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.

Hepatic sinusoidal capillarization is the first event in the process of fibrogenesis， and inhibiting hepatic sinusoidal capillarization can effectively improve the pathological process of liver fibrosis. Various studies have shown that traditional Chinese medicine can significantly inhibit hepatic sinusoidal capillarization. This article systematically reviews the effective constituents， monomers， and compound prescriptions of traditional Chinese medicine， summarizes their mechanism of action in inhibiting hepatic sinusoidal capillarization， and analyzes the theoretical core of traditional Chinese medicine in inhibiting hepatic sinusoidal capillarization from the perspective of traditional Chinese medicine， in order to provide ideas and literature support for the treatment of liver fibrosis.

Hemoglobin (Hb) concentration is a key clinical biomarker for diagnosing and managing anemia, ischemic stroke, perioperative blood loss, and chronic diseases such as renal failure. Traditional venous blood sampling remains the gold standard due to its high accuracy, but its invasive nature limits frequent testing, real time monitoring, and large scale screening. This has driven growing interest in non-invasive Hb detection technologies over the past decade. Among these, optical methods are the most promising because of their safety, potential for continuous monitoring, and compatibility with portable or wearable devices. This paper systematically reviews major advances in optical non invasive Hb detection from the last ten years. We focus on near-infrared spectroscopy branches—photoplethysmography (PPG) and dynamic spectrum (DS)—and also cover color analysis/RGB imaging, Raman spectroscopy, and photoacoustic spectroscopy. For each technology, we explain its detection principles, analyze advantages and limitations, and summarize optimization strategies reported in recent literature. PPG, based on pulsatile blood volume changes, underpins many commercial continuous monitors. However, its accuracy is constrained by motion artifacts, individual physiological variations (e.g., skin tone, tissue thickness), and low AC signal to noise ratio. In contrast, DS—an advanced derivative of PPG—uses a differential principle to extract absorbance changes between systolic and diastolic peaks. This theoretically eliminates interference from static tissues (skin, bone, venous blood) and common mode noise (e.g., ambient light), positioning DS as a more robust framework for high precision Hb quantification. Beyond spectral methods, color analysis/RGB imaging offers a hardware minimalist approach. By analyzing images of vascular rich, thin tissues (e.g., conjunctiva, nail beds, palms), it enables Hb estimation using smartphone cameras. Recent advances have shifted from manual RGB feature extraction to deep learning models and spectral super resolution that reconstruct hyperspectral data from RGB inputs, significantly improving screening accuracy. Our academic perspective emphasizes critical and integrative analysis. We highlight persistent challenges that hinder clinical translation: profound individual biological variability (skin optics, microvascular architecture), sensitivity to measurement conditions (pressure, ambient light), and a lack of standardized validation protocols and multi center trials. A central thesis is that no single optical method is universally superior; each involves trade offs between accuracy, complexity, cost, and practicality. Looking forward, we posit that the next performance leap will come from multimodal information fusion—combining PPG, electrocardiogram (ECG), bioimpedance, or different optical modalities to compensate for individual differences and environmental noise. AI and deep learning are essential not only for image analysis but also for automated, end to end feature extraction from complex waveforms like PPG sequences. Advancing hardware (tunable lasers, quantum dot LEDs, novel sensor designs) is crucial to improve signal fidelity and portability. Finally, we advocate for clinical scenario specific optimization and rigorous standardized evaluation frameworks to gain regulatory approval (e.g., FDA, NMPA) and achieve widespread clinical acceptance. In conclusion, this review synthesizes a decade of progress. Optical non-invasive Hb detection has evolved from proof of concept studies to emerging products and validated screening tools, but the journey toward reliable, clinic ready quantitative devices continues. The convergence of smarter algorithms, fused sensing modalities, and focused clinical validation offers the most promising path to transform this potential into routine medical practice, ultimately enabling personalized, continuous, and accessible hematological management.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.

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.

Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

Hepatitis B virus （HBV） exclusively infects liver parenchymal cells and forms covalently closed circular DNA （cccDNA） within their nuclei. HBV cccDNA serves as the essential template for viral gene transcription， the sole source of progeny virus production， and the key driver of viral antigen expression， and it is the molecular basis for the persistence of HBV infection. Therefore， elimination and/or functional silencing of cccDNA is the key to eradicate chronic HBV infection. This article discusses the critical scientific issues that need to be solved during elimination of the harm of HBV infection from the perspectives of the synthesis， transcription， and clearance of cccDNA， as well as the impact of nonparenchymal cells on cccDNA， in order to provide a reference for eradicating HBV infection in the future.