg/kg/d) or Exenatide (GLP-1 analogue, 1 nmol/kg/d). Before and after treatment, blood glucose levels and weight were assessed. Cardiac function was examined by echocardiographic measurements; cardiac energetics was examined by 18 F-FDG PET/CT. Scanning electron microscopy was used to analyse changes in morphology of cardiac microvessels. Transmission electron microscopy was used to assay cardiac microvascular permeability via lanthanum nitrate tracer. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and cultured in medium alone (control) or medium containing glucose (25 mmol/l), GLP-1 (10 −7 mmol/l), high glucose (25 mmol/l) plus GLP-1 (10 −7 mmol/l). First, GLP-1 receptor (GLP-1R) was detected by immunofluorescence and western blot. Then lucigenin-enhanced chemiluminescence assay and dihydroethidine (DHE) staining were used to assess oxidative stress. Tunnel staining and caspase-3 expression were used to assess apoptosis of CMECs. H89 was used to inhibit cAMP/PKA pathway; fasudil was used to inhibit Rho/Rho-kinase (ROCK) pathway; Rho siRNA was transfected into CMECs to silence Rho. The protein expression of Rho, ROCK, p22 phox , p47 phox and rac-1 was examined by western blot analysis. Results After 12 weeks of treatment with LAF237 or Exetinade, the cardiac function and energetics were improved significantly compared with the vehicle treated groups. Cardiac microvascular barrier function was also improved. We demonstrated that GLP-1R was expressed on CMECs. Compared with vehicle treated groups, ROS production (relative light unit, RLU) (4.06±0.36 vs 2.13±0.31, p phox , p47 phox and rac-1 expression. However, no difference was found in ROS production (RLU) (0.45±0.57 vs 0.53±0.07, p phox , p47 phox and rac-1 expression in high-glucose induced CMECs Conclusions GLP-1 could protect the cardiac microvessels against oxidative stress injury, apoptosis and the resultant microvascular barrier dysfunction in diabetic rats, which contribute to the improvement of cardiac function and energetics. The protective effects of GLP-1 are dependent on downstream inhibition of Rho, which is through cAMP/PKA pathway, resulting in subsequent decreased expression of NADPH oxidase.