Trophoblastic cell migration is essential for the attachment of the placenta to uterine wall, which is a critical step for fetal development. Aberrant migration of trophoblastic cells can lead to pregnant pathologies such as preeclampsia (PE), while the molecular mechanisms remain largely unknown. The current study investigated the effects and molecular mechanisms of the HAND1-Rac1-PAK axis in trophoblast migration using the HTR-8/SVneo cell line, isolated human primary cytotrophoblasts, and human placental tissues. We report herein that HAND1 is highly expressed in human early placenta and promotes trophoblastic cell migration. Mechanistically, HAND1 potentiates human trophoblastic cell migration via activating Vav2/Rac1/PAKs signaling, and the elevated capacity of HAND1 in inducing migration is dependent on its Serine/Threonine phosphorylation status, which is reciprocally regulated by PAK2 and is directly associated with the subsequent degradation of HAND1 protein, thereby generating a positive feed-back for HAND1-mediated trophoblasts migration during human pregnancy. The data suggest that HAND1 is essential for regulating human trophoblast function, potentially enhancing our understanding of pregnancy maintenance and contributing to new therapies for gestational disorders.

Ovarian cancer (OC) is the predominant gynecological cancer and is associated with severe morbidity and high mortality worldwide. Therefore, clarifying the molecular mechanisms underlying OC progression and exploring novel therapeutic targets are important. Here, using human OC samples, different OC cell lines, and xenograft nude mouse models in combination with multiple sequencings, we report that hnRPD, an RNA binding protein that modulates RNA stability, is highly expressed in OC tissues, and contributes to OC cell malignancy in human OC cells cultured in vitro and in OC cell-derived xenograft nude mouse models in vivo. Mechanistically, ectopically expressed GPR137 binds to hnRPD and enhances hnRPD protein stability, which reciprocally transactivates GPR137 through the transcription factor FLI1. On the other hand, elevated hnRPD upregulates RAB8A expression by interacting with RAB8A mRNA and promoting its stability, leading to activation of downstream cell signaling and thereby enhanced OC cell malignant behaviors including cell proliferation, cell invasion, cell migration, and colony formation ability as well as OC xenograft growth in nude mice. Moreover, cisplatin in combination with silencing of hnRPD expression, significantly induces apoptosis in cisplatin-resistant OC cells through regulation of OC cell metabolism. Therefore, our data provide evidence that hnRPD could represent an innovative prognostic indicator for OC and may be an attractive therapeutic target for improving clinical outcomes in OC treatment.

Myocardial infarction (MI) is a severe cardiovascular disorder characterized by an irreversible myocardial necrosis caused by acute ischemia. The typical manifestations of MI include persistent substernal chest pain, dyspnea, nausea, vomiting, and diaphoresis. Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, has been extensively investigated over the past decade. Evidence indicates that AS-IV exerts multifaceted protective effects against MI by modulating various key signaling pathways involved in anti-inflammatory, anti-oxidative stress, and antifibrotic activities, the inhibition of cardiomyocyte apoptosis, and the maintenance of mitochondrial homeostasis. These pathways include TLR4/NF-κB, PI3K/AKT, TGF-β/Smad2, ROS/caspase-1/GSDMD, Wnt/β-catenin, AMPK/ACSS2/PPARα, Sirt3/Drp1, and PINK1/Parkin. Although mechanistic studies have substantially advanced, the clinical application of AS-IV in MI remains in the exploratory stage. Further well-designed clinical trials are necessary in order to validate the therapeutic efficacy and safety of AS-IV, thereby facilitating its translation from experimental research to clinical practice, and offering new insights and potential strategies for MI management.

