Liver fibrosis is a common pathological process, leading to the development of end-stage liver diseases. It is triggered by various etiological drivers including viral hepatitis, metabolic-associated steatotic liver disease (MASLD), and cholestasis. Given the substantial impact of liver fibrosis on individuals and its associated mortality rates, effective management of this condition is crucial for improving public health. Despite a growing number of preclinical studies and clinical trials, a systematic synthesis remains lacking. In this review, the molecular panorama of liver fibrogenesis is summarized at first, encompassing etiological drivers of chronic liver injury, key cellular players, core signaling pathways, and extracellular matrix dynamics. Therapeutic interventions in preclinical or clinical stages are systematically classified into two main categories: etiological treatment as the foundational approach and mechanism-based antifibrotic therapies. Emerging and future therapeutic strategies, including those targeting gut-liver axis, gut microbiota, and cell-based therapies, are also addressed along with inherent challenges. Furthermore, future perspectives centered on precision medicine, combination therapies, novel target discovery, and advanced drug delivery systems are emphasized. This review offers a comprehensive overview of the etiologies, diagnostic approaches, pathogenic mechanisms, current development of antifibrotic agents, and prospects for future therapeutic directions of liver fibrosis.
The major challenge in the clinical treatment of gastrointestinal mucosal injury caused by high-altitude hypoxic environments lies in its unclear underlying mechanisms. In the previous study, we found that hypoxia-induced gastric and small intestinal damage was mainly attributable to ferroptosis mediated by hypoxia-inducible factor-α (HIF-α; mainly HIF-1α and HIF-2α). Both plant exosome-like nanoparticles and Aquilaria malaccensis Lam. have been reported to have antioxidant properties. In the present study, orally delivered A. malaccensis Lam. exosome-like nanoparticles (AELNs) reduced HIF-1α expression and alleviated gastric and small intestinal mucosal ferroptosis induced by hypoxia. We analyzed the compositions of AELNs and hypothesized that ipriflavone was the effector component, as it showed the highest abundance of metabolites. Subsequent experiments demonstrated that ipriflavone downregulated polyunsaturated fatty acid-phospholipids, NADPH oxidase 4 (NOX4), and arachidonate 5-lipoxygenase (ALOX5) by inhibiting HIF-α, consequently alleviating hypoxia-induced gastric and small intestinal mucosal ferroptosis. Ipriflavone was found to inhibit HIF-α by targeting prolyl hydroxylase domain protein 2 (PHD2) to induce it to hydroxylate HIF-α. This study highlights that ipriflavone, a potent HIF-α inhibitor, significantly ameliorates the gastric and small intestinal mucosal damage caused by hypoxia and has promise in clinical applications for treating disorders characterized by high levels of HIF-α.
This study aimed to identify blood pressure-associated metabolites and explore their underlying pathways using multiomics data from 1188 Chinese participants. Serum metabolite levels were profiled using untargeted and widely targeted metabolomic technologies. The associations of metabolites as well as ratios with blood pressure were assessed using generalized linear models (GLM). Targeted metabolomics was used to replicate a subset of metabolites. Genome-wide association studies (GWAS) were performed on all metabolites identified. Potential causality was examined using two-sample Mendelian randomization (MR) analyses, with partial validation against GWAS results from an independent cohort. This study identified 10 blood pressure-associated metabolites supported by GLM and MR analyses. Cortisol demonstrated the strongest association with blood pressure, with l-glutamic acid and its ratios identified as key drivers. Multiomics integration revealed that a genetic variant near the omega-3 metabolism genes (FADS1/FADS2) may influence blood pressure regulation by modulating prostaglandin E3 levels. Mediation analysis indicated that l-glutamic acid statistically mediated 12.16-31.53% of the effect of lifestyle factors on blood pressure. These findings enhance our understanding of metabolic mechanisms underlying hypertension and highlight potential biomarkers and therapeutic targets for further investigation.
