To the Editor:Off-label drug use(OLDU)refers to the use of a drug outside of the age,indication,weight,dose,formulation,or route of administration indicated on the label.It is a major concern and a common practice for...To the Editor:Off-label drug use(OLDU)refers to the use of a drug outside of the age,indication,weight,dose,formulation,or route of administration indicated on the label.It is a major concern and a common practice for clinicians around the globe,especially for pediatricians,owing to the lack of pediatric-specific drug information.[1]Research showed that US office-based physicians had ordered 41.2 million off-label orders per year for children and the trend had been increasing from 2006 to 2015.展开更多
Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been...Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.展开更多
Importance:Recurrent respiratory tract infection(RRTI)is common in children.Inappropriate RRTI treatment will lead to asthma and other diseases,thereby seriously affecting the growth and physical health of children.Im...Importance:Recurrent respiratory tract infection(RRTI)is common in children.Inappropriate RRTI treatment will lead to asthma and other diseases,thereby seriously affecting the growth and physical health of children.Immune function modulation can prevent and alleviate childhood RRTI.Yupingfeng(YPF),a patented traditional Chinese medicine(TCM),has immunomodulatory effects and is widely used in China to treat children with RRTI.Objective:To evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI.Methods:This multicenter,randomized,double-blind,double-simulation,noninferiority clinical trial was conducted from January 2015 to August 2017,with an 8-week treatment period and 52-week follow-up after the drug withdrawal.Children aged 2–6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups(2:2:1 ratio)to receive YPF,pidotimod,or placebo.The primary outcome was the proportion of RRTI returning to normal standard level during the follow-up.The secondary outcomes were reduction in the number of RRTI recurrences,effect on clinical symptoms(in accord with TCM practice),effect per symptom,and safety.The trial was registered at the Chinese Clinical Trials Registry(www.chictr.org.cn)under the unique identifier ChiCTR-IPR-15006847.Results:Three hundred and fifty-one children were enrolled and randomly assigned to 3 groups;124,125,and 61 children in the YPF,pidotimod,and placebo groups,respectively,had completed the trial.During the follow-up,the proportion of RRTI returning to normal standard level was 73.13%,67.15%,and 38.81%with YPF,pidotimod,and placebo,respectively(P<0.0001).The proportion of cases who returned to normal standard level in the YPF group was 34.32%higher than that in the placebo group.The safety profile did not significantly differ among the groups.Interpretation:YPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children,and were superior to placebo,with a high safety profile.展开更多
Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regener...Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF.展开更多
Dear Editors,In recent years,human adenovirus (HAd V) infection has been prevalent in various regions in China (Duan et al.2021).Research in Guangzhou reported that 9.14%of fatal pneumonia cases showed HAd V-PCR posit...Dear Editors,In recent years,human adenovirus (HAd V) infection has been prevalent in various regions in China (Duan et al.2021).Research in Guangzhou reported that 9.14%of fatal pneumonia cases showed HAd V-PCR positive (Ou et al.2007).The severity and high mortality caused by HAd V have aroused the attention of pediatricians.展开更多
Transparency Ecosystemfor Research and Journals inMedicine(TERM)Working Group summarized the essential recommendations that should be considered to review and publish a high-quality guideline.These recommendations fro...Transparency Ecosystemfor Research and Journals inMedicine(TERM)Working Group summarized the essential recommendations that should be considered to review and publish a high-quality guideline.These recommendations fromeditors and reviewers included the 10 components of essential requirements:systematic review of existing relevant guidelines,guideline registration,guideline protocol,stakeholders,conflicts of interest,clinical questions,systematic reviews,recommendation consensus,guideline reporting,and external review.TERMWorking Group abbreviates them as PAGE(essential requirements for Publishing clinical prActice GuidelinEs),recommends guideline authors,editors,and peer reviewers use them for high-quality guidelines.展开更多
Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the c...Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the clinical findings regarding 2009 influenza A(H1N1)-associated pediatric deaths in China,including the risk factors for death.Methods:The definition of 2009 influenza A(H1N1)-associated pediatric death is death in a child who is younger than 14 years and has laboratory-confirmed influenza.We collected data of total 810 hospitalized patients with 2009 influenza A(H 1N 1)infection from September 2009 to February 2010 in 17 hospitals across China.The clinical characteristics,laboratory abnormalities,and treatment course were retrospectively studied.Results:Of the 810 patients hospitalized with 2009 influenza A(H1N1)infection,19(2.3%)died.Ten patients died from severe pneumonia and acute respiratory distress syndrome;eight died from encephalopathy/encephalitis;one died from secondary fungal meningitis.Patients who died were more likely than patients who survived to have neutrophilia,lymphopenia,elevated C-reactive protein,and elevations of lactate dehydrogenase,creatine kinase,creatine kinase-MB,aspartate aminotransferase and alanine aminotransferase.There were no significant differences in the median age,median time from onset of illness to admission,underlying chronic disease,and initiation of antiviral therapy within 48 hours of illness onset,between patients who died and those who survived.Interpretation:The risk factors for pediatric death associated with 2009 influenza A(H 1N 1)infection are different from those of seasonal influenza.The most common causes of death are viral pneumonia,acute respiratory distress syndrome,and encephalopathy/encephalitis.展开更多
文摘To the Editor:Off-label drug use(OLDU)refers to the use of a drug outside of the age,indication,weight,dose,formulation,or route of administration indicated on the label.It is a major concern and a common practice for clinicians around the globe,especially for pediatricians,owing to the lack of pediatric-specific drug information.[1]Research showed that US office-based physicians had ordered 41.2 million off-label orders per year for children and the trend had been increasing from 2006 to 2015.
