To examine the modification of temperature-mortality association by factors at the individual and community levels.
Design and methods
This study investigated this issue using a national database comprising daily data of 66 Chinese communities for 2006–2011. A ‘threshold-natural cubic spline’ distributed lag non-linear model was utilised to estimate the mortality effects of daily mean temperature, and then examined the modification of the relationship by individual factors (age, sex, education level, place of death and cause of death) using a meta-analysis approach and community-level factors (annual temperature, population density, sex ratio, percentage of older population, health access, household income and latitude) using a meta-regression method.
We found significant effects of high and low temperatures on mortality in China. The pooled excess mortality risk was 1.04% (95% CI 0.90% to 1.18%) for a 1°C temperature decrease below the minimum mortality temperature (MMT), and 3.44% (95% CI 3.00% to 3.88%) for a 1°C temperature increase above MMT. At the individual level, age and place of death were found to be significant modifiers of cold effect, while age, sex, place of death, cause of death and education level were effect modifiers of heat effect. At the community level, communities with lower socioeconomic status and higher annual temperature were generally more vulnerable to the mortality effects of high and low temperatures.
This study identifies susceptibility based on both individual-level and community-level effect modifiers; more attention should be given to these vulnerable individuals and communities to reduce adverse health effects of extreme temperatures.
EPIDEMIOLOGY; PUBLIC HEALTH
Post-error slowing (PES) indicates the slower responses after errors than after correct responses. Prior studies mainly focus on how the observation errors influence one own’s performance, there is no study investigating how other’s monitoring influence one own’s performance. Additionally, the issue that whether social context influences the PES effect differently for females and males is still unclear. To address aforementioned issues, we required the participants to interact with a same-sex or opposite-sex partner to complete a color flanker task together (they sat next to each other, Experiment 1). One was the performer (perform the flanker task), and the other was the observer (monitor the error responses of performer). They alternated their roles in two successive blocks. To further verify the role of the interaction context, a control experiment was conducted in the individual context (Experiment 2). The results revealed that (1) larger PES effect was observed in females than in males in the interaction context; (2) the sex difference of PES effect mainly benefited from the opposite-sex interaction; (3) larger PES effect was observed in the interaction context than in the individual context; (4) females’ performance was influenced after an interaction with a same-sex or opposite-sex partner, whereas males’ performance was merely influenced after an interaction with an opposite-sex partner. Taken together, these findings may suggest that (1) interaction context modulates the PES effect differently for females and males; (2) females are more susceptible to social information and hence more effective to adjust the post-error behaviors.
post-error slowing (PES); the same-sex interaction; the opposite-sex interaction; sex difference; color flanker task
There are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES.
We demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups.
To determine the clinical utility of our hospital’s clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools.
Of the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases.
We demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders.
whole exome sequencing; next generation sequencing; diagnosis; children; clinical utility; pediatrics
Hematopoietic stem cell transplantation (HSCT) and consolidation chemotherapy have been used to treat intermediate-risk acute myeloid leukemia (AML) patients in first complete remission (CR1). However, it is still unclear which treatments are most effective for these patients. The aim of our study was to analyze the relapse-free survival (RFS) and overall survival (OS) benefit of allogeneic HSCT (alloHSCT) for intermediate-risk AML patients in CR1. A meta-analysis of prospective trials comparing alloHSCT to non-alloHSCT (autologous HSCT [autoHSCT] and/or chemotherapy) was undertaken. We systematically searched PubMed, Embase, and the Cochrane Library though October 2014, using keywords and relative MeSH or Emtree terms, ‘allogeneic’; ‘acut*’ and ‘leukem*/aml/leukaem*/leucem*/leucaem*’; and ‘nonlympho*’ or ‘myelo*’. A total of 7053 articles were accessed. The primary outcomes were RFS and OS, while the secondary outcomes were treatment-related mortality (TRM) and relapse rate (RR). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for each outcome. The primary outcomes were RFS and OS, while the secondary outcomes were TRM and RR. We included 9 prospective controlled studies including 1950 adult patients. Patients with intermediate-risk AML in CR1 who received either alloHSCT or non-alloHSCT were considered eligible. AlloHSCT was found to be associated with significantly better RFS, OS, and RR than non-alloHSCT (HR, 0.684 [95% CI: 0.48, 0.95]; HR, 0.76 [95% CI: 0.61, 0.95]; and HR, 0.58 [95% CI: 0.45, 0.75], respectively). TRM was significantly higher following alloHSCT than non-alloHSCT (HR, 3.09 [95% CI: 1.38, 6.92]). However, subgroup analysis showed no OS benefit for alloHSCT over autoHSCT (HR, 0.99 [95% CI: 0.70, 1.39]). In conclusion, alloHSCT is associated with more favorable RFS, OS, and RR benefits (but not TRM outcomes) than non-alloHSCT generally, but does not have an OS advantage over autoHSCT specifically, in patients with intermediate-risk AML in CR1.