Pulmonary fibrosis is a chronic and progressive interstitial lung disease with limited treatment options aside from lung transplantation. Bleomycin (BLM)-induced lung injury is the most commonly used experimental model to mimic the key pathological features of human pulmonary fibrosis, which include an early inflammatory phase and a later fibrotic phase. Neutrophil infiltration and M2 macrophage activation are key events in these stages, respectively. However, the molecular mechanisms by which BLM triggers pulmonary inflammation and fibrosis remain incompletely understood. In this study, we found that BLM treatment induced ROS-mediated oxidative damage in the lungs, leading to an inflammatory microenvironment and the release of oxidized mitochondrial DNA (oxid-mtDNA). Oxid-mtDNA was shown to contribute to the early inflammatory response by promoting neutrophil recruitment and enhancing macrophage polarization, which subsequently drove tissue remodeling and fibrosis. Notably, direct injection of oxid-mtDNA into the lungs recapitulated the fibrotic features observed in the BLM model. Furthermore, studies using STING- and NLRP3-deficient mice demonstrated that loss of either pathway significantly attenuated BLM-induced inflammation and fibrosis, implicating their involvement downstream of oxid-mtDNA signaling. Collectively, our findings identify oxid-mtDNA as a critical mediator linking oxidative injury to immune activation and fibrotic remodeling in the lung, offering new insights into pulmonary fibrosis pathogenesis and potential therapeutic targets.
Late-stage cancer diagnosis and limited treatment options for advanced disease remain major contributors to cancer-related morbidity and mortality. Blood-based multicancer early detection (MCED) assays have consequently gained momentum as a means to shift diagnosis toward earlier, more curable stages. Despite their promise, substantial methodological, clinical, and implementation barriers hinder widespread adoption. Integrative approaches coupling multi-omics profiling with advanced molecular imaging may improve detection accuracy and tumor localization, while risk-adapted MCED paradigms could support more targeted, individualized screening strategies. This article reviews the current landscape of MCED technologies, with a primary focus on circulating cell-free DNA and circulating tumor DNA-based assays, and critically evaluates their developmental status, strengths, and limitations relative to established single-cancer screening methods. The contribution of artificial intelligence, particularly advanced deep learning,  to improving sensitivity, specificity, and predictive performance is discussed. The potential of MCED assays to detect aggressive, currently unscreened malignancies and to address the unique challenges of pediatric cancers is examined. In addition, emerging alternative detection strategies, ongoing clinical validation efforts, regulatory requirements, and implementation considerations are reviewed. Finally, the impact of MCED testing on cancer mortality, quality of life, and healthcare systems is outlined, along with key technological trends shaping future development and clinical translation.
Chronic hepatitis B (CHB) remains incurable due to the immune system's tolerance toward the hepatitis B virus (HBV) surface antigen (HBsAg). This study aimed to achieve a functional cure by breaking HBV tolerance through immunotherapy. CHB patients were treated with either standard nucleotide analog (NA) therapy (Adefovir Dipivoxil, ADV) (Cohort 1) or ADV combined with interferon-alpha (IFN-α) (Cohort 2). Additionally, a third cohort received the THRIL-GM-Vac regimen: three low-dose GM-CSF injections followed by one dose of the HBV vaccine, alongside standard treatment. THRIL-GM-Vac treatment (Cohort 3) achieved a significant 2log10 reduction in HBsAg levels in 21.7% of participants, and 8.7% HBsAg clearance in Cohort 3 compared to 0% and 4.17% in Cohorts 1 and 2, respectively. Furthermore, THRIL-GM-Vac significantly reduced HBV-specific tolerogenic T cells (Tregs), explaining the sustained HBsAg decrease. Upregulation of anti-HBV T cell responses confirmed THRIL-GM-Vac's ability to disrupt HBV tolerance and enhance HBsAg-specific cellular immunity. This suggests its potential effectiveness in treating individuals with moderate to low HBsAg levels. THRIL-GM-Vac treatment in Cohort 3 resulted in 8.7% HBsAg clearance alongside Treg depletion and enhanced anti-viral T cell responses. These findings present a promising strategy to overcome immunotolerance and potentially combat chronic HBV infection.
Enterovirus A71 (EV-A71) is recognized as the primary causative agent of hand, foot, and mouth disease (HFMD) and is prevalent worldwide. However, the precise pathogenic mechanisms of EV-A71 remain unclear, and specific drugs targeting it have yet to be successfully developed. To explore the mechanisms underlying EV-A71 pathogenesis and to identify potential therapeutic opportunities, we performed a comprehensive proteogenomic characterization of muscle tissues from BALB/c mice infected with EV-A71, integrating transcriptomic, proteomic, and phosphoproteomic analyses. Our results showed that phagosome, complement, and coagulation cascade pathway-related molecules were activated, and the expression of cell growth-related molecules was downregulated. Concurrently, a rapid activation of the neutrophil extracellular trap pathway was observed at the protein level. Additionally, we mapped the global phosphorylation profiles to dysregulated kinases, predicting 32 drugs corresponding to 27 kinases. We found that kinase inhibitors have antiviral activity in vitro; vandetanib, nintedanib, dasatinib, avitinib, and nilotinib can inhibit virus replication in mice to some extent. Overall, this study provides a multi-omics resource for elucidating EV-A71-induced alterations in target tissues and for linking omics-based target discovery with drug screening and functional validation, providing new insights into both pathogenesis and therapeutic exploration.
