Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant pote...Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant potential for promoting technologic progress in this field.Herein,we present Cu-ZSM-5 zeolite as a highly effective catalyst for alkane aromatization,achieving outstanding aromatics selectivity.In-situ Fourier transform infrared spectra of adsorbed nitric oxide,high-angle annular dark field scanning transmission electron microscopy,X-ray absorption spectroscopy,and electron paramagnetic resonance analyses reveal that the Cu^(2+)species act as the primary active centers for aromatics formation.During aromatization of alkanes,the reduction of Cu^(2+)to Cu^(+)species correlates with diminished aromatics selectivity.Notably,introducing CO_(2)into the reaction feed not only enhances aromatics selectivity by maintaining Cu^(2+)species in their active oxidation state under reducing conditions,but also improves catalytic stability by eliminating coke.Furthermore,CO_(2)is converted into CO and aromatic products during the reaction,offering a novel way for CO_(2)utilization through the coupling reaction of alkane and CO_(2).展开更多
AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which prov...AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which provide estimates of relative risk （RR） and 95%CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke （ETS）： The spouse; household; workplace; childhood; travel; social and other; and total. A wide range of study details were entered into a database, and the RRs for each study, including descriptions of the comparisons made, were entered into a linked database. RRs were derived where necessary. Results were entered, where available, for all lung cancer, and for squamous cell cancer and adenocarcinoma. “Most adjusted” results were entered based on results available, adjusted for the greatest number of potential confounding variables. “Least adjusted” results were also entered, with a preference for results adjusted at least for age for prospective studies. A pre-planned series of fxed-effects and random-effects meta-analyses were conducted. Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex, and results for childhood exposure given by source of ETS exposure. For spousal exposure, more extensive analyses provide results by various aspects of study design and defnition of the RR. For smoking by the husband （or nearest equivalent）, additional analyses were carried out both for overall risk, and for risk per 10 cigarettes per day smoked by the husband. These adjusted for uncontrolled confounding by four factors （fruit, vegetable and dietary fat consumption, and education）, and corrected for misclassification of smoking status of the wife. For the confounding adjustment, estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure, and on the correlations between the factors. The bias due to misclassifcation was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere, and that those who deny smoking have the same risk as those who admit it. This approach, justifed in previous work, balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS： One hundred and two studies were identifed for inclusion, published in 1981 onwards, 45 in Asia, 31 in North America, 21 in Europe, and fve elsewhere. Eighty-fve were of case-control design and 17 were prospective. Significant （P 〈 0.05） associations were noted, with random-effects of （RR = 1.22, 95%CI： 1.14-1.31, n = 93） for smoking by the husband （RR = 1.14, 95%CI： 1.01-1.29, n = 45） for smoking by the wife （RR = 1.22, 95%CI： 1.15-1.30, n = 47） for workplace exposure （RR = 1.15, 95%CI： 1.02-1.29, n = 41） for childhood exposure, and （RR = 1.31, 95%CI： 1.19-1.45, n = 48） for total exposure. No signifcant association was seen for ETS exposure in travel （RR = 1.34, 95%CI： 0.94-1.93, n = 8） or in social situations （RR = 1.01, 95%CI： 0.82-1.24, n = 15）. A signifcant negative association （RR = 0.78, 95%CI： 0.64-0.94, n = 8） was seen for ETS exposure in childhood, specifically from the parents. Significant associations were also seen for spousal smoking for both squamous cell carcinoma （RR = 1.44, 95%CI： 1.15-1.80, n = 24） and adenocarcinoma （RR = 1.33,95%CI： 1.17-1.51, n = 30）. Results generally showed marked heterogeneity between studies. For smoking by either the husband or wife, where 119 RR estimates gave an overall estimate of （RR = 1.21, 95%CI： 1.14-1.29）, the heterogeneity was highly significant （P 〈 0.001）, with evidence that the largest RRs were seen in studies published in 1981-89, in small studies （1-49 cases）, and for estimates unadjusted by age. For smoking by the husband, the additional analyses showed that adjustment for the four factors reduced the overall （RR = 1.22, 95%CI： 1.14-1.31） based on 93 estimates to （RR = 1.14, 95%CI： 1.06-1.22）, implying bias due to uncontrolled confounding of 7%. Further correction for misclassification reduced the estimate to a marginally non-signifcant （RR = 1.08, 95%CI： 0.999-1.16）. In the fully adjusted and corrected analyses, there was evidence of an increase in Asia （RR = 1.18, 95%CI： 1.07-1.30, n = 44）, but not in other regions （RR = 0.96, 95%CI： 0.86-1.07, n = 49）. Studies published in the 1980’s, studies providing dose-response data, and studies only providing results unadjusted for age showed elevated RRs, but later published studies, studies not providing dose-response data, and studies adjusting for age did not. The pattern of results for RRs per 10 cigs/d was similar, with no signifcant association in the adjusted and corrected results （RR = 1.03, 95%CI： 0.994-1.07）.CONCLUSION： Most, if not all, of the ETS/lung cancer association can be explained by confounding adjustment and misclassifcation correction. Any causal relationship is not convincingly demonstrated.展开更多
BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating excl...BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating exclusive cigar smoking to risk of the major smoking-related diseases.METHODS Literature searches detected studies carried out in the United States which estimated the risk of lung cancer,chronic obstructive pulmonary disease(COPD),heart disease,stroke or overall circulatory disease in exclusive cigar smokers as compared to those who had never smoked any tobacco product.Papers were identified from reviews and detailed searches on MEDLINE.For each study,data were extracted onto a study database and a linked relative risk database.Relative risks and 95%CIs were extracted,or estimated,relating to current,former or ever exclusive cigar smokers,and meta-analysed using standard methods.Sensitivity analyses were conducted including or excluding results from studies that did not quite fit the full selection criteria(for example,a paper presenting combined results from five studies,where 86%of the population were in the United States).RESULTS The literature searches identified 17 relevant publications for lung cancer,four for COPD and 12 for heart disease,stroke and circulatory disease.These related to 11 studies for lung