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 therapeutic effect of sequential therapy with butylphthalein on acute cerebral infarction and mild-to-moderate increases in middle cerebral artery blood flow in patients.Methods:The clinical data of 92 patients with acute cerebral infarction and mild-to-moderate increases in middle cerebral artery blood flow who received treatment at the Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to October 2021 were retrospectively analyzed. These patients were divided into a study group and a control group using a random number table method. The control group was given an intravenous infusion of butylphthalein sodium chloride injection, while the study group took oral butylphthalein soft capsules after intravenous infusion of butylphthalein sodium chloride injection. The baseline data, hemodynamics, neurological function, and clinical outcomes were compared between the two groups. At 90 days after treatment, the National Institutes of Health Stroke Scale (NIHSS), the Activity of Daily Living Scale (ADL), and the modified Rankin Scale (mRS) were used to evaluate clinical outcomes. Transcranial Doppler ultrasound (TCD) examination was performed to evaluate hemodynamic changes.Results:A total of 92 patients completed all the observation indices as required, including 48 patients in the study group and 44 patients in the control group. There were no significant differences in demographics, vascular risk factors, laboratory results, NIHSS score, ADL score, or arterial hemodynamics of the diseased brain between the two groups (all P > 0.05). At 90 days after treatment, the NIHSS score in the study group was significantly lower than that in the control group [(4.00 ± 1.95) points vs. (4.91 ± 2.08) points; t =-2.16, P = 0.033]. The ADL score in the study group was significantly higher than that in the control group [(82.71 ± 9.56) points vs. (76.25 ± 11.47) points; t = 2.94, P = 0.004]. The good rate of outcomes in the study group was significantly higher than that in the control group [70.83% (34/48) vs. 50.00% (22/44); χ2 = 4.18, P = 0.041]. There were significant differences in the peak systolic velocity [(152.33 ± 9.58) cm/s vs. (157.41 ± 11.77) cm/s; t = 2.27, P = 0.025] and the mean velocity [(90.00 ± 8.30) cm/s vs. (94.45 ± 9.07) cm/s; t = -2.46, P = 0.016] of the middle cerebral artery between the study and control groups. The difference in pulsitility index between the two groups was not statistically significant [(0.97 ± 1.06) vs. (1.01 ± 1.21); t = 1.69, P = 0.093]. Compared with the poor outcome group, patients in the good outcome group had lower NIHSS and ADL scores after discharge (both P < 0.001), and the proportion of patients who received sequential therapy with butylphthalein in the good outcome group was higher [(60.70% (34/56) vs. 38.90% (14/36); χ2 = 4.18, P = 0.041]. Conclusion:Sequential therapy with butylphthalein can reduce neurological deficits, promote neurological function recovery, improve the hemodynamics of diseased blood vessels, and greatly improve daily living activities in patients with acute cerebral infarction complicated by mild to moderate increases in middle cerebral artery blood flow.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost