支持商密SM9算法框架的多因素认证方案

无线传感器技术使用公开无线信道且存储和计算资源受限,这使其容易遭受潜在的主动攻击(篡改等)和被动攻击(监听等)。身份认证是保障信息系统安全的第一道防线,如何为无线传感器设备设计多因素认证方案是目前安全协议研究的热点。目前,大多数身份认证方案都基于国外密码标准设计,不符合国家核心技术自主可控的网络空间安全发展战略。商密SM9标识密码算法是中国密码标准,已由ISO/IEC标准化并被广泛使用。因此,该文研究如何在商密SM9标识密码算法框架下,将口令、生物特征以及智能卡相结合来设计多因素身份认证方案,并利用模糊验证技术和蜜罐口令方法增强口令安全。该文在随机谕言模型(Random Oracle Model, ROM)下证明了方案的安全性,并给出启发式安全分析。与相关身份认证方案的对比结果表明,该文提出的身份认证方案在提供安全性的同时能够适用于资源受限的无线传感器网络。

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis:potential implications for systemic nitric oxide availability

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity(NRC)and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitratereducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals(P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate(a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment(P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria(P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.

Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients:A systematic review and meta-analysis of randomized controlled trials

Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

Arrhythmic syncope: From diagnosis to management

Syncope is a concerning symptom that affects a large proportion of patients.It can be related to a heterogeneous group of pathologies ranging from trivial causes to diseases with a high risk of sudden death.However,benign causes are the most frequent,and identifying high-risk patients with potentially severe etiologies is crucial to establish an accurate diagnosis,initiate effective therapy,and alter the prognosis.The term cardiac syncope refers to those episodes where the cause of the cerebral hypoperfusion is directly related to a cardiac disorder,while arrhythmic syncope is cardiac syncope specifically due to rhythm disorders.Indeed,arrhythmias are the most common cause of cardiac syncope.Both bradyarrhythmia and tachyarrhythmia can cause a sudden decrease in cardiac output and produce syncope.In this review,we summarized the main guidelines in the management of patients with syncope of presumed arrhythmic origin.Therefore,we presented a thorough approach to syncope work-up through different tests depending on the clinical characteristics of the patients,risk stratification,and the management of syncope in different scenarios such as structural heart disease and channelopathies.

Analysis of tumor-draining vein secretome: A direct access to tumor-derived extracellular vesicles in surgical lung cancer patients

Tumor-secreted extracellular vesicles(EVs)participate in the metastasis process through different mechanisms,including the preparation of the pre-metastatic niche to grant circulating tumor cells(CTCs)implantation and growth.The study of the metastasis process through the analysis of CTCs and tumor-derived EVs is difficult because of the dilution grade of these elements in peripheral blood.In early-stage lung cancer patients,the tumor-secreted products are even more diluted.An attractive strategy in surgical lung cancer patients is to purify them from a pulmonary tumor-draining vein where they are enriched.The information obtained from the analysis of EVs and CTCs purified from this source could give more accurate information about tumor biology and could be an important source of biomarkers to identify patients at high risk of relapse after curative surgery.

Expression of miR‑138 in cryopreserved bovine sperm is related to their fertility potential