A substantial proportion of patients with X‑-linked inhibitor of apoptosis (XIAP) deficiency develop severe and treatment‑-refractory Crohn's disease (CD). Although hematopoietic stem cell transplantation (HSCT) remains the only curative option for these patients, its outcomes are suboptimal, with a long‑-term survival rate of only 50%. Therefore, identifying novel therapeutic targets is crucial to bridge this unmet clinical need. Here, we demonstrate that the abundance of tuft cells is reduced in both XIAP-deficient CD patients and Xiap knockout (Xiap -/-) mice. Mechanistically, XIAP deficiency reduces TLE4 ubiquitination, resulting in elevated TLE4 protein levels and consequent suppression of Wnt/β‑-catenin-ASCL2 signaling, which is critical for secretory lineage differentiation. Tuft cell deficiency may increase susceptibility to microbial dysregulation, thereby promoting intestinal inflammation. Furthermore, we demonstrate that JAK inhibition promotes tuft cell regeneration and ameliorates mucosal inflammation in Xiap -/- mice. Consistently, in an XIAP‑-deficient CD patient, treatment with a selective JAK1 inhibitor effectively increased tuft cell proportion and alleviated colonic symptoms. In conclusion, our study identifies tuft cell deficiency as a trigger of intestinal pathology in XIAP‑-deficient Crohn's disease and suggests JAK inhibition as a promising therapeutic strategy.
Risk stratification in patients with angina and nonobstructive coronary arteries (ANOCA) remains suboptimal. Coronary flow velocity reserve (CFVR) is prognostic but susceptible to hemodynamic variability; we evaluated whether hyperemic coronary flow velocity (hCFV) improves risk prediction. We analyzed 246 consecutively enrolled ANOCA patients and an independent validation cohort (n = 135). Transthoracic Doppler of the mid-distal LAD quantified CFVR and hCFV. The primary end point was major adverse cardiovascular events (MACE). During a median follow-up of 28.8 months, 27 patients (10.9%) experienced MACE. Both CFVR and hCFV were significantly associated with MACE. Among patients with CFVR < 2.5, hCFV ≤ 0.44 m/s independently predicted MACE (adjusted HR 6.6, p = 0.001). A combined CFVR-hCFV scheme yielded graded risk of MACE (Group A: CFVR ≥ 2.5; Group B: CFVR < 2.5 with hCFV > 0.44 m/s; Group C: CFVR < 2.5 with hCFV ≤ 0.44 m/s), with Group C exhibiting the highest risk of MACE (35.5% vs. 6.3%, 10.5%, p < 0.01). Adding reduced hCFV to a model including clinical risk factors and CFVR improved prediction (IDI 0.05, p = 0.011; NRI 0.23, p = 0.0023) and was confirmed in the validation cohort. Reduced hCFV provides incremental prognostic value beyond CFVR and offers a practical approach to identify high-risk ANOCA patients.
Osteoarthritis (OA) is the most common chronic joint disorder and a major cause of disability worldwide. Once regarded as a consequence of cartilage wear, OA is now recognized as a complex whole-joint disease involving coordinated pathological changes in articular cartilage, synovium, and subchondral bone. Disease progression is driven by chronic low-grade inflammation, metabolic dysregulation, oxidative stress, and abnormal cellular responses to mechanical stress. These processes are mediated by interconnected signaling networks that regulate inflammatory responses, extracellular matrix (ECM) metabolism, and tissue remodeling. Epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs, are increasingly recognized as regulators of OA-related gene expression. However, how signaling networks integrate with epigenetic regulation, particularly histone methylation, remains incompletely understood. In this review, we summarize the epidemiological burden and major risk factors of OA, describe pathological remodeling across joint tissues, and discuss key signaling pathways involved in OA pathogenesis before outlining epigenetic mechanisms. We also highlight the role of histone methylation in inflammation, metabolic imbalance, and tissue remodeling, and summarize current nonpharmacological, pharmacological, injectable, and surgical treatment strategies. Together, this review provides an integrated overview of the epidemiology, pathogenesis, and treatment of OA.
