ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription （SQWF） on chronic obstructive pulmonary disease （COPD）. MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide （LPS） combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose SQWF groups （2.835， 5.67， 11.34 g·kg^-1）， and a Yupingfeng group （1.35 g·kg^-1）. Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed， and the lung function in each group was assessed. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid （BALF） was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. The release level of lactate dehydrogenase （LDH） in BALF was detected by a microplate assay. Reactive oxygen species （ROS） levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde （MDA）， total superoxide dismutase （SOD）， and reduced glutathione （GSH） in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein （TXNIP） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， Caspase-1 p20， gasdermin D （GSDMD）， GSDMD N-terminal active fragment （GSDMD-N）， interleukin-1β （IL-1β）， and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group， the model group showed lassitude， fatigue， tachypnea， and audible phlegm sounds， and lung function significantly declined （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly （P0.05）. The number of TUNEL-positive cells increased （P0.01）. Levels of LDH， ROS， and MDA in BALF increased significantly （P0.01）， while GSH and SOD activities decreased significantly （P0.01）. Lung tissue cells showed irregular morphology， swollen mitochondria， disrupted cell membranes， and abundant vesicles， i.e.， pyroptotic bodies. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue were significantly elevated （P0.01）， and serum IL-1β and IL-18 levels also increased significantly （P0.01）. Compared with the model group， each medication group showed alleviation of qi deficiency symptoms and improved lung function （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased （P0.05）. The number of TUNEL-positive cells decreased significantly （P0.01）. Levels of LDH， ROS， and MDA decreased significantly （P0.05）， while GSH and SOD activities significantly increased （P0.01）. Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue significantly decreased （P0.01）， and serum IL-1β and IL-18 levels also decreased significantly （P0.05）. ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.

ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription （SQWF） on chronic obstructive pulmonary disease （COPD）. MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide （LPS） combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose SQWF groups （2.835， 5.67， 11.34 g·kg^-1）， and a Yupingfeng group （1.35 g·kg^-1）. Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed， and the lung function in each group was assessed. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid （BALF） was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. The release level of lactate dehydrogenase （LDH） in BALF was detected by a microplate assay. Reactive oxygen species （ROS） levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde （MDA）， total superoxide dismutase （SOD）， and reduced glutathione （GSH） in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein （TXNIP） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， Caspase-1 p20， gasdermin D （GSDMD）， GSDMD N-terminal active fragment （GSDMD-N）， interleukin-1β （IL-1β）， and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group， the model group showed lassitude， fatigue， tachypnea， and audible phlegm sounds， and lung function significantly declined （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly （P0.05）. The number of TUNEL-positive cells increased （P0.01）. Levels of LDH， ROS， and MDA in BALF increased significantly （P0.01）， while GSH and SOD activities decreased significantly （P0.01）. Lung tissue cells showed irregular morphology， swollen mitochondria， disrupted cell membranes， and abundant vesicles， i.e.， pyroptotic bodies. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue were significantly elevated （P0.01）， and serum IL-1β and IL-18 levels also increased significantly （P0.01）. Compared with the model group， each medication group showed alleviation of qi deficiency symptoms and improved lung function （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased （P0.05）. The number of TUNEL-positive cells decreased significantly （P0.01）. Levels of LDH， ROS， and MDA decreased significantly （P0.05）， while GSH and SOD activities significantly increased （P0.01）. Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue significantly decreased （P0.01）， and serum IL-1β and IL-18 levels also decreased significantly （P0.05）. ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.

