Search Results (800)

Background: Essential tremor (ET) is a common movement disorder that predominantly affects older adults, with rising global prevalence due to population aging. Pharmacological treatments, including propranolol and primidone, are often limited by inadequate efficacy or poor tolerability, and surgical options carry inherent risks. Acupuncture has shown promise as an alternative or adjunctive therapy for ET, but evidence comparing the effectiveness of different acupuncture modalities remains limited. Objective: To systematically evaluate the comparative efficacy and safety of various acupuncture-related interventions for essential tremor (ET) through a network meta-analysis, and to provide evidence-based recommendations for clinical practice. Methods: We systematically searched eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM) from inception to 20 October 2025. Randomized controlled trials (RCTs) evaluating any form of acupuncture therapy for ET were included. Conventional pairwise meta-analysis and network meta-analysis were performed to compare the efficacy (response rate, Tremor Six Score) and safety (adverse events) of different interventions. Surface under the cumulative ranking curve (SUCRA) values were used to rank treatment modalities. Results: Twenty randomized controlled trials involving 1067 participants were included. Traditional meta-analysis indicated that acupuncture-related interventions significantly outperformed controls in improving response rate [RR 4.36, 95% CI (3.14, 6.03), p < 0.00001], reducing Tremor Six Score [MD −1.99, 95% CI (−2.25, −1.73), p < 0.00001], and lowering the incidence of adverse events [RR 0.13, 95% CI (0.07, 0.25), p < 0.00001]. Network meta-analysis based on SUCRA values revealed that: for symptom relief, scalp acupuncture (S) demonstrated the highest effectiveness (SUCRA = 81.5%); for reducing Tremor Six Score, manual acupuncture (A) showed the most significant effect (SUCRA = 76.6%); and for safety outcomes, Acupuncture + Scalp Acupuncture + Propranolol (A+S+P) achieved the highest SUCRA score (SUCRA = 73.1%). Conclusions: This network meta-analysis demonstrates that acupuncture-related interventions are effective and safe for treating essential tremor. However, caution is warranted in interpreting these findings due to methodological limitations in the included randomized controlled trials (small sample sizes, lack of blinding, inadequate allocation concealment), sparse data for some interventions, and the concentration of studies within China, which limits their generalizability. Despite these limitations, acupuncture offers a valuable non-pharmacological treatment option for patients with poor medication tolerance. Future large-scale, multicenter trials with rigorous designs are needed to validate these findings. Full article

Most patients with irritable bowel syndrome have diarrhea or constipation, two opposite bowel habits. Although defecation habits represent opposing phenotypes, patients across all subtypes exhibit visceral hypersensitivity. This review explores the common pathway that causes visceral hypersensitivity: the mast cell–PAR2–TRP axis. The mechanism involves tryptase released by mast cells. Furthermore, tryptase activates PAR2, which sensitizes downstream TRP ion channels that conduct pain signals. The review also examines the factors leading to the formation of different fecal characteristics. In terms of treatment, this review also summarizes therapeutic agents targeting different components of this axis. Future pharmaceutical research should focus more on the mast cell–PAR2–TRP axis. Full article

We developed an AI-based system for facial acupoint recognition and healthcare support, integrating MediaPipe facial and hand tracking technologies to address the problems of inaccurate and non-standardized acupoint identification in traditional Chinese medicine (TCM). By leveraging facial landmark detection and fingertip tracking, the system enables accurate localization of facial acupoints to ensure precise stimulation. The system contributes to the standardization of acupoint recognition, intelligent health consultation, and the digital transformation of TCM practices. Further enhancements are necessary by expanding acupoint recognition to other body parts (e.g., ears, hands, feet, and back) and integrating with wearable devices to further promote personalized and precise TCM healthcare. Full article

Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the pleasant sensation elicited by gentle pressure on a mouse’s nape. However, their potential role in mitigating pain and pain-related negative emotions in response to somatic stimuli remains unclear. Methods: A CFA-induced chronic pain and anxiety comorbidity model was established in C57BL/6J mice. In vivo calcium imaging of dorsal root ganglia (DRG) neurons in Mrgprb4-GCaMP6s transgenic mice characterized neuronal responses to transcutaneous electrical nerve stimulation (TENS) at the Zusanli (ST36) acupoint. Optogenetic activation (Mrgprb4-ChR2 mice) and viral ablation of Mrgprb4-lineage neurons were employed to evaluate their role in mediating TENS effects on mechanical pain thresholds and anxiety-like behaviors. Results: In vivo calcium imaging revealed that 0.5 mA TENS preferentially activated Mrgprb4-lineage neurons compared to 2.0 mA TENS. In CFA model mice, 0.5 mA TENS at ST36 significantly increased mechanical pain thresholds and reduced anxiety-like behaviors in the open-field test. Optogenetic activation of Mrgprb4-lineage neurons at ST36 replicated these analgesic and anxiolytic effects, demonstrating the sufficiency of these neurons for therapeutic outcomes. Conversely, viral ablation of L3–L5 Mrgprb4-lineage neurons substantially attenuated the therapeutic effects of 0.5 mA TENS for both pain relief and anxiety reduction, indicating their necessity in mediating TENS efficacy. Conclusions: Mrgprb4-lineage neurons serve as critical peripheral mediators of TENS-induced analgesia and anxiolysis. These findings identify a specific neuronal population underlying the therapeutic effects of somatic stimulation at ST36, providing mechanistic insights that may guide optimization of TENS parameters for treating chronic pain and comorbid anxiety in clinical settings. Full article

The γ-aminobutyric acid type A receptor subunit delta (GABRD) constitutes a critical component of the principal inhibitory neurotransmitter receptors within the brain. Recent investigations have revealed aberrant expression of GABRD across a spectrum of non-neural malignancies, including breast, colorectal, and gastric cancers, wherein it exhibits a multifaceted and paradoxical role in oncogenesis. This review delineates the biological characteristics of GABRD and its involvement in cancer pathophysiology. Specifically, the activation of GABRD is implicated in the initiation of key downstream signaling pathways that facilitate the proliferation, invasion, and metastasis of cancer cells. Additionally, the review examines the interaction between GABRD and the tumor microenvironment. Furthermore, it provides an analysis of the diverse roles and mechanisms attributed to GABRD across various cancer types. In conclusion, this review encapsulates the current advancements in understanding the oncogenic functions of GABRD and deliberates on its potential and challenges as a novel target for therapeutic intervention. Full article

Background: Fibromyalgia is a chronic disease that predominantly affects women and lasts over several months, causing problems both for individuals and society. While several studies have demonstrated the potential of electroacupuncture (EA) to alleviate fibromyalgia pain in mice, further research is needed to investigate its underlying mechanisms. Programmed cell death ligand 1 (PD-L1)/PD-1 were first identified to be involved in cancer immunotherapy, and their application to pain management has not been yet investigated. Methods: In this study, we aimed to explore the mechanism underlying the action of PD-L1 on the PD-1 pathway in a mouse model of fibromyalgia. Results: We established such a mouse model using intermittent cold stress (ICS) and confirmed mechanical (D4: 2.02 ± 0.13 g, n = 9) and thermal (D4: 4.28 ± 0.21 s, n = 9) hyperalgesia. We found that EA, intracerebral ventricle (ICV) PD-L1 injection, and transient receptor potential vanilloid 1 (Trpv1) knockout effectively counteracted hyperalgesia. We observed low PD-1 expression in the cerebellum of fibromyalgia mice but increased expression of TRPV1 and pain-related kinases. These phenomena could be further reversed by EA, ICV PD-L1 injection, and Trpv1 knockout. To confirm that these effects were caused by PD-L1 release, we added PD-L1-neutralizing antibodies to the EA and PD-L1 treatment. The analgesic effects and EA and PD-L1 mechanisms were inhibited. Conclusions: Our results elucidate the role of the PD-L1/PD-1 pathway in EA treatment of fibromyalgia and reveal its potential value for fibromyalgia management. Full article

