Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

OBJECTIVES: To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress. METHODS: Twenty male SD rats were randomized equally into control group and heat stress group. After exposure to 32 ℃ for 2 weeks in the latter group, the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry. In the cell experiments, cultured rat thoracic aortic endothelial cells (RTAECs) were incubated at 40 ℃ for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA (si-Bmal1) or a negative sequence. In both rat thoracic aorta and RTAECs, the expressions of Bmal1, the cell cycle proteins CDK1, CDK4, CDK6, and cyclin B1, and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting. TUNEL staining was used to detect cell apoptosis in rat thoracic aorta, and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry. RESULTS: Compared with the control rats, the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1, cyclin B1 and CDK1 in the thoracic aorta (P<0.05). In cultured RTAECs, heat stress caused significant increase of Bmal1, cyclin B1 and CDK1 protein expression levels, which were obviously lowered in cells with prior si-Bmal1 transfection. Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2. CONCLUSIONS Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells, which can be partly alleviated by suppressing Bmal1 expression.
Animals ; ARNTL Transcription Factors/genetics* ; Male ; Aorta, Thoracic/metabolism* ; Rats ; Rats, Sprague-Dawley ; Endothelial Cells/metabolism* ; Apoptosis ; Cells, Cultured ; Heat-Shock Response ; Cyclin B1/metabolism* ; CDC2 Protein Kinase/metabolism* ; Cyclins/metabolism* ; RNA, Small Interfering ; bcl-2-Associated X Protein/metabolism*

From a resource efficiency perspective,it aims to guide hospitals achieve strategic development goal in prioritizing public welfare.Through accurately assessing the operational status of various departments,the robust decision-making support for hospital management is provided.Focusing on resource efficiency across departments,it uses a case study hospital to construct a multi-dimensional evaluation framework from the dimensions of revenue,operational efficiency,and resource utilization.In addition,the total resource allocation mode of various departments is deeply explored.According to the research results,for clinical departments,operational efficiency metrics exert the most significant influence on overall efficiency,followed by revenue and resource efficiency indicators.In contrast,for medical technology departments,revenue and operational efficiency are the primary determinants of the overall score.Based on the founding,the suggestion is proposed to enhance economic operational efficiency serves as the central focus for transitioning hospital operational models.Strategic reallocation of internal resources is identified as a critical breakthrough for optimizing resource utilization and driving sustainable transformation.

Objective:To investigate the association between hearing loss and the type of indoor fuel applications in Chinese middle-aged and elderly people through longitudinal cohort study.Methods:Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), including adults aged 45 years and older enrolled in 2011, with follow-up for cooking and heating analyses extending to 2018 and 2015, respectively. The study calculated the incidence of hearing loss based on an indoor cooking or heating fuel type and expressed in terms of per 100 person-years. The Cox proportional hazard model was used to assess the association between solid fuel use and hearing loss, and covariates such as gender, education, and economy were controlled. We also analyzed the impact of indoor fuel type and its switching on hearing loss.Results:A total of 6, 772 participants using household fuels for cooking (2011-2018) and 4, 618 for heating (2011-2015) were included. Those using solid fuels for cooking [(58.0±8.2) years] and heating [(58.1±8.5) years] were generally slightly older than that of those who used clean fuels. In the cooking analysis, the overall incidence of hearing loss was higher among solid fuel users compared to clean fuel users (Clean fuel: 2.6 cases per 100 person-years; solid fuel: 3.6 cases per 100 person-years; the difference between the two was statistically significant, P<0.05). However, no significant difference was observed in the heating analysis ( P>0.05). Further classification of fuel-type use revealed that the incidence of hearing loss was the highest among people who had been using solid fuels consistently. Compared to the clean fuel group, the fully adjusted hazard ratio (HR) was 1.5 (95% CI: 1.3-1.7) in the cooking analysis and 1.5 (95% CI: 1.1-2.0) in the heating analysis. Compared with using clean fuels, switching from clean fuels to solid fuels increased the risk of hearing loss both during cooking and heating processes. Conclusion:In the CHARLS database, individuals who use solid fuels for indoor cooking and heating are older than those who use clean fuels. Compared with clean fuel use, the use of solid fuels increases the risk of hearing loss in middle-aged and elderly people. Reducing the use of solid fuels, choosing clean fuels as substitutes for solid fuels, and avoiding the switch from clean fuels to solid fuels will help protect the hearing health of middle-aged and elderly individuals.

