Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met th...Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.展开更多
Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)...Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)and loss(in the breast or lung)have been implicated in cancer metastasis.Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma(RCC),data indicating the role of Par3 in RCC metastasis are lacking.Given reports of interactions between Par3 and oncoproteins such as Yesassociated protein(YAP)/WW domain-containing transcription regulator 1(TAZ),we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.Methods:Par3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical(IHC)staining,as appropriate.Co-immunoprecipitation(co-IP)and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP.Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation.PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.Results:Higher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines.Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues.Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins.Moreover,Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements.PDZ domain 3 in the PARD3 gene was demonstrated to be particularly important in the interactions between Par3 and YAP.Furthermore,Par3 was found to upregulate intracellular levels of YAP/TAZ molecules and promote nuclear translocation of YAP.Conclusions:Together,these results indicate the role of Par3 in RCC metastasis,via driving metastatic RCC progression by promoting the YAP/TAZ pathway.展开更多
AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.M...AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.METHODS:The clinical data of 50 eyes from 49 patients diagnosed with ERM,who were highly myopic and underwent PPV were retrospectively analyzed.The patients with ERM were classified into five groups based on the characteristics associated with different levels of myopic traction maculopathy.Group 1:Simple ERM without complex vertical and tangential direction traction on retina on optical coherence tomography(OCT)image;Group 2:ERM with obvious macular foveal schisis,without macular hole(MH);Group 3:ERM with inner lamellar MH,with or without macular foveal schisis;Group 4:ERM with outer lamellar MH,with or without foveal retinal detachment(RD);Group 5:ERM with full-thickness MH.Baseline characteristics,changes in best corrected visual acuity(BCVA)before and after surgery,and anatomical characteristics through spectral domain OCT were compared.RESULTS:The 50 eyes were followed for 6mo,with an average age of 58.66y and an average axial length(AL)of 28.69 mm.Among the five groups,postoperative logMAR BCVA improved(P<0.05).Group 1 had better mean BCVA at baseline(0.59±0.36)and at 6mo postoperatively(0.16±0.22)compared to the other groups,while Group 5 had worse mean BCVA at baseline(1.68±0.45)and at 6mo postoperatively(1.27±0.64).There were no statistically significant differences in sex,age or AL between the groups(P>0.05).OCT showed that Groups 4 and 5 exhibited poorer macular anatomy compared to the other three groups,as evidenced by lower rates of central retinal reattachment(64.3%in Group 4,86.7%in Group 5)and integrity of the inner segment/outer segment of photoreceptor junction(28.6%in Group 4,26.7%in Group 5).CONCLUSION:PPV is an effective treatment for ERM in patients with HM.All groups showed postoperative improvement in BCVA compared to preoperative levels,demonstrating the necessity of surgical intervention.Early intervention,particularly before the fourth stage of the disease,may lead to better visual outcomes.展开更多
AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)com...AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.展开更多
Here,we used reverse transcription-PCR(RT-PCR) and western blot to detect protease-activated receptor(PAR) 1,PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma,and invest...Here,we used reverse transcription-PCR(RT-PCR) and western blot to detect protease-activated receptor(PAR) 1,PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma,and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer.The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed.By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells(HEEpiC),we found that among the 28 cases of esophageal squamous cell carcinoma,PAR1(60%) and PAR2(71%) were elevated in 17 and 20 cases,respectively,and PAR4(68%) expression was lowered in 19 cases.Whereas,in human esophageal squamous cells(TE-1 and TE-10),PAR1 and PAR2 expression was increased but PAR4 was decreased.Combined with clinical data,the expression of PAR1 in poorly differentiated(P=0.016) and middle and lower parts of the esophagus(P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower(P=0.049).Regarding TE-1 and TE-10 protein expression,we found that in randomized esophageal carcinoma,PAR1(P=0.027) and PAR2(P=0.039) expressions were increased,but lowered for PAR4(P=0.0001).In HEEpiC,TE-1,TE-10,esophageal and normal esophagus tissue samples(case No.7),the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%,95.2%,83.8%,62.6% and 48.2%,respectively.Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased.Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.展开更多
The integration of academic research methodologies into design thinking processes presents a transformative approach to addressing complex challenges in group housing,fostering inclusive,sustainable,and user-centered ...The integration of academic research methodologies into design thinking processes presents a transformative approach to addressing complex challenges in group housing,fostering inclusive,sustainable,and user-centered solutions.This research explores how methodologies such as Participatory Action Research,post-occupancy evaluations,and Research through Design can be systematically embedded within design thinking to bridge the gap between academic rigor and empathy-driven,iterative design practices.By synthesizing these paradigms,the study proposes a framework for group housing design that prioritizes co-design processes,empathy-based data collection,and participatory evaluation,while emphasizing adaptability through sociocultural insights and user feedback.Case studies analysis demonstrate the effectiveness of flexible,community-driven design,while emerging technologies like IoT-enabled cohousing signal new opportunities for innovation.Challenges,including scalability,long-term validation,and reconciling user autonomy with professional expertise,are critically analyzed.Ultimately,this research advances a hybrid methodology to redefine the conceptualization,implementation,and assessment of group housing,offering actionable pathways to achieve affordable,inclusive,and context-sensitive housing solutions.展开更多
基金supported by the Razi Vaccine and Serum Research Institute(RVSRI)Karaj,Iran,(No.17-18-18-063-01047-011130).
文摘Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.