cancer,to four studies for COPD and to eight studies for heart disease,stroke or overall circulatory disease.As some studies provided results for more than one disease,the total number of studies considered was 13,with results from four of these used in sensitivity analyses.There was evidence of significant heterogeneity in some of the meta-analyses so the random-effects estimates are summarized below.As the results from the sensitivity analyses were generally very similar to those from the main analyses,and involved more data,only the sensitivity results are summarized below.For lung cancer,relative risks(95%CI)for current,former and ever smokers were respectively,2.98(2.08 to 4.26),1.61(1.23 to 2.09),and 2.22(1.79 to 2.74)based on 6,4 and 10 individual study estimates.For COPD,the corresponding estimates were 1.44(1.16 to 1.77),0.47(0.02 to 9.88),and 0.86(0.48 to 1.54)based on 4,2 and 2 estimates.For ischaemic heart disease(IHD)the estimates were 1.11(1.04 to 1.19),1.26(1.03 to 1.53)and 1.15(1.08 to 1.23)based on 6,3 and 4 estimates,while for stroke they were 1.02(0.92 to 1.13),1.08(0.85 to 1.38),and 1.11(0.95 to 1.31)based on 5,3 and 4 estimates.For overall circulatory disease they were 1.10(1.05 to 1.16),1.11(0.84 to 1.46),and 1.15(1.06 to 1.26)based on 3,3 and 4 estimates.CONCLUSION Exclusive cigar smoking is associated with an increased risk of lung cancer,and less so with COPD and IHD.The increases are lower than for cigarettes.展开更多
In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribu...In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribution strategies,i.e.,＇Center of Strength-Center of Mass（CV-CM） coinciding＇ and ＇Balanced Center of Strength-Center of Resistance（CVCR）＇ are adopted.Design charts for the seismic demand of classical uni-directionally and bi-directionally asymmetric systems are developed in a simple unified format.A conceptual framework is also outlined to conveniently apply the design charts.Illustrations are included to explain the use of the current recommendations in practical design.The study also highlights the relative performance of ＇CV-CM coinciding＇ and ＇Balanced CV-CR＇ criteria.展开更多
BACKGROUND Evidence relating tobacco smoking to type 2 diabetes has accumulated rapidly in the last few years,rendering earlier reviews considerably incomplete.AIM To review and meta-analyse evidence from prospective ...BACKGROUND Evidence relating tobacco smoking to type 2 diabetes has accumulated rapidly in the last few years,rendering earlier reviews considerably incomplete.AIM To review and meta-analyse evidence from prospective studies of the relationship between smoking and the onset of type 2 diabetes.METHODS Prospective studies were selected if the population was free of type 2 diabetes at baseline and evidence was available relating smoking to onset of the disease.Papers were identified from previous reviews,searches on Medline and Embase and reference lists.Data were extracted on a range of study characteristics and relative risks(RRs)were extracted comparing current,ever or former smokers with never smokers,and current smokers with non-current smokers,as well as by amount currently smoked and duration of quitting.Fixed-and random-effects estimates summarized RRs for each index of smoking overall and by various subdivisions of the data:Sex;continent;publication year;method of diagnosis;nature of the baseline population(inclusion/exclusion of pre-diabetes);number of adjustment factors;cohort size;number of type 2 diabetes cases;age;length of follow-up;definition of smoking;and whether or not various factors were adjusted for.Tests of heterogeneity and publication bias were also conducted.RESULTS The literature searches identified 157 relevant publications providing results from 145 studies.Fifty-three studies were conducted in Asia and 53 in Europe,with 32 in North America,and seven elsewhere.Twenty-four were in males,10 in females and the rest in both sexes.Fifteen diagnosed type 2 diabetes from selfreport by the individuals,79 on medical records,and 51 on both.Studies varied widely in size of the cohort,number of cases,length of follow-up,and age.Overall,random-effects estimates of the RR were 1.33[95%confidence interval(CI):1.28-1.38]for current vs never smoking,1.28(95%CI:1.24-1.32)for current vs non-smoking,1.13(95%CI:1.11-1.16)for former vs never smoking,and 1.25(95%CI:1.21-1.28)for ever vs never smoking based on,respectively,99,156,100 and 100 individual risk estimates.Risk estimates were generally elevated in each subdivision of the data by the various factors considered(exceptions being where numbers of estimates in the subsets were very low),though there was significant(P<0.05)evidence of variation by level for some factors.Dose-response analysis showed a clear trend of increasing risk with increasing amount smoked by current smokers and of decreasing risk with increasing time quit.There was limited evidence of publication bias.CONCLUSION The analyses confirmed earlier reports of a modest dose-related association of current smoking and a weaker dose-related association of former smoking with type 2 diabetes risk.展开更多
BACKGROUND Previous meta-analyses related smoking to death or severe infection from coronavirus disease 2019(COVID-19)in hospitalized patients,but considered only a few studies,did not adjust for demographics and como...BACKGROUND Previous meta-analyses related smoking to death or severe infection from coronavirus disease 2019(COVID-19)in hospitalized patients,but considered only a few studies,did not adjust for demographics and comorbidities,and inadequately defined smoking.AIM To review and meta-analyse epidemiological evidence on smoking and COVID-19,considering a range of endpoints,populations and smoking definitions and the effect of adjustment.METHODS Studies were identified from publications in English up to 30 September,2020 involving at least 100 individuals,carried out in Europe,Israel,America or Australasia,not restricted to those with specific other diseases,and providing information relating smoking to various COVID-related endpoints.Meta-analyses were carried out for combinations of population and endpoint,with variation studied by smoking definition,adjustment level and other factors.RESULTS From 96 publications,74 studies were identified,37 in the United States,10 in the United Kingdom,with up to four in the other countries.Three involved over a million individuals,and 37 involved less than a thousand.Adjusted results for smoking were available in 42 studies,with adjustment not considered in 20 studies.Results were considered by endpoint.No significant effect of smoking on COVID-19 positivity was seen in the general population,but there was a reduced risk in those tested.Best-adjusted estimates for current(vs never)smoking were 0.87(95%confidence interval:0.52-1.47)in the general population and 0.52(0.43-0.64)in those tested.For those hospitalized due to COVID-19,unadjusted rates were significantly increased in current smokers(1.20,1.01-1.42)and ever smokers(1.64,1.41-1.91),but