Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence h...Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.展开更多
There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as ...There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested,Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.展开更多
Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) ...Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality.Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk stratification.Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups.Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.展开更多
Background Breast cancer(BC)incidence and mortality vary significantly across countries,highlighting the need to update the global burden of female BC,including current trends and future projections.Methods Data were ...Background Breast cancer(BC)incidence and mortality vary significantly across countries,highlighting the need to update the global burden of female BC,including current trends and future projections.Methods Data were sourced from GLOBOCAN 2022,including estimated new cases and deaths from BC across 21 United Nation(UN)regions and 185 countries,the age-standardized incidence rate(ASIR)and mortality rate(ASMR),the estimated annual percentage changes(EAPC),and demographic projections through 2050.The region-specific and country-specific BC burden for women of all ages and for young women(<40 years old)was reorganized and re-plotted to highlight subgroup differences.Linear regression was used to explore the link between ASIR/ASMR and the human development index(HDI).Transitioning countries referred to those with low or medium HDI,while transitioned countries were those with high or very high HDI.Results In 2022,an estimated 2.3 million new BC cases and 666,000 BC-related deaths occurred globally,accounting for 23.8%and 15.4%of all cancer cases and deaths in women,respectively.Regionally,Eastern Asia reported the highest number of cases(480,019,ASIR:37.54/100,000),while South-Central Asia had the highest number of deaths(135,348,ASMR:13.41/100,000).At the country level,China had the highest number of cases due to its large population,whereas India reported the highest number of deaths.ASIR for both overall and early-onset BC increased with HDI,while ASMR for early-onset BC decreased with HDI(P<0.05).Overall BC showed an increasing trend in ASIR during 2003–2015(EAPC:0.92%)and a decreasing trend in ASMR during 2006–2016(EAPC:-1.06%).Early-onset BC showed a more significant rise in ASIR(EAPCs:1.4%)and a slight increase in ASMR(EAPCs:0.16%).If national rates remain stable,BC cases and deaths will increase by 54.7%and 70.9%,respectively,by 2050.Notably,increased early-onset BC cases are only observed in transitioning countries,while decreased cases are seen in transitioned countries.Conclusions Breast cancer remains the leading cancer burden in women,particularly in transitioning countries.Addressing this growing burden requires urgent integration of primary prevention,early detection and high-quality treatment through multi-sectoral collaboration.展开更多
Purpose To investigate the joint impacts of genetic and non-genetic factors on breast cancer(BC)subtypes among Chinese females,and to investigate the performance of optimized subtype-specific polygenic risk scores(PRS...Purpose To investigate the joint impacts of genetic and non-genetic factors on breast cancer(BC)subtypes among Chinese females,and to investigate the performance of optimized subtype-specific polygenic risk scores(PRS)with less single nucleotide polymorphisms(SNPs).Methods A total of 6,916 BC cases and 5,653 controls were used to assess the independent and joint impacts of PRS and non-genetic established risk score(ERS)on risks of overall and subtype-specific BC.The PRS were optimized by excluding low-penetrance SNPs until comparable area under receiver-operator-curve(AUCs)achieved.Results For the preliminary PRS with 21 Chinese BC-specific SNPs,the odds ratio(OR)of overall BC for the top decile compared to bottom decile(top-to-bottom decile)of PRS was 4.21(95%CI:3.47-5.10),and the OR per decile of PRS was 1.15(95%CI:1.13-1.16).For luminal A,luminal B,HER-2 enriched,and basal-like BC,the ORs for top-to-bottom decile were 4.58,4.37,3.08 and 2.90,respectively.After integrating four BC subtypes into two subtypes,relatively higher OR for top-to-bottom decile was observed for luminal BC than non-luminal BC(4.54 vs.3.02),and a similar trend was for OR per decile(1.15 vs.1.11).The optimized 13-SNP-PRS can achieve comparable performance of 21-SNP-PRS for luminal BC.After incorporating PRS into risk prediction of luminal BC,the AUC increased from 0.673 to 0.697,and the joint OR of PRS and ERS was 12.46(95%CI:9.38-16.56).Similar performances of PRS were validated in UK biobank.Conclusion PRS can well identify Chinese women at high-risk of BC,especially for luminal BC,and should be incorporated into risk-stratified BC intervention.展开更多
Periodontitis is an inflammatory disease caused by bacterial biofilms,which leads to the destruction of periodontal tissue.Current treatments,such as mechanical cleaning and antibiotics,struggle to effectively address...Periodontitis is an inflammatory disease caused by bacterial biofilms,which leads to the destruction of periodontal tissue.Current treatments,such as mechanical cleaning and antibiotics,struggle to effectively address the persistent biofilms,inflammation,and tissue damage.A new approach involves developing a Janus nanomotor(J-CeM@Au)by coating cerium dioxide-doped mesoporous silica(CeM)with gold nanoparticles(AuNPs).This nanomotor exhibits thermophoretic motion when exposed to near-infrared(NIR)laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs.The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties,allowing it to penetrate biofilms and kill bacteria.Additionally,the nanomotor's ability to scavenge reactive oxygen species(ROS)can modulate the immune response and create a regenerative environment,promoting the healing of periodontal tissue.Overall,this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.展开更多
Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne ...Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne debris risk analysis,debris flying trajectories,and impact resistance of envelope analysis.The method of debris distribution is developed.The flying trajectories of compact and plate-like debris are solved by using a numerical method according to the different aerodynamic characteristics.The impact resistance of the envelopes is also analyzed.Besides,the process of windborne debris damage analysis is described in detail.An example of industrial building is given to demonstrate the whole method by using the observed data of typhoon Chanchu(2006).The method developed in this paper could be applied to risk assessment of windborne debris for structures in wind hazard.展开更多
P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger cond...P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger condensation or nucleophilic substitution between phosphorus electrophiles and amine nucleo philes.Herein,we report a nitrene-mediated intermolecular P-N coupling reaction between various phos phorus nucleophiles and dioxazolones under simp le iron-catalyzed conditions.These reactions offer an efficient,versatile,and broadly applicable method for synthesis of a range of N-P compounds,including amidophosphines,iminophosphonamides,phosphinamides,aminophosphines,and iminophospho ranes,from readily available precursors under mild conditions.展开更多
Background and Objectives:Patients with inflammatory bowel disease(IBD)are more likely to be confirmed with vitamin D deficiency.However,the association between inflammation and vitamin D remains unclear.The purpose o...Background and Objectives:Patients with inflammatory bowel disease(IBD)are more likely to be confirmed with vitamin D deficiency.However,the association between inflammation and vitamin D remains unclear.The purpose of this study was to evaluate the association between inflammation and vitamin D in hospitalized patients with IBD.Methods and Study Design:All the participants were recruited from one teaching hospital from June 2018 to October 2022.Inflammation was evaluated by serum concentration of C-reactive protein(CRP),using an immunoturbidimetric method at admission.We further divided the participants into five groups based on serum CRP levels:<5,5–9.9,10–19.9,20–39.9,and>40mg/L.Serum 25-hydroxy-vitamin D(25-(OH)-D)was assessed by liquid chromatography tandem mass spectrometry.Additional information,including age,sex,body mass index(BMI),IBD(ulcerative colitis vs.Crohn’s disease)subtype,was abstracted from medical records.Results:This study included 1,989 patients with IBD(average age was 39.4 years,33.8%of them were women,1,365 CD and 624 UC patients).The median CRP was 5.49 mg/L(range of quartiles:1.64~19.5 mg/L)and the prevalence of 25-(OH)-D deficiency was 69.8%.CRP was significantly associated with serum level of 25-(OH)-D.The difference in 25-(OH)-D was-4.28 ng/ml(-5.27 ng/ml,-3.31 ng/ml)between two extremist CRP groups after adjustment of potential covariates(age,sex,BMI,type of IBD,dietary type,season,and lymphocyte count).Subgroup analysis in sex,type of IBD,and age,were similar to the main analysis results.Conclusions:There was a negative association between CRP levels and vitamin D in hospitalized patients with IBD.展开更多
基金supported by grants from the National Key Research and Development Program of China(Grant No.2021YFC2500400)the National Natural Science Foundation of China(Grant Nos.81974439&82204121)+2 种基金the Beijing-Tianjin-Hebei Basic Research Cooperation Special Project(20JCZXJC00090)the Tianjin Health Committee Foundation(Grant No.TJWJ2021MS008)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.
基金supported by AR060456 (F.L.), AR047867 (M.J.S.)the Washington University Musculoskeletal Research Center (NIH P30 AR057235)
文摘There remain unmet clinical needs for safe and effective bone anabolic therapies to treat aging-related osteoporosis and to improve fracture healing in cases of nonunion or delayed union. Wnt signaling has emerged as a promising target pathway for developing novel bone anabolic drugs. Although neutralizing antibodies against the Wnt antagonist sclerostin have been tested,Wnt ligands themselves have not been fully explored as a potential therapy. Previous work has demonstrated Wnt7b as an endogenous ligand upregulated during osteoblast differentiation, and that Wnt7b overexpression potently stimulates bone accrual in the mouse. The earlier studies however did not address whether Wnt7b could promote bone formation when specifically applied to aged or fractured bones. Here we have developed a doxycycline-inducible strategy where Wnt7b is temporally induced in the bones of aged mice or during fracture healing. We report that forced expression of Wnt7b for 1 month starting at 15 months of age greatly stimulated trabecular and endosteal bone formation, resulting in a marked increase in bone mass. We further tested the effect of Wnt7b on bone healing in a murine closed femur fracture model. Induced expression of Wnt7b at the onset of fracture did not affect the initial cartilage formation but promoted mineralization of the subsequent bone callus. Thus, targeted delivery of Wnt7b to aged bones or fracture sites may be explored as a potential therapy.
