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

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women that is a leading cause of infertility. Follicular development disorder, as the main cause of oligoovulation, is the key factor affecting the fertility of PCOS patients. Among them, the disorder of the ovarian microenvironment is an important inducement for follicular development disorder. Emerging research highlights that the ovarian microenvironment plays a sophisticated role in follicular development and maturation through various mechanisms, including the cellular constituents within the ovary, the extracellular matrix's structural support, adequate vascular supply, and the regulation of hormonal and growth factor signaling. These factors collectively ensure the normal growth and ovulation of follicles, thereby safeguarding female reproductive health. In women with PCOS, however, the ovarian microenvironment is compromised, leading to excessive extracellular matrix deposition and fibrosis, abnormalities in vascular architecture and function, immune-inflammatory reactions, and metabolic disturbances. These anomalies collectively hinder follicular growth and development, resulting in ovulation disorders. This comprehensive review will delve into the intricacies of these disruptions and their implications for fertility in PCOS patients.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective:To construct a Du-moxibustion technique operation scheme suitable for patients with ankylosing spondylitis based on the "multidimensional evidence body" model, so as to provide a reference for clinical Du-moxibustion in the treatment of ankylosing spondylitis.Methods:This study was based on the "multidimensional evidence body" model, integrating evidence such as modern literature, ancient Chinese medicine books, and the experience of famous doctors, and combined with semi-structured interviews of 20 patients to form a first draft of the operation plan from April to June 2023. Twenty traditional Chinese medicine experts from 13 regions participated in the review and revision of the plan through two rounds of consultation and expert consensus meetings from July to August 2023, forming the final draft of the operation scheme.Results:Among 20 experts, there were 3 males and 17 females, aged (42.70 ± 6.57) years old. The effective response rates of the questionnaires in the two rounds of correspondence inquiries were 95%(19/20) and 18/18 respectively, and the expert authority coefficients were 0.80 and 0.81. The coefficients of variation were 0.00-0.19 and 0.00-0.21 respectively, and the Kendall harmony coefficients were 0.179 and 0.344 respectively (both P<0.01). The final scheme included 6 first-level items, including "terms and definitions""assessment""operation point""abnormal situations and handling measures""precautions""effect evaluation" and 27 second-level items and 17 third-level items. Conclusions:The operation scheme of Du-moxibustion technique is scientific, feasible and targeted, which can provide effective guidance for clinical practice and ensure the comprehensiveness and effectiveness of treatment.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women that is a leading cause of infertility. Follicular development disorder, as the main cause of oligoovulation, is the key factor affecting the fertility of PCOS patients. Among them, the disorder of the ovarian microenvironment is an important inducement for follicular development disorder. Emerging research highlights that the ovarian microenvironment plays a sophisticated role in follicular development and maturation through various mechanisms, including the cellular constituents within the ovary, the extracellular matrix's structural support, adequate vascular supply, and the regulation of hormonal and growth factor signaling. These factors collectively ensure the normal growth and ovulation of follicles, thereby safeguarding female reproductive health. In women with PCOS, however, the ovarian microenvironment is compromised, leading to excessive extracellular matrix deposition and fibrosis, abnormalities in vascular architecture and function, immune-inflammatory reactions, and metabolic disturbances. These anomalies collectively hinder follicular growth and development, resulting in ovulation disorders. This comprehensive review will delve into the intricacies of these disruptions and their implications for fertility in PCOS patients.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective:To construct a Du-moxibustion technique operation scheme suitable for patients with ankylosing spondylitis based on the "multidimensional evidence body" model, so as to provide a reference for clinical Du-moxibustion in the treatment of ankylosing spondylitis.Methods:This study was based on the "multidimensional evidence body" model, integrating evidence such as modern literature, ancient Chinese medicine books, and the experience of famous doctors, and combined with semi-structured interviews of 20 patients to form a first draft of the operation plan from April to June 2023. Twenty traditional Chinese medicine experts from 13 regions participated in the review and revision of the plan through two rounds of consultation and expert consensus meetings from July to August 2023, forming the final draft of the operation scheme.Results:Among 20 experts, there were 3 males and 17 females, aged (42.70 ± 6.57) years old. The effective response rates of the questionnaires in the two rounds of correspondence inquiries were 95%(19/20) and 18/18 respectively, and the expert authority coefficients were 0.80 and 0.81. The coefficients of variation were 0.00-0.19 and 0.00-0.21 respectively, and the Kendall harmony coefficients were 0.179 and 0.344 respectively (both P<0.01). The final scheme included 6 first-level items, including "terms and definitions""assessment""operation point""abnormal situations and handling measures""precautions""effect evaluation" and 27 second-level items and 17 third-level items. Conclusions:The operation scheme of Du-moxibustion technique is scientific, feasible and targeted, which can provide effective guidance for clinical practice and ensure the comprehensiveness and effectiveness of treatment.

Objective:To investigate the expression of long non-coding RNA growth retard-specific transcript 5 (LncRNA GAS5) and micrornas (miR) 23a-3p in patients with sepsis complicated with acute kidney injury (AKI) and their clinical significance.Methods:A total of 206 patients with sepsis admitted to the Department of Emergency Medicine, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang University of Traditional Chinese Medicine from May 2020 to February 2023 were prospectively selected and divided into AKI group (95 cases) and control group (111 cases) according to whether they had concurrent AKI. Serum LncRNA GAS5 and miR-23a-3p expressions were detected. logistic regression analysis was used to screen the influencing factors of patients with sepsis complicated with AKI, and receiver operating characteristic (ROC) curve was used to analyze the value of LncRNA GAS5 and miR-23a-3p in predicting sepsis complicated with AKI.Results:Mechanical ventilation, blood transfusion treatment ratio, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, white blood cell count (WBC), serum C-reactive protein (CRP), procalcitonin (PCT), blood urea nitrogen (BUN), Scr, blood lactic acid level of the AKI group were higher than those of the control group (all P<0.05); mean arterial pressure (MAP), urine volume, estimate glomerular filtration rate (eGFR) at admission were lower than those of the control group (all P<0.05). Serum LncRNA GAS5 expression (5.12±1.69 vs 2.30±0.42) in AKI group was higher than that in the control group ( P<0.05), and miR-23a-3p expression (1.05±0.13 vs 3.04±0.67) was lower than that in the control group ( P<0.05). Logistic regression analysis showed that high APACHE Ⅱ score, high SOFA score and high expression of LncRNA GAS5 were risk factors for AKI in sepsis patients (all P<0.05). High eGFR and high expression of miR-23a-3p were protective factors (all P<0.05). The area under the curve (AUC) predicted by LncRNA GAS5 and miR-23a-3p for patients with sepsis complicated with AKI was 0.808 and 0.759, and the AUC of combined prediction was 0.882, which was higher than that predicted by single indicator. Conclusions:The expression of LncRNA GAS5 is up-regulated and the expression of miR-23a-3p is down-regulated in serum of patients with sepsis complicated with AKI. The combined detection of LncRNA GAS5 and miR-23a-3p is of high value in predicting the risk of AKI in patients with sepsis.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.