Aim: This study aimed to investigate the efficacy and safety of caspofungin as secondary antifungal prophylaxis (SAP) and subsequent maintenance therapy for SAP in hematological malignancy patients. Methods: Forty four patients receiving caspofungin for SAP and 43 patients not receiving any SAP agents during their subsequent chemotherapy or HSCT were reviewed retrospectively. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. Results: The recurrence rate of IFD in 44 patients with caspofungin for SAP was 9.1% (4/44), which was much lower than that in 43 patients without SAP (9.1% vs 46.5%, P = 0.000). Patients with SAP had lower recurrent IFD-related mortality than that without SAP (12.5% vs 55.6%, P = 0.131). Among the 44 patients with SAP, caspofungin continued as maintenance antifungal prophylaxis therapy in 18 patients after neutropenia and oral medication became possible, while voriconazole in 14 patients and itraconazole in 12 patients. The recurrent IFD occurred in 2, 1, 1 patient respectively. There was no statistical difference in recurrence rates among different maintenance antifungal prophylaxis therapies (P = 0.922). No severe adverse events were observed during SAP treatment. Conclusions: Caspofungin is effective and safe to prevent IFD recurrence in hematological malignancy patients undergoing chemotherapy or HSCT. A subsequent maintenance antifungal prophylaxis therapy of oral voriconazole or itraconazole instead of caspofungin after caspofungin as SAP during neutropenia is as effective as caspofungin given constantly.
Caspofungin; secondary antifungal prophylaxis; maintenance antifungal prophylaxis therapy; hematological malignancy
Despite previous studies reporting spatial in equality in diabetes prevalence across China, potential geographic variations in diabetes mortality have not been explored.
Age and gender stratified annual diabetes mortality counts for 161 counties were extracted from the China Mortality Surveillance System and interrogated using multilevel negative binomial regression. Random slopes were used to investigate spatiotemporal variation and the proportion of variance explained was used to assess the relative importance of geographical region, urbanization, mean temperature, local diabetes prevalence, behavioral risk factors and relevant biomarkers.
Diabetes mortality tended to reduce between 2006 and 2012, though there appeared to be an increase in diabetes mortality in urban (age standardized rate (ASR) 2006–2012: 10.5–13.6) and rural (ASR 10.8–13.0) areas in the Southwest region. A Median Rate Ratio of 1.47, slope variance of 0.006 (SE 0.001) and covariance of 0.268 (SE 0.007) indicated spatiotemporal variation. Fully adjusted models accounted for 37 % of this geographical variation, with diabetes mortality higher in the Northwest (RR 2.55, 95 % CI 1.74, 3.73) and Northeast (RR 2.68, 95 % CI 1.70, 4.21) compared with the South. Diabetes mortality was higher in urbanized areas (RR tertile 3 versus tertile 1 (‘RRt3vs1’) 1.39, 95 % CI 1.17, 1.66), with higher mean body mass index (RRt3vs1 1.46, 95 % CI 1.18, 1.80) and with higher average temperatures (RR 1.05 95 % CI 1.03, 1.08). Diabetes mortality was lower where consumption of alcohol was excessive (RRt3vs1 0.84, 95 % CI 0.72, 0.99). No association was observed with smoking, overconsumption of red meat, high mean sedentary time, systolic blood pressure, cholesterol, and diabetes prevalence.
Declines in diabetes mortality between 2006 and 2012 have been unequally distributed across China, which may imply differentials in diagnosis, management, and the provision of services that warrant further investigation.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1982-0) contains supplementary material, which is available to authorized users.