Objective:To evaluatethe therapeutic efficacy and underlying mechanism of sodium houttuyfonate in treating airway inflammation in allergic asthma induced by co-exposure to the environmental pollutant benzo[a] pyrene (BaP) and ovalbumin (OVA).Methods:Thirty BALB/c mice were randomly divided into five groups with six mice in each group using a block randomization method: control, BaP, asthma model (OVA), BaP-exacerbated asthma (BaP+ OVA), and sodium houttuyfonate-treated BaP-exacerbated asthma (BaP+ OVA+ SH) groups. A mouse model of exacerbated asthma induced by co-exposure to BaP and OVA was established. Airway hyperresponsiveness, leukocyte distribution in bronchoalveolar lavage fluid (BALF), expression of cytokines such as IL-4, IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and IFN-γ, serum OVA-specific antibodies (IgE, IgG2a and IgG1), levels of malondialdehyde and superoxide dismutase (SOD) in lung tissues, and histopathological changes in lung tissues were evaluated. Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of suppression of tumorigenicity 2 (ST2), extracellular regulated protein kinases (ERK), and phosphorylated ERK (p-ERK). Statistical analysis was conducted using analysis of variance and other statistical methods.Results:Compared with the BaP+ OVA group, the mice in the BaP+ OVA+ SH group showed significantly reduced airway hyperresponsiveness ( P<0.01), decreased numbers of total leukocytes ( P<0.01), neutrophils ( P<0.05), and lymphocytes ( P<0.01) in BALF, significantly downregulated secretion of IL-4, IL-13, IL-25, IL-33 and TSLP ( P<0.01), and inhibited production of IgE ( P<0.01) and IgG1 ( P<0.05). Additionally, sodium houttuyfonate treatment significantly decreased the malondialdehyde levels in lung tissues of mice with BaP-exacerbated asthma ( P<0.05) and reduced airway inflammatory cell infiltration, mucus secretion, and collagen fiber proliferation. Sodium houttuyfonate could supress the expression of ST2 and ERK ( P<0.05), inhibit ERK phosphorylation ( P<0.01), alleviate oxidative stress injury, and reduce collagen fiber proliferation in mouse lung tissues, thereby blocking the progression of BaP-exacerbated asthmatic inflammation. Conclusions:BaP exacerbates OVA-sensitized asthmatic airway inflammation in mice by inducing airway remodeling through the IL-33-ST2/ERK pathway. Sodium houttuyfonate inhibits this pathway, thereby preventing the progression of BaP-exacerbated asthma inflammation. This study provides new insights into the prevention and treatment of different phenotypes of asthma.

AIM:To establish a physiologically-based pharmacokinetic(PBPK)model for vitamin D in adults,aiming to provide guidance for the ratio-nal clinical use of vitamin D in individuals with vita-min D deficiency.METHODS:Relevant literature and databases were reviewed to obtain the physi-cochemical properties and pharmacokinetic param-eters of vitamin D3.The PBPK model for adult whole-body vitamin D was constructed,optimized,and predicted using PK-Sim? software.The model's predictive performance was evaluated using confi-dence intervals,goodness of fit,and fold error(FE).The effectiveness of commonly used clinical dosing regimens was assessed based on the final opti-mized model,and personalized dosing recommen-dations were provided.RESULTS:The established adult whole-body PBPK model for vitamin D had a goodness of fit R2 of 0.961,approaching 1,and the FE values for AUC0-∞ and Cmax were both within the range of 0.5 and 2,indicating that the constructed PBPK model possesses good data predictive capa-bility.CONCLUSION:A successful PBPK model for oral vitamin D3 in adults has been established,showing good predictive performance for single oral doses of vitamin D3.Single oral doses of vita-min D3(7 500 μg and 15 000 μg)are safe and effec-tive dosing regimens for improving vitamin D insuf-ficiency or deficiency in Asian adults.Regular moni-toring of vitamin D levels before and during treat-ment is recommended to achieve the optimal out-comes of personalized therapy.

As a new type of model organism， zebrafish is gradually gaining prominence in the field of scientific research. The unique biological characteristics and advantages of zebrafish make them play an increasingly important role in the quality evaluation of traditional Chinese medicine. Compared with other common experimental animals， zebrafish have a fast reproductive and growth speed and high embryo transparency， making them an ideal model for evaluating the quality of traditional Chinese medicine. This provides a new perspective and method for research on traditional Chinese medicine. With the growing global interest in traditional Chinese medicine， it has become crucial to find scientific and accurate methods to evaluate the quality and effectiveness of traditional Chinese medicine. The introduction of the zebrafish model has brought new breakthroughs in the quality evaluation of traditional Chinese medicine. To further promote the application of zebrafish in evaluating the quality of traditional Chinese medicine， this article systematically searched and sorted out the previous studies related to the application of zebrafish for this purpose since 2023. The commonly used disease models and indicators of zebrafish in evaluating the effectiveness of traditional Chinese medicine， as well as the mechanism of zebrafish in exploring the active ingredients of traditional Chinese medicine， were primarily reviewed. The application of zebrafish in evaluating the safety of traditional Chinese medicine and the typical examples in ensuring the quality of traditional Chinese medicine were demonstrated. The limitations encountered by zebrafish models in evaluating the quality of traditional Chinese medicine were highlighted. The resolution of these problems will help further improve the accuracy and reliability of zebrafish in evaluating the quality of traditional Chinese medicine. The article discussed the evaluation of effectiveness， safety， and quality control of zebrafish applied in traditional Chinese medicine， so as to provide a reference for establishing standards for traditional Chinese medicine and promoting its modernization in the future.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique that demonstrates great potential in treatment of neurological disorders due to its high spatial resolution and focused penetration ability, enabling millimetre-level precision modulation of specific brain regions with ultrasound to achieve neuromodulation of targeted areas. At present, numerous animal experiments and human studies have been carried out on the regulation of Alzheimer′s disease by TUS. In this review, the regulation effects of TUS on Alzheimer′s disease were introduced from the perspective of targeting different brain regions, including the hippocampus, frontal lobe and whole brain.