Ferroptosis is a key driver of the onset and progression of chronic obstructive pulmonary disease （COPD）. By exploring the role of ferroptosis in COPD from the perspective of "qi deficiency with retention and stagnation"， it is considered that mitochondrial dysfunction and imbalanced antioxidant defenses are the microscopic manifestations of "qi deficiency"， whereas iron accumulation and lipid peroxide deposition constitute the pathological basis of "retention and stagnation". In traditional Chinese medicine （TCM）， the treatment principle is tonifying deficiency and benefiting qi， scattering retention and unblocking stagnation. Its mechanism involves improving the antioxidant system and mitochondrial function to enhance cellular resistance to ferroptosis， as well as relieving pulmonary iron overload， excessive lipid peroxidation， and inflammatory factor release to reduce the accumulation of pathological products， thereby exerting therapeutic effects on COPD.

Objective:To determine the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition). Methods:A preliminary list of clinical issues for the guidelines was developed through literature review, clinical surveys, and expert interviews. This was followed by two rounds of Delphi questionnaire surveys, with quality control and statistical analysis conducted using expert positive coefficient, mean item scores, full score ratio, coefficient of variation, Cronbach′s α coefficient, and expert authority level to finalize the list of clinical issues.Results:The experts participating in the Delphi questionnaire surveys had multidisciplinary collaborative backgrounds and regional representativeness, with a high level of authority. The overall positive coefficient of expert participation in the surveys was 78.9%. Through two rounds of the Delphi method and based on the screening criteria of a mean score ≥3.5, coefficient of variation ≤30%, and full score ratio ≥30%, 17 clinical issues were ultimately included following an expert consensus meeting.Conclusions:Through the Delphi method and rigorous quality control, the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition) are determined, laying a foundation for the subsequent development of the guidelines.

N6-methyladenosine(m6A)is the most common mRNA modification in eukaryotes,and fat mass and obesity-related protein(FTO),are its demethylases,which efficiently remove the modification of m6A mRNA,and is strongly associated with obesity.Atherosclerosis is a chronic inflammatory lesion of the blood vessel wall driven by lipids.It was found that FTO-mediated m6A may influence the process of atherosclerosis through lipid metabolism,oxidative stress,mitochondrial dysfunction,and macrophage foaminess.

Objective To explore the mechanism of Pingchuanning Formula(PCN)for inhibiting airway inflammation in rats with asthmatic cold syndrome.Methods A total of 105 SD rats were randomized equally into 7 groups,including a control group,an asthmatic cold syndrome model group,3 PCN treatment groups at high,medium and low doses,a Guilong Kechuanning(GLCKN)treatment group,and a dexamethasone(DEX)treatment group.In all but the control rats,asthma cold syndrome models were established and daily gavage of saline,PCN,GLCKN or DEX was administered 29 days after the start of modeling.The changes in general condition,lung function and lung histopathology of the rats were observed,and inflammatory factors in the alveolar lavage fluid(BALF),oxidative stress,lung tissue ultrastructure,cytokine levels,and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed.Results The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass,food intake,and water intake,reduced FEV0.3,FVC,and FEV0.3/FVC,obvious inflammatory cell infiltration in the lung tissue,and increased alveolar inflammation score and counts of neutrophils,eosinophils,lymphocytes,macrophages,and leukocytes in the BALF.The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues,where the expressions of HMGB1,Beclin-1,ATG5,TNF-α,IL-6,IL-1β,and IL-13 and the LC3II/I ratio were increased,while the levels of Bcl-2 and IFN-γ were decreased.PCN treatment significantly improved these pathological changes in the rat models,and its therapeutic effect was better than that of GLKCN and similar to that of DEX.Conclusion PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy,thereby attenuating airway inflammatory damages.