BACKGROUND:Reactive oxygen species (ROS) regulate diverse cellular signaling and metabolic processes, whereas dysregulated ROS accumulation induces oxidative stress (OS) that contributes to the pathogenesis of numerous neurological disorders. However, the molecular mechanisms underlying OS-induced neuronal cell injury remain incompletely understood. METHODS:Here, a hydrogen peroxide (H2O2)-exposed HT22 mouse hippocampal neuronal cell model and an H2O2-exposed mouse astrocyte C8-D1A cell model were used to mimic in vitro OS. Methods, including transfection, RNA extraction, qRT-PCR, luciferase reporter assay, western blotting, cell counting kit-8, immunofluorescence staining, ROS measurement, and apoptosis assay, were used to investigate the role of Lcn2 in OS. RESULTS:We found that, Lipocalin 2 (Lcn 2), an adipokine family protein, was significantly down-regulated upon H2O2 treatment. Lcn2 overexpression enhanced HT22 cell viability and effectively attenuated H2O2-induced ROS production, whereas Lcn2 silencing reduced viability and potentiated ROS accumulation. Mechanistically‌, Lcn2 protects neuronal cells by inactivating the Hippo signaling. Consistent results were obtained in mouse astrocyte C8-D1A cells. CONCLUSIONS:Collectively, our findings indicate that dysregulated Lcn2 expression contributes to H2O2-induced neuronal OS, and suggest that Lcn2 may serve as a potential biomarker for predicting OS-related neurodegenerative disorders.

Preeclampsia (PE), a gestational disorder diagnosed with hypertension and proteinuria, is recognized as a significant cause of both maternal and perinatal morbidity and mortality around the world. Oxidative stress (OS) is found to act as a major positive role in PE progression, which is regulated by the function derived from multiple microRNAs (miRNAs), a group of cellular small endogenous RNAs that modulate gene expression at post-transcriptional level. This review summarizes the role of different miRNAs in the PE development, focusing on their involvement in OS regulation. In addition, the paper also discusses the current knowledge of the molecular mechanisms regarding PE and highlights the possibly therapeutic implications of targeting miRNAs in the management of this condition.

Abstract Objective To investigate the specific mechanisms by which zinc finger DHHC-type containing 7 (ZDHHC7) regulates immune cells and plasma metabolites to reduce the risk of hypertension. Methods Expression quantitative trait loci (eQTL) data for ZDHHC7 were obtained from the eQTLGen database (n = 26,118), while genome-wide association studies (GWAS) data for hypertension (n = 484,598), immune cells (n = 3658), and plasma metabolites (n = 8192) were extracted from the GWAS Catalog. All datasets were derived from European populations. Five Mendelian randomization (MR) methods, including inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were used to evaluate causal relationships. Sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, leave-one-out analysis, and MR-PRESSO. Statistical power of the MR analysis was assessed via post hoc power calculation. Two-step MR was conducted to evaluate the mediating effects of immune cells and plasma metabolites on the relationship between ZDHHC7 and hypertension risk. Results All 5 MR methods indicated a negative association between ZDHHC7 and hypertension risk (IVW: OR = 0.995, 95% CI, 0.992-0.998, P <.001; MR-Egger: OR = 0.994, 95% CI, 0.989-0.998, P = .014; weighted median: OR = 0.994, 95% CI, 0.991-0.998, P = .004; simple mode: OR = 0.993, 95% CI, 0.987-1.000, P = .049; weighted mode: OR = 0.994, 95% CI, 0.990-0.997, P <.001). The summary-level Mendelian randomization (SMR) analysis yielded consistent results (OR = 0.995, 95% CI, 0.990-0.998, P = .011). Sensitivity analyses showed no significant heterogeneity or bias. The estimated post hoc power was 23.73%. Mediation analysis further revealed that 3 immune cell phenotypes (the proportion of B cell subsets lacking IgD and CD27 markers, expression of CD123 on plasmacytoid dendritic cells, and expression of CD123 on CD62L+ plasmacytoid dendritic cells) and 3 plasma metabolites (1-stearoylphosphatidylinositol, nicotinic acid, and lactate) mediated the relationship between ZDHHC7 and hypertension risk. Conclusion ZDHHC7 may reduce the risk of hypertension by modulating specific immune cells and plasma metabolites.

Chronic heart failure (CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine (TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca²⁺ homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR-RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis; attenuates calcium influx and enhances Ca²⁺ reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF; and improves CHF by rebalancing mitochondrial dynamics and autophagy.