those adjusted for comorbidities showed no increase for current(0.82,0.52-1.30)or ever smokers(1.00,0.76-1.32).There was little evidence to suggest that smoking was associated with intensive care admission.For those hospitalized with COVID-19,best-adjusted estimates were 0.88(0.72-1.08)for current smokers and 1.10(0.99-1.22)for ever smokers.In those hospitalized with COVID-19,smoking was not significantly related to subsequent mechanical ventilation,with best-adjusted estimates of 1.12(0.60-2.09)for current smokers and 1.05(0.88-1.25)for ever smokers.For those hospitalized with severe COVID-19,best-adjusted estimates were 0.74(0.49-1.12)for current smokers and 1.15(0.87-1.51)for ever smokers;few estimates were adjusted for comorbidities.While smoking was associated with increased mortality in unadjusted analyses,the association disappeared after adjustment for comorbidities.For example,in those hospitalized with COVID-19,the unadjusted estimate for ever smokers of 1.59(1.37-1.83)reduced to 1.07(0.82-1.38)when adjusted for comorbidities.Studies on those with severe COVID-19 showed that smoking tended to be associated with worsening of the disease.However,no estimate was adjusted,even for demographics.Estimates did not clearly vary by location or study size,and there was too little evidence to usefully study variations by age,amount smoked or years quit.CONCLUSION The increased COVID-19 death rate in smokers seen in unadjusted analyses disappears following adjustment for demographics and comorbidities.Among those tested,smoking is associated with lower COVID-19 infection rates.展开更多
BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and strok...BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and stroke,far less information is available on risks from moist snuff(“snus”)or smokeless tobacco(ST)in United States/Canada,Europe or Japan.AIM To summarize data from the selected countries on risks of the four diseases associated with current ST or snus use.METHODS Publications in English in 1990-2020 were considered that,based on epidemiological studies in North America,Europe or Japan,estimated risks of lung cancer,COPD,IHD/AMI,or stroke according to use of ST or snus.The studies should involve at least 100 cases of the disease considered,and not be restricted to those with specific other diseases.Medline literature searches were conducted,selecting papers initially from examination of titles and abstracts,and then from full texts.Further papers were sought from reference lists in selected papers,reviews and meta-analyses.For each disease,relative risk estimates adjusted at least for age were extracted relating ST or snus use to risk,and combined using random-effects meta-analysis.The estimates were mainly for current vs.never or non-current use,but results for ever vs never use were also considered.RESULTS Seven publications reported results for ST use from six United States studies.The most useful results came from four studies which provided results for current vs.never use.Random-effects meta-analyses of these results showed an increased risk for each disease,clearest for lung cancer(relative risk 1.59,95%confidence interval 1.06-2.39,based on 4 estimates)and COPD(1.57,1.09-2.26,n=3),but also significant(at P<0.05)for IHD(1.26,1.10-1.45,n=4)and stroke(1.27,1.03-1.57,n=4).Also including results for ever vs.never use from two other studies increased the lung cancer estimate to 1.80(1.23-2.64,n=6),but had little effect on the other estimates.For snus,16 publications described results from 12 studies,one in Norway and the rest in Sweden.There were no results for COPD,and only three for lung cancer,with these reporting a relative risk of 0.80(0.40-1.30)for current vs never use.More extensive data were available for IHD/AMI and stroke.Using the latest results from each study,combined estimates for current vs.never use were 1.00(0.91-1.11,n=5)for IHD/AMI and 1.05(0.95-1.17,n=2)for stroke,while for current vs.non-current use they were 1.10(0.92-1.33,n=9)for IHD/AMI and 1.12(0.86-1.45,n=9)for stroke.Meta-analyses including earlier results from some studies also showed no significant association between snus use and IHD/AMI or stroke.No relevant results were found for Japan.CONCLUSION Risks of smoking-related diseases from snus use in Scandinavia are not demonstrated,while those from ST use in the United States are less than from smoking.展开更多
Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemot...Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.展开更多
BACKGROUND There is a need to have up-to-date information for various diseases on the risk related to the use of different smoked products and the use of other nicotinecontaining products.Here,we contribute to the inf...BACKGROUND There is a need to have up-to-date information for various diseases on the risk related to the use of different smoked products and the use of other nicotinecontaining products.Here,we contribute to the information pool by presenting up-to-date quantitative evidence for North America,Europe and Japan and for both lung cancer and chronic obstructive pulmonary disease(COPD)on the relative risk(RR)relating to current vs never product use for each of the three smoked tobacco products,cigarettes,cigars and pipes.AIM To estimate lung cancer and COPD current smoking RRs for the three products using recent data for the three regions.METHODS Publications in English from 2010 to 2020 were considered that,based on epidemiological studies in the three regions,estimated the current smoking RR of lung cancer and/or COPD for one or more of the three products.The studies should involve at least 100 cases of the disease considered,not be restricted to specific lung cancer types or populations with specific medical conditions,and should be of cohort or nested case-control study design or randomized controlled trials.Literature searches were conducted on MEDLINE separately for lung cancer and for COPD,examining titles and abstracts initially,and then full texts.Additional papers were sought from reference lists of selected papers,reviews and metaanalyses.For each study identified,the most recent available data on each product were entered on current smoking,as well as on characteristics of the study and the RR estimates.Combined RR estimates were derived using random-effects meta-analysis.For cigarette smoking,where far more data were available,heterogeneity was studied by a wide range of factors.For cigar and pipe smoking,a more limited heterogeneity analysis was carried out.Results were compared with those from previous meta-analyses published since 2000.RESULTS Current cigarette smoking:For lung cancer,44 studies(26 North American,14 European,three Japanese,and one in multiple continents),gave an overall estimate of 12.14[95%confidence interval(CI)10.30-14.30].The estimates were higher(heterogeneity P<0.001)for North American(15.15,CI 12.77-17.96)and European studies(12.30,CI 9.77-15.49)than for Japanese studies(3.61,CI 2.87-4.55),consistent with previous evidence of lower RRs for