To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary...To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary infection is the most frequent manifestation,affecting nearly 80%of patients,[2]and remains the major cause of morbidity and mortality in patients with CGD.Details of the pathogenic microorganisms responsible for first-episode pulmonary infection provide information on the spectrum of infection in patients with CGD,help guide the empirical choice of antibiotics or antifungal therapy,and contribute to the early identification and management of CGD.Aspergillus is the commonest causative agent of pulmonary infection,but the distribution of other pathogens varies among countries.^([2–5])Few studies have investigated the etiology of pulmonary infection in CGD in a large cohort in China.展开更多
Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has...Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.展开更多
Importance:Surfactant protein C(SP-C)dysfunction is a rare disease associated with interstitial lung disease.Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestatio...Importance:Surfactant protein C(SP-C)dysfunction is a rare disease associated with interstitial lung disease.Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations.Objective:To investigate the manifestations and outcomes of SP-C dysfunction.Methods:We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children's Hospital.Results:The five patients included two boys and three girls with a median age at diagnosis of 1.3 years.All patients presented with interstitial lung disease and had a heterozygous SFTPC mutation,including an I73T mutation in three patients,a V39L mutation in one patient,and a Y 104H mutation in one patient.In addition to common respiratory manifestations,hemoptysis and anemia were observed in one patient with the I73T mutation.Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation,suggesting the presence of diffuse alveolar hemorrage and autoimmunity.Chest high-resolution computed tomography features included ground-glass opacities,reticular opacities,cysts,and pleural thickening.Transbronchial lung biopsy was performed in one patient with the I73T mutation,which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces.All patients received treatment with corticosteroids;two received combined treatment with hydroxychloroquine.During follow-up,the two patients who received hydroxychloroquine showed improved symptoms;of the remaining three patients,two died after their families refused further treatment,while the final patient was lost to follow-up.Interpretation:This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T SFTPC mutation.Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction.展开更多
Importance:Pulmonary mucormycosis is life threatening and carries a poor prognosis.Identification of factors that improve prognosis is urgently necessary.Objective:To analyze the clinical features and outcomes of pulm...Importance:Pulmonary mucormycosis is life threatening and carries a poor prognosis.Identification of factors that improve prognosis is urgently necessary.Objective:To analyze the clinical features and outcomes of pulmonary mucormycosis in children.Methods:A retrospective analysis of clinical data of four cases with pulmonary mucormycosis was conducted in Beijing Children's Hospital from January 2017 to December 2018.Results:Underlying diseases were identified in all four cases(diabetes in three individuals and a hematological malignancy in one individual).The predominant clinical manifestations were fever,cough,chest pain and hemoptysis.Imaging features included consolidation or nodules with cavities.All four cases were treated with liposomal amphotericin B,one case underwent lobectomy,and three cases received a full course ofposaconazole.All four cases were cured.Interpretation:Patients with pulmonary mucormycosis often have underlying diseases.Imaging features are relatively characteristic.Treatment with liposomal amphotericin B at an early stage and a sufficient course of posaconazole for maintenance significantly improves prognosis.展开更多
Importance Pediatric hypervascular primary airway tumors are progressive,fatal lesions with a low incidence,and the disease is often more serious than that in adults.Objective To evaluate the clinical efficacy and saf...Importance Pediatric hypervascular primary airway tumors are progressive,fatal lesions with a low incidence,and the disease is often more serious than that in adults.Objective To evaluate the clinical efficacy and safety of interventional therapeutic bronchoscopy combined with conservative treatment and bronchial arterial embolization in children with primary airway tumors.Methods We retrospectively analyzed the clinical data of four pediatric patients with hypervascular primary airway tumor between 2017 and 2019 at Beijing Children’s Hospital.Results Two patients were low-grade bronchial mucoepidermoid carcinoma,one patient was pleomorphic adenoma,and one was bronchial leiomyoma.Interventional therapeutic bronchoscopy combined with bronchial arterial embolization was used for treatment(all four patients received general anesthesia).The tumors were safely resected in all patients via interventional bronchoscopy.There were no severe complications related to the procedures.All patients were followed up for 5–12 months,and one low-grade bronchial mucoepidermoid carcinoma recurred.Interpretation Interventional therapeutic bronchoscopy combined with bronchial arterial embolization appears to be a safe and efficient therapeutic method associated with less trauma and fewer complications,including no serious adverse events,in children with hypervascular primary airway tumors without bronchus wall infiltration.展开更多
基金supported by a grant from the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(No.HX2X-202103).
