Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and surviva...Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and survival in multiple systems have been gradually discovered with the emergence of transgenic mice.RUNX1 is a powerful transcription factor implicated in diverse signaling pathways and cellular mechanisms that participate in lung development and pulmonary diseases.RUNX1 has recently been identified as a target regulator of fibrotic remodeling diseases,particularly in the kidney.However,the role of RUNX1 in pulmonary fibrosis is unclear.Pulmonary fibrosis is characterized by obscure nosogenesis,limited therapy,and poor prognosis.Moreover,the population of patients with pulmonary fibrosis is gradually increasing.Thus,there is an unmet need for therapeutic targets.In this review,we retrospectively discuss the alteration in RUNX1 mRNA expression in the RNA sequencing data of human fibrotic lungs and the protein levels in mouse pulmonary fibrosis.Subsequently,we focused on the interaction between RUNX1 and several signaling pathways involved in pulmonary fibrosis.Finally,this review highlights the therapeutic potential of RUNX1 as a target for slowing the progression of fibrotic lung disease.展开更多
Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is ...Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is increasingly evident that preserving mitochondrial health in alveolar epithelial cells holds great therapeutic potential for ARDS.2 Mitophagy,a cellular process aimed at maintaining mitochondrial health,plays a critical role in this regard.3 Therefore,gaining a comprehensive understanding of the factors that regulate mitophagy in alveolar epithelial cells during ALI could greatly inform the development of future therapeutic approaches for ARDS.展开更多
Background:Nasal insertion is the preferred method for non-intubated patients in flexible bronchoscopy;however,the relatively narrow nasal cavity results in difficulties related to bronchoscope insertion.This study ai...Background:Nasal insertion is the preferred method for non-intubated patients in flexible bronchoscopy;however,the relatively narrow nasal cavity results in difficulties related to bronchoscope insertion.This study aimed to investigate whether pre-operative nasal probe tests could reduce the time to pass the glottis,improve the first-pass success rate and patients’tolerance,and reduce postoperative bleeding.Methods:This three-arm prospective randomized controlled trial was conducted in a tertiary hospital between May and October 2020.Three hundred patients requiring diagnosis and treatment using flexible bronchoscopy were randomly allocated to three groups:control group,simple cotton bud detection group(CD group),and adrenaline+lidocaine detection group(AD group).The primary outcome was the time to pass the glottis.Secondary outcomes included the first-pass success rate,the patients’tolerance scores,and post-operative bleeding.One-way analysis of variance,Kruskal-WallisH test,Chi-squared test,Fisher’s exact test,and Bonferroni’s multiple comparison tests were used in this study.Results:In total,189 men and 111 women were enrolled in this study,with a mean age of 55.72±12.86 years.The insertion time was significantly shorter in the AD group than in the control group(18.00 s[12.00–26.50 s]vs.24.00 s[14.50–45.50 s],P=0.005).Both the AD(99%vs.83%,χ2=15.62,P<0.001)and CD groups(94%vs.83%,χ2=5.94,P=0.015)had a significantly higher first-pass success rate than the control group.Compared with the control group,post-operative bleeding(1%vs.13%,χ2=11.06,P<0.001)was significantly lower in the AD group.However,no significant difference was found in the patients’tolerance scores.Conclusions:Pre-operative nasal cavity probe tests especially with adrenaline and lidocaine during flexible bronchoscopy can significantly reduce the time to pass the glottis,improve the first-pass success rate,and reduce post-operative nasal bleeding.Pre-operative nasal probe tests are recommended as a time-saving procedure for patients undergoing flexible bronchoscopy.Trial registration:Chinese Clinical Trial Registry(ChiCTR),ChiCTR2000032668;http://www.chictr.org.cn/showprojen.aspx?proj=53321.展开更多
Chronic obstructive pulmonary disease(COPD)is characterized by emphysema and airflow limitation and is one of the leading causes of morbidityand mortalityworldwide.Endoscopic lung volumereduction(ELVR)is a minimally i...Chronic obstructive pulmonary disease(COPD)is characterized by emphysema and airflow limitation and is one of the leading causes of morbidityand mortalityworldwide.Endoscopic lung volumereduction(ELVR)is a minimally invasive technique for patients with severe hyperinflation and advanced emphysema.To date,the most investigated form of ELVR isvalve implantation,which is toplacevalves in all the segments of an emphysematous lobe.However,valve replacements do not achieve adequate lung volume reduction in the,presence of interlobar collateral ventilation(CV).l1 in addition,with the heterogeneity existing withinthe treatment lobe,complete lobar treatment from implants may result in excessive reduction of the less diseased segments.Thus,a more targeted approach of the most severe emphysematous parts of the lobe is warranted.展开更多
Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe...Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes.It is often characterized by ataxia,confusion,and altered mental status.Without appropriate treatment,HACE can rapidly progress to coma,but seizures are infrequent in occurrence.Case presentation Here,we report a severe HACE patient with coma and status epilepticus.The patient is a 23-year-old male who was visiting Lhasa for the first time.He initially experienced headaches and dizziness on the first day,and then he was found in coma with limb convulsions on the next day.Immediate medical attention was sought,and brain CT and MRI scans showed reversible white matter lesions,especially in the corpus callosum and subcortical white matter.Although the lesions disappeared on T1 and T2 sequences,microbleeds were observed on the SWI sequence.After treatment with tracheal intubation,glucocorticoids and hyperbaric oxygen,the cerebral edema has resolved and the clinical symptoms improved,the patient has no seizures anymore.Conclusions HACE typically follows AMS and poses a significant risk to life.Clinical manifestations mainly include ataxia,alterations of behavior,and impaired consciousness,with severe cases progressing to coma.Seizures,though rarely observed,may occur.Imaging shows reversible white matter lesions,with microbleeds being a significant and persistent imaging marker over time.Administration of glucocorticoids plays a crucial role in treatment.Despite experiencing seizures,this patient did not experienced any further episodes once his condition improved.展开更多
Background:Position intervention has been shown to improve oxygenation,but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed.The objective of this study was to investigate the e...Background:Position intervention has been shown to improve oxygenation,but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed.The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19.Methods:This was a single-center,prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020.Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included.Early position intervention(prone or lateral)was commenced for>4 hours daily for 10 days in these patients,while others received standard care.Results:The baseline parameters were comparable between the position intervention group(n=17)and the standard care group(n=35).Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO_(2)/FiO_(2)(409,95%CI 86 to 733)and ROX index(26,95%CI 9 to 43)with decreased Borg scale(−9,95%CI−15 to−3)during the first 7 days.It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2(≥7)on days 7 and 14,with a trend toward faster clinical improvement.Virus shedding and length of hospital stay were comparable between the two groups.Conclusions:This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19,and warrants further randomized trials.展开更多
基金funded by 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,Grant No.ZYJC18021Post-Doctoral Research Project,West China Hospital,Grant No.2021HXBH074+1 种基金the National Natural Science Foundation of China,Grant No.82100075Sichuan Science and Technology Program,Grant Nos.2020YFH0073,2021YFG0329。
文摘Runt-related transcription factor-1(RUNX1),also known as the core-binding factor alpha 2 subunit,is closely related to human leukemia.The functions of RUNX1 in modulating cell proliferation,differentiation,and survival in multiple systems have been gradually discovered with the emergence of transgenic mice.RUNX1 is a powerful transcription factor implicated in diverse signaling pathways and cellular mechanisms that participate in lung development and pulmonary diseases.RUNX1 has recently been identified as a target regulator of fibrotic remodeling diseases,particularly in the kidney.However,the role of RUNX1 in pulmonary fibrosis is unclear.Pulmonary fibrosis is characterized by obscure nosogenesis,limited therapy,and poor prognosis.Moreover,the population of patients with pulmonary fibrosis is gradually increasing.Thus,there is an unmet need for therapeutic targets.In this review,we retrospectively discuss the alteration in RUNX1 mRNA expression in the RNA sequencing data of human fibrotic lungs and the protein levels in mouse pulmonary fibrosis.Subsequently,we focused on the interaction between RUNX1 and several signaling pathways involved in pulmonary fibrosis.Finally,this review highlights the therapeutic potential of RUNX1 as a target for slowing the progression of fibrotic lung disease.
基金This research was supported by the National Key Research and Development Program of China(No.2021YFF0702000-F.L.)the National Natural Science Foundation of China(Nos.81770072-F.L.,32070764-F.L.,82170001-X.T.,and 81800087-X.T.)West China Hospital(No.ZYJC21023-H.W.).The authors gratefully acknowledge support from Jeffrey.A.Whitsett(Cincinnati Children’s Hospital)for reviewing the manuscript,and Yang He(West China Hospital)for providing a confocal microscope.
文摘Dear Editor,Acute lung injury(ALI)is a significant contributor to the development of acute respiratory distress syndrome(ARDS),which is a severe clinical condition associated with high morbidity and mortality.1 It is increasingly evident that preserving mitochondrial health in alveolar epithelial cells holds great therapeutic potential for ARDS.2 Mitophagy,a cellular process aimed at maintaining mitochondrial health,plays a critical role in this regard.3 Therefore,gaining a comprehensive understanding of the factors that regulate mitophagy in alveolar epithelial cells during ALI could greatly inform the development of future therapeutic approaches for ARDS.