Diabetes; Mortality; Geographical variation; Trends; Risk factors
National mortality data are obtained routinely by the Disease Surveillance Points system (DSPs) in China and under-reporting is a big challenge in mortality surveillance.
We carried out an under-reporting field survey in all 161 DSP sites to collect death cases during 2009–2011, using a multi-stage stratified sampling. To identify under-reporting, death data were matched between field survey system and the routine online surveillance system by an automatic computer checking followed by a thorough manual verification. We used a propensity score (PS) weighting method based on a logistic regression to calculate the under-reporting rate in different groups classified by age, gender, urban/rural residency, geographic locations and other mortality related variables. For comparison purposes, we also calculated the under-reporting rate by using capture-mark-recapture (CMR) method.
There were no significant differences between the field survey system and routine online surveillance system in terms of age group, causes of death, highest level of diagnosis and diagnostic basis. The overall under-reporting rate in the DSPs was 12.9 % (95%CI 11.2 %, 14.6 %) based on PS. The under-reporting rate was higher in the west (18.8 %, 95%CI 16.5 %, 21.0 %) than the east (10.1 %, 95%CI 8.6 %, 11.3 %) and central regions (11.2 %, 95%CI 9.6 %, 12.7 %). Among all age groups, the under-reporting rate was highest in the 0–5 year group (23.7 %, 95%CI 16.1 %, 35.5 %) and lowest in the 65 years and above group (12.4 %, 95%CI 10.9 %, 13.6 %). The under-reporting rates in each group by PS were similar to the results calculated by the CMR methods.
The mortality data from the DSP system in China needs to be adjusted. Compared to the commonly used CMR method in the estimation of under-reporting rate, the results of propensity score weighting method are similar but more flexible when calculating the under-reporting rates in different groups. Propensity score weighting is suitable to adjust DSP data and can be used to address under-reporting in mortality surveillance in China.
Mortality; Surveillance; Under-reporting; Propensity scores
3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol (HPN) is a bromophenol derivative from the marine red alga Rhodomela confervoides. We have previously found that HPN exerted an anti-hyperglycemic property in db/db mouse model. In the present study, we found that HPN could protect HepG2 cells against palmitate (PA)-induced cell death. Data also showed that HPN inhibited cell death mainly by blocking the cell apoptosis. Further studies demonstrated that HPN (especially at 1.0 μM) significantly restored insulin-stimulated tyrosine phosphorylation of IR and IRS1/2, and inhibited the PTP1B expression level in HepG2 cells. Furthermore, the expression of Akt was activated by HPN, and glucose uptake was significantly increased in PA-treated HepG2 cells. Our results suggest that HPN could protect hepatocytes from lipid-induced cell damage and insulin resistance via PTP1B inhibition. Thus, HPN can be considered to have potential for the development of anti-diabetic agent that could protect both hepatic cell mass and function.
HPN; palmitate; PTP1B inhibition; anti-cell damage; anti-insulin resistance; HepG2 cell
The perceptual load theory in selective attention literature proposes that the interference from task-irrelevant distractor is eliminated when perceptual capacity is fully consumed by task-relevant information. However, the biased competition model suggests that the contents of working memory (WM) can guide attentional selection automatically, even when this guidance is detrimental to visual search. An intriguing but unsolved question is what will happen when selective attention is influenced by both perceptual load and WM guidance. To study this issue, behavioral performances and event-related potentials (ERPs) were recorded when participants were presented with a cue to either identify or hold in memory and had to perform a visual search task subsequently, under conditions of low or high perceptual load. Behavioural data showed that high perceptual load eliminated the attentional capture by WM. The ERP results revealed an obvious WM guidance effect in P1 component with invalid trials eliciting larger P1 than neutral trials, regardless of the level of perceptual load. The interaction between perceptual load and WM guidance was significant for the posterior N1 component. The memory guidance effect on N1 was eliminated by high perceptual load. Standardized Low Resolution Electrical Tomography Analysis (sLORETA) showed that the WM guidance effect and the perceptual load effect on attention can be localized into the occipital area and parietal lobe, respectively. Merely identifying the cue produced no effect on the P1 or N1 component. These results suggest that in selective attention, the information held in WM could capture attention at the early stage of visual processing in the occipital cortex. Interestingly, this initial capture of attention by WM could be modulated by the level of perceptual load and the parietal lobe mediates target selection at the discrimination stage.
