BACKGROUND Epidemiological surveys on heart failure(HF)in Chinese community are relatively lacking.This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.METHODS Ba...BACKGROUND Epidemiological surveys on heart failure(HF)in Chinese community are relatively lacking.This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.METHODS Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged≥35years in Guangzhou,China.The same survey process was carried out for individuals aged≥65 years after a three-year follow-up.RESULTS The overall prevalence of HF in community residents aged≥35 years was 1.06%.Male had significantly higher risk of HF prevalence[odds ratio(OR)=1.50,P=0.027].The gender-adjusted risk of HF was 1.48 times higher per 10 years aging.HF prevalence was statistically associated with atrial fibrillation,valvular heart disease,hypertension and chronic obstructive pulmonary disease after adjusting for age and gender(OR=8.30,5.17,1.11,2.28,respectively;all P<0.05).HF incidence in individuals aged≥65 years were 847 per 100,000 person-years.Baseline atrial fibrillation,valvular heart disease,and diabetes mellitus were risk factors for HF incidence for individuals aged≥65 years adjusting for age and gender(OR=5.05,3.99,2.11,respectively;all P<0.05).Besides,residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF(OR=14.41,8.54,respectively;all P<0.05).CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China.Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.展开更多
Meiotic recombination is essential for sexual reproduction and its regulation has been extensively studied in many taxa.However,genome-wide recombination landscape has not been reported in ciliates and it remains unkn...Meiotic recombination is essential for sexual reproduction and its regulation has been extensively studied in many taxa.However,genome-wide recombination landscape has not been reported in ciliates and it remains unknown how it is affected by the unique features of ciliates:the synaptonemal complex(SC)-independent meiosis and the nuclear dimorphism.Here,we show the recombination landscape in the model ciliate Tetrahymena thermophila by analyzing single-nucleotide polymorphism datasets from 38 hybrid progeny.We detect 1021 crossover(CO)events(35.8 per meiosis),corresponding to an overall CO rate of 9.9 cM/Mb.However,gene conversion by non-crossover is rare(1.03 per meiosis)and not biased towards G or C alleles.Consistent with the reported roles of SC in CO interference,we find no obvious sign of CO interference.CO tends to occur within germ-soma common genomic regions and many of the 44 identified CO hotspots localize at the centromeric or subtelomeric regions.Gene ontology analyses show that CO hotspots are strongly associated with genes responding to environmental changes.We discuss these results with respect to how nuclear dimorphism has potentially driven the formation of the observed recombination landscape to facilitate environmental adaptation and the sharing of machinery among meiotic and somatic recombination.展开更多
Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse...Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.展开更多
Existing traditional Chinese medicine(TCM)-related databases are still insufficient in data standardization,integrity and precision,and need to be updated urgently.Herein,an Encyclopedia of Traditional Chinese Medicin...Existing traditional Chinese medicine(TCM)-related databases are still insufficient in data standardization,integrity and precision,and need to be updated urgently.Herein,an Encyclopedia of Traditional Chinese Medicine version 2.0(ETCM v2.0,http://www.tcmip.cn/ETCM2/front/#/)was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books,9872 Chinese patent drugs,2079 Chinese medicinal materials and 38,298 ingredients.To facilitate the mechanistic research and new drug discovery,we improved the target identification method based on a two-dimensional ligand similarity search module,which provides the confirmed and/or potential targets of each ingredient,as well as their binding activities.Importantly,five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0,which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy,to summarize the rules of prescription use,and to find alternative drugs for endangered Chinese medicinal materials.Moreover,ETCM v2.0 provides an enhanced Java Script-based network visualization tool for creating,modifying and exploring multi-scale biological networks.ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs,the TCM-derived drug discovery and repurposing,and the pharmacological mechanism investigation of TCMs against various human diseases.展开更多
Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases,stroke and chronic diabetic wounds,which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are ...Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases,stroke and chronic diabetic wounds,which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are of great interest.However,many angiogenic treatments involve the delivery of growth factors which have limited clinical success due to poor stability,high manufacturing cost and poor efficacy.Cerium oxide nanoparticles(nanoceria)can either promote or inhibit angiogenesis depending on their surface corona chemistry.Here,nanoceria were functionalized with an intentional heparin corona,a polysaccharide which binds and signals growth factors,of different chain lengths and surface grafting density to establish their effect on angiogenesis.These nanoparticles promoted angiogenesis in vivo with the surface grafting density positively correlated with angiogenesis over the widest concentration range;however,chain length did not play a role.The heparin–nanoceria supported fibroblast growth factor 2(FGF2)signalling in vitro and promoted FGF2-mediated angiogenesis in vivo.The nanoparticles were internalized by endothelial cells in vitro where they trafficked to the lysosomes and reduced cell viability suggesting that the angiogenic activity of heparin–nanoceria is mediated in the extracellular environment.Together,this study adds to our knowledge of the angiogenic effects of heparin–nanoceria towards finding new angiogenic treatments.展开更多
Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,developmen...Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,development of Tau-targeted active immunotherapy takes much concern.1 Tau protein,a major microtubule-associated protein in the nervous system,was found to be abnormally hyperphosphorylated at six epitopes:Ser396/404,Ser202,Thr205,Ser238,and Ser262 in AD patients.2 Hence,immunotherapy targeting more highly-expressed phosphorylated Tau(pTau)species may induce a sufficient pool of pTau antibodies to eliminate pathological tau and elicit cognitive improvement.展开更多
Objective： To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin （SM） on these changes in vivo. Methods： Sixty Wistar rats were divided randomly...Objective： To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin （SM） on these changes in vivo. Methods： Sixty Wistar rats were divided randomly into four groups： a control group （n=15）, an SM group （n=15）, a myocardial infarction （MI） group （n=15）, and an MI＋SM group （n=15）. Chronic MI was obtained by ligating the left anterior descending branch （LAD） of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels （SACs） was achieved by intramuscular injection of SM （180 mg/（kg·d）） for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential （MAP）. The effect of stretching was examined by assessing the 90% monophasic action potential duration （MAPD90）, premature ventricular beats （PVBs）, and ventricular tachycardia （VT）. Results： The MAPD90 decreased during stretching in both the control （from （50.27±5.61） ms to （46.27±4.51） ms, P〈0.05） and MI groups （from （65.47±6.38） ms to （57.47±5.76 ms）, P〈0.01 ）. SM inhibited the decrease in MAPD90 during inflation （（46.27±4.51） ms vs. （49.53±3.52） ms, P〈0.05 in normal hearts; （57.47±5.76） ms vs. （61.87±5.33） ms, P〈0.05 in MI hearts）. The occurrence of PVBs and VT in the MI group increased compared with that in the control group （PVB： 7.93±1.66 vs. 1.80±0.86, P〈0.01; VT： 7 vs. 1, P〈0.05）. SM decreased the occurrence of PVBs in both normal and MI hearts （0.93±0.59 vs. 1.80±0.86 in normal hearts, P〈0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P〈0.01）. Conclusions： Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback （MEF）, but that there might be other mechanisms involved in causing VT in chronic MI.展开更多
In the process of collating the published data,the authors noticed one inadvertent mistake occurred during the production process in Fig.1u that needs to be corrected.1 The authors mistakenly placed the wrong western ...In the process of collating the published data,the authors noticed one inadvertent mistake occurred during the production process in Fig.1u that needs to be corrected.1 The authors mistakenly placed the wrong western blot figure for the level of pTauS404 in the urea fraction of mice from the onset cohort in Fig.lu.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.展开更多
基金supported by the National Natural Science Foundation of China(No.81870254)the Guangdong Provincial Clinical Research Center for Cardiovascular Disease Foundation(No.2020B1111170011)the Science and Technology Programs of Guangdong Province(No.2019B020230004)。
文摘BACKGROUND Epidemiological surveys on heart failure(HF)in Chinese community are relatively lacking.This study aimed to estimate the prevalence and incidence of HF among community residents in southern China.METHODS Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged≥35years in Guangzhou,China.The same survey process was carried out for individuals aged≥65 years after a three-year follow-up.RESULTS The overall prevalence of HF in community residents aged≥35 years was 1.06%.Male had significantly higher risk of HF prevalence[odds ratio(OR)=1.50,P=0.027].The gender-adjusted risk of HF was 1.48 times higher per 10 years aging.HF prevalence was statistically associated with atrial fibrillation,valvular heart disease,hypertension and chronic obstructive pulmonary disease after adjusting for age and gender(OR=8.30,5.17,1.11,2.28,respectively;all P<0.05).HF incidence in individuals aged≥65 years were 847 per 100,000 person-years.Baseline atrial fibrillation,valvular heart disease,and diabetes mellitus were risk factors for HF incidence for individuals aged≥65 years adjusting for age and gender(OR=5.05,3.99,2.11,respectively;all P<0.05).Besides,residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF(OR=14.41,8.54,respectively;all P<0.05).CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China.Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.
