Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗...目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。展开更多
Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this s...Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.展开更多
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总...目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总并分析该类制剂的研发现状。结果与结论有成药潜力的PD-1/PD-L1小分子抑制剂共20种,包括CA-170(口服小分子抑制剂)、INCB086550(特异性PD-L1抑制剂)、DPPA-1(特异性抑制PD-1/PD-L1相互作用的多肽类拮抗剂)等,其中前两者已进入临床试验阶段。PD-1/PD-L1小分子抑制剂具有特异性抑制免疫检查点的药效作用特点,以及可口服、稳定性较好、膜通透性较高等优点,但其治疗效果仍需临床试验验证。展开更多
目的:根据文献报道,分析4款国产程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)抑制剂不良反应的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、中国知网、万方等数据库,收集关于卡瑞利珠单抗、信迪利单...目的:根据文献报道,分析4款国产程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)抑制剂不良反应的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、中国知网、万方等数据库,收集关于卡瑞利珠单抗、信迪利单抗、特瑞普利单抗和替雷利珠单抗4款PD-1抑制剂导致不良反应的个案报道进行分析。结果:检索到相关合格文献报道105篇,其中卡瑞利珠单抗42篇,共47例患者;信迪利单抗29篇,共30例患者;特瑞普利单抗21篇,共24例患者;替雷利珠单抗13篇,共15例患者。其中男性76例(65.5%),女性40例(34.5%),男女比例为1.9:1.0,年龄在29~84岁,发生时间主要在首次使用PD-1抑制剂后4个月内。免疫相关不良反应主要表现在皮肤及其附件毒性反应41例(34.5%)、内分泌系统不良反应25例(21.0%)、心血管系统不良反应22例(18.5%)。大多数患者经对症支持治疗后好转。结论:在接受4款国产PD-1抑制剂治疗的任何时间段都可能发生免疫相关不良反应(immune-related adverse effects,irAEs),其中皮肤系统不良反应发生率最高,其次是心血管和内分泌系统,提示临床在使用此类药物时,应严格控制适应证,结合患者病情和实际情况合理选择药物,在整个免疫治疗期间需密切监测,以减少或避免irAEs的发生,保障患者用药安全。展开更多
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine agai...Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine against HIV/AIDS.The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART).Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients,the huge burden of ART in developing countries,together with the increasing incidence of drug resistant viruses among treated people,calls for continuous efforts for the development of anti-HIV-1 drugs.Currently,four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including:reverse transcriptase inhibitors (RTIs) (e.g.nucleoside reverse transcriptase inhibitors,NRTIs;and non-nucleoside reverse transcriptase inhibitors,NNRTIs),protease inhibitors (PIs),integrase inhibitors and entry inhibitors (e.g.fusion inhibitors and CCR5 antagonists).Here,we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.展开更多
文摘Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
文摘目的分析缺血性视网膜静脉阻塞继发黄斑水肿(RVO-ME)患者基线血清己糖激酶1抗体滴度与抗血管内皮生长因子(VEGF)治疗后视力改善的相关性。方法招募2017年6月至2020年2月在首都医科大学宣武医院确诊为缺血性RVO-ME并接受初始抗VEGF治疗的53例患者,其中缺血性视网膜中央静脉阻塞(CRVO)23例(CRVO组),缺血性视网膜分支静脉阻塞(BRVO)30例(BRVO组)。另选取该院同期30例行超声乳化的白内障患者作为对照组。研究对象行基线血清己糖激酶1抗体滴度检测、眼科常规检查和光学相干断层成像(OCT)检查。所有RVO-ME患者按照“3+按需治疗方案(pro re nata,PRN)”向玻璃体内注射抗VEGF药物治疗。随访12个月,采用多元线性回归分析缺血性RVO-ME患者抗VEGF治疗后视力改善的影响因素。结果CRVO组基线logMAR BCVA高于对照组和BRVO组,CRVO组和BRVO组基线CRT、基线血清己糖激酶1抗体滴度高于对照组,且CRVO组基线CRT、基线血清己糖激酶1抗体滴度高于BRVO组,差异有统计学意义(P<0.05)。RVO-ME患者基线血清己糖激酶1抗体滴度与随访6个月(r=0.377,P=0.005)、9个月(r=0.362,P=0.008)和12个月(r=0.465,P<0.001)时BCVA改善呈正相关,与随访12个月时中断EZ横向长度减少值(r=0.401,P=0.001)呈正相关。多元线性回归分析结果显示,基线logMAR BCVA、基线血清己糖激酶1抗体滴度是缺血性RVO-ME患者抗VEGF治疗随访12个月时BCVA改善的影响因素(P<0.05)。结论己糖激酶1抗体作为一种新的血清生物标志物,与缺血性RVO-ME患者抗VEGF治疗后的视力改善相关。
基金National Natural Science Foundation of China [grant no. 82060610]National Natural Science Foundation of China [grant no. 82103899]+2 种基金Guangxi Scientific and Technological Key Project[Gui Ke AB19245038]Guangxi Scientific and Technological Key Project [Guike 2022AC23005, 2022AC20031,2022JJA141110]Science and Technology Project of Nanning [20223051]。
