ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.

Among numerous medical imaging modalities, diffusion weighted imaging (DWI) is extremely sensitive to acute ischemic stroke lesions, especially small infarcts. However, magnetic resonance imaging is time-consuming and expensive, and it is also prone to interference from metal implants. Therefore, the aim of this study is to design a medical image synthesis method based on generative adversarial network, Stroke-p2pHD, for synthesizing DWI images from computed tomography (CT). Stroke-p2pHD consisted of a generator that effectively fused local image features and global context information (Global_to_Local) and a multi-scale discriminator (M ²Dis). Specifically, in the Global_to_Local generator, a fully convolutional Transformer (FCT) and a local attention module (LAM) were integrated to achieve the synthesis of detailed information such as textures and lesions in DWI images. In the M ²Dis discriminator, a multi-scale convolutional network was adopted to perform the discrimination function of the input images. Meanwhile, an optimization balance with the Global_to_Local generator was ensured and the consistency of features in each layer of the M ²Dis discriminator was constrained. In this study, the public Acute Ischemic Stroke Dataset (AISD) and the acute cerebral infarction dataset from Yantaishan Hospital were used to verify the performance of the Stroke-p2pHD model in synthesizing DWI based on CT. Compared with other methods, the Stroke-p2pHD model showed excellent quantitative results (mean-square error = 0.008, peak signal-to-noise ratio = 23.766, structural similarity = 0.743). At the same time, relevant experimental analyses such as computational efficiency verify that the Stroke-p2pHD model has great potential for clinical applications.
Humans ; Tomography, X-Ray Computed/methods* ; Diffusion Magnetic Resonance Imaging/methods* ; Cerebral Infarction/diagnostic imaging* ; Stroke/diagnostic imaging* ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Algorithms

OBJECTIVE: To establish a three-dimensional finite element model of a digital wire loop space maintainer for the mandible and primary tooth loss, in order to investigate the stress, deformation, and shear force experienced by patients with the loss of the second primary molar when wearing the wire loop space maintainer. METHODS: Cone beam computed tomography (CBCT) scans were performed on the patients to create a digital model of the mandible with the absence of the second primary molar using Mimics 21.0 software. A digital model integrating the crown's retention and the wire loop structure of the full crown and ring wire loop space maintainer was constructed using pediatric space maintainer design software, utilizing three different materials: cobalt-chromium alloy, polyether ether ketone (PEEK), and titanium alloy. In ANSYS Work Beach 2023 R2 software, vertical loads of 70 N, tilted 45° along the long axis of the tooth loads of 70 N, and a 10 N load on the surface of the wire loop were applied to the occlusal surfaces of models 46 and 84, simulating centric and lateral occlusions during chewing with the wire loop space maintainer in place. The stress states of the wire loop space maintainer and supporting teeth were analyzed. RESULTS: Under various loading conditions, the maximum principal stress of the ring wire loop space maintainer was significantly lower than that of the full crown. Stress contour maps indicated that the peak of the maximum principal stress occurred at the junction of the wire loop and crown structure, indicating that this area was more susceptible to fracture. The ring wire loop space maintainer made from PEEK material exhibited the lowest maximum shear stress on the internal organizational surfaces, with equivalent stresses of 23.18 MPa and 36.35 MPa for models 46 and 84, respectively. Stress contour maps demonstrated that the maximum stress on tooth 46 was located at its mesial, while the maximum stress on tooth 84 was situated near the root area on its distal, in contact with the wire loop space maintainer. CONCLUSION In cases of second primary molar loss, wearing the digital ring wire loop space maintainer can effectively distribute stress, and the ring wire loop space maintainer made from PEEK material reduces the stress experienced by supporting teeth to some extent, demonstrating its superiority in clinical application.
Finite Element Analysis ; Humans ; Tooth, Deciduous ; Cone-Beam Computed Tomography ; Space Maintenance, Orthodontic/methods* ; Imaging, Three-Dimensional ; Orthodontic Wires ; Dental Stress Analysis ; Mandible ; Stress, Mechanical