Background/Objectives: Neck disorders encompass a range of discomforts impacting a person’s quality of life. Traditional diagnostic methods, such as physical tests and imaging techniques, rely heavily on clinician expertise, leading to potential variability in assessments. While ultrasound imaging is commonly used, the application of machine learning models to assess neck disorders, particularly fascial abnormalities, remains limited. This study seeks to fill this gap by developing a machine learning model using ultrasound images to provide accurate and efficient support for diagnosing neck disorders. Methods: Due to limited availability of labeled ultrasound data for neck disorders, developing robust and generalizable models remains a challenge. In this study, a neck disorder assessment system was developed using ultrasound images collected from 184 patients by employing various machine learning algorithms. To address data scarcity and improve model generalizability, an approach utilizing EfficientNet with transfer learning was introduced and thoroughly assessed using the trained model on a completely clean test dataset, ensuring the robustness of the solution. The model was trained using 5-fold cross-validation with the respective weight of each class and AdamW as the optimizer. Results: The results showed promising performance, with the deep fascia fuzzy texture and deep fascia and myofascial adhesion at lower cervical regions demonstrating the highest weighted average F1-scores of 76% and 81%, respectively. The macro averages reflected similar performance, at 74% and 78%, respectively, indicating consistent class-wise accuracy for these regions. Conclusions: The proposed model demonstrated robust classification performance for neck disorder assessment, particularly in evaluating the lower cervical region. This approach has the potential to support clinical decision-making by providing consistent, efficient, and accurate diagnostic assistance. Further refinement and validation across diverse clinical settings will be critical to enhance its real-world applicability. Full article

Microfluidics-based preparation methods for cell-laden hydrogel microspheres are well-suited for large-scale comparative analysis of single or few cells. However, in existing studies, the preparation of cell-laden hydrogel microspheres and the cell culture process are typically separated, requiring the fabricated microspheres to be eluted and transferred from the preparation device to cell culture dishes or plates for cultivation. This transfer process can easily compromise sterility, while conventional cell culture methods consume more reagents and cause microsphere stacking, hindering single-cell observation and analysis. To address these issues, this paper presents an integrated microfluidic chip that sequentially enables droplet generation with cell encapsulation, gel droplet solidification, hydrogel microsphere trapping, and microsphere-based cell culture and analysis, facilitating the cultivation and observation of single or small numbers of cells. Integrating cell-laden microsphere preparation and 3D cell culture within a sealed chip structure reduces contamination risks associated with cell transfer, enables automation of multiple cell analysis workflows, and minimizes reagent and sample consumption. Using polydimethylsiloxane (PDMS) with good gas permeability and processability as the chip material, biocompatible fluorinated oil was selected as the oil phase for microsphere preparation. A mild sodium alginate-calcium ion gelation system was employed, where calcium ions were released under acidic conditions after droplet generation to trigger solidification, yielding uniform hydrogel microspheres. Under optimized conditions, the single-cell encapsulation efficiency for test samples of human myeloid leukemia cells (K562) was 33.8% ± 1.8%, with a size uniformity coefficient of variation (CV) reaching 3.85%. Cells encapsulated within hydrogel microspheres were cultured in 286 on-chip independent cell culture chambers, achieving >95% viability after 24 h. Full article

Peripheral nerve regeneration is most rapid during the early post-injury period but gradually slows over time, often limiting functional recovery. Electrical stimulation (ES) delivered via percutaneous needle electrodes has been shown to modulate the local neural microenvironment and promote axonal regeneration; however, the optimal temporal window and duration of stimulation remain unclear. This study aimed to evaluate the time-dependent effects of needle-based ES on peripheral nerve regeneration in a rat model of sciatic nerve transection, using a well-established silicone nerve conduit as a stable and reproducible non-biodegradable repair model. Female Sprague–Dawley rats underwent sciatic nerve transection and repair. Postoperatively (PO), animals were randomly assigned to control (C) needle insertion or needle-based ES groups, receiving stimulation for either 3 weeks (C-3W-PO and ES-3W-PO, respectively) or 7 weeks (C-7W-PO and ES-7W-PO, respectively). Functional recovery was evaluated using cold plate latency and rotarod performance tests. Electrophysiological assessments included measurements of nerve conduction velocity (NCV), compound muscle action potential amplitude, and muscle action potential (MAP) area. Histomorphometric analysis of regenerated nerve tissue quantified total nerve cross-sectional area, endoneurial space, axon number, and axon density. Retrograde labeling with fluoro-gold (FG) was used to quantify reinnervated motor neurons. Immunohistochemical analyses of calcitonin gene-related peptide (CGRP) and macrophage-associated markers were conducted to assess sensory neuropeptide expression and immune cell infiltration within the regenerated nerve. ES significantly improved both sensory and motor recovery in a duration-dependent manner. Behavioral data showed increased cold pain thresholds and improved motor coordination in ES groups, with the most pronounced functional gains observed in the ES-7W-PO group. Electrophysiological measures revealed higher NCV, amplitude, and MAP area in ES-treated animals, with the most pronounced improvements at 7 weeks. Morphologically, ES enhanced nerve regeneration, as evidenced by increased total and endoneurial areas, axonal counts, and axon density. FG-labeled neuron counts were significantly elevated in ES groups, indicating enhanced motor reinnervation. At 3 weeks, ES induced higher CGRP expression and macrophage density, suggesting transient activation of sensory-associated and pro-regenerative immune responses during the early post-injury phase. These findings demonstrate that ES accelerates peripheral nerve repair in rats and that sustained stimulation across the early regenerative window yields superior structural and functional outcomes. Full article