Objective To explore the mechanism of Shenqi Buzhong(SQBZ)Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease(COPD)in light of the AMPK/SIRT1/PGC-1α pathway.Methods Fifty male SD rat models of COPD,established by intratracheal lipopolysaccharide(LPS)instillation,exposure to cigarette smoke,and gavage of Senna leaf infusion,were randomized into 5 groups(n=10)for treatment with saline(model group),SQBZ Formula at low,moderate and high doses(3.08,6.16 and 12.32 g/kg,respectively),or aminophylline(0.024 g/kg)by gavage for 4 weeks,with another 10 untreated rats as the control group.Pulmonary function of the rats were tested,and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy.The levels of SOD,ATP,MDA,and mitochondrial membrane potential in the lungs were detected using WST-1,colorimetric assay,TBA,and JC-1 methods.Flow cytometry was used to analyze ROS level in the lung tissues,and the protein expression levels of P-AMPKα,AMPKα,SIRTI,and PGC-1α were detected using Western blotting.Results The rat models of COPD showed significantly decreased lung function,severe histopathological injuries of the lungs,decreased pulmonary levels of SOD activity,ATP and mitochondrial membrane potential,increased levels of MDA and ROS,and decreased pulmonary expressions of P-AMPKα,SIRTI,and PGC-1α proteins.All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline,and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group.Conclusion SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.

Objective To investigate the therapeutic mechanism of Sangma Zhike Formula(SMZKF)for relieving cough sensitivity and airway inflammation in rats with postinfectious cough(PIC).Methods Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation.From day 19 following the start of PIC modeling,the rats received daily treatment with saline(model group),low-,medium-,and high-dose SMZKF,and compound methoxyphenamine(ASM)via gavage for 10 consecutive days(n=8).The assessments included behavioral changes,cough sensitivity(latency and frequency),lung histopathology,inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid(BALF),oxidative stress markers in the lung tissue,and expressions of proteins related with cough hypersensitivity and pyroptosis.Results The rat models of PIC exhibited reduced mental alertness,accelerated respiration,and pronounced symptoms such as coughing,sneezing,and facial scratching with significantly shortened cough latency and increased 5-min cough frequency.Histopathological analysis revealed collapsed alveolar structures,thickened alveolar septa,and extensive inflammatory cell infiltration in the bronchi and peribronchial regions,accompanied by elevated bronchial and alveolar inflammation scores of the rat models.In the BALF,inflammatory cell counts and the levels of IL-1β,TNF-α,IL-6,COX-2,PGE-2,and TXA-2 were all markedly elevated,and the pulmonary oxidative stress markers(ROS and MDA)and myeloperoxidase(MPO)activity were also significantly increased.The pulmonary expressions of cough hypersensitivity-related proteins(TRPV1,SP,CGRP,and NK1R)and pyroptosis-associated markers(P-NF-κB,NLRP3,ACS,cleaved caspase-1,cleaved IL-1β,and GSDMD-N)were significantly upregulated in the model group.SMZKF interventions significantly ameliorated these pathological changes in the rat models,and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM.Conclusion SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

OBJECTIVES: To explore the mechanism of Pingchuanning Formula (PCN) for inhibiting airway inflammation in rats with asthmatic cold syndrome. METHODS: A total of 105 SD rats were randomized equally into 7 groups, including a control group, an asthmatic cold syndrome model group, 3 PCN treatment groups at high, medium and low doses, a Guilong Kechuanning (GLCKN) treatment group, and a dexamethasone (DEX) treatment group. In all but the control rats, asthma cold syndrome models were established and daily gavage of saline, PCN, GLCKN or DEX was administered 29 days after the start of modeling. The changes in general condition, lung function and lung histopathology of the rats were observed, and inflammatory factors in the alveolar lavage fluid (BALF), oxidative stress, lung tissue ultrastructure, cytokine levels, and expressions of the genes related to the HMGB1/Beclin-1 axis and autophagy were analyzed. RESULTS: The rat models had obvious manifestations of asthmatic cold syndrome with significantly decreased body mass, food intake, and water intake, reduced FEV_0.3, FVC, and FEV_0.3/FVC, obvious inflammatory cell infiltration in the lung tissue, and increased alveolar inflammation score and counts of neutrophils, eosinophils, lymphocytes, macrophages, and leukocytes in the BALF. The rat models also had significantly increased MDA level and decreased SOD level and exhibited obvious ultrastructural changes in the lung tissues, where the expressions of HMGB1, Beclin-1, ATG5, TNF-α, IL-6,IL-1β, and IL-13 and the LC3II/I ratio were increased, while the levels of Bcl-2 and IFN-γ were decreased. PCN treatment significantly improved these pathological changes in the rat models, and its therapeutic effect was better than that of GLKCN and similar to that of DEX. CONCLUSIONS PCN can effectively alleviate airway inflammation in rat models of asthmatic cold syndrome possibly by modulating the HMGB1/Beclin-1 signaling axis to suppress cell autophagy, thereby attenuating airway inflammatory damages.
Animals ; Rats ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Asthma/pathology* ; Beclin-1 ; HMGB1 Protein/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Male ; Lung/pathology* ; Inflammation

