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: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 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.

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 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.

In order to standardize the postoperative pain management in adults in China, the Chinese Society of Anesthesiology formulated the "Clinical practice guidelines for postoperative pain management in adults (2024 edition)" according to the methods and steps of the "Principles for Formulation/Revision of Clinical Diagnosis and Treatment Guidelines in China (2022 Edition)". This protocol mainly introduced the purpose of guideline formulation, the formation and responsibilities of the working group, the collection and selection of clinical questions, the evaluation and synthesis of evidence, the formation of recommendations and other processes.

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.

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.