The clinical treatment of ischemic stroke(IS) has long been plagued by the time window and complication risks of recanalization therapies, as well as the bleeding risk of antithrombotic therapy, making it urgent to explore safe and effective new regimens. Salvianolic Acid for Injection(SAFI), a TCM preparation with neuroprotective properties and the ability to improve cerebral blood flow, lacks large-sample clinical validation regarding its systematicness, efficacy, and safety of application in IS patients. This study relied on a clinical trial based on a multicenter, prospective, single-arm objective performance criteria method(registration No. ChiCTR1900026178), enrolling 2 203 IS patients with an onset time of 7-90 d and National Institutes of Health Stroke scale(NIHSS) scores of 4-20. All patients received intravenous infusion of SAFI at dose of 100 mg per day for 14 consecutive days. The primary efficacy indicator was the proportion of patients with a modified Rankin scale(mRS) scores of 0-1 at 90 d after treatment(preset target value of 35%). Secondary efficacy indicators include the proportion of patients with mRS scores recovers to 0-1 at 28 d after treatment, the comparison of NIHSS scores at 7, 14 d after treatment with the baseline, the proportion of patients with Barthel index(BI) scores≥75 at 7, 14, 28, and 90 d after treatment, and the comparison of MMSE scores with the baseline. The incidence, severity, and drug correlation of adverse events were evaluated via vital sign monitoring, laboratory examinations, etc. The binomial test(one-sided α=0.025) was used for primary endpoint analysis, and the 95%CI was calculated by the Clopper-Pearson. RESULTS:: show that among 2 127 patients who completed the trial, 47.91% of these patients(95%CI[45.77%, 50.06%]) achieve the primary endpoint, which is significantly higher than the preset objective value(P&lt;0.000 1). NIHSS scores of patients decrease significantly from baseline scores of(6.57±3.20) to(4.62±3.33) at 14 d after treatment(P&lt;0.000 1), with 23.79% of patients achieving scores improvement of ≥4 points or scores of 0-1. The proportion of patients with BI scores ≥75 increases from the baseline of 41.18% to 74.52% at 90 d after treatment(P&lt;0.000 1), and MMSE scores rises from baseline scores of(22.16±8.03) to(23.95±7.38) at 90 d after treatment(P&lt;0.000 1). In terms of safety, the incidence rates of adverse events and serious adverse reactions are 27.49% and 3.19%, respectively, with no fatal event reported. This study confirmed that SAFI can significantly improve neurological function, capabilities of daily living, and cognitive function in patients with mild to moderate IS at 7-90 d after onset, with a favorable safety profile. The trial design combining single-arm and objective performance criteria method employed in this study provides an innovative paradigm for the clinical evaluation of TCM injections and offers high-quality evidence for the clinical treatment of IS.

Abstract Background Renal cell carcinoma (RCC) is known as one of the three major malignant tumors of the urinary system, and clear‐cell RCC (ccRCC) is the most frequent and aggressive pathological subtype and is correlated with high mortality. Despite diverse treatments, the clinical prognosis of patients with RCC remains poor. Therefore, further characterization of the mechanisms underlying ccRCC progression is urgently required. Methods Different RCC celllines were used to study cell malignancies in vitro and to elucidate mechanisms. Nude mice were used for validating results in vivo. Sequencing, database and bioinformatic analysis were applied for screening candidate genes and signalings. Clinical samples were used to verify the expression pattern of key genes. Results ETS1 expression is significantly higher in clinical ccRCC tissue samples, and consistent withthese findings, ETS1 overexpression increases RCC cell malignancies in cultured cell models in vitro as well as tumor growth in nude mice in vivo. Mechanistically, ETS1 binds to EGR2 and destabilizes the EGR2 protein, and the decreased EGR2 levels mitigate its inhibitory effect on NOTCH signaling through RBP‐J, resulting in activation of the NOTCH signaling pathway, ultimately leading to RCC development. Conclusion Therefore, targeting the ETS1‒EGR2‒NOTCH signaling axis may be a promising therapeutic strategy for ccRCC. Key points ETS1 expression is significantly higher in ccRCC samples, and ETS1‐overexpression increases RCC cell malignancies in vitro and tumour growth in nude mice. ETS1 binds to EGR2 and destabilises EGR2 protein, which relieves EGR2's inhibitory effect on NOTCH signalling. NOTCH signalling activation promotes RCC development. The ETS1‒EGR2‒NOTCH axis would potentially be a promising therapeutic strategy in ccRCC.

