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.

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

Objective:To analyze the factors influencing the achievement of "textbook outcome" (TO) after pancreaticoduodenectomy (PD) and explore the relationship of postoperative prognoses with TO.Methods:The clinical and pathological data of 169 patients treated by PD between January 2021 and December 2023 at the First Affiliated Hospital of Harbin Medical University were retrospectively analyzed. The patients were divided into the TO group ( n=91) and the non-TO group ( n=78) based on whether they met the TO criteria after sugery. According to the benignity or malignancy of the tumor, patients in the two groups above were futher divided into a non-malignant tumor subgroup (benign and junctional) and a malignant tumor subgroup, of which there were 10 cases of non-malignant tumor subgroup and 81 cases of malignant tumor subgroup in the TO group, and 9 cases of non-malignant tumor subgroup and 69 cases of malignant tumor subgroup in the non-TO group. Data collected included general patient information, laboratory indices on postoperative day 3, pathological findings, intraoperative blood loss, operative duration, and the like. Patients with malignant tumors were followed up until December 2024. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values for clinical data. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors affecting TO achievement. Survival curves for patients with malignant tumors in the TO and non-TO groups were plotted using the Kaplan-Meier method and compared with the Log-rank test. Results:Among the 169 patients, 91 patients (53.8%) achieved TO. There were 150 patients (88.76%) with malignant tumors, all of whom achieved R0 resection. Univariate analysis showed that a history of cardiovascular/cerebrovascular disease, main pancreatic duct diameter, white blood cell count on postoperative day 3, aspartate aminotransferase level, total bilirubin level, serum urea nitrogen level, pancreatic texture, and operative duration were factors influencing TO achievement (all P value <0.05). Multivariate analysis identified that a postoperative white blood cell count greater than 16.35×10 9/L ( OR=3.558, 95% CI 1.319-9.596), a postoperative serum urea nitrogen levels exceeding 5.42 mmol/L ( OR=2.154, 95% CI 1.070-4.334), soft pancreatic texture ( OR=2.321, 95% CI 1.035-5.203), and an operative duration exceeding 312.50 min ( OR=2.043, 95% CI 1.005-4.154) were independent risk factors that prevented the achievement of TO (all P value <0.05). Kaplan-Meier survival analysis revealed that the 1-, 2-, and 3-year survival rates for patients with malignant tumors in the TO group were 67.90%, 47.73%, and 36.84%, respectively, which were significantly higher than those in the non-TO group (57.90%, 32.00%, and 31.58%, respectively; all P value <0.05). The median survival time was 28 months in the TO group and 16 months in the non-TO group, with a statistically significant difference ( P<0.05). Conclusions:Postoperative white blood cell count, serum urea nitrogen level, pancreatic texture, and operative duration are independent risk factors affecting the achievement of TO. For patients with malignant tumors, achieving TO is beneficial for prolonging survival time and improving survival rates.

Pediatric urological non-Hodgkin lymphoma is relatively rare.When a single renal or ureteral tumor with multiple lymph node or bone metastases is present, it is very easy to be misdiagnosed as urinary tumor with metastasis, resulting in unnecessary radical nephrectomy. This paper reports two cases of non-Hodgkin lymphoma presenting with single urinary nodules. Case 1 was diagnosed with a 4.5cm tumor in the right kidney due to fever and fatigue. CT and PET-CT showed multiple bone destruction and lymph node metastasis. Renal biopsy was performed and ALK-positive anaplastic large cell lymphoma was diagnosed. Chemotherapy was effective for 6 months. Case 2 was diagnosed with left hydronephrosis due to intermittent low back pain for 2 weeks. Ultrasound examination revealed ureteral dilation with left hydronephrosis and low echo occupying of the lower ureter. The patient had sudden blurred vision before surgery. MRI examination revealed space occupying in the right optic nerve frame, and PET-CT found multiple bone, lymph nodes and nerve invasion. A lymph node biopsy was performed and Burkitt lymphoma was diagnosed. After 6 months of chemotherapy and radiotherapy, the tumor shrank significantly.

Objective To systematically evaluate the incidence and influencing factors of axillary web syndrome(AWS)in postoperative breast cancer patients,and to provide evidence for reducing the incidence of axillary web syndrome.Methods A computer search was performed in China National Knowledge Infrastructure(CNKI),VIP,Wanfang,SinoMed,PubMed,Medline,Scopus,The Cochrane Library,Web of Science,Embase,searched for articles on AWS influencing factors of breast cancer published from the establishment of the database to January 6th,2025.The articles were screened according to the inclusion and exclusion criteria.Revman5.4 and Stata17.0 were used for systematic review.Results Fifteen studies involving 3979 breast cancer patients and 1 156 patients with AWS were included.The results of the Meta-analysis showed that there was significant statistical heterogeneity among the included studies(I2=97.0%,P<0.0001).Using the random effects model,the incidence of AWS was 32.2%[95%CI(0.24,0.40),P<0.0001].The influencing factors for AWS after breast cancer surgery are age,body mass index(BMI),total mastectomy,lymph node metastasis,and neoadjuvant chemotherapy.NAC),axillary lymph node dissection(ALND),and the number of harvested axillary lymph nodes.Conclusion The incidence of AWS after breast cancer surgery was high.Clinicians should give early nursing to the influencing factors,reduce the incidence of AWS and improve patients'quality of life after surgery.

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.