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

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Traditional Chinese medicine and Western medicine exhibit significant differences in their modes of thinking， yet this very distinction creates opportunities for their mutual learning and integration. TCM ethics are grounded in the robust theoretical and practical foundations of TCM. From the three-dimensional ethical perspective of cognition， decision-making， and treatment， it demonstrates prominent characteristics in the cognitive regulation of “taking images to operate numbers，” the decision-making principle of “treatment based on syndrome differentiation，” and the therapeutic criteria of “harmony between humanity and nature.” TCM and Western medicine possess distinct features in image-based thinking and reductionism， dynamic nonlinearity and static linearity， as well as holism and antagonism， influencing how they address doctor-society， doctor-doctor， and doctor-patient relationships. Furthermore， the integration of TCM and Western medicine can foster mutual learning and allow them to complement each other’s strengths. Against the backdrop of growing emphasis on TCM modernization and the steady advancement of the Healthy China initiative， enhancing the healthcare system’s adaptability to diverse health demands is crucial. Efforts should be made to promote proper subject-object regulations in the doctor-society relationship， a harmonious yet competitive plurality in the doctor-doctor relationship， and harmonious coexistence in the doctor-patient relationship. It is also essential to uphold the parallel progression of ethical reflection and practical exploration， thereby providing ethical support for the further development of integrated Chinese and Western medicine.

Objective To systematically evaluate the efficacy and safety of pyrotinib-based therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer based on real-world data, and to explore factors associated with prognosis. Methods A total of 102 patients with HER2-positive advanced breast cancer who received pyrotinib at Zhongshan Hospital, Fudan University, were included retrospectively from January 1, 2019, to January 31, 2024, and prospectively from February 1, 2024, to November 30, 2025. Follow-up was conducted until March 31, 2026. Clinical and follow-up data of the patients were collected, and survival analysis was performed by Kaplan-Meier method. Prognostic factors were analyzed through multivariable Cox regression and logistic regression. Results Among the 102 patients, the median follow-up duration was 31.3 months, the median progression-free survival (PFS) was 12.9 months, the median overall survival (OS) has not been reached (estimated to be 64.8 months), and the objective response rate (ORR) was 35.29%. Multivariate Cox regression analysis revealed that lung metastasis (HR＝2.562，P＝0.006), third-line and subsequent treatment (HR＝3.857，P＝0.010), and pyrotinib monotherapy (HR＝3.682，P＝0.015) were associated with shorter PFS. Eastern Cooperative Oncology Group performance status (ECOG PS)≥2 (HR＝16.948，P＜0.001) and third-line and subsequent treatment (HR＝3.958，P＝0.034) were associated with shorter OS. No associated factors related to ORR were found. Regarding safety, diarrhea was the most common adverse event, occurring in 74.51% of patients. Conclusions In real-world clinical practice, pyrotinib-based therapy demonstrated clinical efficacy and manageable safety in patients with HER2-positive advanced breast cancer. Lung metastasis, pyrotinib monotherapy, ECOG PS≥2, and pyrotinib administration in multiple lines of therapy may affect patient prognosis.

This study analyzed the epidemiological characteristics and strain genotypic distribution of varicella in Fengtai District, Beijing, utilizing population-based surveillance data from March 2024 to February 2025 combined with laboratory nucleic acid detection and genotyping.We reported 522 varicella cases with male predominance (282 cases, 54.41%) and a majority aged >15 years (358 cases, 68.58%).A bimodal incidence pattern peaked in May and November, while 161 breakthrough infections (30.8%) occurred predominantly among students aged 6-20 years.The multivariate logistic regression model analysis showed that, compared to the 0-5 years age group, individuals aged 6-14 years ( OR: 2.729, 95% CI: 1.083-6.88), 15-20 years ( OR: 2.495, 95% CI: 1.158-5.378), and>20 years ( OR: 5.382, 95% CI: 2.478-11.689) exhibited progressively higher odds of oderate-to-severe rash; females demonstrated a lower risk compared to males ( OR: 0.485, 95% CI: 0.286-0.822); regarding vaccination status, recipients of one vaccine dose ( OR: 0.301, 95% CI: 0.161-0.564) and two doses ( OR: 0.203, 95% CI: 0.086-0.48) showed significantly reduced risks relative to unvaccinated individuals. Genotyping of 174 specimens identified 161 VZV-positive samples, with successful ORF22/38/62 sequencing in 142 samples confirming Clade 2 predominance (141 strains, 99.3%) and one Clade 5 strain; local isolates exhibited high vaccine-strain homology (ORF22 nucleotide:99.5%-100%, amino acid:99.3%-100%) with mutation sites partially overlapping other Chinese regions.

A 67-year-old male had undergone bilateral lung transplantation for chronic obstructive pulmonary disease 11 months before the current presentation. He was admitted with a 5-day history of cough with sputum, and a 2-day history of fever. Computed tomography (CT) of the chest revealed rapidly progressive bilateral diffuse "ground glass" opacities. Despite anti-infective therapy and methylprednisolone pulse therapy, his condition deteriorated, necessitating endotracheal intubation with mechanical ventilation and veno-venous extracorporeal membrane oxygenation (V-V ECMO) for life support. A bedside cryobiopsy was undertaken, with pathology confirming the organizing pneumonia diagnosis. Comprehensive treatment was continued: methylprednisolone, tacrolimus for immunosuppression, and prophylactic anti-infectives. His partial pressure of oxygen in the blood by the fraction of inspired oxygen ratio and imaging findings improved gradually. ECMO support was discontinued after 2 weeks, and he was discharged 1-month later, resuming normal daily activities. At 2-month follow-up, he exhibited improved exercise tolerance. Chest CT showed bilateral upper-lobe emphysema (predominantly upper-lobe reticular shadows) and significant bilateral upper-lobe pleural thickening. After 12 months of fllow-up, a diagnosis of chronic lung allograft dysfunction was made based on imaging findings and the trajectory of pulmonary function.

