Objective Current guidelines recommend discontinuing screening for women≥65 years with a history of normal primary cervical cancer screening results.However,the necessity of continued screening in this population rem...Objective Current guidelines recommend discontinuing screening for women≥65 years with a history of normal primary cervical cancer screening results.However,the necessity of continued screening in this population remains debated.This study aims to evaluate the importance of cervical cancer screening in women aged≥65.Methods This retrospective study analysed cervical cancer screening data from Shenzhen(2017–2023)to assess the distribution of high-risk human papillomavirus(hr-HPV),the prevalence of cervical intraepithelial neoplasia grade 2 or worse(CIN2+)and the association between hr-HPV and CIN2+risk in women aged≥65 and<65,comparing the two age groups.Results A total of 2152766 records were analysed,including 17420 women aged≥65(0.81%).The hr-HPV prevalence in women aged≥65 was 13.67%,with a CIN2+detection rate of 3.33‰ and a cancer rate of 0.92‰,compared with 8.08%,1.55‰ and 0.1‰,respectively,in women aged<65(all p<0.001).Single,double and triple hr-HPV infections were found in 10.56%(n=1839),2.32%(n=404)and 0.57%(n=99)of cases in women aged≥65,with CIN2+detection rates of 2.01%,2.73%and 4.04%,respectively,all exceeding those aged<65(all p<0.001).The most common genotypes in older women were HPV52,HPV16,HPV58,HPV56 and HPV68,with HPV18,HPV16 and HPV33 being major causes of CIN2+,along with frequent double infections such as HPV52/58,HPV16/52 and HPV52/56,while CIN2+was predominantly associated with HPV33/39,HPV35/31 and HPV18/39,which differ from those in younger women.A dose-response relationship between hr-HPV infections and CIN2+risk was observed in women aged≥65(p for trend<0.001).ORs for CIN2+were 55.86(95%CI 21.81 to143.07),65.95(95%CI 22.63 to 192.18)and 85.45(95%CI 24.15 to 302.35)for single,double and triple or more hr-HPV infections,respectively,but the ORs were lower in women aged<65.Conclusions Women aged≥65 bear a higher cervical cancer burden than those<65.Moreover,hr-HPV infections and their pathogenicity exhibit unique patterns in this older group.Therefore,targeted screening and intervention are essential for women aged≥65.Tailored strategies should be implemented based on national contexts.展开更多
Objective:This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse(HSIL+)and determine the need for endocervical curettage(ECC)in patients referred for colpos...Objective:This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse(HSIL+)and determine the need for endocervical curettage(ECC)in patients referred for colposcopy.Methods:This retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results.ECC data were extracted from the medical records.Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+on ECC.Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing.The model was externally validated and tested in patients from two additional hospitals.The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis.Results:HSIL+was found on ECC in 38.8%(n=388)of cases.Our predictive nomogram included age group,cytology,human papillomavirus(HPV)status,visibility of the cervix and colposcopic impression.The nomogram had good overall discrimination,which was internally validated[area under the receiver-operator characteristic(AUC),0.839;95%confidence interval(95%CI),0.773-0.904].In terms of external validation,the AUC was 0.843(95%CI,0.773-0.912)for the consecutive sample and 0.843(95%CI,0.783-0.902)for the comparative sample.Calibration analysis suggested good consistency between predicted and observed probabilities.Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities.Conclusions:This internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+who need ECC.展开更多
Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-L...Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-LOD,PIL)was fabricated to combine cascade reaction with photothermal for tumor therapy.In detail,the overexpressed LA in tumor microenvironment(TME)was a key factor to activate the PIL-based cascade reaction:(1)Plenty of H_(2)O_(2)could be generated from LA by the catalysis of LOD with O_(2);(2)potent·OH was produced from H_(2)O_(2)due to the peroxidase(POD)-like activity of PIL;(3)meantime,PIL’s catalase(CAT)-like activity could decompose part H_(2)O_(2)into O_(2)to achieve the purpose of LA cyclic oxidization.Moreover,the reduced glutathione(GSH)scavenging capability of PIL might protect the produced reactive oxygen species(ROS)from being cleared to further improve the cascade therapeutic effect.More importantly,PIL had excellent photothermal conversion efficiency(37.35%)and manifested a surprising temperature rising effect in tumor.Taken together,the decreasing LA concentration,accumulation of high-toxic ROS,the depletion of GSH together with the higher intra-tumoral temperature potently enhanced in vivo antitumor therapy.Therefore,a promising therapeutic tactic based on PIL integrating endogenous LA consumption,chemodynamic therapy(CDT),and photothermal therapy(PTT)has been put forward.展开更多
Pulmonary fibrosis(PF)is a devastating lung disease with limited treatment options.During this pathological process,the profibrogenic macrophage subpopulation plays a crucial role,making the characterization of this s...Pulmonary fibrosis(PF)is a devastating lung disease with limited treatment options.During this pathological process,the profibrogenic macrophage subpopulation plays a crucial role,making the characterization of this subpopulation fundamentally important.The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass(Mø^(mitohigh))and fibrosis.Among the Mø^(mitohigh)subpopulation of CD206^(+)M2,characterized by higher expression of dynamin 1-like(Drp1),as determined by flow cytometry and RNA-seq analysis,a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics.A pathfinder exosome called“exosome^(MMP19)(Exo^(MMP19))”,was constructed to display matrix metalloproteinase-19(^(MMP19))on the surface to locally break down the excessive extracellular matrix(ECM)in the fibrotic lung.A therapeutic exosome called“exosome therapeutics(Exo^(Tx))”,was engineered to display D-mannose on the surface while encapsulating siDrp1 inside.Prior delivery of Exo^(MMP19)degraded excessive ECM and thus paved the way for Exo^(Tx)to be delivered into Mø^(mitohigh),where Exo^(Tx)inhibited mitochondrial fission and alleviated PF.This study has not only identified Mø^(mitohigh)as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.展开更多
基金supported by the Sanming Project of Medicine in Shenzhen(No.SZSM202211032)。
文摘Objective Current guidelines recommend discontinuing screening for women≥65 years with a history of normal primary cervical cancer screening results.However,the necessity of continued screening in this population remains debated.This study aims to evaluate the importance of cervical cancer screening in women aged≥65.Methods This retrospective study analysed cervical cancer screening data from Shenzhen(2017–2023)to assess the distribution of high-risk human papillomavirus(hr-HPV),the prevalence of cervical intraepithelial neoplasia grade 2 or worse(CIN2+)and the association between hr-HPV and CIN2+risk in women aged≥65 and<65,comparing the two age groups.Results A total of 2152766 records were analysed,including 17420 women aged≥65(0.81%).The hr-HPV prevalence in women aged≥65 was 13.67%,with a CIN2+detection rate of 3.33‰ and a cancer rate of 0.92‰,compared with 8.08%,1.55‰ and 0.1‰,respectively,in women aged<65(all p<0.001).Single,double and triple hr-HPV infections were found in 10.56%(n=1839),2.32%(n=404)and 0.57%(n=99)of cases in women aged≥65,with CIN2+detection rates of 2.01%,2.73%and 4.04%,respectively,all exceeding those aged<65(all p<0.001).The most common genotypes in older women were HPV52,HPV16,HPV58,HPV56 and HPV68,with HPV18,HPV16 and HPV33 being major causes of CIN2+,along with frequent double infections such as HPV52/58,HPV16/52 and HPV52/56,while CIN2+was predominantly associated with HPV33/39,HPV35/31 and HPV18/39,which differ from those in younger women.A dose-response relationship between hr-HPV infections and CIN2+risk was observed in women aged≥65(p for trend<0.001).ORs for CIN2+were 55.86(95%CI 21.81 to143.07),65.95(95%CI 22.63 to 192.18)and 85.45(95%CI 24.15 to 302.35)for single,double and triple or more hr-HPV infections,respectively,but the ORs were lower in women aged<65.Conclusions Women aged≥65 bear a higher cervical cancer burden than those<65.Moreover,hr-HPV infections and their pathogenicity exhibit unique patterns in this older group.Therefore,targeted screening and intervention are essential for women aged≥65.Tailored strategies should be implemented based on national contexts.