Cancer neuroscience has emerged as a paradigm-shifting discipline that reveals the active role of the nervous system in tumor development and progression. This review synthesizes current understanding of how bidirectional interactions between neurons and cancer cells influence tumorigenesis, metastasis, and therapy response. While earlier frameworks have established the fundamental mechanisms of nerve-tumor interactions, the present study proposes an expanded classification scheme that incorporates two additional mechanisms: perineural invasion as a unique metastatic pathway and neuro-microbic-oncology, which incorporates the gut-brain-immune axis into cancer biology. The remodeling of tumor microenvironment is structured around three principal mechanisms: electrochemical signaling, paracrine communication, and neuroimmune modulation. The contribution of these interactions to cancer-associated comorbidities, including pain, cachexia, and cognitive dysfunction, is highlighted, and their translational relevance is discussed in the context of emerging neurotherapeutic strategies. This review provides an integrated conceptual framework that connects neurobiology, oncology, and immunology, thereby informing the development of nerve-targeted therapeutic strategies with potential to improve clinical outcomes in cancer.
Neoadjuvant immunotherapy-based combination holds promises in reducing surgical risk and improving survival for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). However, its role in RCC-VTT has been less explored. To evaluate the efficacy and safety of neoadjuvant toripalimab plus axitinib in nonmetastatic RCC-VTT, we conducted a combined analysis of two Phase II trials with similar design. Thirty-four patients with nonmetastatic clear cell RCC (ccRCC) and Mayo Level 0-IV VTT were enrolled. Toripalimab plus axitinib was administered for up to 12 weeks before surgery. The primary endpoint was objective response rate (ORR). In this study, the ORR and disease control rates were 41% (14 out of 34) and 97% (33 out of 34), respectively. 47% (16 out of 34) patients experienced a reduction in VTT levels. Grade 3 treatment-related adverse events (TRAEs) occurred in 24% (eight out of 34) patients, and no Grade 4 or 5 TRAEs were observed. Thirty patients were eligible for surgery, and the surgical strategy was simplified in 53% (16 out of 30) patients. One-year disease-free survival and overall survival were 76.7% (95% CI, 59.1-88.2%) and 91.2% (95% CI, 77.0-97.0%), respectively. Multiomics analysis revealed the nonresponder group exhibited significant tumor heterogeneity and a stroma-characterized tumor microenvironment. In conclusion, neoadjuvant toripalimab plus axitinib was clinically active and safe in patients with nonmetastatic ccRCC-VTT.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of premature mortality, but data on sex differences in mortality remain limited. We compared the overall, nonliver-related, and liver-related mortality rates per 1000 person-years in MASLD patients by sex. Propensity score matching (PSM) yielded 3579 pairs of females and males with balanced characteristics from a cohort of 8517 MASLD patients (53.1% female, 46.6% male) seen at Stanford University Medical Center (1995-2023). In the total PSM cohort, the overall (12.68 vs. 12.92), nonliver-related (11.43 vs. 11.60), and liver-related (1.25 vs. 1.32) mortality rates were similar between males and females. However, in age-stratified analyses, females had higher overall (7.99 vs. 4.95, p = 0.02) and nonliver-related (7.20 vs. 4.71, p = 0.05) mortality rates among younger (≤50 years) patients, with opposite direction among the older group with higher overall (21.40 vs. 16.51, p = 0.02) and nonliver-related (19.02 vs. 14.80, p = 0.04) mortality rates in males. In Cox regression analyses, male sex was associated with lower risks of overall and nonliver-related mortality (adjusted hazard ratio [aHR] 0.59 and 0.61) among patients ≤50 years, but with higher risks among those >50 years (aHR 1.32 and 1.30). Sex and age should be considered in the management strategies for people with MASLD.
