This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

Based on the similarity of chemical constituents between Panax notoginseng flowers and rhizomes, this study investigated their lipid-lowering effects and impacts on the intestinal flora of rats. The main components of P. notoginseng flowers and rhizomes were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) to compare their chemical similarities. A hyperlipidemia rat model was induced using a high-fat diet. After successful modeling, the rats were divided into the blank control group, blank administration group(0.090 g·kg~(-1)), model group, low-(0.045 g·kg~(-1)), medium-(0.090 g·kg~(-1)), high-dose(0.180 g·kg~(-1)) P. notoginseng flower group, P. notoginseng rhizome group(0.270 g·kg~(-1)), and simvastatin group(0.900 mg·kg~(-1)). After modeling, the rats were given intragastric administration for 3 weeks, once daily, while their body weight was recorded regularly. Before the last administration, fresh feces were collected for analysis of changes in intestinal flora using 16S rDNA high-throughput sequencing technology. One hour after the last administration, the rats were anesthetized with 1% pentobarbital sodium, and blood was collected from the abdominal aorta. Serum biochemical indexes were detected using an automatic biochemical analyzer. Organs(heart, liver, spleen, lung, and kidney) were harvested, and organ index were calculated. Liver tissue pathology was assessed through HE staining and oil red O staining. The results indicated that there were 33 identical chemical constituents in P. notoginseng flowers and rhizomes, accounting for 75.00% of the total constituents. After treatment, high-dose P. notoginseng flower group and P. notoginseng rhizome group exhibited similar effects on body weight, serum biochemical indexes, and liver histopathological conditions. Compared with model control group, the abundance of Firmicutes and Actinobacteria increased in high-dose P. notoginseng flower and rhizome groups, while the abundance of Bacteroidetes and Thermodesulfobacteria decreased. Cluster analysis showed no significant difference between the two groups. Both P. notoginseng flowers and rhizomes possess similar chemical components and lipid-lowering effects, and they can regulate the intestinal flora imbalance caused by hyperlipidemia, indicating their potential for use in hyperlipidemia treatment.
Animals ; Hyperlipidemias/microbiology* ; Panax notoginseng/chemistry* ; Rats ; Rhizome/chemistry* ; Male ; Flowers/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/administration & dosage* ; Gastrointestinal Microbiome/drug effects* ; Humans ; Liver/drug effects*