OBJECTIVES: To investigate the therapeutic mechanism of Sangma Zhike Formula (SMZKF) for relieving cough sensitivity and airway inflammation in rats with postinfectious cough (PIC). METHODS: Male SD rat models were established by cigarette smoke exposure with intranasal LPS instillation and capsaicin aerosol inhalation. From day 19 following the start of PIC modeling, the rats received daily treatment with saline (model group), low-, medium-, and high-dose SMZKF, and compound methoxyphenamine (ASM) via gavage for 10 consecutive days (n=8). The assessments included behavioral changes, cough sensitivity (latency and frequency), lung histopathology, inflammatory cell counts and cytokine/mediator levels in the bronchoalveolar lavage fluid (BALF), oxidative stress markers in the lung tissue, and expressions of proteins related with cough hypersensitivity and pyroptosis. RESULTS: The rat models of PIC exhibited reduced mental alertness, accelerated respiration, and pronounced symptoms such as coughing, sneezing, and facial scratching with significantly shortened cough latency and increased 5-min cough frequency. Histopathological analysis revealed collapsed alveolar structures, thickened alveolar septa, and extensive inflammatory cell infiltration in the bronchi and peribronchial regions, accompanied by elevated bronchial and alveolar inflammation scores of the rat models. In the BALF, inflammatory cell counts and the levels of IL-1β, TNF-α, IL-6, COX-2, PGE-2, and TXA-2 were all markedly elevated, and the pulmonary oxidative stress markers (ROS and MDA) and myeloperoxidase (MPO) activity were also significantly increased. The pulmonary expressions of cough hypersensitivity-related proteins (TRPV1, SP, CGRP, and NK1R) and pyroptosis-associated markers (P-NF-κB, NLRP3, ACS, cleaved caspase-1, cleaved IL-1β, and GSDMD-N) were significantly upregulated in the model group. SMZKF interventions significantly ameliorated these pathological changes in the rat models, and high-dose SMZKF produced a similar therapeutic efficacy to that of ASM. CONCLUSIONS SMZKF alleviates cough sensitivity and airway inflammation in PIC rats possibly by inhibiting TRPV1-mediated SP/NK1R signaling and the NLRP3/caspase-1/GSDMD pyroptosis pathway.
Animals ; Cough/metabolism* ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Male ; TRPV Cation Channels/metabolism* ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Inflammation ; Signal Transduction

Objective:To determine the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition). Methods:A preliminary list of clinical issues for the guidelines was developed through literature review, clinical surveys, and expert interviews. This was followed by two rounds of Delphi questionnaire surveys, with quality control and statistical analysis conducted using expert positive coefficient, mean item scores, full score ratio, coefficient of variation, Cronbach′s α coefficient, and expert authority level to finalize the list of clinical issues.Results:The experts participating in the Delphi questionnaire surveys had multidisciplinary collaborative backgrounds and regional representativeness, with a high level of authority. The overall positive coefficient of expert participation in the surveys was 78.9%. Through two rounds of the Delphi method and based on the screening criteria of a mean score ≥3.5, coefficient of variation ≤30%, and full score ratio ≥30%, 17 clinical issues were ultimately included following an expert consensus meeting.Conclusions:Through the Delphi method and rigorous quality control, the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition) are determined, laying a foundation for the subsequent development of the guidelines.