We previously reported that 7-hydroxy-5, 4’-dimethoxy-2-arylbenzofuran (HDAB) purified from Livistona chinensis is a key active agent. The present study investigated the function and molecular mechanism of HDAB. HDAB treatment of cervical cancer cells resulted in S phase arrest and apoptosis, together with cyclin A2 and CDK2 upregulation. Cyclin A2 siRNA and a CDK inhibitor efficiently relieved S phase arrest but increased the apoptosis rate. Mechanistic studies revealed that HDAB treatment significantly increased DNA strand breaks in an alkaline comet assay and induced ATM, CHK1, CHK2 and H2A.X phosphorylation. Wortmannin (a broad inhibitor of PIKKs) and CGK733 (a specific ATM inhibitor), but not LY294002 (a phosphatidylinositol 3-kinase inhibitor) or NU7026 (a DNA-PK specific inhibitor), prevented H2A.X phosphorylation and γH2A.X-positive foci formation in the nuclei, reversed S phase arrest and promoted the HDAB-induced apoptosis, suggesting that HDAB is a DNA damaging agent that can activate the ATM-dependent DNA repair response, thereby contributing to cell cycle arrest. In addition, molecular docking and in vitro activity assays revealed that HDAB can correctly dock into the hydrophobic pocket of PARP-1 and suppress PARP-1 ADP-ribosylation activity. Thus, the results indicated that HDAB can function as an anti-cancer agent by inducing DNA damage and inhibiting PARP activity.
RecQ family helicases function as safeguards of the genome. Unlike Escherichia coli, the Gram-positive Bacillus subtilis bacterium possesses two RecQ-like homologues, RecQ[Bs] and RecS, which are required for the repair of DNA double-strand breaks. RecQ[Bs] also binds to the forked DNA to ensure a smooth progression of the cell cycle. Here we present the first biochemical analysis of recombinant RecQ[Bs]. RecQ[Bs] binds weakly to single-stranded DNA (ssDNA) and blunt-ended double-stranded DNA (dsDNA) but strongly to forked dsDNA. The protein exhibits a DNA-stimulated ATPase activity and ATP- and Mg2+-dependent DNA helicase activity with a 3′→5′ polarity. Molecular modeling shows that RecQ[Bs] shares high sequence and structure similarity with E. coli RecQ. Surprisingly, RecQ[Bs] resembles the truncated Saccharomyces cerevisiae Sgs1 and human RecQ helicases more than RecQ[Ec] with regard to its enzymatic activities. Specifically, RecQ[Bs] unwinds forked dsDNA and DNA duplexes with a 3′-overhang but is inactive on blunt-ended dsDNA and 5′-overhung duplexes. Interestingly, RecQ[Bs] unwinds blunt-ended DNA with structural features, including nicks, gaps, 5′-flaps, Kappa joints, synthetic replication forks, and Holliday junctions. We discuss these findings in the context of RecQ[Bs]'s possible functions in preserving genomic stability.
Varied stresses to cells can lead to a repression in translation by triggering phosphorylation of eukaryotic translation initiator factor 2α (eIF2α), which is central to a process known as the integrated stress response (ISR). PKR-like ER-localized eIF2 kinase (PERK), one of the kinases that phosphorylates eIF2α and coordinates the ISR, is activated by stress occurring from the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER). Mutant Cu/Zn superoxide dismutase (mtSOD1) is thought to cause familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Published studies have suggested that ER stress is involved in FALS pathogenesis since mtSOD1 accumulates inside the ER and activates PERK leading to phosphorylated eIF2α (p-eIF2α). We previously used a genetic approach to show that haploinsufficiency of PERK significantly accelerates disease onset and shortens survival of G85R mtSOD1 FALS transgenic mice. We now show that G85R mice that express reduced levels of active GADD34, which normally dephosphorylates p-eIF2α and allows recovery from the global suppression of protein synthesis, markedly ameliorates disease. These studies emphasize the importance of the ISR, and specifically the PERK pathway, in the pathogenesis of mtSOD1-induced FALS and as a target for treatment. Furthermore, the ISR may be an appropriate therapeutic target for sporadic ALS and other neurodegenerative diseases since misfolded proteins have been implicated in these disorders.