The ongoing evolution of SARS-CoV-2 and its immune-evading variants underscores an urgent requirement for broad-spectrum antiviral drugs. In this study, a series of lycorine derivatives was synthesized. This led to the identification of compound 7 as a promising antiviral candidate. Compound 7 exhibited potent inhibitory activity against SARS-CoV-2 and its variants, including Alpha, Beta, Delta, and Omicron, in vitro. The antiviral efficacy of compound 7 was then validated in vivo. Treatment with compound 7 significantly reduced viral loads and alleviated lung pathologies in SARS-CoV-2-infected hamsters. Mechanistically, compound 7 directly targeted the short isoform of the zinc-finger antiviral protein (ZAP-S) and bound to specific residues (E111, E115, and F549). This result was confirmed using cellular thermal shift assays, bio-layer interferometry, and mutagenesis studies. This interaction enhanced the ZAP-S stability and disrupted -1 programmed ribosomal frameshifting (-1PRF), a critical process for viral polyprotein synthesis. The antiviral activity of compound 7 was ZAP-S-dependent, as ZAP-S knockdown abolished its efficacy while overexpression enhanced it. These results established compound 7 as a novel antiviral candidate that can combat SARS-CoV-2 and its variants by targeting ZAP to inhibit -1PRF. This compound, therefore, represents a promising therapeutic strategy.
Oncolytic virotherapy is an emerging cancer immunotherapy that combines selective tumor cell lysis with activation of systemic antitumor immunity. Various DNA- and RNA-based oncolytic viruses (OVs) have demonstrated favorable safety profiles and therapeutic activity across different malignancies. Despite these advancements, clinical efficacy remains inconsistent because of several biological barriers, including rapid immune clearance, insufficient tumor targeting, limited intratumoral spread, and the immunosuppressive tumor microenvironment (TME). In this review, we examine the key mechanisms of OV infection, tumor selectivity, and virus-induced antitumor immune responses. It also explores the factors that limit therapeutic efficacy, particularly host antiviral immunity, structural barriers within solid tumors, and the immunosuppressive networks in the TME. To address these challenges, a range of strategies have been developed, with a focus on optimizing viral delivery. Current approaches, such as cell-based carriers, extracellular vesicle-mediated transport, and nanomaterial-assisted delivery systems, aim to enhance tumor targeting, protect viral integrity, and improve intratumoral distribution. Additionally, combination therapies designed to enhance antitumor immunity and reshape the TME are outlined, including immune checkpoint blockade, chemoradiotherapy, and metabolic modulation. Collectively, these advancements transform OVs from standalone cytolytic agents into adaptable immunotherapeutic platforms, with their effectiveness determined by the delivery method, microenvironmental conditions, and therapeutic integration.
Cerebral infarction, the pathological basis of ischemic stroke, remains a leading cause of mortality and long-term disability worldwide. Its clinical heterogeneity reflects the complex interplay among vascular pathology, metabolic failure, immune responses, and genetic susceptibility, posing persistent challenges to effective risk stratification and individualized therapy. This review provides an integrative overview of cerebral infarction from a precision medicine perspective, synthesizing advances across epidemiology, pathophysiology, diagnostics, and therapeutics to bridge the gap between mechanistic insight and clinical outcomes. We first summarize global epidemiological trends, highlighting persistent disparities and the shift toward understanding modifiable and emerging risk factors. We then critically examine the evolution of stroke classification from traditional systems (e.g., Trial of Org 10172 in Acute Stroke Treatment [TOAST]) toward phenotype-driven and molecularly informed frameworks. The core of the review delves into key pathophysiological mechanisms-including neurovascular unit dysfunction, energy metabolism disturbance, and regulated cell death pathways such as ferroptosis-and their implications for targeted intervention. We further appraise contemporary diagnostic advances, encompassing multimodal imaging, circulating biomarkers, and artificial intelligence-assisted tools, alongside current treatment strategies like reperfusion therapy and emerging neuroprotective approaches. Finally, we discuss how multiomics technologies and data-driven models are redefining stroke subtyping and guiding individualized management. By employing a mechanism-phenotype-decision framework, this review offers a coherent synthesis of the field, providing a roadmap to support the transition from empirical care toward precision-oriented management in cerebral infarction.
We aimed to evaluate associations of chronotype, genetic risk, and lifestyle with depression and anxiety. A total of 242,391 participants without anxiety and depression at baseline in UK Biobank were included. During a total of 3,393,260.1 and 1,371,872.8 person-years follow-up, we found 11,824 (4.88%) incident depression and 10,051 (4.15%) incident anxiety cases, respectively. Compared with definite morning group, individuals with intermediate (HR = 1.09, 95% CI = 1.04‒1.13) and definite evening chronotype (HR = 1.45, 95% CI = 1.36‒1.55) have higher risks of depression, and individuals with definite evening chronotype (HR = 1.27, 95% CI = 1.18‒1.37) have a higher risk of anxiety. We found joint association between chronotype and genetic risk, those with high genetic risk and definite evening chronotype had the highest risk of depression (HR = 2.01, 95% CI = 1.81‒2.23) and anxiety (HR = 1.40, 95% CI = 1.24‒1.58). We also found joint association between chronotype and lifestyle, those with least healthy lifestyle and definite evening chronotype had the highest risk of depression (HR = 1.99, 95% CI = 1.65‒2.40) and anxiety (HR = 1.69, 95% CI = 1.36‒2.10). Individuals with evening chronotype are associated with higher risks of depression and anxiety.