The regulator of G-protein signaling 2 (RGS2) plays a key role during pregnancy, whose dysregulation is closely associated with the progression of gestational disorders such as preeclampsia (PE). Therefore, investigating the downstream mechanisms regarding to RGS2-mediated biological events in trophoblasts would provide a better understanding of maintenance and progression of pregnancy. The present study describes the roles and underlying mechanisms of a regulation loop between RGS2 and the Hippo pathway in human trophoblasts, and additionally clarify that RGS2 independently mediates Connective tissue growth factor (CTGF) protein degradation by promoting its ubiquitination. At the molecular level, the ectopic expression of RGS2 deactivates the Hippo signaling but destabilizes CTGF by the Dual-specificity phosphatase 1(DUSP1)-Itchy E3 ubiquitin protein ligase (ITCH)-mediated ubiquitination of CTGF. Reciprocally, as a transcriptional co-activator, TAZ transactivates RGS2 through binding to and activating CREB. Consistently, the results could be verified in transgenic mouse placentas. Our results therefore identify the critical role of the RGS2-Hippo loop in regulating physiological function of trophoblasts during gestation.

Currently, there are many diseases worldwide that seriously affect women's health. Among these, gestational disorders and female cancers such as ovarian cancer are particularly notable for their high morbidity and mortality rates. Over the past decade, ferroptosis, a distinct form of programmed cell death primarily driven by iron-dependent phospholipid peroxidation, has been implicated in the pathogenesis of various female-related diseases. Despite many studies individually reporting that ferroptosis plays a crucial pathogenic role in common female disorders, there has yet to be a systematic overview addressing the mechanisms linking ferroptosis with women's health and disease. Thus, we herein provide a comprehensive review of the relationship between cellular pathways of ferroptosis and women's health and disease and describe the current progress of targeted therapy for ferroptosis. Following a succinct introduction to the disease, we summarize the regulatory role of ferroptosis in women's health and its implications for disease progression, with the aim of facilitating a clearer understanding of the relationship between ferroptosis and women's health. Finally, we discuss the emerging challenges and opportunities presented by various agonists or inhibitors targeting ferroptosis as potential therapeutic strategies for female-related diseases, providing additional protective approaches contributing to female health.

Deregulated reactive oxygen species (ROS) levels trigger oxidative stress (OS) injury that is closely associated with the pathophysiology of various neurological disorders. Therefore, therapeutic efforts at oxidative events in the pathway of neuronal degeneration would be promisingly helpful for intervention and treatment of related diseases. Here, we report that gastrodin, the main bioactive constituent of Rhizoma Gastrodiae, protects the mouse hippocampal HT22 cells from OS caused by hydrogen peroxide (H2O2), including the increased cell viability, elevated Glutathione (GSH) levels, decreased Malondialdehyde (MDA) activity, and down-regulated ROS levels with restored cell morphology. Through RNA-sequencing (RNA-Seq) and multiple experiments, we screened the gene Mamdc2 that could be a potential regulating target of gastrodin. Mechanistically, gastrodin exerts its protective effects on neuronal cells from oxidative injury by suppressing miRNA-125b-5p, which increases its target Mamdc2 expression. Overexpression of miR-125b-5p mimics significantly attenuates the gastrodin-triggered protective effects against H2O2 in HT22 cells, including the decreased cell viability, down-regulated GSH activity, increased MDA activity, and up-regulated ROS production, compared to the gastrodin-administration with control miRNA group. However, these results could be effectively restored by the ectopic expression of Mamdc2, leading to the opposite outcomes to those of miR-125b-5p mimics-overexpression. Thus, the current study provides evidence that gastrodin has the potential for intervention and therapy of OS injury-associated neurological diseases in future.