The Stroop effect is one of the most robust and well-studied phenomena in cognitive psychology and cognitive neuroscience. However, little is known about the relationship between intrinsic brain activity and the individual differences of this effect. In the present study, we explored this issue by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals could predict individual differences in the Stroop effect of healthy individuals. A partial correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and Stroop effect size, while controlling for age, sex, and framewise displacement (FD). The results showed positive correlations in the left inferior frontal gyrus (LIFG), the left insula, the ventral anterior cingulate cortex (vACC), and the medial frontal gyrus (MFG), and negative correlation in the left precentral gyrus (LPG). These results indicate the possible influences of the LIFG, the left insula, and the LPG on the efficiency of cognitive control, and demonstrate that the key nodes of default mode network (DMN) may be important in goal-directed behavior and/or mental effort during cognitive control tasks.
Plasma nuclear and mitochondrial DNA (mtDNA) levels are altered in many diseases. However, it is not known whether they are also altered in acute myocardial infarction (AMI). In the present study, we examined plasma nuclear and mtDNA levels in the patients with AMI before and after a percutaneous coronary intervention (PCI) to explore their potential as biomarkers.
Methods and results
Plasma nuclear and mtDNA levels were measured by quantitative PCR in 25 AMI patients, 25 non-myocardial infarction (MI) control participants (with MI risk), and 20 healthy individuals during the study period. The concentrations of nuclear and mtDNA were significantly higher in the AMI group on hospital day 1 than that in the non-MI controls (nuclear: 0.4948±0.0830 vs. 0.2047±0.0222 ng/μl, P<0.05; mitochondrial: 3.754±0.384 vs. 1.851±0.3483 ng/μl, P<0.05) and healthy individuals (nuclear: 0.4948±0.0830 vs. 0.1683±0.0254 ng/μl, P=0.001; mitochondrial: 3.754±0.384 vs. 0.1517±0.0924 ng/μl, P<0.05) and decreased shortly after PCI.
Both plasma nuclear and mtDNA levels are elevated in AMI patients, but return to normal levels immediately after PCI, suggesting that they are potentially novel biomarkers for AMI.
acute myocardial infarction; mitochondrial DNA; nuclear DNA
A Love wave humidity sensor is developed by using a multilayer structure consisting of PVA/SiO2 layers on an ST-90°X quartz substrate. The theoretical result shows that the sensor with such a two-layer structure can achieve a higher sensitivity and a smaller loss than the structures with a single polymer layer. Comparative experiments are performed for the sensor incorporating PVA/SiO2 layers and the sensor incorporating a PVA layer. The experimental results agree well with the theoretical predication.
Love wave; humidity sensor; viscoelastic; multiple layers
Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs) can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs), the effective pulse amplitude was reduced to 50 V/cm (main field)/15 V/cm (alignment field) at the optimized pulse frequency (5 Hz) of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses.
electrical pulse; electroporation; tumour cell ablation; carbon nanotubes; cell membrane permeabilization
Leiomyosarcoma of the esophagus is a rare type of tumor, characterized by a malignant phenotype and smooth muscle histology. Previously, barium studies have been used to identify areas of luminal narrowing, expansile intraluminal masses or large intramural masses with ulceration or tracking. Furthermore, endoscopic biopsies appear to be associated with a high false negative rate, particularly in cases where the mucosa is intact. The optimal treatment strategy is surgical resection, while the role of adjuvant radiotherapy and chemotherapy is controversial. In addition, the prognosis of patients with leiomyosarcoma of the esophagus is improved compared with patients suffering from squamous esophageal cancer. The present study described the case of a 48-year-old woman who presented with dysphagia and was diagnosed with a large leiomyosarcoma of the esophagus. The patient was successfully treated with radiotherapy and remains disease-free two years after the completion of treatment. In addition, the present study conducted a review of the relevant literature, reporting previous cases of esophageal leiomyosarcoma and potential strategies for the management of this disease.