Asia.RRs were higher(P<0.05)for death(14.85,CI 11.99-18.38)than diagnosis(10.82,CI 8.61-13.60).There was some variation(P<0.05)by study population,with higher RRs for international and regional studies than for national studies and studies of specific populations.RRs were higher in males,as previously reported,the within-study male/female ratio of RRs being 1.52(CI 1.20-1.92).RRs did not vary significantly(P≥0.05)by other factors.For COPD,RR estimates were provided by 18 studies(10 North American,seven European,and one Japanese).The overall estimate of 9.19(CI 6.97-12.13),was based on heterogeneous data(P<0.001),and higher than reported earlier.There was no(P>0.1)variation by sex,region or exclusive use,but limited evidence(0.05<P<0.1)that RR estimates were greater where cases occurring shortly after baseline were ignored;where bronchiectasis was excluded from the COPD definition;and with greater confounder adjustment.Within-study comparisons showed adjusted RRs exceeded unadjusted RRs.Current cigar smoking:Three studies gave an overall lung cancer RR of 2.73(CI 2.36-3.15),with no heterogeneity,lower than the 4.67(CI 3.49-6.25)reported in an earlier review.Only one study gave COPD results,the RR(2.44,CI 0.98-6.05)being imprecise.Current pipe smoking:Four studies gave an overall lung cancer RR of 4.93(CI 1.97-12.32),close to the 5.20(CI 3.50-7.73)given earlier.However,the estimates were heterogeneous,with two above 10,and two below 3.Only one study gave COPD results,the RR(1.12,CI 0.29-4.40),being imprecise.For both diseases,the lower RR estimates for cigars and for pipes than for current smoking of cigarettes aligns with earlier published evidence.CONCLUSION Current cigarette smoking substantially increases lung cancer and COPD risk,more so in North America and Europe than Japan.Limited evidence confirms lower risks for cigars and pipes than cigarettes.展开更多
Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relev...Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.展开更多
In this paper,we prove a wall-crossing formula,a crucial ingredient needed to prove that the correlation function of gauged linear-model is independent of the choice of perturbations.
Herpes virus is a typical nuclear DNA virus whose nucleocapsids are assembled in cell nuclei. However, it was found in the past few years that duck plague virus (a duck herpes virus) and herpes simplex virus can be as...Herpes virus is a typical nuclear DNA virus whose nucleocapsids are assembled in cell nuclei. However, it was found in the past few years that duck plague virus (a duck herpes virus) and herpes simplex virus can be assembled in the cytoplasm while being assembled in the nuclei as well. This phenomenon is quite different from the classical virology, but the reports concerning it are few. Much less is known abeut the mechanism of cytoplasmic morphogenesis.展开更多
Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer ...Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.展开更多
Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their releva...Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.展开更多
A Reynolds averaged Navier-Stokes(RANS)computational fluid dynamics(CFD)model is built to investigate the hydrodynamic response of a circular ice floe under the influence of a passing ship in calm waters.The ship,mirr...A Reynolds averaged Navier-Stokes(RANS)computational fluid dynamics(CFD)model is built to investigate the hydrodynamic response of a circular ice floe under the influence of a passing ship in calm waters.The ship,mirroring the KRISO Container Ship’s hull design,progresses near an ice floe whose diameter is 30%of the ship’s length and its thickness is 3 m.The ship advances at a constant speed,which is handled by using the overset mesh technique.This study focuses on the ice floe’s motions and the hydrodynamic forces induced by three speeds and three transverse distances of the passing ship.Findings reveal that ship-generated wakes notably influence the ice floe’s motions,with a greater influence on sway than surge.Additionally,the ship’s speed and proximity distinctly affect the ice floe’s motions.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study i...Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study investigates the nutritional quality of A.japonicus from different geographical regions and identifies genetic markers associated with these traits through a genome-wide association study(GWAS).We observed significant regional variations in the nutritional content of A.japonicus.Samples collected from Nanhuangcheng Island displayed the highest levels of saponins,whereas those from Laizhou exhibited the highest concentrations of glycosaminoglycans.Lingshan Island samples were the richest in amino acids,while samples from Rizhao contained the highest levels of polyunsaturated fatty acids.Through GWAS,265 candidate genes and related single nucleotide polymorphisms(SNPs)were identified as being significantly associated with essential nutritional traits,including genes like ubiquitin domain-containing protein 1(UBTD1),inactive pancreatic lipase-related protein 1,protein arginine N-methyltransferase 5(PRMT5)and GDP-fucose protein O-fucosyltransferase 1(POFUT1).This study advanced our knowledge of the genetic mechanisms underlying the nutritional quality of A.japonicus.The genetic markers identified herein o ffer crucial insights for breeding initiatives aimed at optimizing the nutritional profile of sea cucumbers.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.22288101,22472016)the National Key Research and Development Program of the Ministry of Science and Technology(No.2022YFE0116000)+1 种基金the Chinese Academy of Sciences Strategy Leading Technology Project(No.XDA29000000)the Youth Innovation Promotion Association CAS(No.2021182)。
文摘Aromatization of alkanes represents an important process in the chemical industry,traditionally relying on noble metal catalysts.Developing a non-noble metal catalyst and a relevant new process offers significant potential for promoting technologic progress in this field.Herein,we present Cu-ZSM-5 zeolite as a highly effective catalyst for alkane aromatization,achieving outstanding aromatics selectivity.In-situ Fourier transform infrared spectra of adsorbed nitric oxide,high-angle annular dark field scanning transmission electron microscopy,X-ray absorption spectroscopy,and electron paramagnetic resonance analyses reveal that the Cu^(2+)species act as the primary active centers for aromatics formation.During aromatization of alkanes,the reduction of Cu^(2+)to Cu^(+)species correlates with diminished aromatics selectivity.Notably,introducing CO_(2)into the reaction feed not only enhances aromatics selectivity by maintaining Cu^(2+)species in their active oxidation state under reducing conditions,but also improves catalytic stability by eliminating coke.Furthermore,CO_(2)is converted into CO and aromatic products during the reaction,offering a novel way for CO_(2)utilization through the coupling reaction of alkane and CO_(2).
