Objective:To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour(TURBT)and explore the risk factors of upgrading.Methods:The me...Objective:To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour(TURBT)and explore the risk factors of upgrading.Methods:The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed.Comparative analysis of the tumour grade of biopsy and operation specimens was performed.Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading.Logistic regression an-alyses were performed to identify the risk factors of upgrading.Results:For the 205 patients,the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639.The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912,respectively.Univariate and multivariate logistic regression analyses showed that older age,tumour multifocality,high neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and low lymphocyte-to-monocyte ratio(LMR)were significantly associated with upgrading(odds ratio ranging from 0.412 to 4.364).The area under the curve of the different multivariate models was improved from 0.752 to 0.821,and decision curve analysis demonstrated a high net benefit when NLR,LMR,and PLR were added.Conclusion:Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer,especially for outpatients with low-grade bladder cancer.Moreover,older age,tumour multifocality,high NLR,PLR,and low LMR are risk factors of upgrading,and systemic inflammatory markers improve the predictive ability.展开更多
Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer...Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.展开更多
One of the critical problems in bladder cancer(BC)management is the local recurrence of disease.However,achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack ...One of the critical problems in bladder cancer(BC)management is the local recurrence of disease.However,achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology.Herein,survivin molecular beacon(MB)and R11 peptide-linked spherical nucleic acids(SNAs)were synthesized as nanoprobes(AuNP-MB@R11)for sensitive detection of BC margins.Physicochemical properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs.AuNP-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA(ssDNA)in vitro.According to cytology,R11 peptides could increase the BC targeting ability and membrane penetrability of SNAs.Notably,R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging quality.Further RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated,such as AGPAT5,GPD1L,and GRB2.In orthotopic BC models and a clinical sample from a patient with BC,AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs.R11 peptide-linked SNAs present promising potential to identify BC margin,which may help to improve the R0 resection rate in surgery and improve patients’quality of life.展开更多
Recently,surface-enhanced Raman scattering(SERS)has been successfully used in the non-invasive detection of bladder tumor(BCa).The internal standard method was considered as an effective ratiometric strategy for calib...Recently,surface-enhanced Raman scattering(SERS)has been successfully used in the non-invasive detection of bladder tumor(BCa).The internal standard method was considered as an effective ratiometric strategy for calibrating signal fluctuation originated from the interference of measurement conditions and samples.However,it is still difficult to detect the target mRNA quantitatively using the current ratiometric SERS nanosensors.In this study,we developed an internal reference based ratiometric SERS assay.Two kinds of molecular beacons(MB)carrying Raman reporter molecules were anchored on sea-urchinlike Au nanoclusters(AuNCs).Thymidine kinase1(TK1)MBs with hexachlorofluorescein(HEX)were used to capture tumor biomarker TK1 mRNA,and glyceraldehyde 3-phosphate dehydrogenase(GAPDH)MBs with 5(6)-carboxyfluorescein(FAM)were used to offer internal standard signals.The internal reference GAPDH MB can reflect the consistent content of the GAPDH mRNA in single cells.The ratiometric method(I745/I645)can more accurately reflect the content of target mRNA in single cells.The ratiometric nanoprobes had excellent stability(coefficient of variation:0.3%),high sensitivity(detection limit:3.4 pM),high specificity(capable of single-base mismatch recognition)and ribozyme-resistant stability.Notably,the nanoprobes can effectively distinguish BCa cells from normal cells,and it was easy to contour the single BCa cell using the ratiometric method.By combining asymmetric polymerase chain reaction(PCR)and ratiometric nanoprobes,it was easy to distinguish the SERS ratio(I_(745)/I_(645))as low concentration as 10-14 M.Further clinical detection in urine samples from patients with BCa confirmed its potential for early noninvasive diagnosis of BCa with the sensitivity of 80%and specificity of 100%,which is superior to the current urine cytological method.展开更多
Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemic...Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemical/biological study and analysis.Taking advantage of the discrete compartment with a confined volume,(1)isolation and manipulation of a single cell,(2)improvement of in-droplet effective concen-trations,(3)elimination of heterogeneous population effects,(4)diminution of contamination risks can be achieved,making it a powerful tool for rapid,sensitive,and high-throughput detection and analysis of bacteria,even for rare or unculturable strains in conventional methods.This mini-review will focus on the generation and manipulation of micro-droplets and bacteria detection and analysis carried out by droplet-based microfluidics.Finally,applications with high potential of droplet-based bacteria analysis are briefly introduced.Due to the advantages of rapid,sensitive,high throughput,and compatibility with rare and unculturable bacteria in conventional methods,droplet-based microfluidics has tremendous potential of providing novel solutions for biological medicine,microbiological engineering,environmental ecology,etc.展开更多
基金This study was supported by the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University,China(No.XJTU1AF-CRF-2015-002 to DH).
文摘Objective:To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour(TURBT)and explore the risk factors of upgrading.Methods:The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed.Comparative analysis of the tumour grade of biopsy and operation specimens was performed.Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading.Logistic regression an-alyses were performed to identify the risk factors of upgrading.Results:For the 205 patients,the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639.The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912,respectively.Univariate and multivariate logistic regression analyses showed that older age,tumour multifocality,high neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and low lymphocyte-to-monocyte ratio(LMR)were significantly associated with upgrading(odds ratio ranging from 0.412 to 4.364).The area under the curve of the different multivariate models was improved from 0.752 to 0.821,and decision curve analysis demonstrated a high net benefit when NLR,LMR,and PLR were added.Conclusion:Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer,especially for outpatients with low-grade bladder cancer.Moreover,older age,tumour multifocality,high NLR,PLR,and low LMR are risk factors of upgrading,and systemic inflammatory markers improve the predictive ability.