基金supported by CAMS Innovation Fund for Medical Sciences(No.CAMS 2021-I2M-1-004)。
文摘Objective:This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse(HSIL+)and determine the need for endocervical curettage(ECC)in patients referred for colposcopy.Methods:This retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results.ECC data were extracted from the medical records.Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+on ECC.Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing.The model was externally validated and tested in patients from two additional hospitals.The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis.Results:HSIL+was found on ECC in 38.8%(n=388)of cases.Our predictive nomogram included age group,cytology,human papillomavirus(HPV)status,visibility of the cervix and colposcopic impression.The nomogram had good overall discrimination,which was internally validated[area under the receiver-operator characteristic(AUC),0.839;95%confidence interval(95%CI),0.773-0.904].In terms of external validation,the AUC was 0.843(95%CI,0.773-0.912)for the consecutive sample and 0.843(95%CI,0.783-0.902)for the comparative sample.Calibration analysis suggested good consistency between predicted and observed probabilities.Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities.Conclusions:This internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+who need ECC.
基金supported by the National Natural Science Foundation of China(No.22075233)Natural Science Foundation of Fujian Province(No.2022J01023).
文摘Lactic acid(LA)plays a major role in the occurrence,development,and spread of cancer.Enlightened by its high accumulation in tumor site,a novel lactate oxidase(LOD)conjugated two-dimensional Pd@Ir nanoplatform(Pd@Ir-LOD,PIL)was fabricated to combine cascade reaction with photothermal for tumor therapy.In detail,the overexpressed LA in tumor microenvironment(TME)was a key factor to activate the PIL-based cascade reaction:(1)Plenty of H_(2)O_(2)could be generated from LA by the catalysis of LOD with O_(2);(2)potent·OH was produced from H_(2)O_(2)due to the peroxidase(POD)-like activity of PIL;(3)meantime,PIL’s catalase(CAT)-like activity could decompose part H_(2)O_(2)into O_(2)to achieve the purpose of LA cyclic oxidization.Moreover,the reduced glutathione(GSH)scavenging capability of PIL might protect the produced reactive oxygen species(ROS)from being cleared to further improve the cascade therapeutic effect.More importantly,PIL had excellent photothermal conversion efficiency(37.35%)and manifested a surprising temperature rising effect in tumor.Taken together,the decreasing LA concentration,accumulation of high-toxic ROS,the depletion of GSH together with the higher intra-tumoral temperature potently enhanced in vivo antitumor therapy.Therefore,a promising therapeutic tactic based on PIL integrating endogenous LA consumption,chemodynamic therapy(CDT),and photothermal therapy(PTT)has been put forward.
基金supported by the National Natural Science Foundation of China(Grant Nos.NSFC 81970076)Key R&D Program of Shaanxi Province,China(2022ZDLSF01-10)。
文摘Pulmonary fibrosis(PF)is a devastating lung disease with limited treatment options.During this pathological process,the profibrogenic macrophage subpopulation plays a crucial role,making the characterization of this subpopulation fundamentally important.The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass(Mø^(mitohigh))and fibrosis.Among the Mø^(mitohigh)subpopulation of CD206^(+)M2,characterized by higher expression of dynamin 1-like(Drp1),as determined by flow cytometry and RNA-seq analysis,a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics.A pathfinder exosome called“exosome^(MMP19)(Exo^(MMP19))”,was constructed to display matrix metalloproteinase-19(^(MMP19))on the surface to locally break down the excessive extracellular matrix(ECM)in the fibrotic lung.A therapeutic exosome called“exosome therapeutics(Exo^(Tx))”,was engineered to display D-mannose on the surface while encapsulating siDrp1 inside.Prior delivery of Exo^(MMP19)degraded excessive ECM and thus paved the way for Exo^(Tx)to be delivered into Mø^(mitohigh),where Exo^(Tx)inhibited mitochondrial fission and alleviated PF.This study has not only identified Mø^(mitohigh)as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.
