Objective Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samp...Objective Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.展开更多
AIM To characterize the understanding of hepatitis B virus(HBV) and determine if outreach improves HBV understanding among Greater Boston Area immigrants. METHODS Six outreach sessions were held in various community v...AIM To characterize the understanding of hepatitis B virus(HBV) and determine if outreach improves HBV understanding among Greater Boston Area immigrants. METHODS Six outreach sessions were held in various community venues in the Greater Boston Area. Verbal consent was obtained from participants prior to starting each session. Each session included a pre-session questionnaire, followed by a teaching session, and then a post-session questionnaire. In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed. The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations. Questionnaires included Likerttype scale, open-ended, and true-false questions. All results were anonymous. RESULTS One hundred and one people participated in this study. Participants were 30% male with ages ranging from 19 to 87 years. The study population included immigrants from 21 countries, as well as seven United States-born participants. The greatest numbers of participants were from Somalia(44%), Morocco(10%), and Cameroon(8%). Pre session questionnaires revealed that 42% of participants were unaware that HBV can cause cancer, and 50% were unaware that therapies for HBV exist. Our brief teaching intervention led to improved scores on post session questionnaires. For example, at baseline, 58% of participants responded correctly to the question "HBV infection can cause scarring of the liver and liver cancer", whereas 79% of participants responded correctly after the teaching session(P = 0.01). Furthermore, the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6(P < 0.001).CONCLUSION A teaching session targeting Boston Immigrants atrisk for HBV helped improve scores on HBV knowledge questionnaires. Outreach may empower at-risk patients to pro-actively seek HBV care.展开更多
Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their...Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.展开更多
Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite spec...Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay (ELISA). Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus (Der p 1 ), Blomia tropicalis (BIot ) and Tyrophagus putrescentia (Tyr p) were detected in dust samples. Dermatophagoides farinae (Der f 1 ), Lepidoglyphus destructor (Lep d 2), and Acarus siro (Aca s ) were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.展开更多
TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for tw...TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.展开更多
Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor...Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment strategies.In this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues.Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.展开更多
Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to th...Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.展开更多
Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)pr...Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.展开更多
文摘Objective Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.
文摘AIM To characterize the understanding of hepatitis B virus(HBV) and determine if outreach improves HBV understanding among Greater Boston Area immigrants. METHODS Six outreach sessions were held in various community venues in the Greater Boston Area. Verbal consent was obtained from participants prior to starting each session. Each session included a pre-session questionnaire, followed by a teaching session, and then a post-session questionnaire. In person interpreters were present for translation during the teaching session and assistance for questionnaire completion when needed. The questions were developed based on the HBV clinical experience of physicians who serve largely immigrant populations. Questionnaires included Likerttype scale, open-ended, and true-false questions. All results were anonymous. RESULTS One hundred and one people participated in this study. Participants were 30% male with ages ranging from 19 to 87 years. The study population included immigrants from 21 countries, as well as seven United States-born participants. The greatest numbers of participants were from Somalia(44%), Morocco(10%), and Cameroon(8%). Pre session questionnaires revealed that 42% of participants were unaware that HBV can cause cancer, and 50% were unaware that therapies for HBV exist. Our brief teaching intervention led to improved scores on post session questionnaires. For example, at baseline, 58% of participants responded correctly to the question "HBV infection can cause scarring of the liver and liver cancer", whereas 79% of participants responded correctly after the teaching session(P = 0.01). Furthermore, the mean of total correct answers in the true or false portion of the questionnaire increased from 5.5 to 7.6(P < 0.001).CONCLUSION A teaching session targeting Boston Immigrants atrisk for HBV helped improve scores on HBV knowledge questionnaires. Outreach may empower at-risk patients to pro-actively seek HBV care.
基金supported by the funding from the National Natural Science Foundation of China(No.82070211 to Dr.Liang Huang)the National Key R&D Program of China(No.2022YFC2502604 to Dr.Liang Huang).
文摘Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.
基金The project was partly supported by a grant from Natural Science Foundation of Hainan Province, China (No. 808206).
文摘Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay (ELISA). Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus (Der p 1 ), Blomia tropicalis (BIot ) and Tyrophagus putrescentia (Tyr p) were detected in dust samples. Dermatophagoides farinae (Der f 1 ), Lepidoglyphus destructor (Lep d 2), and Acarus siro (Aca s ) were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.