Background MicroRNAs(miRNAs)are small,single-stranded,non-coding RNA molecules of 22–24 nucleotides that regulate gene expression.In the last decade,miRNAs have been described in sperm of several mammals,including cattle.It is known that miRNAs can act as key gene regulators of early embryogenesis in mice and humans;however,little is known about the content,expression,and function of sperm-borne miRNAs in early bovine embryo.In this study,total sperm RNA was isolated from 29 cryopreserved sperm samples(each coming from a separate bull)using a RNeasy kit and treatment with DNase I.RNA concentration and purity were determined through an Epoch spectrophotometer and an Agilent Bioanalyzer.The expression of 10 candidate miRNAs in bovine sperm(bta-miR-10a,bta-miR-10b,bta-miR-138,bta-miR-146b,bta-miR-19b,bta-miR-26a,bta-miR-34a,bta-miR-449a,bta-miR-495 and btamiR-7),previously identified in testis and/or epididymis,was evaluated with RT-qPCR.The cel-miR-39-3p was used as a spike-in exogenous control.Nonparametric Mann–Whitney tests were run to evaluate which miRNAs were differentially expressed between bulls with high fertility[HF;non-return rates(NRR)ranging from 39.5 to 43.5]and those with subfertility(SF;NRR ranging from 33.3 to 39.3).Several sperm functionality parameters(e.g.,viability,membrane stability or oxygen consumption,among others)were measured by multiplexing flow cytometry and oxygen sensing technologies.Results RNA concentration and purity(260/280 nm ratio)(mean±SD)from the 29 samples were 99.3±84.6 ng/μL and 1.97±0.72,respectively.Bioanalyzer results confirmed the lack of RNA from somatic cells.In terms of the presence or absence of miRNAs,and after applying the Livak method,8 out of 10 miRNAs(bta-miR-10b,-138,-146b,-19b,-26a,-449a,-495,-7)were consistently detected in bovine sperm,whereas the other two(bta-miR-10a,and-34a)were absent.Interestingly,the relative expression of one miRNA(bta-miR-138)in sperm was significantly lower in the SF than in the HF group(P=0.038).In addition to being associated to fertility potential,the presence of this miRNA was found to be negatively correlated with sperm oxygen consumption.The expression of three other miRNAs(bta-miR-19b,bta-miR-26a and bta-miR-7)was also correlated with sperm function variables.Conclusions In conclusion,although functional validation studies are required to confirm these results,this study suggests that sperm bta-miR-138 is involved in fertilization events and beyond,and supports its use as a fertility biomarker in cattle.

Comparative effects of different types of exercise on health-related quality of life during and after active cancer treatment:A systematic review and network meta-analysis

Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer remains unknown.The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment.Methods MEDLINE,SPORTDiscus,the Cochrane Library,Web of Science,and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer.Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires.We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains.Results In total,93 studies involving 7435 people with cancer were included.Network effect size estimates comparing exercise intervention vs.usual care were significant for combined exercise(0.35,95%confidence interval(95%CI):0.14–0.56)for HRQoL as measured by general questionnaires,and for combined(0.31,95%CI:0.13–0.48),mind–body exercise(0.54,95%CI:0.18–0.89),and walking(0.39,95%CI:0.04–0.74)for HRQoL as measured by cancer-specific questionnaires.Conclusion Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment.The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.

实时经支气管超声引导针吸活检在肺癌分期中的应用

线性经支气管超声引导针吸活检(endobronchial ultrasound-guided transbronchial needle aspiration,EBUS-TBNA)是新引进的技术,它是实时超声下可视淋巴结的针吸活检。尽管有研究显示,其为肺癌纵隔分期的有效方法,但全世界多数机构并未应用该技术。本报道旨在分享我们应用EBUS-TBNA的经验,并对相关文献做一简要概述。我们对有关该技术的已有文献进行综述,并特别介绍了我们应用该技术方面的经验。EBUS-TBNA用以探查肺癌患者的转移性纵隔淋巴结和/或肺门淋巴结是有效且安全的。在其它病理状态下,其亦为有效的诊断方法。

Neurodegeneration:An early event of diabetic retinopathy

Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research.

Familial aggregation in inflammatory bowel disease:Is it genes or environment?

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.

Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.

Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease

Inflammatory bowel disease (IBD) includes two entities, Crohn’s disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient’s quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependant disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn’s disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunossupressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn’s disease and ulcerative colitis, and (3) demonstration that early immunossupression has a very positive impact on pediatric, recently diagnosed Crohn’s disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn’s disease patients (AZTEC study).

社会媒体对多媒体网络平台的推荐研究：基于Europeana的案例分析

Europeanaeu是一个多语言网站，提供了数以百万计的来自于欧洲博物馆、图书馆、档案馆以及多媒体资源收藏的数字化条目。本文研究了该网站的使用情况，尤其是社会媒体对该网站的推荐。我们采用了三种方法搜集相关数据，包括GoogleAnalytics、ClickStream日志及http服务器日志。本文特别展示了利用GoogleAnalytics分析得到的结果。

Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

Hepatitis C virus(HCV)infection represents a major public health issue.Hepatitis C can be cured bytherapy,but many infected individuals are unaware of their status.Effective HCV screening,fast diagnosis and characterization,and hepatic fibrosis staging are highly relevant for controlling transmission,treating infected patients and,consequently,avoiding end-stage liver disease.Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays.Additionally,the use of point-of-care tests can increase HCV screening opportunities.However,active HCV infection must be confirmed by direct diagnosis methods.Additionally,HCV genotyping is required prior to starting any treatment.Increasingly,high-volume clinical laboratories use different types of automated platforms,which have simplified sample processing,reduced hands-on-time,minimized contamination risks and human error and ensured full traceability of results.Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods,such as imaging techniques and serum-based tests.However,no single test is currently available that is able to completely replace liver biopsy.This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests.

Cardiorespiratory fitness measured with cardiopulmonary exercise testing and mortality in patients with cardiovascular disease:A systematic review and meta-analysis

Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiovascular disease(CVD)mortality in patients with established CVD is lacking.This study aimed to quantify this association.Methods We searched for prospective cohort studies that measured CRF with cardiopulmonary exercise testing in patients with CVD and that examined all-cause and CVD mortality with at least 6 months of follow-up.Pooled hazard ratios(HRs)were calculated using random-effect inverse-variance analyses.Results Data were obtained from 21 studies and included 159,352 patients diagnosed with CVD(38.1%female).Pooled HRs for all-cause and CVD mortality comparing the highest vs.lowest category of CRF were 0.42(95%confidence interval(95%CI):0.28–0.61)and 0.27(95%CI:0.16–0.48),respectively.Pooled HRs per 1 metabolic equivalent(1-MET)increment were significant for all-cause mortality(HR=0.81;95%CI:0.74–0.88)but not for CVD mortality(HR=0.75;95%CI:0.48–1.18).Coronary artery disease patients with high CRF had a lower risk of all-cause mortality(HR=0.32;95%CI:0.26–0.41)than did their unfit counterparts.Each 1-MET increase was associated with lower all-cause mortality risk among coronary artery disease patients(HR=0.83;95%CI:0.76–0.91)but not lower among those with heart failure(HR=0.69;95%CI:0.36–1.32).Conclusion A better CRF was associated with lower risk of all-cause mortality and CVD.This study supports the use of CRF as a powerful predictor of mortality in this population.

通过手术导致的重量损失由胃绕过在疾病的肥胖的病人改进非含酒精的脂肪肝疾病

AIM:To evaluate the effects of surgical weight loss(Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients.METHODS:A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index 】 40 kg/m 2 who underwent open surgical weight loss operations had paired liver biopsies,the first at surgery and the second after 16 ± 3 mo of weight loss.Biopsies were evaluated and compared in a blinded fashion.The presence of metabolic syndrome,anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy.RESULTS:Percentage of excess weight loss was 72.1% ± 6.6%.There was a reduction in prevalence of metabolic syndrome from 57.7%(15 patients) to 7.7%(2 patients)(P 【 0.001).Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery.There were improvements in steatosis(P 【 0.001),lobular(P 【 0.001) and portal(P 【 0.05) inflammation and fibrosis(P 【 0.001) at the second biopsy.There were 25(96.1%) patients with non alcoholic steatohepatitis(NASH) in their index biopsy and only four(15.3%) of the repeat biopsies fulfilled the criteria for NASH.The persistence of fibrosis(F 】 1) was present in five patients at second biopsy.Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery.CONCLUSION:Restrictive mildly malabsorptive surgery provides significant weight loss,resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.

Mechanisms of autophagy and apoptosis:Recent developments in breast cancer cells

Autophagy,the pathway whereby cell components are degraded by lysosomes,is involved in the cell response to environmental stresses,such as nutrient deprivation,hypoxia or exposition to chemotherapeutic agents.Under these conditions,which are reminiscent of certain phases of tumor development,autophagy either promotes cell survival or induces cell death. This strengthens the possibility that autophagy could be an important target in cancer therapy,as has been proposed.Here,we describe the regulation of survival and death by autophagy and apoptosis,especially in cultured breast cancer cells.In particular,we discuss whether autophagy represents an apoptosis-independent process and/or if they share common pathways. We believe that understanding in detail the molecular mechanisms that underlie the relationships between autophagy and apoptosis in breast cancer cells could improve the available treatments for this disease.