Nonalcoholic fatty liver disease frequently coexists with diabetes (DM), and both are associated with an increased risk of coronary heart disease (CHD). The effect of nonalcoholic fatty liver disease progression or regression on the severity of coronary artery disease (CAD) in patients with CHD or DM remains unclear. In this multicenter study, 3126 patients with CHD, hepatic steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and fibrosis-4 index. CAD severity was evaluated using coronary angiography. After adjusting for confounders, hepatic steatosis (HSI > 36) was found to be associated with an increased risk of multivessel CAD. In patients with both hepatic steatosis and significant fibrosis (HSI > 36, fibrosis-4 index ≥ 1.3), the risk was further elevated (odds ratio [OR]: 1.596; 95% confidence interval [CI]: 1.245-2.046), with a stronger association in patients with DM (OR: 1.988; 95% CI: 1.041-3.835). Hepatic steatosis and/or significant fibrosis were associated with CAD severity, especially in individuals with both CHD and DM.

Nitric oxide (NO) is a crucial gaseous signaling molecule, and its local concentration fluctuations in vivo can reflect the onset and progression of various pulmonary diseases, such as idiopathic pulmonary fibrosis and viral lung infections. Previous studies have demonstrated a positive correlation between in vivo NO concentration and disease progression, highlighting the urgent need to develop a class of bioprobes capable of highly sensitive and specific real-time NO sensing within living organisms. Herein, we report a "turn-on" near-infrared fluorescence sensing nanoprobe for nitric oxide (NO), which integrates a near-infrared-to-visible triplet-triplet annihilation upconversion (TTA-UC) system with an NO-responsive Bodipy dye. By co-encapsulating both components into the amphiphilic polymer F127, we constructed TTA micelles with excellent photostability and biocompatibility. In vitro studies demonstrated that the TTA nanomicelles can sensitively and specifically respond to exogenous NO. In a pseudotyped mouse model of pulmonary viral infection induced by SARS-CoV-2 spike protein (SP), the upconversion fluorescence of the TTA nmicelles was gradually activated over time, indicating that the developed nanoprobe can dynamically reflect the real-time progression of lung infection in mice. Therefore, the TTA micelles can rapidly diagnose the onset of lung infection at early stages, thereby potentially improving the efficiency of subsequent treatments.

Objective:To investigate the antidepressant mechanism of Jiaotaiwan (JTW), a classic Traditional Chinese Medicine formula, by examining its effects on the gut microbiota short-chain fatty acid (SCFA) neurotransmitter/immune axis in patients with depression.Methods:In this 8-week multicenter randomized controlled trial, 120 patients with depression were randomized to receive JTW, selective serotonin reuptake inhibitors (SSRIs), or JTW+SSRIs, and 30 healthy volunteers were enrolled as controls without intervention (healthy controls, n = 30). Gut microbiota profiling (16S ribosomal RNA [16S rDNA] gene sequencing), fecal SCFA quantification (gas chromatography-mass spectrometry), and plasma levels of neurotransmitters (5-hydroxytryptamine [5-HT], norepinephrine [NE], dopamine [DA]) and gut barrier/inflammatory markers (lipopolysaccharide [LPS], soluble zonula occludens-1 [sZO-1], high mobility group box 1 [HMGB1]) were assessed pre- and post-treatment. Correlations between brain gut peptides, gut flora, SCFAs, and gut barrier/inflammatory markers were analyzed using Spearman correlation analysis.Results:Treatment with JTW, particularly in combination with SSRIs, significantly modulated gut microbiota composition by reducing Bacteroidetes abundance and increasing Firmicutes. It selectively ameliorated SCFA metabolic disturbances, notably elevating fecal levels of branched-chain fatty acids, including isobutyric and isovaleric acids. These changes were accompanied by increased plasma levels of 5-HT and DA, and reduced levels of LPS and HMGB1, suggesting improved gut barrier integrity and attenuated systemic inflammation. Correlation analysis revealed a positive association between Firmicutes abundance and sZO-1 levels, and overall coordination among microbial shifts, metabolic changes, and neurotransmitter improvements.Conclusion:JTW may alleviate depressive symptoms through multitarget modulation of the microbiota-SCFA-neurotransmitter/immune axis, potentially involving the restoration of microbial composition, enhanced beneficial SCFA production, improved intestinal barrier function, reduced inflammation, and elevated monoamine neurotransmitters. Synergistic effects were observed when JTW was combined with SSRIs, thereby providing a mechanistic basis for using JTW in microbiota-directed approaches for treating depression.

