Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with N...Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with NP caused by RMPP who were admitted to our hospital from January 2008 to December 2015, and the clinical manifestations, laboratory data, imaging performances, hospital courses and outcomes were analyzed. Results Twenty-five patients with NP caused by RMPP were collected, with a median age of 5.1 (4.0–7.9) years. The mean duration of fever and hospital stay was 21.0 ± 8.9 and 19.9 ± 9.9 days, respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein, interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the pleural fluid cell count, LDH and protein were also increased. 80.0% of the patients had pleural effusion;and a high incidence of lobar atelectasis and pulmonary consolidation was found the patients. The mean duration from the onset of symptoms to the discovery of necrotic lesions was 21.0 ± 6.9 days. 80.0% of the patients were administrated corticosteroids, and bronchoalveolar lavage was extracted separately from all patients. Of the 20 patients who presented with pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest drainage. All patients received prolonged courses of antibiotics (32.2 ± 8.7 days). All patients were dischaged home and recovered without surgical intervention;and chest lesions were resolved or only minimal residual fibrotic changes were residual within 3.0 (2.0–6.0) months. Conclusions Necrotizing pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good outcomes can be achieved with appropriate management.展开更多
Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute...Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These 展开更多
基金This work was partially supported by Grants from Zheji-ang Province Natural Science Foundation of China(LY17H100004,LY18H100002)Social Development Program of Science Technology Department of Zhejiang Province(2015C33127)the Key Projects of Zhejiang Medicine and Health Research Fund(no.2018268955).
文摘Background To investigate the clinical features of necrotizing pneumonia (NP) caused by refractoryMycoplasma pneumo-niae pneumonia (RMPP). Methods A retrospective observational study was carried out in patients with NP caused by RMPP who were admitted to our hospital from January 2008 to December 2015, and the clinical manifestations, laboratory data, imaging performances, hospital courses and outcomes were analyzed. Results Twenty-five patients with NP caused by RMPP were collected, with a median age of 5.1 (4.0–7.9) years. The mean duration of fever and hospital stay was 21.0 ± 8.9 and 19.9 ± 9.9 days, respectively. The levels of lactate dehydrogenase (LDH), C-reactive protein, interleukin (IL)-6, IL-10 and interferon-gamma were elevated. Meanwhile, the pleural fluid cell count, LDH and protein were also increased. 80.0% of the patients had pleural effusion;and a high incidence of lobar atelectasis and pulmonary consolidation was found the patients. The mean duration from the onset of symptoms to the discovery of necrotic lesions was 21.0 ± 6.9 days. 80.0% of the patients were administrated corticosteroids, and bronchoalveolar lavage was extracted separately from all patients. Of the 20 patients who presented with pleural effusion, 11 underwent thoracocentesis alone and 2 underwent chest drainage. All patients received prolonged courses of antibiotics (32.2 ± 8.7 days). All patients were dischaged home and recovered without surgical intervention;and chest lesions were resolved or only minimal residual fibrotic changes were residual within 3.0 (2.0–6.0) months. Conclusions Necrotizing pneumonia caused by RMPP is severe, however, self-limiting and reversible. Good outcomes can be achieved with appropriate management.
基金The author thanks the National Natural Science Foundation of China （No. 81470266）.
文摘Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These