Near infrared spectroscopy(NIRS)technology has been widely applied in quantitative analysis of pharmaceuticals,food,and chemical industries.In this study,a NIRS quantitative analysis model(MDCSpecNet)based on a multi-scale dilated convolutional neural network was proposed.The model consisted of a one-dimensional convolutional layer,a batch normalization layer,a max-pooling layer,a multi-scale dilated convolutional neural network,and a full-connected layer.Among which,the one-dimensional convolutional layer and the max-pooling layer performed preliminary featured extraction and dimensionality reduction on the original spectra,the batch normalization layer accelerated the convergence of the model,the multi-scale dilated convolutional neural network extracted and fused spectral features,and the fully-connected layer linearly represented the feature information,enhancing the model's prediction accuracy and generalization ability.MDCSpecNet prediction models were established using publicly available NIRS datasets of pharmaceuticals,grains,wheat,milk,and gasoline.The prediction results were compared and analyzed with those of one dimensional convolution neural network(1D-CNN),partial least squares(PLS),support vector regression(SVR),and extreme learning machine regression(ELM)modeling methods.The results showed that,in prediction of the content of active pharmaceutical ingredient(API)in pharmaceuticals,the glucose content in grains,the lactate content in grains,the moisture content in grains,the protein content in wheat,the octane number in gasoline and the cloud point of melamine,the accuracy of the MDCSpecNet model increased by 16%,36.7%,25.1%,22.6%,34.2%,15.2%and 22.6%compared to 1D-CNN,46.9%,66.7%,73.2%,65.8%,16.6%,15.9%and 13.7%compared to PLS,68.1%,70.6%,81.7%,73.9%,69.2%,77.9%and 56%compared to SVR,and 62%,20.4%,48.9%,85.6%,50.4%,13%and 44.6%compared to ELM,respectively.The MDCSpecNet model based on the multi-scale dilated convolutional neural network addressed the issues of low accuracy and poor generalization ability of traditional NIRS modeling methods,and it was feasible to use the MDCSpecNet model for quantitative analysis of NIRS of various substances.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Thyroid hormone（TH）plays an important role in human development and is involved in gene and protein expression in almost all tissues，especially in the development of the central nervous system.TH requires a TH transporter to enter the cell，and three families of TH transporter proteins are known，namely monocarboxylate transporters（MCTs），organic anion transporting polypeptides（OATPs）and L-type amino acid transporter（LAT）.MCT8 has been found to be a specific TH transporter，and OATP1C1 also plays an important role.Deficiency of TH transporters may lead to different degrees of dysfunction in the nervous system and endocrine system.Currently，more studies have been conducted on MCT8 deficiency，which presents with characteristic psychomotor retardation and TH abnormalities，and there are no specific treatment options.In this paper，we summarize the research progress on clinical phenotype，pathogenic mechanism，and treatment of thyroid hormone transporter defects related diseases to provide reference for clinical research.

Objective To evaluate the value of combined detection of serum fibrinogen/albumin ratio(FAR)and milk fat globule epidermal growth factor 8(MFG-E8)in predicting the fetal protection outcome of threatened abortion patients.Methods From May 2022 to May 2023,a total of 89 patients with threatened abortion who received fetal protection treatment in Jianli People's Hospital were regarded as the observation group.They were grouped into a miscarriage group(19 cases)and a successful group(70 cases)based on the fetal protection outcomes.89 normal pregnant women who underwent prenatal examinations were regarded as the control group.Enzyme-linked immunosorbent assay was applied to detect the levels of serum fibrinogen,albumin and MFG-E8.Multivariate Logistic regression was applied to analyze the influencing factors on the fe-tal protection outcome of patients with threatened abortion.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum FAR and MFG-E8 level on the fetal protection outcome of patients with threatened abortion.Results Compared with the control group,serum FAR was higher in the observation group(P<0.05)and serum MFG-E8 level was lower(P<0.05).The proportion of thyroid dys-function,serum C-reactive protein(CRP),and FAR in the miscarriage group were higher than those in the successful group(P<0.05),while serum MFG-E8 level was lower than that in the successful group(P<0.05).Serum FAR,CRP and thyroid dysfunction were risk factors for fetal protection outcome of patients with threatened abortion,while serum MFG-E8 was a protective factor for fetal protection outcome of patients with threatened abortion(P<0.05).The area under the curve(AUC)of serum FAR,MFG-E8,and their combination in predicting the fetal protection outcome of patients with threatened abortion was 0.787,0.853,and 0.954,respectively,and the efficacy of combination of the two in predicting the fetal protection outcome of patients with threatened abortion was better than that of serum FAR and MFG-E8 alone(Zcombination-FAR=2.805,Zcombination-MFG-E8=2.076,P=0.005,0.038),with sensitivity and specificity of 94.74%and 88.57%,re-spectively.Conclusion Serum FAR increases and MFG-E8 level decreases of patients with threatened abor-tion,and the combination of the two has higher predictive value for the fetal protection outcome of patients with threatened abortion.