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*

Objective This study aims to explore the correlation between the grade of testicular tissue damage and clinical features which is used to evaluate the viability of testicular tissue after the orchidopexy for testicular torsion.Methods We conducted a retrospective,multicenter analysis of pathological specimens obtained from patients who under-went unilateral orchiectomy due to testicular torsion.Tissue viability was reassessed by the Mikuz grading scale.The corre-lations among tissue viability,duration of torsion symptoms,the angle of torsion,preoperative Doppler ultrasound image and intraoperative testicular resuscitation methods were analyzed.Results Eighty-five pathological specimens were en-rolled from 4 medical centers.The age range was 18 years(IQR 14-33),with a median torsion angle of 480°(IQR 180°-1080°).The interval from the torsion onset to surgical intervention was 18 hours(IQR 9-84).In the subgroup analysis of different torsion durations,the distribution of Grade I injuries was as follows.The subgroup within 12 hours ac-counted for 37.5％.The subgroup between 12 to 24 hours accounted for 14.28％.And the subgroup between 24 to 48 hours ac-counted for 6.45％.The subgroup exceeding 48 hours only accounted for 3.13％.Four patients received orchiectomy due to pre-operative ultrasound image indicating necrosis,correlating with Mikuz grade 3 tissue damage.The decision was made based on the failure of color recovery of affected testis in 57 cases,revealing 12.28％with grade 1 and 35.89％with grade Ⅱ damage.Twenty-four cases were identified as an Arda score of 3,with 4.16％showing grade 1 and 20.83％showing grade Ⅱ Mikuz damage.The method of Arda's grading could be used to determine the vitality of testicular tissue more accurately compared to the post-resusci-tation color observation method(P=0.032).Conclusion Pathological reassessment provides a precise determination of tis-sue viability in the affected testis.In some instances,the testicular tissue damage can be found potentially reversible.

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 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.

Objective This study aims to explore the correlation between the grade of testicular tissue damage and clinical features which is used to evaluate the viability of testicular tissue after the orchidopexy for testicular torsion.Methods We conducted a retrospective,multicenter analysis of pathological specimens obtained from patients who under-went unilateral orchiectomy due to testicular torsion.Tissue viability was reassessed by the Mikuz grading scale.The corre-lations among tissue viability,duration of torsion symptoms,the angle of torsion,preoperative Doppler ultrasound image and intraoperative testicular resuscitation methods were analyzed.Results Eighty-five pathological specimens were en-rolled from 4 medical centers.The age range was 18 years(IQR 14-33),with a median torsion angle of 480°(IQR 180°-1080°).The interval from the torsion onset to surgical intervention was 18 hours(IQR 9-84).In the subgroup analysis of different torsion durations,the distribution of Grade I injuries was as follows.The subgroup within 12 hours ac-counted for 37.5％.The subgroup between 12 to 24 hours accounted for 14.28％.And the subgroup between 24 to 48 hours ac-counted for 6.45％.The subgroup exceeding 48 hours only accounted for 3.13％.Four patients received orchiectomy due to pre-operative ultrasound image indicating necrosis,correlating with Mikuz grade 3 tissue damage.The decision was made based on the failure of color recovery of affected testis in 57 cases,revealing 12.28％with grade 1 and 35.89％with grade Ⅱ damage.Twenty-four cases were identified as an Arda score of 3,with 4.16％showing grade 1 and 20.83％showing grade Ⅱ Mikuz damage.The method of Arda's grading could be used to determine the vitality of testicular tissue more accurately compared to the post-resusci-tation color observation method(P=0.032).Conclusion Pathological reassessment provides a precise determination of tis-sue viability in the affected testis.In some instances,the testicular tissue damage can be found potentially reversible.

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.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg^-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4⁺， CD8⁺， and CD4⁺/CD8⁺） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV_0.3）， FEV_0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4⁺ level （P<0.01） and CD4⁺/CD8⁺ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg^-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.