基金the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32000667)+5 种基金the Shanghai Science and Technology Innovation Action(21ZR1470600)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022264)the National Natural Science Foundation of China(81771465 and 81930033)the Science and Technology Project of the Department of Education of Jiangxi Province(GJJ211248)the Division of Intramural Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health(grant 1ZIA-Al-001169)the US-China Biomedical Collaborative Research Program(grant Al-129775).
文摘Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.
文摘Importance:Recurrent respiratory tract infection(RRTI)is common in children.Inappropriate RRTI treatment will lead to asthma and other diseases,thereby seriously affecting the growth and physical health of children.Immune function modulation can prevent and alleviate childhood RRTI.Yupingfeng(YPF),a patented traditional Chinese medicine(TCM),has immunomodulatory effects and is widely used in China to treat children with RRTI.Objective:To evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI.Methods:This multicenter,randomized,double-blind,double-simulation,noninferiority clinical trial was conducted from January 2015 to August 2017,with an 8-week treatment period and 52-week follow-up after the drug withdrawal.Children aged 2–6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups(2:2:1 ratio)to receive YPF,pidotimod,or placebo.The primary outcome was the proportion of RRTI returning to normal standard level during the follow-up.The secondary outcomes were reduction in the number of RRTI recurrences,effect on clinical symptoms(in accord with TCM practice),effect per symptom,and safety.The trial was registered at the Chinese Clinical Trials Registry(www.chictr.org.cn)under the unique identifier ChiCTR-IPR-15006847.Results:Three hundred and fifty-one children were enrolled and randomly assigned to 3 groups;124,125,and 61 children in the YPF,pidotimod,and placebo groups,respectively,had completed the trial.During the follow-up,the proportion of RRTI returning to normal standard level was 73.13%,67.15%,and 38.81%with YPF,pidotimod,and placebo,respectively(P<0.0001).The proportion of cases who returned to normal standard level in the YPF group was 34.32%higher than that in the placebo group.The safety profile did not significantly differ among the groups.Interpretation:YPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children,and were superior to placebo,with a high safety profile.
基金This work was supported by the National Natural Science Foundation Committee of China[grant numbers 81373444,81570142,81670018]the Chinese Ministry of Science and Technology[grant number 2016YFA0101300]the Key Grant from the Chongqing Science and Technology Commission[grant number cstc2014yykfC10003].
文摘Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF.
基金supported by the Education Committee of Chongqing, China for Young Scholars (Chongqing Education Department [2019] No.13)Millions Talent Projects of Chongqing (Chongqing Commission [2018] NO.187)the Foundation of Children’s Hospital of Chongqing Medical University。
文摘Dear Editors,In recent years,human adenovirus (HAd V) infection has been prevalent in various regions in China (Duan et al.2021).Research in Guangzhou reported that 9.14%of fatal pneumonia cases showed HAd V-PCR positive (Ou et al.2007).The severity and high mortality caused by HAd V have aroused the attention of pediatricians.
基金supported by the Foundation of Chinese Medical Association Publishing House.
文摘Transparency Ecosystemfor Research and Journals inMedicine(TERM)Working Group summarized the essential recommendations that should be considered to review and publish a high-quality guideline.These recommendations fromeditors and reviewers included the 10 components of essential requirements:systematic review of existing relevant guidelines,guideline registration,guideline protocol,stakeholders,conflicts of interest,clinical questions,systematic reviews,recommendation consensus,guideline reporting,and external review.TERMWorking Group abbreviates them as PAGE(essential requirements for Publishing clinical prActice GuidelinEs),recommends guideline authors,editors,and peer reviewers use them for high-quality guidelines.
文摘Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the clinical findings regarding 2009 influenza A(H1N1)-associated pediatric deaths in China,including the risk factors for death.Methods:The definition of 2009 influenza A(H1N1)-associated pediatric death is death in a child who is younger than 14 years and has laboratory-confirmed influenza.We collected data of total 810 hospitalized patients with 2009 influenza A(H 1N 1)infection from September 2009 to February 2010 in 17 hospitals across China.The clinical characteristics,laboratory abnormalities,and treatment course were retrospectively studied.Results:Of the 810 patients hospitalized with 2009 influenza A(H1N1)infection,19(2.3%)died.Ten patients died from severe pneumonia and acute respiratory distress syndrome;eight died from encephalopathy/encephalitis;one died from secondary fungal meningitis.Patients who died were more likely than patients who survived to have neutrophilia,lymphopenia,elevated C-reactive protein,and elevations of lactate dehydrogenase,creatine kinase,creatine kinase-MB,aspartate aminotransferase and alanine aminotransferase.There were no significant differences in the median age,median time from onset of illness to admission,underlying chronic disease,and initiation of antiviral therapy within 48 hours of illness onset,between patients who died and those who survived.Interpretation:The risk factors for pediatric death associated with 2009 influenza A(H 1N 1)infection are different from those of seasonal influenza.The most common causes of death are viral pneumonia,acute respiratory distress syndrome,and encephalopathy/encephalitis.