文摘AIM： To review evidence relating passive smoking to lung cancer risk in never smokers, considering various major sources of bias.METHODS： Epidemiological prospective or case-control studies were identifed which provide estimates of relative risk （RR） and 95%CI for never smokers for one or more of seven different indices of exposure to environmental tobacco smoke （ETS）： The spouse; household; workplace; childhood; travel; social and other; and total. A wide range of study details were entered into a database, and the RRs for each study, including descriptions of the comparisons made, were entered into a linked database. RRs were derived where necessary. Results were entered, where available, for all lung cancer, and for squamous cell cancer and adenocarcinoma. “Most adjusted” results were entered based on results available, adjusted for the greatest number of potential confounding variables. “Least adjusted” results were also entered, with a preference for results adjusted at least for age for prospective studies. A pre-planned series of fxed-effects and random-effects meta-analyses were conducted. Overall analyses and analyses by continent were run for each exposure index,with results for spousal smoking given by sex, and results for childhood exposure given by source of ETS exposure. For spousal exposure, more extensive analyses provide results by various aspects of study design and defnition of the RR. For smoking by the husband （or nearest equivalent）, additional analyses were carried out both for overall risk, and for risk per 10 cigarettes per day smoked by the husband. These adjusted for uncontrolled confounding by four factors （fruit, vegetable and dietary fat consumption, and education）, and corrected for misclassification of smoking status of the wife. For the confounding adjustment, estimates for never smoking women were derived from publications on the relationship of the four factors to both lung cancer risk and at home ETS exposure, and on the correlations between the factors. The bias due to misclassifcation was calculated on the basis that the proportion of ever smokers denying smoking is 10% in Asian studies and 2.5% elsewhere, and that those who deny smoking have the same risk as those who admit it. This approach, justifed in previous work, balances higher true denial rates and lower risk in deniers compared to non-deniers.RESULTS： One hundred and two studies were identifed for inclusion, published in 1981 onwards, 45 in Asia, 31 in North America, 21 in Europe, and fve elsewhere. Eighty-fve were of case-control design and 17 were prospective. Significant （P 〈 0.05） associations were noted, with random-effects of （RR = 1.22, 95%CI： 1.14-1.31, n = 93） for smoking by the husband （RR = 1.14, 95%CI： 1.01-1.29, n = 45） for smoking by the wife （RR = 1.22, 95%CI： 1.15-1.30, n = 47） for workplace exposure （RR = 1.15, 95%CI： 1.02-1.29, n = 41） for childhood exposure, and （RR = 1.31, 95%CI： 1.19-1.45, n = 48） for total exposure. No signifcant association was seen for ETS exposure in travel （RR = 1.34, 95%CI： 0.94-1.93, n = 8） or in social situations （RR = 1.01, 95%CI： 0.82-1.24, n = 15）. A signifcant negative association （RR = 0.78, 95%CI： 0.64-0.94, n = 8） was seen for ETS exposure in childhood, specifically from the parents. Significant associations were also seen for spousal smoking for both squamous cell carcinoma （RR = 1.44, 95%CI： 1.15-1.80, n = 24） and adenocarcinoma （RR = 1.33,95%CI： 1.17-1.51, n = 30）. Results generally showed marked heterogeneity between studies. For smoking by either the husband or wife, where 119 RR estimates gave an overall estimate of （RR = 1.21, 95%CI： 1.14-1.29）, the heterogeneity was highly significant （P 〈 0.001）, with evidence that the largest RRs were seen in studies published in 1981-89, in small studies （1-49 cases）, and for estimates unadjusted by age. For smoking by the husband, the additional analyses showed that adjustment for the four factors reduced the overall （RR = 1.22, 95%CI： 1.14-1.31） based on 93 estimates to （RR = 1.14, 95%CI： 1.06-1.22）, implying bias due to uncontrolled confounding of 7%. Further correction for misclassification reduced the estimate to a marginally non-signifcant （RR = 1.08, 95%CI： 0.999-1.16）. In the fully adjusted and corrected analyses, there was evidence of an increase in Asia （RR = 1.18, 95%CI： 1.07-1.30, n = 44）, but not in other regions （RR = 0.96, 95%CI： 0.86-1.07, n = 49）. Studies published in the 1980’s, studies providing dose-response data, and studies only providing results unadjusted for age showed elevated RRs, but later published studies, studies not providing dose-response data, and studies adjusting for age did not. The pattern of results for RRs per 10 cigs/d was similar, with no signifcant association in the adjusted and corrected results （RR = 1.03, 95%CI： 0.994-1.07）.CONCLUSION： Most, if not all, of the ETS/lung cancer association can be explained by confounding adjustment and misclassifcation correction. Any causal relationship is not convincingly demonstrated.
基金Supported by the JT International SA,Assignment Schedule,No.14.