文摘To the Editor:Chronic granulomatous disease(CGD)is an inherited primary immunodeficiency disease characterized by recurrent life-threatening bacterial or fungal infection and tissue granuloma formation.^([1])Pulmonary infection is the most frequent manifestation,affecting nearly 80%of patients,[2]and remains the major cause of morbidity and mortality in patients with CGD.Details of the pathogenic microorganisms responsible for first-episode pulmonary infection provide information on the spectrum of infection in patients with CGD,help guide the empirical choice of antibiotics or antifungal therapy,and contribute to the early identification and management of CGD.Aspergillus is the commonest causative agent of pulmonary infection,but the distribution of other pathogens varies among countries.^([2–5])Few studies have investigated the etiology of pulmonary infection in CGD in a large cohort in China.
基金supported by the National Natural Science Foundation of China (81874288, 82003590 and 92053105)the Natural Science Foundation of Shandong Province (ZR2020QH342, China)+1 种基金the Key Project of Natural Science Foundation of Anhui Province for College Scholar (2022AH051216, China)Scientific Research Project of Anhui Provincial Health Commission (AHWJ2022b005, China)。
文摘Dysregulation of histone deacetylases(HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors(HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.
文摘Importance:Surfactant protein C(SP-C)dysfunction is a rare disease associated with interstitial lung disease.Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations.Objective:To investigate the manifestations and outcomes of SP-C dysfunction.Methods:We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children's Hospital.Results:The five patients included two boys and three girls with a median age at diagnosis of 1.3 years.All patients presented with interstitial lung disease and had a heterozygous SFTPC mutation,including an I73T mutation in three patients,a V39L mutation in one patient,and a Y 104H mutation in one patient.In addition to common respiratory manifestations,hemoptysis and anemia were observed in one patient with the I73T mutation.Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation,suggesting the presence of diffuse alveolar hemorrage and autoimmunity.Chest high-resolution computed tomography features included ground-glass opacities,reticular opacities,cysts,and pleural thickening.Transbronchial lung biopsy was performed in one patient with the I73T mutation,which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces.All patients received treatment with corticosteroids;two received combined treatment with hydroxychloroquine.During follow-up,the two patients who received hydroxychloroquine showed improved symptoms;of the remaining three patients,two died after their families refused further treatment,while the final patient was lost to follow-up.Interpretation:This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T SFTPC mutation.Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction.
文摘Importance:Pulmonary mucormycosis is life threatening and carries a poor prognosis.Identification of factors that improve prognosis is urgently necessary.Objective:To analyze the clinical features and outcomes of pulmonary mucormycosis in children.Methods:A retrospective analysis of clinical data of four cases with pulmonary mucormycosis was conducted in Beijing Children's Hospital from January 2017 to December 2018.Results:Underlying diseases were identified in all four cases(diabetes in three individuals and a hematological malignancy in one individual).The predominant clinical manifestations were fever,cough,chest pain and hemoptysis.Imaging features included consolidation or nodules with cavities.All four cases were treated with liposomal amphotericin B,one case underwent lobectomy,and three cases received a full course ofposaconazole.All four cases were cured.Interpretation:Patients with pulmonary mucormycosis often have underlying diseases.Imaging features are relatively characteristic.Treatment with liposomal amphotericin B at an early stage and a sufficient course of posaconazole for maintenance significantly improves prognosis.
文摘Importance Pediatric hypervascular primary airway tumors are progressive,fatal lesions with a low incidence,and the disease is often more serious than that in adults.Objective To evaluate the clinical efficacy and safety of interventional therapeutic bronchoscopy combined with conservative treatment and bronchial arterial embolization in children with primary airway tumors.Methods We retrospectively analyzed the clinical data of four pediatric patients with hypervascular primary airway tumor between 2017 and 2019 at Beijing Children’s Hospital.Results Two patients were low-grade bronchial mucoepidermoid carcinoma,one patient was pleomorphic adenoma,and one was bronchial leiomyoma.Interventional therapeutic bronchoscopy combined with bronchial arterial embolization was used for treatment(all four patients received general anesthesia).The tumors were safely resected in all patients via interventional bronchoscopy.There were no severe complications related to the procedures.All patients were followed up for 5–12 months,and one low-grade bronchial mucoepidermoid carcinoma recurred.Interpretation Interventional therapeutic bronchoscopy combined with bronchial arterial embolization appears to be a safe and efficient therapeutic method associated with less trauma and fewer complications,including no serious adverse events,in children with hypervascular primary airway tumors without bronchus wall infiltration.