Knee osteoarthritis (KOA) is a chronic degenerative joint disorder driven largely by persistent inflammation and progressive cartilage damage. Naringin, a bioactive flavonoid abundant in citrus fruits, has shown potential anti-inflammatory effects; however, its molecular mechanisms in KOA remain unclear. In this study, an integrated approach combining network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments was employed to investigate the anti-inflammatory effects of naringin in KOA. Network pharmacology analysis identified 59 potential KOA-related targets of naringin, among which TNF, PTGS2, TP53, CASP3, and PPARG were recognized as core targets. Functional enrichment indicated these targets were primarily associated with inflammation- and apoptosis-related pathways, especially the TNF and IL-17 signaling pathways. Molecular docking and MD simulations revealed strong binding affinity and stable interactions between naringin and the key inflammatory mediators TNF-α and PTGS2. In an IL-1β-stimulated C28/I2 human chondrocyte model, naringin dose-dependently improved cell viability and significantly suppressed TNF-α and PTGS2 expression at both mRNA and protein levels. These findings provide mechanistic evidence that naringin alleviates KOA-associated chondrocyte inflammation by modulating key inflammatory mediators, supporting its potential as an anti-inflammatory therapeutic candidate for KOA. Full article

Chronic inflammation-driven colorectal cancer (CRC) is critically mediated by interleukin-17A (IL-17A)-dependent immune responses and nuclear factor-κB (NF-κB) signaling, which promote immune cell infiltration and tumor progression. In this study, the anti-tumor efficacy and molecular mechanisms of a standardized extract of Hedyotis diffusa Willd. (HD) and its constituent, ferulic acid (FA), were investigated using an azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated CRC mouse model. HD and FA treatment markedly alleviated colitis, reduced tumor number and size, improved survival, and attenuated histopathological damage. Transcriptomic analysis revealed significant modulation of immune-related pathways, with prominent suppression of IL-17A and NF-κB signaling. Molecular docking demonstrated binding of FA to IL-17A at Pro59 and Arg101, suggesting potential disruption of the IL-17A/IL-17RA interaction. Consistently, both HD and FA reduced immune cell infiltration, downregulated IL-17A production, and inhibited NF-κB activation in colonic tissues. Collectively, these findings demonstrated that HD exerted protective effects against inflammation-associated CRC through targeting the IL-17A/IL-17RA axis and downstream NF-κB signaling, providing mechanistic insight into IL-17A-centered immunomodulation in colorectal tumorigenesis. Full article

Background and Objectives: Degenerative lumbar spinal stenosis (DLSS) frequently manifests as lower leg radiating pain (LLRP), requiring selective nerve root block (SNRB). Comprehensive and Integrative Medical Services (CIMS)—a multimodal program consisting of acupuncture, cupping, and manual therapy—have been increasingly incorporated into clinical practice in Korea. However, randomized evidence remains limited. This study evaluated the efficacy and safety of adjunctive CIMS in patients with DLSS presenting neuropathic LLRP requiring SNRB. Materials and Methods: In a single-center, parallel-group, assessor-blinded randomized controlled trial (CRIS KCT0006036), adults with DLSS (LANSS > 7; VAS > 5) were randomized 1:1 to experimental or control groups (n = 77; experimental 38, control 39). All participants received SNRB plus pharmacotherapy (limaprost, pregabalin). The experimental group additionally received CIMS, delivered eight times over 4 weeks. The primary outcome was pain intensity (VAS) at baseline and weeks 4, 8, and 12. Secondary outcomes included SF-36, ODI, and RMDQ at baseline and weeks 4, 8, and 12. Repeated-measures two-factor ANOVA assessed the main effects and time × group interaction. Results: Mean VAS (experimental vs. control) was 4.73 ± 1.67 vs. 4.70 ± 1.95 at baseline; 3.74 ± 1.68 vs. 4.66 ± 1.60 at week 4; 3.93 ± 2.03 vs. 4.79 ± 1.55 at week 8; and 3.98 ± 1.98 vs. 4.98 ± 1.68 at week 12. The significant time × group interaction was identified (p = 0.040), indicating a greater pain reduction with CIMS. No significant time × group interactions were observed across SF-36 domains. Adherence to CIMS modalities was high, and no unexpected adverse events occurred. Conclusions: In DLSS patients receiving SNRB and pharmacotherapy, adjunctive CIMS resulted in greater pain reduction over 12 weeks compared with standard care alone, without introducing new safety concerns. These findings support the clinical utility of CIMS as an effective adjunctive treatment option for DLSS. Full article