基金supported by grants from the National Key Research and Development Program of China (Grant No. 2021YFC2500400)the National Natural Science Foundation of China (Grant No. 82172894)。
文摘Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality.Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk stratification.Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups.Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.
基金supported by the National Key R&D Program of China(grant number:2021YFC2500400)Tianjin Health Committee Foundation(grant number:TJWJ2021MS008).
文摘Background Breast cancer(BC)incidence and mortality vary significantly across countries,highlighting the need to update the global burden of female BC,including current trends and future projections.Methods Data were sourced from GLOBOCAN 2022,including estimated new cases and deaths from BC across 21 United Nation(UN)regions and 185 countries,the age-standardized incidence rate(ASIR)and mortality rate(ASMR),the estimated annual percentage changes(EAPC),and demographic projections through 2050.The region-specific and country-specific BC burden for women of all ages and for young women(<40 years old)was reorganized and re-plotted to highlight subgroup differences.Linear regression was used to explore the link between ASIR/ASMR and the human development index(HDI).Transitioning countries referred to those with low or medium HDI,while transitioned countries were those with high or very high HDI.Results In 2022,an estimated 2.3 million new BC cases and 666,000 BC-related deaths occurred globally,accounting for 23.8%and 15.4%of all cancer cases and deaths in women,respectively.Regionally,Eastern Asia reported the highest number of cases(480,019,ASIR:37.54/100,000),while South-Central Asia had the highest number of deaths(135,348,ASMR:13.41/100,000).At the country level,China had the highest number of cases due to its large population,whereas India reported the highest number of deaths.ASIR for both overall and early-onset BC increased with HDI,while ASMR for early-onset BC decreased with HDI(P<0.05).Overall BC showed an increasing trend in ASIR during 2003–2015(EAPC:0.92%)and a decreasing trend in ASMR during 2006–2016(EAPC:-1.06%).Early-onset BC showed a more significant rise in ASIR(EAPCs:1.4%)and a slight increase in ASMR(EAPCs:0.16%).If national rates remain stable,BC cases and deaths will increase by 54.7%and 70.9%,respectively,by 2050.Notably,increased early-onset BC cases are only observed in transitioning countries,while decreased cases are seen in transitioned countries.Conclusions Breast cancer remains the leading cancer burden in women,particularly in transitioning countries.Addressing this growing burden requires urgent integration of primary prevention,early detection and high-quality treatment through multi-sectoral collaboration.
基金supported by the Chinese National Key Research and Development Project(No.2021YFC2500400,for Kexin Chen)National Natural Science Foundation of China(No.81974488 for Fangfang Song,No.81502476 for Yubei Huang)Tianjin Science and Technology Committee Foundation(No.18 JCQNJC80300 for Yubei Huang).
文摘Purpose To investigate the joint impacts of genetic and non-genetic factors on breast cancer(BC)subtypes among Chinese females,and to investigate the performance of optimized subtype-specific polygenic risk scores(PRS)with less single nucleotide polymorphisms(SNPs).Methods A total of 6,916 BC cases and 5,653 controls were used to assess the independent and joint impacts of PRS and non-genetic established risk score(ERS)on risks of overall and subtype-specific BC.The PRS were optimized by excluding low-penetrance SNPs until comparable area under receiver-operator-curve(AUCs)achieved.Results For the preliminary PRS with 21 Chinese BC-specific SNPs,the odds ratio(OR)of overall BC for the top decile compared to bottom decile(top-to-bottom decile)of PRS was 4.21(95%CI:3.47-5.10),and the OR per decile of PRS was 1.15(95%CI:1.13-1.16).For luminal A,luminal B,HER-2 enriched,and basal-like BC,the ORs for top-to-bottom decile were 4.58,4.37,3.08 and 2.90,respectively.After integrating four BC subtypes into two subtypes,relatively higher OR for top-to-bottom decile was observed for luminal BC than non-luminal BC(4.54 vs.3.02),and a similar trend was for OR per decile(1.15 vs.1.11).The optimized 13-SNP-PRS can achieve comparable performance of 21-SNP-PRS for luminal BC.After incorporating PRS into risk prediction of luminal BC,the AUC increased from 0.673 to 0.697,and the joint OR of PRS and ERS was 12.46(95%CI:9.38-16.56).Similar performances of PRS were validated in UK biobank.Conclusion PRS can well identify Chinese women at high-risk of BC,especially for luminal BC,and should be incorporated into risk-stratified BC intervention.