文摘BACKGROUND Little information has been published on the risks of cigar smoking.Since 1990 cigar smoking has become more prevalent in the United States.AIM To summarise the evidence from the United States relating exclusive cigar smoking to risk of the major smoking-related diseases.METHODS Literature searches detected studies carried out in the United States which estimated the risk of lung cancer,chronic obstructive pulmonary disease(COPD),heart disease,stroke or overall circulatory disease in exclusive cigar smokers as compared to those who had never smoked any tobacco product.Papers were identified from reviews and detailed searches on MEDLINE.For each study,data were extracted onto a study database and a linked relative risk database.Relative risks and 95%CIs were extracted,or estimated,relating to current,former or ever exclusive cigar smokers,and meta-analysed using standard methods.Sensitivity analyses were conducted including or excluding results from studies that did not quite fit the full selection criteria(for example,a paper presenting combined results from five studies,where 86%of the population were in the United States).RESULTS The literature searches identified 17 relevant publications for lung cancer,four for COPD and 12 for heart disease,stroke and circulatory disease.These related to 11 studies for lung cancer,to four studies for COPD and to eight studies for heart disease,stroke or overall circulatory disease.As some studies provided results for more than one disease,the total number of studies considered was 13,with results from four of these used in sensitivity analyses.There was evidence of significant heterogeneity in some of the meta-analyses so the random-effects estimates are summarized below.As the results from the sensitivity analyses were generally very similar to those from the main analyses,and involved more data,only the sensitivity results are summarized below.For lung cancer,relative risks(95%CI)for current,former and ever smokers were respectively,2.98(2.08 to 4.26),1.61(1.23 to 2.09),and 2.22(1.79 to 2.74)based on 6,4 and 10 individual study estimates.For COPD,the corresponding estimates were 1.44(1.16 to 1.77),0.47(0.02 to 9.88),and 0.86(0.48 to 1.54)based on 4,2 and 2 estimates.For ischaemic heart disease(IHD)the estimates were 1.11(1.04 to 1.19),1.26(1.03 to 1.53)and 1.15(1.08 to 1.23)based on 6,3 and 4 estimates,while for stroke they were 1.02(0.92 to 1.13),1.08(0.85 to 1.38),and 1.11(0.95 to 1.31)based on 5,3 and 4 estimates.For overall circulatory disease they were 1.10(1.05 to 1.16),1.11(0.84 to 1.46),and 1.15(1.06 to 1.26)based on 3,3 and 4 estimates.CONCLUSION Exclusive cigar smoking is associated with an increased risk of lung cancer,and less so with COPD and IHD.The increases are lower than for cigarettes.
文摘In view of the recognition of the importance of the interdependent behavior of strength and stiffness of walltype structural elements,the seismic demand of plan-asymmetric systems is revisited.Useful strength distribution strategies,i.e.,＇Center of Strength-Center of Mass（CV-CM） coinciding＇ and ＇Balanced Center of Strength-Center of Resistance（CVCR）＇ are adopted.Design charts for the seismic demand of classical uni-directionally and bi-directionally asymmetric systems are developed in a simple unified format.A conceptual framework is also outlined to conveniently apply the design charts.Illustrations are included to explain the use of the current recommendations in practical design.The study also highlights the relative performance of ＇CV-CM coinciding＇ and ＇Balanced CV-CR＇ criteria.
基金Supported by Japan Tobacco International,No.PO 4700389462.
文摘BACKGROUND Evidence relating tobacco smoking to type 2 diabetes has accumulated rapidly in the last few years,rendering earlier reviews considerably incomplete.AIM To review and meta-analyse evidence from prospective studies of the relationship between smoking and the onset of type 2 diabetes.METHODS Prospective studies were selected if the population was free of type 2 diabetes at baseline and evidence was available relating smoking to onset of the disease.Papers were identified from previous reviews,searches on Medline and Embase and reference lists.Data were extracted on a range of study characteristics and relative risks(RRs)were extracted comparing current,ever or former smokers with never smokers,and current smokers with non-current smokers,as well as by amount currently smoked and duration of quitting.Fixed-and random-effects estimates summarized RRs for each index of smoking overall and by various subdivisions of the data:Sex;continent;publication year;method of diagnosis;nature of the baseline population(inclusion/exclusion of pre-diabetes);number of adjustment factors;cohort size;number of type 2 diabetes cases;age;length of follow-up;definition of smoking;and whether or not various factors were adjusted for.Tests of heterogeneity and publication bias were also conducted.RESULTS The literature searches identified 157 relevant publications providing results from 145 studies.Fifty-three studies were conducted in Asia and 53 in Europe,with 32 in North America,and seven elsewhere.Twenty-four were in males,10 in females and the rest in both sexes.Fifteen diagnosed type 2 diabetes from selfreport by the individuals,79 on medical records,and 51 on both.Studies varied widely in size of the cohort,number of cases,length of follow-up,and age.Overall,random-effects estimates of the RR were 1.33[95%confidence interval(CI):1.28-1.38]for current vs never smoking,1.28(95%CI:1.24-1.32)for current vs non-smoking,1.13(95%CI:1.11-1.16)for former vs never smoking,and 1.25(95%CI:1.21-1.28)for ever vs never smoking based on,respectively,99,156,100 and 100 individual risk estimates.Risk estimates were generally elevated in each subdivision of the data by the various factors considered(exceptions being where numbers of estimates in the subsets were very low),though there was significant(P<0.05)evidence of variation by level for some factors.Dose-response analysis showed a clear trend of increasing risk with increasing amount smoked by current smokers and of decreasing risk with increasing time quit.There was limited evidence of publication bias.CONCLUSION The analyses confirmed earlier reports of a modest dose-related association of current smoking and a weaker dose-related association of former smoking with type 2 diabetes risk.