基金supported by the Wuhan Branch,Supercomputing Center,Chinese Academy of Sciences,Chinasupported by the National Aquatic Biological Resource Center(NABRC)+4 种基金supported by the Bureau of Frontier Sciences and Education,Chinese Academy of Sciences(ZDBS-LY-SM026)the National Natural Science Foundation of China(32370457,32122015,32130011,31900316,and 31900339)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000)PJA3 grant of ARC Foundation(ARCPJA2021060003830)Equipes 2022 grant of Foundation Recherche Medicale(EQU202203014651).
文摘Meiotic recombination is essential for sexual reproduction and its regulation has been extensively studied in many taxa.However,genome-wide recombination landscape has not been reported in ciliates and it remains unknown how it is affected by the unique features of ciliates:the synaptonemal complex(SC)-independent meiosis and the nuclear dimorphism.Here,we show the recombination landscape in the model ciliate Tetrahymena thermophila by analyzing single-nucleotide polymorphism datasets from 38 hybrid progeny.We detect 1021 crossover(CO)events(35.8 per meiosis),corresponding to an overall CO rate of 9.9 cM/Mb.However,gene conversion by non-crossover is rare(1.03 per meiosis)and not biased towards G or C alleles.Consistent with the reported roles of SC in CO interference,we find no obvious sign of CO interference.CO tends to occur within germ-soma common genomic regions and many of the 44 identified CO hotspots localize at the centromeric or subtelomeric regions.Gene ontology analyses show that CO hotspots are strongly associated with genes responding to environmental changes.We discuss these results with respect to how nuclear dimorphism has potentially driven the formation of the observed recombination landscape to facilitate environmental adaptation and the sharing of machinery among meiotic and somatic recombination.
基金National Natural Science Foundation of China,Grant/Award Number:81870254Science and Technology Programs of Guangdong Province,Grant/Award Number:2019B020230004+1 种基金National Key Research and Development Project,Grant/Award Number:2018YFC1312502Guangdong Special Funds for Science and Technology Innovation Strategy,China(Stability support for scientific research institutions affiliated to Guangdong Province,GDCI 2021)。
文摘Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved significantly.However,the incidence of cardiovascular adverse events has also increased,which can affect tumor treatment.In this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy.Methods:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed databases.All included trials examined all grade and grades 3–5 cardiac and vascular adverse events.These involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent.The odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel method.Results:Overall,20 trials were included.CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular toxicity.The incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically significant.Conclusion:Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors.In addition,the risk of serious cardiovascular toxic events was independent of the type of adverse event.From these results,physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.
基金supported by Key project at the National Natural Science Foundation of China(Grant Nos.81830111 and 82030122,China)the Innovation Project of China Academy of Chinese Medical Sciences(Grant No.CI2021A04907,China)。
文摘Existing traditional Chinese medicine(TCM)-related databases are still insufficient in data standardization,integrity and precision,and need to be updated urgently.Herein,an Encyclopedia of Traditional Chinese Medicine version 2.0(ETCM v2.0,http://www.tcmip.cn/ETCM2/front/#/)was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books,9872 Chinese patent drugs,2079 Chinese medicinal materials and 38,298 ingredients.To facilitate the mechanistic research and new drug discovery,we improved the target identification method based on a two-dimensional ligand similarity search module,which provides the confirmed and/or potential targets of each ingredient,as well as their binding activities.Importantly,five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0,which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy,to summarize the rules of prescription use,and to find alternative drugs for endangered Chinese medicinal materials.Moreover,ETCM v2.0 provides an enhanced Java Script-based network visualization tool for creating,modifying and exploring multi-scale biological networks.ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs,the TCM-derived drug discovery and repurposing,and the pharmacological mechanism investigation of TCMs against various human diseases.