基金Fundamental Research Funds for the Central Universities(2042022kf1206)National Natural Science Foundation of China(82271010).
文摘Periodontitis is an inflammatory disease caused by bacterial biofilms,which leads to the destruction of periodontal tissue.Current treatments,such as mechanical cleaning and antibiotics,struggle to effectively address the persistent biofilms,inflammation,and tissue damage.A new approach involves developing a Janus nanomotor(J-CeM@Au)by coating cerium dioxide-doped mesoporous silica(CeM)with gold nanoparticles(AuNPs).This nanomotor exhibits thermophoretic motion when exposed to near-infrared(NIR)laser light due to the temperature gradient produced by the photothermal effects of asymmetrically distributed AuNPs.The NIR laser provides the energy for propulsion and activates the nanomotor's antibacterial properties,allowing it to penetrate biofilms and kill bacteria.Additionally,the nanomotor's ability to scavenge reactive oxygen species(ROS)can modulate the immune response and create a regenerative environment,promoting the healing of periodontal tissue.Overall,this multifunctional nanomotor offers a promising new approach for treating periodontitis by simultaneously addressing biofilm management and immune modulation with autonomous movement.
文摘Windborne debris is one of the most important causes of the envelop destruction according to the postdamage investigations.The problem of windborne debris damage could be summarized as three parts,including windborne debris risk analysis,debris flying trajectories,and impact resistance of envelope analysis.The method of debris distribution is developed.The flying trajectories of compact and plate-like debris are solved by using a numerical method according to the different aerodynamic characteristics.The impact resistance of the envelopes is also analyzed.Besides,the process of windborne debris damage analysis is described in detail.An example of industrial building is given to demonstrate the whole method by using the observed data of typhoon Chanchu(2006).The method developed in this paper could be applied to risk assessment of windborne debris for structures in wind hazard.
基金the Natural Science Foundation of China(nos.21421062 and 21901127)the China Postdoctoral Science Foundation(nos.2018M640225 and 2019T120179)Nankai-Cangzhou Green Chemistry Institute(no.NCC2020FH02)for financial support of this work.
文摘P-N and P=N bonds play important roles in the design and synthesis of functional molecules such as bioactive compounds and organic ligands for catalysis.Existing methods for P-N coupling mostly rely on Staudinger condensation or nucleophilic substitution between phosphorus electrophiles and amine nucleo philes.Herein,we report a nitrene-mediated intermolecular P-N coupling reaction between various phos phorus nucleophiles and dioxazolones under simp le iron-catalyzed conditions.These reactions offer an efficient,versatile,and broadly applicable method for synthesis of a range of N-P compounds,including amidophosphines,iminophosphonamides,phosphinamides,aminophosphines,and iminophospho ranes,from readily available precursors under mild conditions.
文摘Background and Objectives:Patients with inflammatory bowel disease(IBD)are more likely to be confirmed with vitamin D deficiency.However,the association between inflammation and vitamin D remains unclear.The purpose of this study was to evaluate the association between inflammation and vitamin D in hospitalized patients with IBD.Methods and Study Design:All the participants were recruited from one teaching hospital from June 2018 to October 2022.Inflammation was evaluated by serum concentration of C-reactive protein(CRP),using an immunoturbidimetric method at admission.We further divided the participants into five groups based on serum CRP levels:<5,5–9.9,10–19.9,20–39.9,and>40mg/L.Serum 25-hydroxy-vitamin D(25-(OH)-D)was assessed by liquid chromatography tandem mass spectrometry.Additional information,including age,sex,body mass index(BMI),IBD(ulcerative colitis vs.Crohn’s disease)subtype,was abstracted from medical records.Results:This study included 1,989 patients with IBD(average age was 39.4 years,33.8%of them were women,1,365 CD and 624 UC patients).The median CRP was 5.49 mg/L(range of quartiles:1.64~19.5 mg/L)and the prevalence of 25-(OH)-D deficiency was 69.8%.CRP was significantly associated with serum level of 25-(OH)-D.The difference in 25-(OH)-D was-4.28 ng/ml(-5.27 ng/ml,-3.31 ng/ml)between two extremist CRP groups after adjustment of potential covariates(age,sex,BMI,type of IBD,dietary type,season,and lymphocyte count).Subgroup analysis in sex,type of IBD,and age,were similar to the main analysis results.Conclusions:There was a negative association between CRP levels and vitamin D in hospitalized patients with IBD.