This paper summarizes Professor HAN Mingxiang's clinical experience in the use of Zeqi （Euphorbia HelioscopiaL.）. It is believed that Zeqi （Euphorbia HelioscopiaL.） has the effects of promoting qi， relieving water retention and swelling， resolving phlegm， stopping cough， dissipating masses， activating blood， removing stasis， and detoxifying. In clinical practice， Zeqi （Euphorbia HelioscopiaL.） is flexibly applied in the treatment of skin diseases， respiratory diseases， tumors， etc. For instance， in treating psoriasis with the pathogenesis of damp-heat toxin， a compound prescription of Zeqi Decoction （泽漆汤） is formulated. For bronchial asthma with kidney deficiency and water retention， Zeqi Decoction is commonly combined with Wuling Powder （五苓散） in adjusted doses. For lung nodules with a combination of deficiency， phlegm， stasis， and toxin， a Lung Nodule Prescription is proposed. For advanced lung cancer with both qi and yin deficiency and toxin accumulation， Qiyu Sanlong Decoction （芪玉三龙汤） is suggested， and for cancer-related ascites with qi deficiency and water retention， Wuling Powder combined with Zeqi （Euphorbia HelioscopiaL.）is chosen.

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

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Objective:To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model.Methods:In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn.Results:A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR=1.37, 95% CI: 1.16-1.62; OR=2.85, 95% CI: 1.56-5.20; OR=1.50, 95% CI: 1.18-1.91; OR=1.18, 95% CI: 1.02-1.37; OR=1.34, 95% CI: 1.04-1.72; OR=1.62, 95% CI: 1.21-2.17; OR=1.48, 95% CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR=0.56, 95% CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI: 0.70-0.75, P<0.001) . Conclusion:The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43 126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14 642 patients,with a higher proportion of female patients(57.32％).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.

Objective To investigate the effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease(MAFLD)based on the KLF16/PPAR-α signaling pathway.Methods C57 BL/6 mice were randomly divided into normal group,model group and Shenling Baizhu San low-,medium-and high-dose groups(2.685,5.369,10.738 g·kg-1·d-1),with seven mice in each group.Except for the normal group,the mice in the other groups were given high-fat diet for 12 weeks to replicate the MAFLD model.After the modeling,intragastric administration was started once a day for five weeks.The body mass and liver coefficient of mice were measured.HE and oil red O staining were used to observe the pathological changes of liver tissue in mice.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were detected.The mRNA expression levels of PPAR-α,KLF16,FAS and SREBP-1c in liver tissue were detected by RT-qPCR.Results Compared with the normal group,the body mass,liver mass and liver coefficient of mice in the model group were significantly increased(P＜0.05,P＜0.01).The levels of serum TG,TC,ALT and AST were significantly increased(P＜0.001).There were a large number of vacuoles in the cytoplasm of the liver tissue,and a large number of red-stained lipid droplets appeared in the cytoplasm.The NAS pathological score and oil red O staining IOD value were significantly increased(P＜0.05,P＜0.001).The mRNA expressions of PPAR-α and KLF16 in liver tissue were significantly down-regulated(P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c was significantly up-regulated(P＜0.05,P＜0.001).Compared with the model group,the body mass,liver mass and liver coefficient of mice in the high-dose group of Shenling Baizhu San were significantly decreased(P＜0.05).The levels of serum TG,TC and ALT in the low-,medium-and high-dose groups of Shenling Baizhu San were significantly decreased(P＜0.05,P＜0.01,P＜0.001).The serum AST level of mice in the medium-and high-dose groups of Shenling Baizhu San was significantly decreased(P＜0.01,P＜0.001).The pathological changes of liver tissue in each administration group were significantly improved,and the orange-red lipid droplets in the cytoplasm of hepatocytes were significantly reduced.The NAS pathological score and oil red O staining IOD value of the high-dose group of Shenling Baizhu San were significantly reduced(P＜0.05,P＜0.01);the mRNA expressions of PPAR-α and KLF16 in liver tissue of mice in Shenling Baizhu San low-,medium-and high-dose groups were significantly up-regulated(P＜0.05,P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c were significantly down-regulated(P＜0.05,P＜0.01,P＜0.001).Conclusion Shenling Baizhu San can significantly improve hepatic lipid metabolism in MAFLD mice,and its mechanism may be related to transcriptional regulation of nuclear receptor KLF16/PPAR-α signaling pathway.