Gut microbiota is a potential therapeutic target for type 2 diabetes (T2D), but its role remains unclear. Investigating causal associations between them could further our understanding of their biological and clinical significance. A two-sample Mendelian randomization (MR) analysis was conducted to assess the causal relationship between gut microbiota and T2D. Key genes and mechanisms were identified through the integration of Genome-Wide Association Studies (GWAS) and cis-expression quantitative trait loci (cis-eQTL) data. Network pharmacology was applied to identify potential drugs and targets. Additionally, gut microbiota community analysis and machine learning models were used to construct a diagnostic model for T2D. MR analysis identified 17 gut microbiota taxa associated with T2D, with three showing significant associations: Actinomyces (odds ratio [OR] = 1.106; 95% confidence interval [CI]: 1.06–1.15; p < 0.01; adjusted p-value [p_adj] = 0.0003), Ruminococcaceae (UCG010 group) (OR = 0.897; 95% CI: 0.85–0.95; p < 0.01; p_adj = 0.018), and Deltaproteobacteria (OR = 1.072; 95% CI: 1.03–1.12; p < 0.01; p_adj = 0.029). Ten key genes, such as EXOC4 and IGF1R, were linked to T2D risk. Network pharmacology identified INSR and ESR1 as target driver genes, with drugs like Dienestrol showing promise. Gut microbiota analysis revealed reduced α-diversity in T2D patients (p < 0.05), and β-diversity showed microbial community differences (R² = 0.012, p = 0.001). Furthermore, molecular docking confirmed the binding affinity of potential therapeutic agents to their targets. Finally, we developed a class-weight optimized Extreme Gradient Boosting (XGBoost) diagnostic model, which achieved an area under the curve (AUC) of 0.84 with balanced sensitivity (95.1%) and specificity (83.8%). Integrating machine learning predictions with MR causal inference highlighted Bacteroides as a key biomarker. Our findings elucidate the gut microbiota-T2D causal axis, identify therapeutic targets, and provide a robust tool for precision diagnosis. Full article

To achieve precise and safe laser acupuncture treatment, a computational model of the skin acupoint was constructed utilizing COMSOL Multiphysics (Version 6.1). This model incorporates its multilayer anatomical structure: the epidermis, papillary dermis, reticular dermis, hypodermis, and muscle layer. A coupled multiphysics approach integrating geometric optics, radiation beams, and bioheat transfer was employed to investigate the effects of light source parameters and cooling layers on the photothermal response and thermal damage of acupoints. Under optimized parameters (808 nm, 3 mm beam waist, 50 mW) with a 0.5 mm glycerol layer, 600 s irradiation achieved a stable dermal temperature (40.86–42.04 °C) and a negligible epidermal thermal damage factor (0.0063), significantly below the subclinical injury threshold of 0.15; under identical parameters, the dermal temperature for the Gaussian periodic pulsed source was maintained between 38.85 and 40.35 °C, with a corresponding epidermal thermal damage factor of merely 0.0010. The model exhibited good robustness, tolerating variations of ±5% in laser power and ±40% in glycerol layer thickness. The resultant temperature deviations in the epidermis and dermis were well within the safe range, and the thermal damage factor remained below the injury threshold. This work serves as a guideline for selecting laser acupuncture parameters according to acupoint depth. Full article