Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with...Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.展开更多
Pharmaceuticals and personal care products(PPCPs)are a unique group of emerging environmental contaminants,due to their inherent ability to induce physiological effects in human at low doses.An increasing number of st...Pharmaceuticals and personal care products(PPCPs)are a unique group of emerging environmental contaminants,due to their inherent ability to induce physiological effects in human at low doses.An increasing number of studies has confirmed the presence of various PPCPs in different environmental compartments,which raises concerns about the potential adverse effects to humans and wildlife.Therefore,this article reviews the current state-of-knowledge on PPCPs in the freshwater aquatic environment.The environmental risk posed by these contaminants is evaluated in light of the persistence,bioaccumulation and toxicity criteria.Available literature on the sources,transport and degradation of PPCPs in the aquatic environment are evaluated,followed by a comprehensive review of the reported concentrations of different PPCP groups in the freshwater aquatic environment(water,sediment and biota)of the five continents.Finally,future perspectives for research on PPCPs in the freshwater aquatic environment are discussed in light of the identified research gaps in current knowledge.展开更多
Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung ca...Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.展开更多
At present, it is projected that about 4 zettabytes （or 10^＊＊21 bytes） of digital data are being generated per year by everything from underground physics experiments to retail transactions to security cameras to ...At present, it is projected that about 4 zettabytes （or 10^＊＊21 bytes） of digital data are being generated per year by everything from underground physics experiments to retail transactions to security cameras to global positioning systems. In the U. S., major research programs are being funded to deal with big data in all five sectors （i.e., services, manufacturing, construction, agriculture and mining） of the economy. Big Data is a term applied to data sets whose size is beyond the ability of available tools to undertake their acquisition, access, analytics and/or application in a reasonable amount of time. Whereas Tien （2003） forewarned about the data rich, information poor （DRIP） problems that have been pervasive since the advent of large-scale data collections or warehouses, the DRIP conundrum has been somewhat mitigated by the Big Data approach which has unleashed information in a manner that can support informed - yet, not necessarily defensible or valid - decisions or choices. Thus, by somewhat overcoming data quality issues with data quantity, data access restrictions with on-demand cloud computing, causative analysis with correlative data analytics, and model-driven with evidence-driven applications, appropriate actions can be undertaken with the obtained information. New acquisition, access, analytics and application technologies are being developed to further Big Data as it is being employed to help resolve the 14 grand challenges （identified by the National Academy of Engineering in 2008）, underpin the 10 breakthrough technologies （compiled by the Massachusetts Institute of Technology in 2013） and support the Third Industrial Revolution of mass customization.展开更多
文摘Advanced glycation end products (AGEs) are produced through the non enzymatic glycation and oxidation of proteins, lipids and nucleic acids. Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus (DM). AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modification of the structure, function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs (RAGE)]. A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure. Moreover, some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with heart failure (HF). The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure, focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.
文摘Pharmaceuticals and personal care products(PPCPs)are a unique group of emerging environmental contaminants,due to their inherent ability to induce physiological effects in human at low doses.An increasing number of studies has confirmed the presence of various PPCPs in different environmental compartments,which raises concerns about the potential adverse effects to humans and wildlife.Therefore,this article reviews the current state-of-knowledge on PPCPs in the freshwater aquatic environment.The environmental risk posed by these contaminants is evaluated in light of the persistence,bioaccumulation and toxicity criteria.Available literature on the sources,transport and degradation of PPCPs in the aquatic environment are evaluated,followed by a comprehensive review of the reported concentrations of different PPCP groups in the freshwater aquatic environment(water,sediment and biota)of the five continents.Finally,future perspectives for research on PPCPs in the freshwater aquatic environment are discussed in light of the identified research gaps in current knowledge.
基金This work was supported by the Grant from Chinese National Major Project for New Drug Innovation(Grant No.2017ZX09304015)
文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.
文摘At present, it is projected that about 4 zettabytes （or 10^＊＊21 bytes） of digital data are being generated per year by everything from underground physics experiments to retail transactions to security cameras to global positioning systems. In the U. S., major research programs are being funded to deal with big data in all five sectors （i.e., services, manufacturing, construction, agriculture and mining） of the economy. Big Data is a term applied to data sets whose size is beyond the ability of available tools to undertake their acquisition, access, analytics and/or application in a reasonable amount of time. Whereas Tien （2003） forewarned about the data rich, information poor （DRIP） problems that have been pervasive since the advent of large-scale data collections or warehouses, the DRIP conundrum has been somewhat mitigated by the Big Data approach which has unleashed information in a manner that can support informed - yet, not necessarily defensible or valid - decisions or choices. Thus, by somewhat overcoming data quality issues with data quantity, data access restrictions with on-demand cloud computing, causative analysis with correlative data analytics, and model-driven with evidence-driven applications, appropriate actions can be undertaken with the obtained information. New acquisition, access, analytics and application technologies are being developed to further Big Data as it is being employed to help resolve the 14 grand challenges （identified by the National Academy of Engineering in 2008）, underpin the 10 breakthrough technologies （compiled by the Massachusetts Institute of Technology in 2013） and support the Third Industrial Revolution of mass customization.
