BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of...BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently.AIM To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer,and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer.METHODS A total of 374 patients with colorectal cancer were enrolled.The clinical data,tumor-node-metastasis(TNM)stage,and Dukes stage were recorded.All patients received examinations including carcinoembryonic antigen(CEA),carbohydrate antigen 199,C-reactive protein,albumin,D-dimer,and fibrinogen as well as routine blood tests one week before surgery.The tumor location,size,depth of invasion,lymph node metastasis,and distant metastasis were recorded during surgery.The pathological tissue typing and expression of proliferating cell nuclear antigen(PCNA)and p53 were observed.All patients were followed for 3 years,and patients with endpoint events were defined as a poor prognosis group,and the remaining patients were defined as a good prognosis group.The differences in clinical data,serology,and histology were analyzed between the two groups.Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer.The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer.RESULTS The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group.The TNM stage,PCNA,Glasgow prognostic score(GPS),neutrophil-lymphocyte ratio(NLR),C-reactive protein/albumin ratio(CAR),D-dimer,and CEA were independent influencing factors for the prognosis of colorectal cancer(P=0.000).NLR had the highest predictive power for colorectal cancer prognosis[area under the receiver operating characteristic curve(AUC)=0.925],followed by D-dimer(AUC=0.879)and GPS(AUC=0.872).The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest(AUC=0.973),which was significantly higher than that of any of the indicators alone(P<0.05).The sensitivity and specificity of the combination were 92.59%and 90.51%,respectively.CONCLUSION The independent influence factors for the prognosis of colorectal cancer include TNM stage,PCNA,GPS,NLR,CAR,D-dimer,and CEA.The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.展开更多
BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted th...BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.展开更多
BACKGROUND We describe a case of relentless placoid chorioretinitis(RPC)that progressed despite administration of peribulbar and systemic corticosteroids,and was resolved by systemic combined with intravitreal methotr...BACKGROUND We describe a case of relentless placoid chorioretinitis(RPC)that progressed despite administration of peribulbar and systemic corticosteroids,and was resolved by systemic combined with intravitreal methotrexate.CASE SUMMARY A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week.Due to widespread distribution and continuous enlargement,multimodal imaging of the lesions led to the diagnosis of RPC.Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide,but the progression was immediately terminated by a single dose of intravitreal methotrexate.A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate.CONCLUSION Systemic immunosuppressants should be given upon RPC diagnosis.Intravitreal methotrexate immediately halted progression and may be considered for sightthreatening cases as part of the initial therapy.展开更多
基金supported by the National Natural Science Foundation of China(11821404,11804330)the Key Research Program of Frontier Sciences,CAS(QYZDY-SSW-SLH003)+3 种基金the Science Foundation of the CAS(ZDRW-XH2019-1)the Fundamental Research Funds for the Central Universities(WK2470000026,WK2470000027,WK2470000028,WK2470000038)the Anhui Initiative in Quantum Information Technologies(AHY020100)the National Program for Support of Topnotch Young Professionals(BB2470000005).
文摘BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently.AIM To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer,and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer.METHODS A total of 374 patients with colorectal cancer were enrolled.The clinical data,tumor-node-metastasis(TNM)stage,and Dukes stage were recorded.All patients received examinations including carcinoembryonic antigen(CEA),carbohydrate antigen 199,C-reactive protein,albumin,D-dimer,and fibrinogen as well as routine blood tests one week before surgery.The tumor location,size,depth of invasion,lymph node metastasis,and distant metastasis were recorded during surgery.The pathological tissue typing and expression of proliferating cell nuclear antigen(PCNA)and p53 were observed.All patients were followed for 3 years,and patients with endpoint events were defined as a poor prognosis group,and the remaining patients were defined as a good prognosis group.The differences in clinical data,serology,and histology were analyzed between the two groups.Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer.The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer.RESULTS The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group.The TNM stage,PCNA,Glasgow prognostic score(GPS),neutrophil-lymphocyte ratio(NLR),C-reactive protein/albumin ratio(CAR),D-dimer,and CEA were independent influencing factors for the prognosis of colorectal cancer(P=0.000).NLR had the highest predictive power for colorectal cancer prognosis[area under the receiver operating characteristic curve(AUC)=0.925],followed by D-dimer(AUC=0.879)and GPS(AUC=0.872).The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest(AUC=0.973),which was significantly higher than that of any of the indicators alone(P<0.05).The sensitivity and specificity of the combination were 92.59%and 90.51%,respectively.CONCLUSION The independent influence factors for the prognosis of colorectal cancer include TNM stage,PCNA,GPS,NLR,CAR,D-dimer,and CEA.The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.
文摘BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.
基金the National Natural Science Foundation of China,No.81800847and the Tenth“Academic Star”project of Peking University People's Hospital,No.RS2018-05.
文摘BACKGROUND We describe a case of relentless placoid chorioretinitis(RPC)that progressed despite administration of peribulbar and systemic corticosteroids,and was resolved by systemic combined with intravitreal methotrexate.CASE SUMMARY A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week.Due to widespread distribution and continuous enlargement,multimodal imaging of the lesions led to the diagnosis of RPC.Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide,but the progression was immediately terminated by a single dose of intravitreal methotrexate.A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate.CONCLUSION Systemic immunosuppressants should be given upon RPC diagnosis.Intravitreal methotrexate immediately halted progression and may be considered for sightthreatening cases as part of the initial therapy.