基金British-American Tobacco(Investments)Ltd.,No.5700014230Japan Tobacco International S.A.,No.4700562109and Philip Morris Products S.A.,No 5700131814。
文摘BACKGROUND Previous meta-analyses related smoking to death or severe infection from coronavirus disease 2019(COVID-19)in hospitalized patients,but considered only a few studies,did not adjust for demographics and comorbidities,and inadequately defined smoking.AIM To review and meta-analyse epidemiological evidence on smoking and COVID-19,considering a range of endpoints,populations and smoking definitions and the effect of adjustment.METHODS Studies were identified from publications in English up to 30 September,2020 involving at least 100 individuals,carried out in Europe,Israel,America or Australasia,not restricted to those with specific other diseases,and providing information relating smoking to various COVID-related endpoints.Meta-analyses were carried out for combinations of population and endpoint,with variation studied by smoking definition,adjustment level and other factors.RESULTS From 96 publications,74 studies were identified,37 in the United States,10 in the United Kingdom,with up to four in the other countries.Three involved over a million individuals,and 37 involved less than a thousand.Adjusted results for smoking were available in 42 studies,with adjustment not considered in 20 studies.Results were considered by endpoint.No significant effect of smoking on COVID-19 positivity was seen in the general population,but there was a reduced risk in those tested.Best-adjusted estimates for current(vs never)smoking were 0.87(95%confidence interval:0.52-1.47)in the general population and 0.52(0.43-0.64)in those tested.For those hospitalized due to COVID-19,unadjusted rates were significantly increased in current smokers(1.20,1.01-1.42)and ever smokers(1.64,1.41-1.91),but those adjusted for comorbidities showed no increase for current(0.82,0.52-1.30)or ever smokers(1.00,0.76-1.32).There was little evidence to suggest that smoking was associated with intensive care admission.For those hospitalized with COVID-19,best-adjusted estimates were 0.88(0.72-1.08)for current smokers and 1.10(0.99-1.22)for ever smokers.In those hospitalized with COVID-19,smoking was not significantly related to subsequent mechanical ventilation,with best-adjusted estimates of 1.12(0.60-2.09)for current smokers and 1.05(0.88-1.25)for ever smokers.For those hospitalized with severe COVID-19,best-adjusted estimates were 0.74(0.49-1.12)for current smokers and 1.15(0.87-1.51)for ever smokers;few estimates were adjusted for comorbidities.While smoking was associated with increased mortality in unadjusted analyses,the association disappeared after adjustment for comorbidities.For example,in those hospitalized with COVID-19,the unadjusted estimate for ever smokers of 1.59(1.37-1.83)reduced to 1.07(0.82-1.38)when adjusted for comorbidities.Studies on those with severe COVID-19 showed that smoking tended to be associated with worsening of the disease.However,no estimate was adjusted,even for demographics.Estimates did not clearly vary by location or study size,and there was too little evidence to usefully study variations by age,amount smoked or years quit.CONCLUSION The increased COVID-19 death rate in smokers seen in unadjusted analyses disappears following adjustment for demographics and comorbidities.Among those tested,smoking is associated with lower COVID-19 infection rates.
文摘BACKGROUND While extensive information exists relating cigarette smoking to the risk of lung cancer,chronic obstructive pulmonary disease(COPD),ischaemic heart disease(IHD)or acute myocardial infarction(AMI),and stroke,far less information is available on risks from moist snuff(“snus”)or smokeless tobacco(ST)in United States/Canada,Europe or Japan.AIM To summarize data from the selected countries on risks of the four diseases associated with current ST or snus use.METHODS Publications in English in 1990-2020 were considered that,based on epidemiological studies in North America,Europe or Japan,estimated risks of lung cancer,COPD,IHD/AMI,or stroke according to use of ST or snus.The studies should involve at least 100 cases of the disease considered,and not be restricted to those with specific other diseases.Medline literature searches were conducted,selecting papers initially from examination of titles and abstracts,and then from full texts.Further papers were sought from reference lists in selected papers,reviews and meta-analyses.For each disease,relative risk estimates adjusted at least for age were extracted relating ST or snus use to risk,and combined using random-effects meta-analysis.The estimates were mainly for current vs.never or non-current use,but results for ever vs never use were also considered.RESULTS Seven publications reported results for ST use from six United States studies.The most useful results came from four studies which provided results for current vs.never use.Random-effects meta-analyses of these results showed an increased risk for each disease,clearest for lung cancer(relative risk 1.59,95%confidence interval 1.06-2.39,based on 4 estimates)and COPD(1.57,1.09-2.26,n=3),but also significant(at P<0.05)for IHD(1.26,1.10-1.45,n=4)and stroke(1.27,1.03-1.57,n=4).Also including results for ever vs.never use from two other studies increased the lung cancer estimate to 1.80(1.23-2.64,n=6),but had little effect on the other estimates.For snus,16 publications described results from 12 studies,one in Norway and the rest in Sweden.There were no results for COPD,and only three for lung cancer,with these reporting a relative risk of 0.80(0.40-1.30)for current vs never use.More extensive data were available for IHD/AMI and stroke.Using the latest results from each study,combined estimates for current vs.never use were 1.00(0.91-1.11,n=5)for IHD/AMI and 1.05(0.95-1.17,n=2)for stroke,while for current vs.non-current use they were 1.10(0.92-1.33,n=9)for IHD/AMI and 1.12(0.86-1.45,n=9)for stroke.Meta-analyses including earlier results from some studies also showed no significant association between snus use and IHD/AMI or stroke.No relevant results were found for Japan.CONCLUSION Risks of smoking-related diseases from snus use in Scandinavia are not demonstrated,while those from ST use in the United States are less than from smoking.
文摘Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.
