BACKGROUND:High-frequency repetitive transcranial magnetic stimulation has garnered significant attention due to its potential non-invasive benefits in modulating brain function.However,no studies have comprehensively analyzed the current research landscape and development trends of this field from a macroscopic perspective.OBJECTIVE:To explore research hotspots,current trends,and emerging frontiers in the field of high-frequency repetitive transcranial magnetic stimulation through visualized analysis.METHODS:Data were collected from the Web of Science Core Collection database from January 1,2014 to November 15,2024.CiteSpace was used for analyzing publication volume,collaborations among countries/regions,institutions and authors,citation analysis of journals and co-cited literature,as well as disciplinary distribution.Additionally,keyword co-occurrence,clustering,and burst analyses were conducted,and visualized knowledge maps were generated.RESULTS AND CONCLUSION:A total of 860 articles were included.The publication volume of high-frequency repetitive transcranial magnetic stimulation showed an overall upward trend from 2014 to 2022,followed by a decline from 2022 to 2024.China had the highest publication volume,while Ghent University ranked as the most productive institution.Universities acted as the most high-output institutions.Chris Baeken from Ghent University was identified as the most prolific author.Collaboration among leading authors and institutions worldwide remained limited.The main research hotspots in this field were associated with keywords such as depression,stroke,neuropathic pain,and Parkinson's disease.Burst keywords focused on mild cognitive impairment,reflecting a diversification in research directions.The overall research activity in high-frequency repetitive transcranial magnetic stimulation continues to rise,with primary focuses on its clinical applications for psychiatric and neurological disorders,as well as explorations of its underlying mechanisms.Future research may focus on optimizing treatment parameters for targeting different brain regions in clinical applications and expanding its applications and mechanisms across various domains.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.

Chronic diabetic wounds, severely complicated by multidrug-resistant (MDR) bacterial infections, represent a profound and escalating global health crisis. The intrinsically hostile microenvironment of diabetic wounds, characterized by localized hypoxia, persistent oxidative stress, and poor vascularization, creates an ideal niche for opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. These bacteria readily construct dense extracellular polymeric substance (EPS) biofilms, which not only physically shield the microbes from host immune responses but also actively trap the wound in a state of chronic, unresolved inflammation. Consequently, conventional systemic and topical antibiotic therapies are becoming increasingly futile, as poor perfusion at the wound site restricts drug bioavailability, while the rapid genetic evolution of bacteria and the impenetrable nature of biofilms lead to catastrophic treatment failures, often culminating in severe tissue necrosis and lower-extremity amputations. To circumvent the limitations of traditional antimicrobials, therapeutic gas delivery has emerged as a highly promising, paradigm-shifting strategy. Gaseous signaling molecules, particularly nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and hydrogen (H₂), possess unique physicochemical properties that allow them to seamlessly penetrate dense biofilm matrices and cellular membranes. Once inside, these gases operate via multi-targeted mechanisms that are incredibly difficult for bacteria to develop resistance against; for instance, NO induces severe lipid peroxidation and DNA cleavage in bacteria, CO downregulates pro-inflammatory cytokines, H₂S significantly accelerates endothelial cell migration for neovascularization, and H₂ acts as a powerful selective antioxidant to neutralize tissue-damaging reactive oxygen species (ROS). Together, these therapeutic gases not only exert broad-spectrum bactericidal effects but also actively reprogram the wound bed by promoting the critical M1-to-M2 macrophage polarization and stimulating angiogenesis. Despite their immense biological potential, the direct clinical translation of gas therapies is severely hindered by inherent physicochemical drawbacks, including extreme volatility, short physiological half-lives, poor aqueous solubility, and the high risk of off-target systemic toxicity, if applied indiscriminately. To conquer these immense pharmacokinetic barriers, cutting-edge advancements in materials science have driven the development of gas-releasing micro- and nanoplatforms. Utilizing sophisticated carriers such as metal-organic frameworks (MOFs), mesoporous silica, polymeric nanoparticles, liposomes, and injectable hydrogels, researchers can now encapsulate gas-donor molecules to achieve sustained, localized delivery. More importantly, these advanced nanoplatforms are ingeniously engineered to be stimuli-responsive. By exploiting the pathological hallmarks of the diabetic wound environment, such as elevated glucose concentrations, acidic pH, and overexpressed ROS, or by utilizing external triggers like near-infrared (NIR) light irradiation and ultrasound, these intelligent platforms ensure on-demand, precise spatio-temporal gas release. This often allows for powerful synergistic combinations, such as photothermal or photodynamic therapy coupled with gas release, thereby obliterating biofilms while sparing healthy tissue. While the therapeutic outcomes of these smart delivery systems in eradicating MDR infections and accelerating tissue repair are unprecedented, several critical challenges remain before widespread clinical adoption, as long-term biosafety profiles of the carrier nanomaterials, complexities in large-scale good manufacturing practice (GMP) production, and stringent regulatory hurdles must be rigorously addressed. Looking forward, the next frontier lies in the realm of precision medicine and theranostics, where future research must focus on the seamless integration of these gas-releasing platforms with flexible, wearable biosensors capable of continuously monitoring wound biomarkers (e.g., pH, temperature, uric acid) in real-time. Coupled with artificial intelligence algorithms to govern automated, closed-loop adaptive dosing, these next-generation smart dressings hold the ultimate potential to comprehensively transform the clinical management of complex, infected diabetic wounds.