OBJECTIVES: To explore the effects of exogenous trigger (hCG/GnRHa) versus endogenous LH surge in natural cycle IVF/ICSI (NC-IVF/ICSI) for patients with diminished ovarian reserve (DOR). METHODS: A retrospective analysis was conducted on 1,118 NC-IVF/ICSI cycles from two reproductive centers between 2013 and 2024. Propensity score matching (PSM) and multivariate logistic regression were used to adjust for confounding factors. The trigger-day hormone threshold was determined using receiver operating characteristic (ROC) curve analysis. Outcome measures included oocyte retrieval rate, 2PN fertilization rate, clinical available embryo rate, high-quality embryo rate, fresh cycle clinical pregnancy rate (CPR), and live birth rate (LBR). RESULTS: After adjusting for confounders via PSM and logistic regression, the exogenous trigger group demonstrated significantly better outcomes across all the evaluated parameters (oocyte retrieval rate, 2PN fertilization rate, transferable embryo rate, high-quality embryo rate, fresh cycle CPR, and LBR) than the endogenous LH surge group (P<0.05). Age-stratified analysis revealed that for the entire cohort, exogenous triggering significantly increased the number of transferable embryos and high-quality embryos (P<0.001). In the 35-39 years old subgroup, exogenous triggering showed significant advantages in oocyte yield, high-quality embryo rate, CPR, and LBR (P<0.05) and resulted in the most pronounced improvement in LBR (OR=6.25, 95% CI: 1.34-29.23). ROC analysis established a decision-day LH threshold of 19.055 mIU/mL (AUC=0.945, specificity=93.3%) for precise stratification of the clinical pathways. CONCLUSIONS For DOR patients undergoing NC-IVF/ICSI, exogenous triggering comprehensively improves the treatment outcomes, particularly providing significant live birth benefits for women aged 35-40 years. An individualized protocol incorporating the LH threshold (19.055 mIU/mL) effectively enhances embryonic developmental potential and live birth rates.
Humans ; Female ; Ovarian Reserve ; Pregnancy ; Propensity Score ; Retrospective Studies ; Fertilization in Vitro ; Sperm Injections, Intracytoplasmic ; Chorionic Gonadotropin ; Pregnancy Rate ; Logistic Models ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone ; Adult ; Oocyte Retrieval

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

ObjectiveTo explore the mechanism of Huanglian Jiedutang in inhibiting the pyroptosis mediated by NOD-like receptor protein 3 （NLRP3） inflammasomes and alleviating the acute liver injury （ALI） induced by lipopolysaccharide （LPS） in the mouse model of sepsis. MethodFifty-four male C57BL/6 mice were randomized into blank， model， low- （3.08 g·kg^-1）， medium- （6.15 g·kg^-1）， and high-dose （12.30 g·kg^-1） Huanglian Jiedutang， and positive control （dexamethasone） groups （n=9）. The mice were administrated with Huanglian Jiedutang at different doses by gavage for 7 days， and then LPS （15 mg·kg^-1） was injected intraperitoneally for the modeling of sepsis. In the positive control group， dexamethasone （0.05 g·kg^-1） was injected intraperitoneally 1.5 h after modeling， and the mouse sepsis score （MSS） was recorded 12 h after modeling. The mice were sacrificed for the collection of blood and liver tissue samples. The levels of alanine transaminase （ALT） and aspartate transaminase （AST） were measured by a biochemical analyzer. The levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， IL-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the pathological changes in the liver tissue. The content of NLRP3 was observed by the immunofluorescence assay. The expression of apoptosis-associated speck-like protein containing CARD （ASC） was detected by immunohistochemistry. The protein levels of NLRP3， ASC， Caspase-1， and gasdermin D （GSDMD） in the liver tissue were determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18. ResultCompared with the blank group， the model group showed elevated levels of ALT and AST （P<0.01） and risen levels of inflammatory cytokines in the serum （P<0.01）. In addition， the modeling resulted in edema and necrosis in the liver， and up-regulated the protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.01） and the mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.01）. Compared with the model group， the drug intervention groups showed reduced content of inflammatory cytokines （P<0.01）， alleviated pathological damage in the liver tissue， and down-regulated protein levels of GSDMD， NLRP3， ASC， and Caspase-1 （P<0.05，P<0.01） and mRNA levels of GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05，P<0.01） in the liver tissue. ConclusionHuanglian Jiedutang can inhibit pyroptosis and reduce inflammation by inhibiting the activation of NLRP3 inflammasomes， thus demonstrating a therapeutic effect on acute liver injury in the mouse model of sepsis induced by LPS.

Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factor-α(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-α and NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-α and NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conclusion Xixin Decoction can improve the spatial learning and memory ability of AD model mice,and its mechanism is related to regulating the permeability of the blood-brain barrier and related protein expression,and inhibiting neuroinflammation.