Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Objective To evaluate the value of serum Mac-2 binding protein (M2BP) for assessment of the severity of schisto somiasis-induced liver fibrosis, so as to provide insights into non-invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis. Methods A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B-ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis groups) according to B-ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7∶3. Serum M2BP concentration was measured in four groups using the enzyme-linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis-induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group. Results Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis-induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B-ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis-induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B-ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induceed liver fibrosis were 69.23%, 85.71% and 71.43% (χ2 = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1]. Conclusions Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis-induced liver fibrosis; however, its diagnostic value for early-stage schistosomiasis-induced liver fibrosis remains limited.

Allergen specific immunotherapy（AIT）, as an effective treatment for allergic rhinitis, asthma, and other allergic diseases, has received widespread attention in the field of health economic evaluation in recent years. This article reviews the current status and progress of economic research on AIT, mainly discussing the socioeconomic burden of allergic rhinitis, the results of health economic studies from different countries, and the primary methods used in health economic research on allergic rhinitis. Existing studies indicate that, although AIT involves high initial costs, it offers significant long-term economic benefits by reducing healthcare resource utilization, improving patient quality of life, and decreasing medication dependence. Moreover, reducing initial costs, applying standardized assessment tools, and conducting cross-national comparative analyses have become key directions for future research. Overall, AIT demonstrates strong potential in terms of long-term health benefits and cost savings, providing solid economic evidence for the management of allergic diseases.
Humans ; Desensitization, Immunologic/economics* ; Cost-Benefit Analysis ; Rhinitis, Allergic/economics* ; Economics, Medical

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.