AIM: To evaluate whether the level of thrombospondin-1(TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma(PACG). METHODS: This case-control study involv...AIM: To evaluate whether the level of thrombospondin-1(TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma(PACG). METHODS: This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy(case group) and 78 age-and sex-matched patients with PACG who underwent successful trabeculectomy(control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. RESULTS: The mean TSP-1 aqueous concentrations were significantly higher in the case group(20.67±9.79 ng/mL) than the control group(5.17±2.29 ng/mL)(P<0.001). The transforming growth factor-β2(TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively(P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy(OR=3.540; 95%CI=1.092-11.482). CONCLUSION: The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.展开更多
During the outbreak of coronavirus disease 2019(COVID-19),the identification of a SARS-CoV-2 infected case with untraceable epidemic origin has three values:(1)the region has community transmission of the virus;(2)a c...During the outbreak of coronavirus disease 2019(COVID-19),the identification of a SARS-CoV-2 infected case with untraceable epidemic origin has three values:(1)the region has community transmission of the virus;(2)a certain portion of population in the community is getting immunized and more individuals have already been immunized;(3)an unpredictable future risk exists for regions where there are no infected cases with untraceable epidemic origin.Minimizing or avoiding the aggregation infection through individuals with no clinical symptoms is crucial and possible as its occurrence is mainly attributed to the local environment as opposed to the super spreader with or without clinical symptoms.As infected cases are not necessarily positive with gene test by definition,proper application of gene test is crucial in the identification of asymptomatic cases.In the early stage of an outbreak of infectious disease,gene test can be used to identify asymptomatic cases but it should not be used to exclude cases with typical clinical symptoms and signs.In the middle or late stages of an outbreak gene test should be applied in evaluation of infection rate of the population of a region,in addition to be used in spreader identification and isolation.Although asymptomatic cases are attributed to the overwhelming effect of personalized defense against pathogens,they are still a source of infection.Asymptomatic cases are considered to be Qi deficiency and with lingering toxicity in traditional Chinese medicine(TCM).Treatment in such cases,typically,involves therapy focused on replenishing the Qi,tonifying the lung,clearing the fever,and detoxification in order to return to a normal health condition.The recommended Chinese medicines include Qing Fei Pai Du Decoction,Yi Qi Qu Du Decoction,Xuan Fei Bai Du Granule,Lian Hua Qing Wen Capsule(Granule),and Jin Hua Qing Gan Granule,etc.展开更多
Accumulating evidence indicates that long non-coding RNAs(lncRNAs)can play a pivotal role in regulation of diverse cellular processes.In particular,lncRNAs can serve as master gene regulators at transcriptional and po...Accumulating evidence indicates that long non-coding RNAs(lncRNAs)can play a pivotal role in regulation of diverse cellular processes.In particular,lncRNAs can serve as master gene regulators at transcriptional and posttranscriptional levels,leading to tumorigenesis.In this review,we discuss latest developments in lncRNA-meditated gene expression at the post-transcriptional level,including gene splicing,mRNA stability,protein stability and nuclear trafficking.展开更多
The red blood cell distribution width(RDW)is a measure of red blood cell(RBC)size heterogeneity,which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume.Recent reporter sugg...The red blood cell distribution width(RDW)is a measure of red blood cell(RBC)size heterogeneity,which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume.Recent reporter suggested that,besides haematological diseases and anaemia,many human disorders may be closely associated with the elevated RDW.A literature review has revealed the RDW may be closely related to the development of ischaemic stroke,carotid artery atherosclerosis and cerebral embolism.Higher RDW could independently predict adverse outcomes in patients in these conditions.展开更多
Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion.Immune checkpoint blockade(ICB)therapy that reinvigorates exhausted T cells have achi...Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion.Immune checkpoint blockade(ICB)therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment.However,the limited clinical response rate and off-tumor toxicities restrict ICB therapy.Herein,cellular vesicles displaying anti-programmed cell death-1(PD-1)single-chain variable fragment antibody(aPD-1-scFv)were prepared to reinvigorate T cell immunity to counteract cancer.The nanovesicles displaying aPD-1-scFv(aPD-1-scFv NVs)could enhance the anti-tumor activation of T cells through PD-1 blockade.Furthermore,NVs loading the A_(2a)adenosine receptor(A_(2a)R)antagonist CPI-444 assisted T cells to antagonize adenosine,an immunosuppressive metabolite produced by cancer cells.Hence,CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells,directly restraining tumor progress and metastasis.展开更多
Increasing evidence indicates that mRNAs are often subject to posttranscriptional modifications.Among them,N6-methyladenosine(m6A),which has been shown to play key roles in RNA splicing,stability,nuclear export,and tr...Increasing evidence indicates that mRNAs are often subject to posttranscriptional modifications.Among them,N6-methyladenosine(m6A),which has been shown to play key roles in RNA splicing,stability,nuclear export,and translation,is the most abundant modification of RNA.Extensive studies of m6A modification of mRNAs have been carried out,while little is known about m6A modification of long non-coding RNAs(lncRNAs).Recently,several studies reported m6A modification of lncRNAs.In this review,we focus on these m6A-modified lncRNAs and discuss possible functions of m6A modification.展开更多
Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facil...Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis.These discoveries not only expand our understanding of circRNAs biology in tumor,but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism.Therefore,these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.展开更多
Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system ...Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.展开更多
文摘AIM: To evaluate whether the level of thrombospondin-1(TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma(PACG). METHODS: This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy(case group) and 78 age-and sex-matched patients with PACG who underwent successful trabeculectomy(control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. RESULTS: The mean TSP-1 aqueous concentrations were significantly higher in the case group(20.67±9.79 ng/mL) than the control group(5.17±2.29 ng/mL)(P<0.001). The transforming growth factor-β2(TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively(P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy(OR=3.540; 95%CI=1.092-11.482). CONCLUSION: The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.
基金funding support from the Major Project on Prevention and Treatment of COVID-19 with TCM of Hunan TCM Bureau(No.KYGG06)the Special Project of Changzhutan National Independent Innovation Demonstration Zone of Hunan Province(No.2018XK2106)。
文摘During the outbreak of coronavirus disease 2019(COVID-19),the identification of a SARS-CoV-2 infected case with untraceable epidemic origin has three values:(1)the region has community transmission of the virus;(2)a certain portion of population in the community is getting immunized and more individuals have already been immunized;(3)an unpredictable future risk exists for regions where there are no infected cases with untraceable epidemic origin.Minimizing or avoiding the aggregation infection through individuals with no clinical symptoms is crucial and possible as its occurrence is mainly attributed to the local environment as opposed to the super spreader with or without clinical symptoms.As infected cases are not necessarily positive with gene test by definition,proper application of gene test is crucial in the identification of asymptomatic cases.In the early stage of an outbreak of infectious disease,gene test can be used to identify asymptomatic cases but it should not be used to exclude cases with typical clinical symptoms and signs.In the middle or late stages of an outbreak gene test should be applied in evaluation of infection rate of the population of a region,in addition to be used in spreader identification and isolation.Although asymptomatic cases are attributed to the overwhelming effect of personalized defense against pathogens,they are still a source of infection.Asymptomatic cases are considered to be Qi deficiency and with lingering toxicity in traditional Chinese medicine(TCM).Treatment in such cases,typically,involves therapy focused on replenishing the Qi,tonifying the lung,clearing the fever,and detoxification in order to return to a normal health condition.The recommended Chinese medicines include Qing Fei Pai Du Decoction,Yi Qi Qu Du Decoction,Xuan Fei Bai Du Granule,Lian Hua Qing Wen Capsule(Granule),and Jin Hua Qing Gan Granule,etc.
基金This work was supported by NIH grant R01 CA154989(YM).