esophagus; leiomyosarcoma; radiotherapy
Post-error slowing (PES) reflects efficient outcome monitoring, manifested as slower reaction time after errors. Cognitive control account assumes that PES depends on error information, whereas orienting account posits that it depends on error frequency. This raises the question how the outcome valence and outcome frequency separably influence the generation of PES. To address this issue, we varied the probability of observation errors (50/50 and 20/80, correct/error) the “partner” committed by employing an observation-execution task and investigated the corresponding behavioral and neural effects. On each trial, participants first viewed the outcome of a flanker-run that was supposedly performed by a ‘partner’, and then performed a flanker-run themselves afterwards. We observed PES in the two error rate conditions. However, electroencephalographic data suggested error-related potentials (oERN and oPe) and rhythmic oscillation associated with attentional process (alpha band) were respectively sensitive to outcome valence and outcome frequency. Importantly, oERN amplitude was positively correlated with PES. Taken together, these findings support the assumption of the cognitive control account, suggesting that outcome valence and outcome frequency are both involved in PES. Moreover, the generation of PES is indexed by oERN, whereas the modulation of PES size could be reflected on the alpha band.
Small RNA OxyS is induced during oxidative stress in Escherichia coli and it is an Hfq-dependent negative regulator of mRNA translation. OxyS represses the translation of fhlA and rpoS mRNA, which encode the transcriptional activator and σs subunit of RNA polymerase, respectively. However, little is known regarding how Hfq, an RNA chaperone, interacts with OxyS at the atomic level. Here, using fluorescence polarization and tryptophan fluorescence quenching assays, we verified that the A-rich linker region of OxyS sRNA binds Hfq at its distal side. We also report two crystal structures of Hfq in complex with A-rich RNA fragments from this linker region. Both of these RNA fragments bind to the distal side of Hfq and adopt a different conformation compared with those previously reported for the (A-R-N)n tripartite recognition motif. Furthermore, using fluorescence polarization, electrophoresis mobility shift assays and in vivo translation assays, we found that an Hfq mutant, N48A, increases the binding affinity of OxyS for Hfq in vitro but is defective in the negative regulation of fhlA translation in vivo, suggesting that the normal function of OxyS depends on the details of the interaction with Hfq that may be related to the rapid recycling of Hfq in the cell.
Bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL). Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM). Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL) significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL) completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9) is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK) is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents.
bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM); anti-metastatic activity; cell adhesion; β1-integrin; FAK; BEL-7402 cell
Purpose: This study was designed to investigate the effect of losartan on the myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) rats. Methods: In this study, a total of 48 male Wister rats (3 groups of 16 animals each) were examined, including the control group, DCM group and losartan-treated (DCM + L) group. Control group was fed with standard diet (14 KJ/g); DCM group and losartan-treated (DCM + L) group were both fed with high glucose and fat diet (20 KJ/g). Diabetes was induced by streptozotocin (STZ) intraperitoneal injuction (IP, 30 mg/kg body weight). Rats of DCM + L group were treated with losartan (30 mg/kg body weight) daily by oral gavage for 16 weeks. Biochemical, hemodynamic, histological and western blotting analyses were performed. Results: Compared with DCM rats, the quantity of p-JAK2 and p-STAT3 in myocardium of rats treated with losartan was lower, the expression of TGF-β1 was down-regulate, the content of collagen in myocardium decreased, LVSP and ± dp/dt increased, LVEDP decreased, the level of myocardial fibrosis reduced, and heart function improved evidently. Conclusion: Losartan has a protective effect on heart function against myocardial interstitial fibrosis of DCM by inhibiting JAK/STAT signaling pathway and lowering the expression of TGF-β1.
Diabetes mellitus; diabetic cardiomyopathy; myocardial interstitial fibrosis; losartan; JAK; STAT
Invasive fungal disease (IFD) causes morbidity and mortality in patients with hematological malignancy. Recurrence of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is associated with poor prognosis. The present study aimed to investigate the efficacy of different strategies of secondary antifungal prophylaxis (SAP) for IFD and choose an appropriate SAP regimen.
Clinical data of patients with previous IFD who underwent chemotherapy or HSCT between Jan 2008 and Jun 2013 were retrospectively reviewed and followed up to 180 days post-chemotherapy or HSCT. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. The efficacy of different strategies for SAP and risk factors influencing the failure of SAP were evaluated.