基金We are grateful to the faculty and staff of the Clinical and Laboratory Unit of the Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,for clinical and technical support.Wuhan BioRaid Biotechnology CO.,LTD.is acknowledged for cell manufacturing and qualitycontrol.Dr.Pengcheng Wang of Hubei Clinical Research Center for Emergency and Resuscitation,Zhongnan Hospital of Wuhan University,is appreciated for kind assistance in statistical analysis.The current project was funded by the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.J.Z.)the National Natural Science Foundation of China(82070211 and 81670152,to Dr.L.H.,82070217 and 81873427,to Dr.J.W.,81770211 to Dr.M.X.)the Young Topnotch Talent Cultivation Program of Hubei Province(to Dr.L.H.)and CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.J.W.).
文摘TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.
文摘Gene engineering and combinatorial approaches with other cancer immunotherapy agents may confer capabilities enabling full tumor rejection by adoptive T cell therapy(ACT).The provision of proper costimulatory receptor activity and cytokine stimuli,along with the repression of inhibitory mechanisms,will conceivably make the most of these treatment strategies.In this sense,T cells can be genetically manipulated to become refractory to suppressive mechanisms and exhaustion,last longer and differentiate into memory T cells while endowed with the ability to traffic to malignant tissues.Their antitumor effects can be dramatically augmented with permanent or transient gene transfer maneuvers to express or delete/repress genes.A combination of such interventions seeks the creation of the ultimate bionic T cell,perfected to seek and destroy cancer cells upon systemic or local intratumor delivery.
基金This work was supported by fundings from the National Natural Science Foundation of China(82070217 and 81873427,toDr.JiaWei,81770211,toDr.Min Xiao,81670152,to Dr.Liang Huang,and 81700145 to Dr.Li Yang)fundings from the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.Jianfeng Zhou)funding from CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.JiaWei).
文摘Dear Editor,Chimeric antigen receptor-engineered(CAR)-T cell therapy has achieved unprecedented efficacy on refractory/relapsed B-cell malignancies[1].Yet,CAR-T recipients are highly susceptible to infection due to the immunodeficiency caused by B-cell aplasia and the pretreatment with chemotherapy.However,due to the systematic use of empirical broad-spectrum antibiotics and immunosuppressors to control cytokine release syndrome(CRS)reaction,microbiological diagnosis of infection has remained challenging in CAR-T recipients.
基金supported by the National Natural Science Foundation of China(8170010813 to Z.S.,81830008 to J.Z.,81600125 to J.W.,81800160 to T.L.,and 81400122 to K.Z.)the Natural Science Foundation of Hubei Province(2016CFA011 and 2018ACA140).
文摘Internal tandem duplication(ITD)mutations of FMS-like tyrosine kinase-3(FLT3)are the most frequent genetic alterations in acute myeloid leukemia(AML)and predict a poor prognosis.FLT3 tyrosine kinase inhibitors(TKIs)provide short-term clinical responses,but the long-term prognosis of FLT3/ITD^(+)AML patients remains poor.Notch signaling is important in numerous types of tumors.However,the role of Notch signaling in FLT3/ITD^(+)AML remains to be elucidated.In the current study,we found that Notch signaling was activated upon FLT3-TKI treatment in FLT3/ITD^(+)cell lines and primary cells.As Notch signaling can be blocked byγ-secretase inhibitors(GSIs),we examined the combinatorial antitumor efficacy of FLT3-TKIs and GSIs against FLT3/ITD^(+)AML and explored the underlying molecular mechanisms.As a result,we observed synergistic cytotoxic effects,and the treatment preferentially reduced cell proliferation and induced apoptosis in FLT3/ITD^(+)AML cell lines and in primary AML cells.Furthermore,the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in an FLT3/ITD^(+)patient-derived xenograft AML model.Mechanistically,differential expression analysis suggested that CXCR3 may be partially responsible for the observed synergy,possibly through ERK signaling.Our findings suggest that combined therapies of FLT3-TKIs with GSI may be exploited as a potential therapeutic strategy to treat FLT3/ITD^(+)AML.