基金supported by the National Natural Science Foundation of China(Grant No.81825016,81772719,81772728,81572514)the Key Areas Research and Development Program of Guangdong(Grant No.2018B010109006)Medical Scientific Research Foundation of Guangdong Province(Grant No.A2018388).
文摘Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.
基金the National Natural Science Foundation of China(No.81901838)Key research and development plan in Shaanxi province(Nos.2020SF-123 and 2020SF-195)+1 种基金Medical Technology Plan of Zhejiang Province(No.2021KY042)Medical research program of department of science and technology of Xi’an,Shaanxi Province(No.2019115713YX012SF048(4)).
文摘One of the critical problems in bladder cancer(BC)management is the local recurrence of disease.However,achieving the accurate delineation of tumor margins intraoperatively remains extremely difficult due to the lack of effective tumor margin recognition technology.Herein,survivin molecular beacon(MB)and R11 peptide-linked spherical nucleic acids(SNAs)were synthesized as nanoprobes(AuNP-MB@R11)for sensitive detection of BC margins.Physicochemical properties proved that R11 peptides and survivin MB were successfully loaded onto the surface of SNAs.AuNP-MB@R11 had good stability against nuclease activity and high sensitivity and specificity to detect survivin single strand DNA(ssDNA)in vitro.According to cytology,R11 peptides could increase the BC targeting ability and membrane penetrability of SNAs.Notably,R11 peptides significantly promoted the disintegration of lysosomes and the release of SNAs to enhance fluorescence imaging quality.Further RNA sequencing proved that some genes and pathways related to endocytosis and lysosomes were significantly regulated,such as AGPAT5,GPD1L,and GRB2.In orthotopic BC models and a clinical sample from a patient with BC,AuNP-MB@R11 showed a more legible cancerous fluorescence margin and offered remarkably improved detection compared to those achieved by SNAs.R11 peptide-linked SNAs present promising potential to identify BC margin,which may help to improve the R0 resection rate in surgery and improve patients’quality of life.
基金This work was supported by the National Natural Science Foundation of China(No.81901838)the Key Research and Development Plan in Shaanxi Province(Nos.2020SF-123 and 2020SF-195)+1 种基金the Natural Science Foundation of Zhejiang Province(No.LQ21H160041)the Medical Research Program of Department of Science and Technology of Xi’an,Shaanxi Province(No.2019115713YX012SF048(4)).
文摘Recently,surface-enhanced Raman scattering(SERS)has been successfully used in the non-invasive detection of bladder tumor(BCa).The internal standard method was considered as an effective ratiometric strategy for calibrating signal fluctuation originated from the interference of measurement conditions and samples.However,it is still difficult to detect the target mRNA quantitatively using the current ratiometric SERS nanosensors.In this study,we developed an internal reference based ratiometric SERS assay.Two kinds of molecular beacons(MB)carrying Raman reporter molecules were anchored on sea-urchinlike Au nanoclusters(AuNCs).Thymidine kinase1(TK1)MBs with hexachlorofluorescein(HEX)were used to capture tumor biomarker TK1 mRNA,and glyceraldehyde 3-phosphate dehydrogenase(GAPDH)MBs with 5(6)-carboxyfluorescein(FAM)were used to offer internal standard signals.The internal reference GAPDH MB can reflect the consistent content of the GAPDH mRNA in single cells.The ratiometric method(I745/I645)can more accurately reflect the content of target mRNA in single cells.The ratiometric nanoprobes had excellent stability(coefficient of variation:0.3%),high sensitivity(detection limit:3.4 pM),high specificity(capable of single-base mismatch recognition)and ribozyme-resistant stability.Notably,the nanoprobes can effectively distinguish BCa cells from normal cells,and it was easy to contour the single BCa cell using the ratiometric method.By combining asymmetric polymerase chain reaction(PCR)and ratiometric nanoprobes,it was easy to distinguish the SERS ratio(I_(745)/I_(645))as low concentration as 10-14 M.Further clinical detection in urine samples from patients with BCa confirmed its potential for early noninvasive diagnosis of BCa with the sensitivity of 80%and specificity of 100%,which is superior to the current urine cytological method.
基金supported by National Natural Science Foundation of China (No. 22104117)“the Fundamental Research Funds for the Central Universities” (No. JC2110)+1 种基金Wuhu and Xidian University special fund for industry-university-research cooperation (No. XWYCXY-012020012)Open Fund of Zhijiang Lab (No. 2021MC0AB02)
文摘Droplet-based microfluidics enables the generation of uniform microdroplets at picoliter or nanoliter scale with high frequency(∼kHz)under precise control.The droplets can function as bioreactors for versatile chemical/biological study and analysis.Taking advantage of the discrete compartment with a confined volume,(1)isolation and manipulation of a single cell,(2)improvement of in-droplet effective concen-trations,(3)elimination of heterogeneous population effects,(4)diminution of contamination risks can be achieved,making it a powerful tool for rapid,sensitive,and high-throughput detection and analysis of bacteria,even for rare or unculturable strains in conventional methods.This mini-review will focus on the generation and manipulation of micro-droplets and bacteria detection and analysis carried out by droplet-based microfluidics.Finally,applications with high potential of droplet-based bacteria analysis are briefly introduced.Due to the advantages of rapid,sensitive,high throughput,and compatibility with rare and unculturable bacteria in conventional methods,droplet-based microfluidics has tremendous potential of providing novel solutions for biological medicine,microbiological engineering,environmental ecology,etc.
