The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Bruch's membrane opening(BMO)is the true anatomical border of the optic nerve head and provides higher anatomical accuracy, structural stability and measurement repeatability than traditional assessments based on the clinically visible optic disc margin. Optical coherence tomography(OCT)serves as a key technical tool for quantitative assessment of BMO-associated structural parameters. With the development of spectral-domain OCT(SD-OCT)and swept-source OCT(SS-OCT), parameters such as BMO-minimum rim width(BMO-MRW), BMO-minimum rim area(BMO-MRA), BMO area, offset, tilt, and torsion have emerged as important imaging biomarkers for evaluating optic nerve head morphology and for assisting in the diagnosis, staging, and longitudinal monitoring of glaucoma, myopia, and pathological myopia. Traditionally, the acquisition of these parameters has relied heavily on manual segmentation, which is limited by low efficiency, strong subjectivity, and considerable inter-observer variability. In recent years, artificial intelligence has been increasingly applied to OCT image segmentation, quality control, cross-device calibration, and automated quantitative analysis, thereby improving efficiency, objectivity, and reproducibility, particularly in eyes with complex optic disc morphology. This review summarizes recent advances in the BMO-related terminology standardization, imaging and quantitative methodologies, quality control,artificial intelligence-assisted analysis, as well as clinical evidence of its application in glaucoma, myopia and pathological myopia. Particular emphasis is placed on their potential value in the differential diagnosis and follow-up evaluation of highly myopic eyes with glaucoma, aiming to provide a reference for the standardized clinical application and future translational use of BMO-related parameters.

OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

OBJECTIVES: This study aimed to explore the impact of cell spreading area on odontoblast polarization and differentiation using micropatterned surfaces ge-nerated by photolithography. METHODS: Micropatterned surfaces with differential adhesive properties were prepared using polyethylene glycol diacrylate (PEGDA)-ba-sed photolithography. Human dental pulp stem cells (hD-PSCs) were isolated into single cells and cultured on micropatterned surfaces with areas of 1 800, 2 700, and 3 600 μm². Immunofluorescence staining was used to observe cell morphology and analyze the relocating of the golgi apparatus and nucleus. Alkaline phosphatase staining was preformed to examine odontogenic differentiation. RESULTS: The hDPSCs were successfully isolated and cultured on micropatterned surfaces mimicking the morphology of polarized odontoblasts. Phalloidin staining confirmed that the isolated hDPSCs successfully recapitulated the morphology of predesigned micropatterns. Immunofluorescence staining showed that the polarization and differentiation levels of the hDPSCs with a 3600 μm² area were significantly higher than those with 1 800 and 2 700 μm² areas (P<0.05). CONCLUSIONS The polarization and differentiation of single hDPSCs increased with the cell areas on micropatterned surfaces.
Cell Differentiation ; Humans ; Dental Pulp/cytology* ; Odontoblasts/cytology* ; Stem Cells/cytology* ; Cells, Cultured ; Cell Polarity ; Surface Properties

Multi-rehabilitation treatment and early nutritional support are closely related to the recovery of critical ill patients.At present,a number of nutritional and rehabilitation interventions have been applied to critically ill patients to aid in their treatment and improve their nutritional status and motor dysfunction..In recent years,certain progress has been made in related research.This paper aims to summarize the latest literature on the application of multidisciplinary rehabilitation therapy in patients with CI under early nutritional support,provide comprehensive,systematic and practically valuable reference for clinical medical staff when formulating comprehensive treatment plans for CI patients under early nutritional support,and improve the treatment effect and quality of life of CI patients.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*