BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

Implementation evaluation frameworks are essential tools in implementation science for assessing the quality and effectiveness of evidence-based interventions. This paper systematically reviews eight internationally representative evaluation frameworks, outlining their development backgrounds and structural features. It then compares their usability, applicability, and testability. Two case studies are presented to illustrate how evaluation frameworks can be integrated with process models and determinant frameworks to enhance the understanding and guidance of complex interventions. This paper aims to offer practical guidancefor selecting and applying evaluation frameworks, thereby supporting the advancement of implementation science in both local and global health contexts.

Objective:To investigate the effect of circular RNA bromodomain PHD finger transcription factor (circBPTF) targeting microRNA (miR)-224-3p on the damage of human retinal vascular endothelial cells (HRECs) induced by high glucose.Methods:HRECs were divided into control group and high glucose group, which were cultured with medium containing 5.5 mmol/L glucose and 30 mmol/L glucose for 48 hours, respectively.HRECs were transfected with siRNA negative control (si-NC), siRNA of circBPTF (si-circBPTF), miRNA mimic control (miR-NC), and miR-224-3p by Lipofectamine 2000, followed by cultured in 30 mmol/L glucose medium for 48 hours and were recorded as si-NC group, si-circBPTF group, miR-NC group and miR-224-3p group, respectively.HRECs were transfected with si-circBPTF and anti-miR-NC or si-circBPTF and anti-miR-224-3p by double transfection method, and then treated with 30 mmol/L glucose medium for 48 hours and were recorded as anti-miR-NC group and anti-miR-224-3p group, respectively.The expression of circBPTF and miR-224-3p was detected by real-time fluorescence quantitative PCR.Cell apoptosis was detected by flow cytometry.Reactive oxygen species (ROS) level was determined by 2′, 7′-dichlorodihydrofluorescein diacetate probe.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric method.Expression of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9 proteins was detected by Western blot.The interaction between circBPTF and miR-224-3p was identified by the dual luciferase reporter method.Results:Compared with the control group, the apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, ROS level, MDA content, and circBPTF relative expression were significantly increased and SOD activity and miR-224-3p expression were decreased in the high glucose group (all P<0.05).Compared with the si-NC group, circBPTF relative expression, ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, and cell apoptosis rate were significantly reduced and SOD activity was significantly increased in the si-circBPTF group (all P<0.05).Compared with the miR-NC group, miR-224-3p relative expression and SOD activity were significantly enhanced and ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression and cell apoptosis rate were significantly reduced in the miR-224-3p group (all P<0.05).The relative luciferase activity of HRECs after co-transfection of wild type circBPTF and miR-224-3p mimic was 0.43±0.04, which was significantly decreased compared with 0.99±0.06 after co-transfection of wild type circBPTF and miR-NC ( t=23.297, P<0.05).Compared with anti-miR-NC group, the relative expression of miR-224-3p and SOD activity were significantly decreased and ROS level, MDA content, cell apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, and cleaved-caspase-9/caspase-9 protein expression were significantly increased in the anti-miR-224-3p group (all P<0.05). Conclusions:Interfering with circBPTF can inhibit high glucose induced HRECs apoptosis and oxidative stress damage by targeting miR-224-3p.

By measuring how patients with skeletal muscle injuries move and assisting healthcare professionals in instructing patients to perform specific movements in a gamified manner, serious games can effectively increase exercise adherence and positively improve clinical outcomes for patients, ultimately resulting in reduced health education costs and accessible rehabilitation programs. This paper describes the conceptual framework for the creation of serious games and their content characteristics, reviews the training methods and effects of serious games in the motor function rehabilitation among patients with skeletal muscle injuries, and puts forward the future prospects for the application of serious games in motor function rehabilitation.

Objective:To investigate the effect of circular RNA bromodomain PHD finger transcription factor (circBPTF) targeting microRNA (miR)-224-3p on the damage of human retinal vascular endothelial cells (HRECs) induced by high glucose.Methods:HRECs were divided into control group and high glucose group, which were cultured with medium containing 5.5 mmol/L glucose and 30 mmol/L glucose for 48 hours, respectively.HRECs were transfected with siRNA negative control (si-NC), siRNA of circBPTF (si-circBPTF), miRNA mimic control (miR-NC), and miR-224-3p by Lipofectamine 2000, followed by cultured in 30 mmol/L glucose medium for 48 hours and were recorded as si-NC group, si-circBPTF group, miR-NC group and miR-224-3p group, respectively.HRECs were transfected with si-circBPTF and anti-miR-NC or si-circBPTF and anti-miR-224-3p by double transfection method, and then treated with 30 mmol/L glucose medium for 48 hours and were recorded as anti-miR-NC group and anti-miR-224-3p group, respectively.The expression of circBPTF and miR-224-3p was detected by real-time fluorescence quantitative PCR.Cell apoptosis was detected by flow cytometry.Reactive oxygen species (ROS) level was determined by 2′, 7′-dichlorodihydrofluorescein diacetate probe.Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric method.Expression of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase-9 proteins was detected by Western blot.The interaction between circBPTF and miR-224-3p was identified by the dual luciferase reporter method.Results:Compared with the control group, the apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, ROS level, MDA content, and circBPTF relative expression were significantly increased and SOD activity and miR-224-3p expression were decreased in the high glucose group (all P<0.05).Compared with the si-NC group, circBPTF relative expression, ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression, and cell apoptosis rate were significantly reduced and SOD activity was significantly increased in the si-circBPTF group (all P<0.05).Compared with the miR-NC group, miR-224-3p relative expression and SOD activity were significantly enhanced and ROS level, MDA content, cleaved-caspase-3/caspase-3 protein expression, cleaved-caspase-9/caspase-9 protein expression and cell apoptosis rate were significantly reduced in the miR-224-3p group (all P<0.05).The relative luciferase activity of HRECs after co-transfection of wild type circBPTF and miR-224-3p mimic was 0.43±0.04, which was significantly decreased compared with 0.99±0.06 after co-transfection of wild type circBPTF and miR-NC ( t=23.297, P<0.05).Compared with anti-miR-NC group, the relative expression of miR-224-3p and SOD activity were significantly decreased and ROS level, MDA content, cell apoptosis rate, cleaved-caspase-3/caspase-3 protein expression, and cleaved-caspase-9/caspase-9 protein expression were significantly increased in the anti-miR-224-3p group (all P<0.05). Conclusions:Interfering with circBPTF can inhibit high glucose induced HRECs apoptosis and oxidative stress damage by targeting miR-224-3p.

Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Background: Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective: The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods: An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results: Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01], while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions: SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.