Of the 164 patients enrolled, 121 patients received SAP regimen (73.78%), and IFD recurred in 40 patients: 16.5% (20/121) in SAP group and 46.5% (20/43) in non-SAP group. In SAP group, 58 received SAP agents which were proven effective for their previous IFD, while other 63 patients received other broad-spectrum antifungal agents. There was no significant difference in the recurrence rates between these two subgroups (13.8% (8/58) vs 19.0% (12/63), P = 0.437). The IFD recurrence rates were statistically significant between patients with allogeneic HSCT and chemotherapy or autologous HSCT (25% vs 8.2%, P = 0.013). Multivariate analysis indicated that allogeneic HSCT was the independent risk factor of IFD recurrence after SAP.
Secondary antifungal prophylaxis is necessary to prevent IFD recurrence in patients with hematological malignancy, especially for patients in the setting of allogeneic HSCT.
Only a small amount of solar ultraviolet C (UV-C) radiation reaches the Earth's surface. This is because of the filtering effects of the stratospheric ozone layer. Artificial UV-C irradiation is used on leaves and fruits to stimulate different biological processes in plants. Grapes are a major fruit crop and are grown in many parts of the world. Research has shown that UV-C irradiation induces the biosynthesis of phenols in grape leaves. However, few studies have analyzed the overall changes in gene expression in grape leaves exposed to UV-C.
In the present study, transcriptional responses were investigated in grape (Vitis vinifera L.) leaves before and after exposure to UV-C irradiation (6 W·m−2 for 10 min) using an Affymetrix Vitis vinifera (Grape) Genome Array (15,700 transcripts). A total of 5274 differentially expressed probe sets were defined, including 3564 (67.58%) probe sets that appeared at both 6 and 12 h after exposure to UV-C irradiation but not before exposure. A total of 468 (8.87%) probe sets and 1242 (23.55%) probe sets were specifically expressed at these times. The probe sets were associated with a large number of important traits and biological pathways, including cell rescue (i.e., antioxidant enzymes), protein fate (i.e., HSPs), primary and secondary metabolism, and transcription factors. Interestingly, some of the genes involved in secondary metabolism, such as stilbene synthase, responded intensely to irradiation. Some of the MYB and WRKY family transcription factors, such as VvMYBPA1, VvMYB14, VvMYB4, WRKY57-like, and WRKY 65, were also strongly up-regulated (about 100 to 200 fold).
UV-C irridiation has an important role in some biology processes, especially cell rescue, protein fate, secondary metabolism, and regulation of transcription.These results opened up ways of exploring the molecular mechanisms underlying the effects of UV-C irradiation on grape leaves and have great implications for further studies.
Transparency has become a hottest topic and a growing movement in the health care system worldwide. This study used a quasi-experimental design method to explore whether public reporting of medicine use information can improve rational drug use.
20 township hospitals and 274 doctors of City Y in Hubei Province, China were divided into the intervention and control groups on the basis of their characteristics. In the intervention group, the values and rankings of the average expenditure per prescription, percentage of prescriptions requiring antibiotics and percentage of prescriptions requiring injections of each hospital and doctor were publicly released to patients and doctors in an appropriate format monthly. Data were gathered both four months before and after the intervention. Propensity score matching (PSM) was used to minimize the observed covariate (gender, age, experience, education level, title, and monthly income) differences in the doctors’ characteristics. 108 pairs of doctors were obtained after PSM. Chi-square test and t-test were employed to explore the effect of public reporting of medicine use information on rational drug use. The study was approved by the Committee of Tongji Medical College, Hua Zhong University of Science and Technology (IORG No: IORG0003571).
In baseline, the average expenditure per prescription of the 274 doctors was 42.82 RMB yuan (USD 6.97), the percentage of prescriptions requiring antibiotics was 63.00%, and the percentage of prescriptions requiring injections was 70.79%, all higher than the average of Hubei Province and the standard recommended by WHO. Before the intervention all the three indicators were all comparable (p > 0.05), whereas after the intervention, a significant difference (p < 0.05) was found for the percentage of prescriptions requiring injections between the intervention (64.66%) and control groups (70.52%).
Irrational drug use remains a policy issue in township hospitals in the study area. We demonstrated that publicly reporting medicine use information could decrease the percentage of prescriptions requiring injections in township hospitals in China, but this effect was not observed on prescription costs and antibiotics use. Analyses of the mechanism and long-term effect of public reporting of medicine use information are recommended for further studies.
Quasi-experimental design; Propensity score; Township hospitals; Transparency; Rational drug use; China