BACKGROUND:High-frequency repetitive transcranial magnetic stimulation has garnered significant attention due to its potential non-invasive benefits in modulating brain function.However,no studies have comprehensively analyzed the current research landscape and development trends of this field from a macroscopic perspective.OBJECTIVE:To explore research hotspots,current trends,and emerging frontiers in the field of high-frequency repetitive transcranial magnetic stimulation through visualized analysis.METHODS:Data were collected from the Web of Science Core Collection database from January 1,2014 to November 15,2024.CiteSpace was used for analyzing publication volume,collaborations among countries/regions,institutions and authors,citation analysis of journals and co-cited literature,as well as disciplinary distribution.Additionally,keyword co-occurrence,clustering,and burst analyses were conducted,and visualized knowledge maps were generated.RESULTS AND CONCLUSION:A total of 860 articles were included.The publication volume of high-frequency repetitive transcranial magnetic stimulation showed an overall upward trend from 2014 to 2022,followed by a decline from 2022 to 2024.China had the highest publication volume,while Ghent University ranked as the most productive institution.Universities acted as the most high-output institutions.Chris Baeken from Ghent University was identified as the most prolific author.Collaboration among leading authors and institutions worldwide remained limited.The main research hotspots in this field were associated with keywords such as depression,stroke,neuropathic pain,and Parkinson's disease.Burst keywords focused on mild cognitive impairment,reflecting a diversification in research directions.The overall research activity in high-frequency repetitive transcranial magnetic stimulation continues to rise,with primary focuses on its clinical applications for psychiatric and neurological disorders,as well as explorations of its underlying mechanisms.Future research may focus on optimizing treatment parameters for targeting different brain regions in clinical applications and expanding its applications and mechanisms across various domains.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objective: To analyze the association between intraoperative blood transfusion and adverse perinatal outcomes(a composite of maternal death, hepatic encephalopathy, etc) in patients with acute fatty liver of pregnancy (AFLP), identify independent risk factors for these outcomes, and develop and validate a risk prediction model for early identification of high-risk patients. Methods: Clinical data of 56 AFLP patients admitted to our hospital from January 2008 to January 2025 were retrospectively analyzed. The chi-square test was used to compare the incidence of adverse perinatal outcomes between the transfusion group and the non-transfusion group. Univariate and multivariate Firth-penalized logistic regression analyses were performed to identify independent predictors of adverse outcomes. Based on the identified independent risk factors, a combined prediction model was developed. Internal validation was performed using the Bootstrap method (1 000 resamplings) to assess the model′s generalizability. Model performance was evaluated using receiver operating characteristic(ROC) curves and calibration curves. Finally, a nomogram for predicting adverse perinatal outcomes in AFLP was constructed. Results: Overall, 57.1%(32/56) of the patients received blood product transfusion during the termination of pregnancy. Multivariate Firth-penalized logistic regression analysis showed that, given the limited sample size, intraoperative blood transfusion had no independent statistical effect on adverse outcomes (OR=0.812, 95%CI:0.133-3.698, P=0.797). Mediation analysis also revealed no significant indirect effect. The independent risk factors were decreased preoperative fibrinogen (OR=14.062, 95%CI:2.389-126.656, P=0.003), pregnancy with infection (OR= 4.536, 95%CI:1.143-22.107, P=0.031), and cesarean section (OR=8.691, 95%CI:1.321-90.081, P=0.023). The combined prediction model achieved an AUC of 0.881 (95% CI:0.793-0.969, P<0.001), indicating good discrimination. At the optimal cut-off value, the sensitivity was 65.6%, specificity 95.8%, positive predictive value 95.5%, and negative predictive value 67.6%. Internal validation by the Bootstrap method showed that the predictive model had good discrimination and no obvious overfitting. The calibration curve demonstrated that the model′s predicted risk was consistent with the actual observed risk. Based on this, an AFLP perinatal adverse outcome nomogram model was constructed. Conclusion: Under the limited sample size of this study, no independent statistical effect of intraoperative blood product infusion on adverse perinatal outcomes in AFLP patients was detected. A multivariate Firth-penalized logistic regression model incorporating decreased preoperative fibrinogen, pregnancy with infection, and cesarean delivery demonstrated good discrimination and calibration. The derived nomogram may serve as an exploratory tool for early risk stratification and proactive intervention.

Background/Aims: MicroRNA (miRNA) isoforms (isomiRs) broaden the regulatory landscape of canonical miRNAs, but their role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. We aimed to characterize the hepatic isomiR landscape in MASLD and define their association with disease activity and fibrosis. Methods: Small RNA (sRNA) sequencing was performed on liver biopsies from 79 patients across the histological spectrum of MASLD. IsomiRs were annotated and quantified. Their association to disease activity and fibrosis score was assessed by differential expression, ordinal regression, and machine learning. Parallel mRNA sequencing and pathway enrichment were used to map isomiR–mRNA interactions and regulatory networks, which were validated against an independent dataset. Results: MiRNAs accounted for 75% of sRNAs in liver tissue, of which 67% were isomiRs. Across MASLD severity, 173 isomiRs correlated with disease activity and 58 with fibrosis stage. Key findings included a miR-122 isomiR uniquely targeting INSIG1 (cholesterol metabolism) and a miR-21 isomiR targeting PPARA and HMGCS2 (lipid and fibrosis pathways). Integration with mRNA data revealed 33 dysregulated pathways, including PPAR signaling, insulin resistance, and TGF-β response. Several novel isomiRs from miR-26b, let-7c, and miR-32 families were also linked to lipid metabolism and fibrosis progression. Conclusions IsomiRs represent the majority of hepatic miRNAs and uncover novel regulatory networks masked by canonical miRNA analysis. These findings provide new insights into the molecular heterogeneity of MASLD, highlight candidate pathways driving disease progression, and identify potential biomarkers and therapeutic targets for precision hepatology.