The systemic inflammation response index (SIRI) is a novel inflammatory biomarker that reflects the chronic inflammatory status. This study aimed to evaluate its clinical utility in determining coronary heart disease (CHD) severity. Participants in this study, sourced from the Cohort Study on the Treatment of Cardiovascular Diseases with Traditional Chinese Medicine (CSCD-TCMplus), were divided into tertiles (T) based on their SIRI values. The number of diseased vessels (single- and multi-vessel CHD) was used as a measure of disease severity, assessed by coronary angiography. Logistic regression analysis was used to investigate the relationship between SIRI and the severity of CHD. Among the 7706 participants, 6215 (80.6%) had multi-vessel disease. Logistic regression analysis revealed a significant association between SIRI and CHD severity (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.03-1.15). Compared with males, females had a higher risk of CHD severity at the SIRI T3 tertile (OR: 1.64; 95% CI: 1.28-2.10). Also, patients >55 years of age had a greater risk than those ≤55 years old (OR: 1.93; 95% CI: 1.67-2.01). The association between SIRI and CHD severity persisted even after adjusting for confounding factors.

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in signal transduction and cellular communication. GPCR proteins are involved in a wide range of physiological processes, including cell growth, migration, and survival. Dysregulation of GPCR protein expression has been implicated in the pathogenesis of various diseases, including cancer, and GPCR proteins have been shown to modulate these processes in various types of cancer, highlighting their importance as potential therapeutic targets. In this review, we summarize the expression regulation of GPCRs in cancer cells, update the various ways by which the abnormal expression of GPCR protein affects the behavior of tumor cells, and discuss the current research directions and potentially facing problems of strategies on GPCR-targeting therapy.

Gastrodia elata Blume (GE), a traditional Chinese medicine clinically employed to treat neurological disorders, demonstrates therapeutic efficacy supported by robust clinical evidence. Nowadays, conventional pharmacotherapies for neurological conditions—such as cholinesterase inhibitors for Alzheimer’s or Ldopa for Parkinson’s—often provide limited symptom relief, exhibit side effects, and fail to halt disease w, underscoring the need for alternative strategies. The primary bioactive compounds of Gastrodia elata Blume (GE) include gastrodin, p-hydroxybenzyl alcohol, Vanillyl alcohol, Polysaccharides, and β-sitosterol. Modern research has demonstrated that GE and its active components exhibit neuropharmacological effects, including neuron protection, reduction of neurotoxicity, and promotion of nerve regeneration and survival. For example, Gastrodin, exerts neuroprotection by scavenging reactive oxygen species, suppressing pro-inflammatory cytokines, and enhancing GABAergic transmission, thereby alleviating oxidative stress and neuronal apoptosis. Vanillin, potentiates GABA receptor activity, enhancing inhibitory neurotransmission and reducing seizure susceptibility.GE polysaccharides modulate the gut-brain axis and suppress microglial activation, mitigating neuroinflammation. Current studies primarily focus on GE and its active ingredients for the treatment of neurological diseases such as Parkinson’s disease, Alzheimer’s disease, epilepsy, convulsions, depression, schizophrenia, as well as enhancing learning and memory, and preventing or treating cerebral ischemic injury. This review explores the neuropharmacological effects of GE and its active compounds, elucidates the underlying mechanisms, and suggests potential preventive and therapeutic strategies for neurological diseases using herbal remedies.