基金supported by grants from the American Urology Association(AUA)Urology Care Foundation Research Scholar AwardKidney Cancer Research Alliance Research Grant+3 种基金Simmons Comprehensive Cancer Center(SCCC)Early-Stage Clinical Investigator AwardDedman Scholar Awardsupported by the Simmons Cancer Center’s Tissue Management Shared Resourcethe National Cancer Institute of the National Institutes of Health(grant No.P30 CA142543)。
文摘Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)and loss(in the breast or lung)have been implicated in cancer metastasis.Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma(RCC),data indicating the role of Par3 in RCC metastasis are lacking.Given reports of interactions between Par3 and oncoproteins such as Yesassociated protein(YAP)/WW domain-containing transcription regulator 1(TAZ),we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.Methods:Par3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical(IHC)staining,as appropriate.Co-immunoprecipitation(co-IP)and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP.Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation.PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.Results:Higher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines.Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues.Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins.Moreover,Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements.PDZ domain 3 in the PARD3 gene was demonstrated to be particularly important in the interactions between Par3 and YAP.Furthermore,Par3 was found to upregulate intracellular levels of YAP/TAZ molecules and promote nuclear translocation of YAP.Conclusions:Together,these results indicate the role of Par3 in RCC metastasis,via driving metastatic RCC progression by promoting the YAP/TAZ pathway.
基金Supported by the National Natural Science Foundation of China(No.82371084).
文摘AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.METHODS:The clinical data of 50 eyes from 49 patients diagnosed with ERM,who were highly myopic and underwent PPV were retrospectively analyzed.The patients with ERM were classified into five groups based on the characteristics associated with different levels of myopic traction maculopathy.Group 1:Simple ERM without complex vertical and tangential direction traction on retina on optical coherence tomography(OCT)image;Group 2:ERM with obvious macular foveal schisis,without macular hole(MH);Group 3:ERM with inner lamellar MH,with or without macular foveal schisis;Group 4:ERM with outer lamellar MH,with or without foveal retinal detachment(RD);Group 5:ERM with full-thickness MH.Baseline characteristics,changes in best corrected visual acuity(BCVA)before and after surgery,and anatomical characteristics through spectral domain OCT were compared.RESULTS:The 50 eyes were followed for 6mo,with an average age of 58.66y and an average axial length(AL)of 28.69 mm.Among the five groups,postoperative logMAR BCVA improved(P<0.05).Group 1 had better mean BCVA at baseline(0.59±0.36)and at 6mo postoperatively(0.16±0.22)compared to the other groups,while Group 5 had worse mean BCVA at baseline(1.68±0.45)and at 6mo postoperatively(1.27±0.64).There were no statistically significant differences in sex,age or AL between the groups(P>0.05).OCT showed that Groups 4 and 5 exhibited poorer macular anatomy compared to the other three groups,as evidenced by lower rates of central retinal reattachment(64.3%in Group 4,86.7%in Group 5)and integrity of the inner segment/outer segment of photoreceptor junction(28.6%in Group 4,26.7%in Group 5).CONCLUSION:PPV is an effective treatment for ERM in patients with HM.All groups showed postoperative improvement in BCVA compared to preoperative levels,demonstrating the necessity of surgical intervention.Early intervention,particularly before the fourth stage of the disease,may lead to better visual outcomes.
基金Supported by Shanghai Municipal Health Commission(No.202140183).
文摘AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.
基金supported by the National Natural Foundation of China(81160302)the Major Research Project of Yunnan Province(2011FZ109)Research project of Yunnan Education Bureau(2014Y153)
文摘Here,we used reverse transcription-PCR(RT-PCR) and western blot to detect protease-activated receptor(PAR) 1,PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma,and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer.The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed.By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells(HEEpiC),we found that among the 28 cases of esophageal squamous cell carcinoma,PAR1(60%) and PAR2(71%) were elevated in 17 and 20 cases,respectively,and PAR4(68%) expression was lowered in 19 cases.Whereas,in human esophageal squamous cells(TE-1 and TE-10),PAR1 and PAR2 expression was increased but PAR4 was decreased.Combined with clinical data,the expression of PAR1 in poorly differentiated(P=0.016) and middle and lower parts of the esophagus(P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower(P=0.049).Regarding TE-1 and TE-10 protein expression,we found that in randomized esophageal carcinoma,PAR1(P=0.027) and PAR2(P=0.039) expressions were increased,but lowered for PAR4(P=0.0001).In HEEpiC,TE-1,TE-10,esophageal and normal esophagus tissue samples(case No.7),the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%,95.2%,83.8%,62.6% and 48.2%,respectively.Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased.Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.
文摘The integration of academic research methodologies into design thinking processes presents a transformative approach to addressing complex challenges in group housing,fostering inclusive,sustainable,and user-centered solutions.This research explores how methodologies such as Participatory Action Research,post-occupancy evaluations,and Research through Design can be systematically embedded within design thinking to bridge the gap between academic rigor and empathy-driven,iterative design practices.By synthesizing these paradigms,the study proposes a framework for group housing design that prioritizes co-design processes,empathy-based data collection,and participatory evaluation,while emphasizing adaptability through sociocultural insights and user feedback.Case studies analysis demonstrate the effectiveness of flexible,community-driven design,while emerging technologies like IoT-enabled cohousing signal new opportunities for innovation.Challenges,including scalability,long-term validation,and reconciling user autonomy with professional expertise,are critically analyzed.Ultimately,this research advances a hybrid methodology to redefine the conceptualization,implementation,and assessment of group housing,offering actionable pathways to achieve affordable,inclusive,and context-sensitive housing solutions.