文摘Objective The mode of human immunodeficiency virus(HIV) transmission via injection drug use(IDU)still exists, and the recent shift in IDU-related transmission of HIV infection is largely unknown. The purpose of this study was to analyze the spatiotemporal sources and dynamics of HIV-1 transmission through IDU in Guangxi.Methods We performed a molecular epidemiological investigation of infections across Guangxi from2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.Results Among the 535 subjects, CRF08_BC(57.4%), CRF01_AE(28.4%), and CRF07_BC(10.7%) were the top 3 HIV strains;72.6% of infections were linked to other provinces in the transmission network;93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces,predominantly Guangdong and Yunnan;92.1% of the HIV transmission among people who inject drugs tended to be transmitted between HIV-positive IDUs.Conclusion HIV recombinants were high diversity, and circulating local strains were the transmission sources among IDUs in Guangxi. However, there were still cases of IDUs linked to other provinces.Coverage of traditional prevention strategies should be expanded, and inter-provincial collaboration between Guangxi, Yunnan, and Guangdong provinces should be strengthened.
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
文摘目的为新型程序性死亡受体-1(PD-1)/程序性死亡配体-1(PD-L1)小分子抑制剂的研发提供参考。方法检索PubMed、Embase、Web of Science、ClinicalTrails.gov、中国知网、万方数据库2010年至2023年的PD-1/PD-L1小分子抑制剂相关文献,汇总并分析该类制剂的研发现状。结果与结论有成药潜力的PD-1/PD-L1小分子抑制剂共20种,包括CA-170(口服小分子抑制剂)、INCB086550(特异性PD-L1抑制剂)、DPPA-1(特异性抑制PD-1/PD-L1相互作用的多肽类拮抗剂)等,其中前两者已进入临床试验阶段。PD-1/PD-L1小分子抑制剂具有特异性抑制免疫检查点的药效作用特点,以及可口服、稳定性较好、膜通透性较高等优点,但其治疗效果仍需临床试验验证。
文摘目的:根据文献报道,分析4款国产程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)抑制剂不良反应的发生情况与临床特点,为临床安全用药提供参考。方法:检索PubMed、中国知网、万方等数据库,收集关于卡瑞利珠单抗、信迪利单抗、特瑞普利单抗和替雷利珠单抗4款PD-1抑制剂导致不良反应的个案报道进行分析。结果:检索到相关合格文献报道105篇,其中卡瑞利珠单抗42篇,共47例患者;信迪利单抗29篇,共30例患者;特瑞普利单抗21篇,共24例患者;替雷利珠单抗13篇,共15例患者。其中男性76例(65.5%),女性40例(34.5%),男女比例为1.9:1.0,年龄在29~84岁,发生时间主要在首次使用PD-1抑制剂后4个月内。免疫相关不良反应主要表现在皮肤及其附件毒性反应41例(34.5%)、内分泌系统不良反应25例(21.0%)、心血管系统不良反应22例(18.5%)。大多数患者经对症支持治疗后好转。结论:在接受4款国产PD-1抑制剂治疗的任何时间段都可能发生免疫相关不良反应(immune-related adverse effects,irAEs),其中皮肤系统不良反应发生率最高,其次是心血管和内分泌系统,提示临床在使用此类药物时,应严格控制适应证,结合患者病情和实际情况合理选择药物,在整个免疫治疗期间需密切监测,以减少或避免irAEs的发生,保障患者用药安全。
基金supported by HKU-UDF,HKSARG FHB/RFCID09080772the National Basic Research Program of China(2008ZX10001-011 and 2008ZX10001-015)
文摘Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).After over 26 years of efforts,there is still not a therapeutic cure or an effective vaccine against HIV/AIDS.The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART).Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients,the huge burden of ART in developing countries,together with the increasing incidence of drug resistant viruses among treated people,calls for continuous efforts for the development of anti-HIV-1 drugs.Currently,four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including:reverse transcriptase inhibitors (RTIs) (e.g.nucleoside reverse transcriptase inhibitors,NRTIs;and non-nucleoside reverse transcriptase inhibitors,NNRTIs),protease inhibitors (PIs),integrase inhibitors and entry inhibitors (e.g.fusion inhibitors and CCR5 antagonists).Here,we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