文摘Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases,stroke and chronic diabetic wounds,which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are of great interest.However,many angiogenic treatments involve the delivery of growth factors which have limited clinical success due to poor stability,high manufacturing cost and poor efficacy.Cerium oxide nanoparticles(nanoceria)can either promote or inhibit angiogenesis depending on their surface corona chemistry.Here,nanoceria were functionalized with an intentional heparin corona,a polysaccharide which binds and signals growth factors,of different chain lengths and surface grafting density to establish their effect on angiogenesis.These nanoparticles promoted angiogenesis in vivo with the surface grafting density positively correlated with angiogenesis over the widest concentration range;however,chain length did not play a role.The heparin–nanoceria supported fibroblast growth factor 2(FGF2)signalling in vitro and promoted FGF2-mediated angiogenesis in vivo.The nanoparticles were internalized by endothelial cells in vitro where they trafficked to the lysosomes and reduced cell viability suggesting that the angiogenic activity of heparin–nanoceria is mediated in the extracellular environment.Together,this study adds to our knowledge of the angiogenic effects of heparin–nanoceria towards finding new angiogenic treatments.
基金supported by National Natural Science Foundation of China[No.31971142]Science&Technology Development Plan of Jilin Province[No.20190201185JC,No.20190103073JH,No.2018C004]+1 种基金Fundamental Research Funds for the Central Universities[No.2019JCXK-55]Science&Technology Research Project of The Education Department of Jilin Province[No.JJKH20200949KJ].
文摘Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,development of Tau-targeted active immunotherapy takes much concern.1 Tau protein,a major microtubule-associated protein in the nervous system,was found to be abnormally hyperphosphorylated at six epitopes:Ser396/404,Ser202,Thr205,Ser238,and Ser262 in AD patients.2 Hence,immunotherapy targeting more highly-expressed phosphorylated Tau(pTau)species may induce a sufficient pool of pTau antibodies to eliminate pathological tau and elicit cognitive improvement.
基金Project supported by the National Natural Science Foundation of China(No.81301343)
文摘Objective： To investigate stretch-induced electrophysiological changes in chronically infarcted hearts and the effect of streptomycin （SM） on these changes in vivo. Methods： Sixty Wistar rats were divided randomly into four groups： a control group （n=15）, an SM group （n=15）, a myocardial infarction （MI） group （n=15）, and an MI＋SM group （n=15）. Chronic MI was obtained by ligating the left anterior descending branch （LAD） of rat hearts for eight weeks. The in vivo blockade of stretch-activated ion channels （SACs） was achieved by intramuscular injection of SM （180 mg/（kg·d）） for seven days after operation. The hearts were stretched for 5 s by occlusion of the aortic arch. Suction electrodes were placed on the anterior wall of left ventricle to record the monophasic action potential （MAP）. The effect of stretching was examined by assessing the 90% monophasic action potential duration （MAPD90）, premature ventricular beats （PVBs）, and ventricular tachycardia （VT）. Results： The MAPD90 decreased during stretching in both the control （from （50.27±5.61） ms to （46.27±4.51） ms, P〈0.05） and MI groups （from （65.47±6.38） ms to （57.47±5.76 ms）, P〈0.01 ）. SM inhibited the decrease in MAPD90 during inflation （（46.27±4.51） ms vs. （49.53±3.52） ms, P〈0.05 in normal hearts; （57.47±5.76） ms vs. （61.87±5.33） ms, P〈0.05 in MI hearts）. The occurrence of PVBs and VT in the MI group increased compared with that in the control group （PVB： 7.93±1.66 vs. 1.80±0.86, P〈0.01; VT： 7 vs. 1, P〈0.05）. SM decreased the occurrence of PVBs in both normal and MI hearts （0.93±0.59 vs. 1.80±0.86 in normal hearts, P〈0.05; 5.40±1.18 vs. 7.93±1.66 in MI hearts, P〈0.01）. Conclusions： Stretch-induced MAPD90 changes and arrhythmias were observed in chronically infarcted myocardium. The use of SM in vivo decreased the incidence of PVBs but not of VT. This suggests that SACs may be involved in mechanoelectric feedback （MEF）, but that there might be other mechanisms involved in causing VT in chronic MI.
文摘In the process of collating the published data,the authors noticed one inadvertent mistake occurred during the production process in Fig.1u that needs to be corrected.1 The authors mistakenly placed the wrong western blot figure for the level of pTauS404 in the urea fraction of mice from the onset cohort in Fig.lu.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.