Emerging immunotherapy holds promise to achieve treatment-free remission (TFR) for chronic myeloid leukemia (CML) patients, the development of which depends on full understanding of mechanisms driving immune evasion. Our current investigation in a mouse CML model revealed dominant presence of neutrophils during CML progression, accompanied by significant reductions and exhaustion of T cells. In coculture, these BCR-ABL1 expressing neutrophil-like CML cells significantly inhibited T cell proliferation. Gene expression profiling revealed that there was a global activation of both neutrophil markers and related immune suppression genes in these CML cells. Correlative analysis revealed strong correlations between the expression of BCR-ABL1 and immune suppression genes, suggesting a potential regulation of those genes by BCR-ABL1. Importantly, we identified CEBPB as a critical transcription factor that directly regulated the expression of master immune modulators TGFB1 and ARG2 through promoter binding, in both human and mouse CML samples. Therefore, blocking BCR-ABL1, or its downstream C/EBPβ, TGF-β and arginase with inhibitors or shRNAs rescued T cell suppression by neutrophil-like CML cells. Accordingly, combination treatment with targeted therapy using ponatinib and immunotherapy with anti-PD1 antibody not only provides rapid remission, but also delayed relapses after treatment discontinuation, justifying combination treatment for TFR of CML.
Lucitanib is a novel multi-target inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-3, and platelet-derived growth factor receptor α/β. This open-label, multicenter, single-arm Phase II study evaluated lucitanib plus the anti-programmed cell death 1 (PD-1) antibody toripalimab in patients with advanced solid tumors refractory to standard therapies. Patients received lucitanib (10 mg) once daily plus toripalimab (240 mg) every 3 weeks until progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) and secondary endpoints included disease control rate, duration of response, progression-free survival (PFS), overall survival, and safety. Among 131 patients across four cohorts (PD-1-treated recurrent/metastatic nasopharyngeal carcinoma [NPC], PD-1-naïve NPC, recurrent/metastatic endometrial cancer [EC], and other tumors), ORR was 34.1%, 45.8%, 38.5%, and 13.5%, respectively. Median PFS was 4.2 months (95% confidence interval [CI], 4.1-5.6), 6.5 months (95% CI, 4.0-not estimable [NE]), 5.6 months (95% CI, 2.78-11.21), and 9.7 months (95% CI, 5.4-NE). The most common Grade ≥ 3 treatment-related adverse events were hypertension (37.4%), proteinuria (10.7%), and thrombocytopenia (10.7%). Lucitanib plus toripalimab showed encouraging antitumor activity with manageable safety in heavily pretreated advanced solid tumors, supporting further randomized evaluation, particularly in NPC and EC. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2400087935.
Neurological and psychiatric disorders, arising from disruptions in neural circuitry, pose a major and growing challenge to global healthcare systems. Brain-computer interface (BCI) technology has emerged as a promising approach, enabling direct communication between the brain and external devices. By facilitating bidirectional interaction with the nervous system, BCIs open new avenues for both diagnosis and treatment. In this review, we examine recent advances in recording and stimulation technologies within the BCI framework and evaluate their therapeutic potential across major neuropsychiatric disorders. We focus particularly on post-stroke motor rehabilitation as a representative paradigm, providing detailed analysis of the mechanisms, clinical evidence, and future prospects of endovascular BCI, BCI-integrated epidural spinal cord stimulation, and BCI-driven deep brain stimulation. We further extend the discussion to movement disorders such as Parkinson's disease and epilepsy, as well as cognitive and psychiatric conditions including Alzheimer's disease and depression, highlighting how BCI-based approaches enable symptom detection and closed-loop neuromodulation. Additionally, we address ethical and societal considerations accompanying clinical translation of these advanced neurotechnologies. By integrating current evidence, this review highlights a paradigm shift toward more active, precise, and personalized neural rehabilitation enabled by BCI systems, while outlining key challenges and future directions for research and clinical application.