文摘Accumulating evidence indicates that long non-coding RNAs(lncRNAs)can play a pivotal role in regulation of diverse cellular processes.In particular,lncRNAs can serve as master gene regulators at transcriptional and posttranscriptional levels,leading to tumorigenesis.In this review,we discuss latest developments in lncRNA-meditated gene expression at the post-transcriptional level,including gene splicing,mRNA stability,protein stability and nuclear trafficking.
文摘The red blood cell distribution width(RDW)is a measure of red blood cell(RBC)size heterogeneity,which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume.Recent reporter suggested that,besides haematological diseases and anaemia,many human disorders may be closely associated with the elevated RDW.A literature review has revealed the RDW may be closely related to the development of ischaemic stroke,carotid artery atherosclerosis and cerebral embolism.Higher RDW could independently predict adverse outcomes in patients in these conditions.
基金supported by grants from the National Natural Science Foundation of China(No.31971268)the Natural Science Foundation of Guangdong Province(No.2020A1515010802)+9 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020A1515110166)Shenzhen Excellent Science and Technology Innovation Talent Training Project(Excellent Youth Project,No.RCYX20200714114643121)Science,Technology&Innovation Commission of Shenzhen Municipality(No.JCYJ20200109142610136)Basic Research Program of Shenzhen(No.JCYJ20180507181654186)Health System Scientific Research Project of Shenzhen Guangming District Science and Innovation Bureau(Nos.2020R01073,and 2020R01061)Special Fund for Economic Development of Guangming District,Shenzhen(No.2021R01128)University of Chinese Academy of Sciences-Shenzhen Hospital Research Funding(No.HRF2020004)the Fundamental Research Funds for the Central Universities(No.19lgzd45)Disciplinary Construction of Posts of Zhujiang Scholars(No.4SG21005G)Discipline Construction Project of Guangdong Medical University(No.4SG21008G).
文摘Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion.Immune checkpoint blockade(ICB)therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment.However,the limited clinical response rate and off-tumor toxicities restrict ICB therapy.Herein,cellular vesicles displaying anti-programmed cell death-1(PD-1)single-chain variable fragment antibody(aPD-1-scFv)were prepared to reinvigorate T cell immunity to counteract cancer.The nanovesicles displaying aPD-1-scFv(aPD-1-scFv NVs)could enhance the anti-tumor activation of T cells through PD-1 blockade.Furthermore,NVs loading the A_(2a)adenosine receptor(A_(2a)R)antagonist CPI-444 assisted T cells to antagonize adenosine,an immunosuppressive metabolite produced by cancer cells.Hence,CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells,directly restraining tumor progress and metastasis.
基金This work was supported by the Natural Science Foundation of China(81773165)Hunan Province Science Fund for Distinguished Young Scholars(2018JJ1021)+1 种基金the Key R&D Program of Hunan Province(2017SK2172)the Science and Technology Foundation of Chenzhou(jsyf2017023).
文摘Increasing evidence indicates that mRNAs are often subject to posttranscriptional modifications.Among them,N6-methyladenosine(m6A),which has been shown to play key roles in RNA splicing,stability,nuclear export,and translation,is the most abundant modification of RNA.Extensive studies of m6A modification of mRNAs have been carried out,while little is known about m6A modification of long non-coding RNAs(lncRNAs).Recently,several studies reported m6A modification of lncRNAs.In this review,we focus on these m6A-modified lncRNAs and discuss possible functions of m6A modification.
基金Natural Science Foundation of China(81773165)Hunan Province Science Fund for Distinguished Young Scholars(2018JJ1021)+1 种基金the Key R&D Program of Hunan Province(2017SK2172)the Science and Technique Foundation of Chenzhou(jsyf2017023).
文摘Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis.These discoveries not only expand our understanding of circRNAs biology in tumor,but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism.Therefore,these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.
基金supported by the Science and Technology Planning Project of Guangdong Province,China(Grant No.2015A030302018).
文摘Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.