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*

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.

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.

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.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most intractable malignancy, with an only 6% 5-year relative survival rate. The dismal therapeutic effect is attributed to the chemotherapy resistance and unique pathophysiology with abundant inflammatory cytokines and abnormal hyperplasia of extracellular matrix (ECM). Based on the theory that bone marrow mesenchymal stem cells (BM-MSCs) can influence the tumorous microenvironment and malignant growth of PDAC, we employed exosomes (Exos) derived from BM-MSCs as PDAC-homing vehicles to surpass the restrictions of pathological ECM and increase the accumulation of therapeutics in tumor site. To overcome chemoresistance of PDAC, paclitaxel (PTX) and gemcitabine monophosphate (GEMP)-an intermediate product of gemcitabine metabolism-were loaded in/on the purified Exos. In this work, the Exo delivery platform showed superiorities in homing and penetrating abilities, which were performed on tumor spheroids and PDAC orthotopic models. Meanwhile, the favorable anti-tumor efficacy and , plus relatively mild systemic toxicity, was found. Loading GEMP and PTX, benefitting from the naturally PDAC selectivity, the Exo platform we constructed performs combined functions on excellent penetrating, anti-matrix and overcoming chemoresistance (Scheme 1). Worth expectantly, the Exo platform may provide a prospective approach for targeted therapies of PDAC.

Objective To observe the clinical effect of traditional Chinese medicine (TCM) characteristic lung rehabilitation in treatment of patients with chronic obstructive pulmonary disease (COPD) and TCM syndrome of lung and kidney qi deficiency at stable period. Methods Sixty patients with stable COPD and lung and kidney qi deficiency syndrome admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from June to August 2017 were enrolled, and they were divided into routine treatment group and lung rehabilitation treatment group according to the random number table method, each group 30 cases. The routine treatment group was given Seretide (serevent/futicasone) dry powderi nhalation therapy; on the basis of therapy in the routine treatment group, the lung rehabilitation treatment group was treated with TCM characteristic lung rehabilitation technology (acupoint application + Chinese medicine ionic induction + oral administration of Chinese medicine Liuweibuqi granules, delivery at appropriate intervals); both groups were treated for 2 months. The changes of TCM syndrome score, western medicine symptom score, the times of acute exacerbation of COPD, COPD assessment test (CAT) score, lung function indexes: forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) were observed before and after treatment in two groups. Results After treatment, TCM syndrome score, western medicine symptom score, CAT score, and after treatment the times of acute exacerbation of COPD in both groups were significantly lower than those before treatment, and the above indexes in the lung rehabilitation treatment group were markedly lower than those in routine treatment group [TCM syndrome score:11.93±1.80 vs. 14.27±2.88, western medicine symptom score: 14.20±2.75 vs. 11.93±4.23, CAT score: 14.87±2.60 vs. 16.23±4.39, the times of acute exacerbation of COPD (times): 0.63±0.49 vs. 0.95±0.83, all P < 0.05]. The improvement of FEV1 in the two groups was not significant; but FEV1/FVC in lung rehabilitation treatment group was obviously higher than that before treatment, FEV1/FVC in lung rehabilitation treatment group was significantly higher than that in the routine treatment group [(57.93±7.27)% vs. (52.49±6.61)%, P < 0.05]. Conclusion The application of TCM characteristic lung rehabilitation in the treatment of COPD patients with stable lung and kidney qi deficiency syndrome based on bronchodilators and glucocorticoids can reduce the number of acute exacerbation, improve the patients' clinical symptoms and living quality, but the improvement of lung function is not significant.

Oncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certain concentration to function, it is intensely difficult to build an effective delivery system for them. The purpose of this work is to construct a self-assembled glutathione (GSH)-responsive system with tumor accumulation capacity for effective anti-miR21 delivery and cancer therapy. A novel drug delivery nanosphere carrying millions of anti-miR21 sequences was developed through the rolling circle transcription (RCT) method. GSH-responsive cationic polymer polyethyleneimine (pOEI) was synthesized to protect the nanosphere from degradation by Dicer or other RNase in normal cells and optimize the pompon-like nanoparticle to suitable size. Dehydroascorbic acid (DHA), a targeting molecule, which is a substrate of glucose transporter 1 (GLUT 1) and highly expressed on malignant tumor cells, was connected to pOEI through PEG, and then the polymer was used for contracting a RNA nanospheres into nanopompons. The anti-miR21 nanopompons showed its potential for effective cancer therapy.

The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

Objective To summarize the anesthesia management and surgical characteristic of modified extended Morrow procedure in treating hypertrophic obstructive cardiomyopathy (HOCM). Methods This retrospective study was conducted in 139 patients (male 83 and female 56)aged from 1 1 to 66 years.They underwent general anesthesia by high dose intravenous fentanyl or sufentanyl combined with propofol infusion and low concentration sevoflurane inhalation.The surgeons chose ap-propriate surgical procedures,including modified extended Morrow procedure,or combined with mi-tral valve repair (replacement)and coronary artery bypass grafting,etc.All patients received intraop-erative transesophageal echocardiography (TEE ) or epicardial echocardiography monitoring. Results There was no death case in hospital.All patients were hemodynamically stable and there were no malignant adverse events such as ventricular fibrillation during perioperative period.70 (50.4%)of patients automatically recovered to cardiac rhythm after aortic unclamping,and 1 1 (7.9%)of patients needed temporary pacemaker due to atrioventricular block.Cardiopulmonary by-pass (CPB)were weaned off successfully without positive inotropic drugs in 103(74.1%)of patients, while others 36(25.9%)needed low dose dopamine,epinephrine or norepinephrine to maintain hemo-dynamics stable.The CPB time was (142 ± 5 1 )min and the time of aortic clamping was (96 ± 37 ) min.Blood protection was used in all patients and 129 (92.8%)of the patients didn’t receive any blood product.Conclusion Modified extended Morrow procedure was a safe and effective surgical pro-cedure for treatment of HOCM.Experienced teamwork was essential to achieve satisfactory clinical results.The key points of anesthesia management were administration of appropriate preoperative drugs,maintaining adequate anesthesia depth,appropriate preload and afterload,heart rate and rhythm.Intraoperative TEE monitoring was the golden standard for guiding and evaluating the effec-tiveness of the surgical procedures.Meanwhile protection of myocardium,lung,brain and blood can help to obtain satisfactory clinical outcomes.