文摘BACKGROUND There is a need to have up-to-date information for various diseases on the risk related to the use of different smoked products and the use of other nicotinecontaining products.Here,we contribute to the information pool by presenting up-to-date quantitative evidence for North America,Europe and Japan and for both lung cancer and chronic obstructive pulmonary disease(COPD)on the relative risk(RR)relating to current vs never product use for each of the three smoked tobacco products,cigarettes,cigars and pipes.AIM To estimate lung cancer and COPD current smoking RRs for the three products using recent data for the three regions.METHODS Publications in English from 2010 to 2020 were considered that,based on epidemiological studies in the three regions,estimated the current smoking RR of lung cancer and/or COPD for one or more of the three products.The studies should involve at least 100 cases of the disease considered,not be restricted to specific lung cancer types or populations with specific medical conditions,and should be of cohort or nested case-control study design or randomized controlled trials.Literature searches were conducted on MEDLINE separately for lung cancer and for COPD,examining titles and abstracts initially,and then full texts.Additional papers were sought from reference lists of selected papers,reviews and metaanalyses.For each study identified,the most recent available data on each product were entered on current smoking,as well as on characteristics of the study and the RR estimates.Combined RR estimates were derived using random-effects meta-analysis.For cigarette smoking,where far more data were available,heterogeneity was studied by a wide range of factors.For cigar and pipe smoking,a more limited heterogeneity analysis was carried out.Results were compared with those from previous meta-analyses published since 2000.RESULTS Current cigarette smoking:For lung cancer,44 studies(26 North American,14 European,three Japanese,and one in multiple continents),gave an overall estimate of 12.14[95%confidence interval(CI)10.30-14.30].The estimates were higher(heterogeneity P<0.001)for North American(15.15,CI 12.77-17.96)and European studies(12.30,CI 9.77-15.49)than for Japanese studies(3.61,CI 2.87-4.55),consistent with previous evidence of lower RRs for Asia.RRs were higher(P<0.05)for death(14.85,CI 11.99-18.38)than diagnosis(10.82,CI 8.61-13.60).There was some variation(P<0.05)by study population,with higher RRs for international and regional studies than for national studies and studies of specific populations.RRs were higher in males,as previously reported,the within-study male/female ratio of RRs being 1.52(CI 1.20-1.92).RRs did not vary significantly(P≥0.05)by other factors.For COPD,RR estimates were provided by 18 studies(10 North American,seven European,and one Japanese).The overall estimate of 9.19(CI 6.97-12.13),was based on heterogeneous data(P<0.001),and higher than reported earlier.There was no(P>0.1)variation by sex,region or exclusive use,but limited evidence(0.05<P<0.1)that RR estimates were greater where cases occurring shortly after baseline were ignored;where bronchiectasis was excluded from the COPD definition;and with greater confounder adjustment.Within-study comparisons showed adjusted RRs exceeded unadjusted RRs.Current cigar smoking:Three studies gave an overall lung cancer RR of 2.73(CI 2.36-3.15),with no heterogeneity,lower than the 4.67(CI 3.49-6.25)reported in an earlier review.Only one study gave COPD results,the RR(2.44,CI 0.98-6.05)being imprecise.Current pipe smoking:Four studies gave an overall lung cancer RR of 4.93(CI 1.97-12.32),close to the 5.20(CI 3.50-7.73)given earlier.However,the estimates were heterogeneous,with two above 10,and two below 3.Only one study gave COPD results,the RR(1.12,CI 0.29-4.40),being imprecise.For both diseases,the lower RR estimates for cigars and for pipes than for current smoking of cigarettes aligns with earlier published evidence.CONCLUSION Current cigarette smoking substantially increases lung cancer and COPD risk,more so in North America and Europe than Japan.Limited evidence confirms lower risks for cigars and pipes than cigarettes.
基金supported by grants from the National Natural Science Foundation of China(81971641,82071200,82272039,and 82021002)the STI2030-Major Project(2022ZD0211600)+2 种基金the Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1038B,SHDC2020CR4007)the National Key R&D Program of China(2022YFC2009902,2022YFC2009900)Medical Innovation Research Project of Shanghai Science and Technology Commission(21Y11903300).
文摘Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.
文摘In this paper,we prove a wall-crossing formula,a crucial ingredient needed to prove that the correlation function of gauged linear-model is independent of the choice of perturbations.
文摘Herpes virus is a typical nuclear DNA virus whose nucleocapsids are assembled in cell nuclei. However, it was found in the past few years that duck plague virus (a duck herpes virus) and herpes simplex virus can be assembled in the cytoplasm while being assembled in the nuclei as well. This phenomenon is quite different from the classical virology, but the reports concerning it are few. Much less is known abeut the mechanism of cytoplasmic morphogenesis.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020,accessed on 01 July 2025)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020,accessed on 01 July 2025).Institutional.
文摘Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.
文摘Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.
文摘A Reynolds averaged Navier-Stokes(RANS)computational fluid dynamics(CFD)model is built to investigate the hydrodynamic response of a circular ice floe under the influence of a passing ship in calm waters.The ship,mirroring the KRISO Container Ship’s hull design,progresses near an ice floe whose diameter is 30%of the ship’s length and its thickness is 3 m.The ship advances at a constant speed,which is handled by using the overset mesh technique.This study focuses on the ice floe’s motions and the hydrodynamic forces induced by three speeds and three transverse distances of the passing ship.Findings reveal that ship-generated wakes notably influence the ice floe’s motions,with a greater influence on sway than surge.Additionally,the ship’s speed and proximity distinctly affect the ice floe’s motions.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
基金Supported by the Key Research and Development Program of Shandong(Nos.2021LZGC029,2023LZGC019)the National Natural Science Foundation of China(No.42076093)+1 种基金the Special Funds for the Central Government to Guide Local Science and Technology Development(No.YDZX2023043)the Taishan Scholars Program(No.tsqn202306279)。
文摘Sea cucumber Apostichopus japonicus is a crucial aquatic species known for its nutritional value.However,the genetic basis and regulatory mechanisms underlying its nutritional quality remain underexplored.This study investigates the nutritional quality of A.japonicus from different geographical regions and identifies genetic markers associated with these traits through a genome-wide association study(GWAS).We observed significant regional variations in the nutritional content of A.japonicus.Samples collected from Nanhuangcheng Island displayed the highest levels of saponins,whereas those from Laizhou exhibited the highest concentrations of glycosaminoglycans.Lingshan Island samples were the richest in amino acids,while samples from Rizhao contained the highest levels of polyunsaturated fatty acids.Through GWAS,265 candidate genes and related single nucleotide polymorphisms(SNPs)were identified as being significantly associated with essential nutritional traits,including genes like ubiquitin domain-containing protein 1(UBTD1),inactive pancreatic lipase-related protein 1,protein arginine N-methyltransferase 5(PRMT5)and GDP-fucose protein O-fucosyltransferase 1(POFUT1).This study advanced our knowledge of the genetic mechanisms underlying the nutritional quality of A.japonicus.The genetic markers identified herein o ffer crucial insights for breeding initiatives aimed at optimizing the nutritional profile of sea cucumbers.