基金National Natural Science Foundation of China(NSFC No.81770072)The"1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18021)Chengdu Science and Technology Bureau(No.2018-CY02-00064-GX)。
文摘Background:Nasal insertion is the preferred method for non-intubated patients in flexible bronchoscopy;however,the relatively narrow nasal cavity results in difficulties related to bronchoscope insertion.This study aimed to investigate whether pre-operative nasal probe tests could reduce the time to pass the glottis,improve the first-pass success rate and patients’tolerance,and reduce postoperative bleeding.Methods:This three-arm prospective randomized controlled trial was conducted in a tertiary hospital between May and October 2020.Three hundred patients requiring diagnosis and treatment using flexible bronchoscopy were randomly allocated to three groups:control group,simple cotton bud detection group(CD group),and adrenaline+lidocaine detection group(AD group).The primary outcome was the time to pass the glottis.Secondary outcomes included the first-pass success rate,the patients’tolerance scores,and post-operative bleeding.One-way analysis of variance,Kruskal-WallisH test,Chi-squared test,Fisher’s exact test,and Bonferroni’s multiple comparison tests were used in this study.Results:In total,189 men and 111 women were enrolled in this study,with a mean age of 55.72±12.86 years.The insertion time was significantly shorter in the AD group than in the control group(18.00 s[12.00–26.50 s]vs.24.00 s[14.50–45.50 s],P=0.005).Both the AD(99%vs.83%,χ2=15.62,P<0.001)and CD groups(94%vs.83%,χ2=5.94,P=0.015)had a significantly higher first-pass success rate than the control group.Compared with the control group,post-operative bleeding(1%vs.13%,χ2=11.06,P<0.001)was significantly lower in the AD group.However,no significant difference was found in the patients’tolerance scores.Conclusions:Pre-operative nasal cavity probe tests especially with adrenaline and lidocaine during flexible bronchoscopy can significantly reduce the time to pass the glottis,improve the first-pass success rate,and reduce post-operative nasal bleeding.Pre-operative nasal probe tests are recommended as a time-saving procedure for patients undergoing flexible bronchoscopy.Trial registration:Chinese Clinical Trial Registry(ChiCTR),ChiCTR2000032668;http://www.chictr.org.cn/showprojen.aspx?proj=53321.
基金This work was supported by grants from the National Natural Science Foundationof China(NSFC No.81770072)the“1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18021)”Chengdu Science and Technology Bureau(No.2018SZ0240).
文摘Chronic obstructive pulmonary disease(COPD)is characterized by emphysema and airflow limitation and is one of the leading causes of morbidityand mortalityworldwide.Endoscopic lung volumereduction(ELVR)is a minimally invasive technique for patients with severe hyperinflation and advanced emphysema.To date,the most investigated form of ELVR isvalve implantation,which is toplacevalves in all the segments of an emphysematous lobe.However,valve replacements do not achieve adequate lung volume reduction in the,presence of interlobar collateral ventilation(CV).l1 in addition,with the heterogeneity existing withinthe treatment lobe,complete lobar treatment from implants may result in excessive reduction of the less diseased segments.Thus,a more targeted approach of the most severe emphysematous parts of the lobe is warranted.
基金Tibet Science and Technology Program(No.XZ202201ZY0002G)Sichuan Science and Technology Program(No.2021YFQ0030).
文摘Background Acute high-altitude illness(AHAI)refers to a series of syndromes including acute mountain sickness(AMS),high-altitude pulmonary edema(HAPE)and high-altitude cerebral edema(HACE).Among these,HACE is a severe and potentially life-threatening condition that can occur when individuals ascend to high altitudes.It is often characterized by ataxia,confusion,and altered mental status.Without appropriate treatment,HACE can rapidly progress to coma,but seizures are infrequent in occurrence.Case presentation Here,we report a severe HACE patient with coma and status epilepticus.The patient is a 23-year-old male who was visiting Lhasa for the first time.He initially experienced headaches and dizziness on the first day,and then he was found in coma with limb convulsions on the next day.Immediate medical attention was sought,and brain CT and MRI scans showed reversible white matter lesions,especially in the corpus callosum and subcortical white matter.Although the lesions disappeared on T1 and T2 sequences,microbleeds were observed on the SWI sequence.After treatment with tracheal intubation,glucocorticoids and hyperbaric oxygen,the cerebral edema has resolved and the clinical symptoms improved,the patient has no seizures anymore.Conclusions HACE typically follows AMS and poses a significant risk to life.Clinical manifestations mainly include ataxia,alterations of behavior,and impaired consciousness,with severe cases progressing to coma.Seizures,though rarely observed,may occur.Imaging shows reversible white matter lesions,with microbleeds being a significant and persistent imaging marker over time.Administration of glucocorticoids plays a crucial role in treatment.Despite experiencing seizures,this patient did not experienced any further episodes once his condition improved.
基金This work was supported by the National Key Development Plan for Precision Medicine Research(Grant No.2017YFC0910004)Sichuan Science and Technology Project(Grants No.2020YFS0005 and 2020YFS0009)the 1.3.5 Project for Disciplines of Excellence–Clinical Research Incubation Project,West China Hospital,Sichuan University(Grant No.ZYJC18001).
文摘Background:Position intervention has been shown to improve oxygenation,but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed.The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19.Methods:This was a single-center,prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020.Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included.Early position intervention(prone or lateral)was commenced for>4 hours daily for 10 days in these patients,while others received standard care.Results:The baseline parameters were comparable between the position intervention group(n=17)and the standard care group(n=35).Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO_(2)/FiO_(2)(409,95%CI 86 to 733)and ROX index(26,95%CI 9 to 43)with decreased Borg scale(−9,95%CI−15 to−3)during the first 7 days.It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2(≥7)on days 7 and 14,with a trend toward faster clinical improvement.Virus shedding and length of hospital stay were comparable between the two groups.Conclusions:This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19,and warrants further randomized trials.