Introduction: Heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of 64 million people globally. After many years of use and development, Traditional Chinese Medicine (TCM) has accumulated rich clinical usefulness in many diseases. This network meta-analysis aimed to assess the effectiveness of nine different Chinese traditional patent medicines (CTPMs) in the treatment of heart failure developing after acute myocardial infarction. Methods: Determine the eligibility criteria for inclusion and exclusion in advance. Starting from literature search until September 20, 2024, conduct comprehensive data retrieval on 7 different databases. Network plots, league tables, surface-under-the-cumulative ranking (SUCRA), and funnel plots were created for each outcome. A previous registration (PROSPERO CRD42024519394) of this review protocol was undertaken. Results: A total of 56 eligible RCTs involving 5,567 patients with heart failure secondary to acute myocardial infarction in which nine CTPMs were used as treatment are included. The CTPMs included Qili Qiangxin capsule (QLQXC), Compound Danshen Dripping Pills (CDDP), Shexiang Baoxin pill (SXBXP), Stilbene yiqi dropping refs (SYQDR), Xintong oral liquid (XTOL), Wenxin granule (WXG), Tongxinluo capsule (TXLC), and Guanxinshutong capsule (GXSTC) and Huangqibaoxin particle (HQBXP). The experimental group received CTPM therapy in addition to conventional Western medicine (CWM) treatment, whereas the control group received just CWM treatment. The results showed that compared to those treated with CWM alone, those treated with CPTM + CWM considerably improved in all relevant measures. When evaluating clinical effectiveness based on left ventricular end-diastolic diameter and the New York Heart Association's (NYHA) cardiac functional classification, WXG + CWM was shown to be the most successful in enhancing cardiac efficiency. The 6-minute walking test results were most improved by SXBXP + CWM, but N-terminal pro-brain natriuretic peptide reduction, left ventricular ejection percent, and left ventricular end-systolic diameter were best achieved by XTOL + CWM. When compared to the other combination treatments, the QLQXC + CWM therapy was the most successful in increasing left ventricular end-diastolic volume while the GXSTC + CWM treatment was the most successful in increasing left ventricular end-systolic volume. There were no appreciable variations in safety between the groups treated with CWM alone and the ones treated with CTPMs plus CWM. Discussion: In contrast to CWM therapy alone, the combination of CTPMs and CWM treatment offers greater therapeutic benefits and is safe for treating heart failure that follows an acute myocardial infarction. For heart failure that develops after an acute myocardial infarction, combo therapy using WXG + CWM and QLQXC + CWM may be the best integrative medicine-based interventions. Due to the study's limitations, additional large-scale, multicenter, double-blind, randomized controlled trials with high quality are required for comprehensive validation and to establish a solid body of evidence supporting the prudent use of medications in the treatment of heart failure resulting from acute myocardial infarction.

Preeclampsia (PE) is a multisystem disorder with increased maternal and perinatal mortality and morbidity while the treatment of PE remains largely unknown in clinic. Therefore, it is necessary to find more effective therapeutic methods of PE. We report herein that, Tianma Gouteng Decoction (TGD) generates protective effects against PE by activating Wnt 3a/β-catenin signaling and simultaneously suppressing ferroptosis in placental trophoblast cells. Particularly, Gastrodin (Gtd), the active component in TGD, plays a major role in protection against PE. Mechanistically, Gtd up-regulates the Wnt 3a/β-catenin signaling activity by inducing Wnt 3a mRNA expression, resulting in the increased expression of β-catenin-controlled target genes. On the other hand, Gtd-triggered Wnt activation obviously exerts negative effects on ferroptosis by promoting expression levels of the anti-ferroptosis proteins accompanied by the down-regulated reactive oxygen species (ROS) production and total iron content but the up-regulated L-Glutathione (GSH) levels. Consistently, Gtd-administration reveals apparent anti-hypertensive effects in a PE-like mouse model with diminished ferroptosis, whereas deactivation of β-catenin by administration with the specific antagonist ICG001 disrupts the protective effects derived from Gtd. Therefore, our results provide an innovative basis for the role of Gtd as a new therapy for PE.