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 investigate the effects of influenza A virus(IAV)on macrophages based on expression of cytokines mediated by Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway,and to further explore the intervention effects of Ma Xing Shigan decoction drug containing serum.Methods:RAW264.7 was divided into control group,JAK/STAT signal pathway activator group,inhibitor group,model group,oseltamivir group,antiviral granule group and Ma Xing Shigan decoction group.Cell samples were collected after the intervention of IAV and subsequent treating of drug-containing serum for 24 and 48 hours.Secretion levels of IL-1β and CXCL2 in supernatant were detected by ELISA.mRNA expression levels of influenza virus Nuclear Pro-tein(NP),JAK1/2 and STAT1 of cells were detected by RT-qPCR.Protein expression levels of JAK1/2 and STAT1 were detected by Western blot,and protein expression levels of p-STAT1 was detected by immunofluorescence.Correlation between protein expression levels of p-STAT1 and secretion of IL-1β and CXCL2 were evaluated by Pearson correlation analysis.Results:Secretion levels of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2,STAT1,protein levels of JAK1/2,STAT1 and p-STAT1 were increased,and protein levels of p-STAT1 was positively correlated with the secretion of IL-1β and CXCL2.Ma Xing Shigan decoction could down-regulate secretions of IL-1β and CXCL2,mRNA expression levels of NP,JAK1/2 and STAT1,protein expression levels of JAK1,JAK2,STAT1 and p-STAT1.Conclusion:Activation of JAK1/2-STAT1 signal pathway and imbalance of inflammatory factors may be one of the molecular mechanisms of immunopathological damage of macrophages induced by IAV.Ma Xing Shigan decoction may alle-viate pathogenic effects of IAV by regulating this signal pathway.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective:To investigate the effect of cytoskeleton-associated protein 4 (CKAP4) gene knockout on maxillary expansion osteogenesis and its regulatory mechanism on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC).Methods:Nineteen wild type (WT) and nineteen CKAP4 gene knockout (Ckap4 -/-) mice aged 6-8 weeks were selected to establish a mouse model of rapid maxillary expansion. Samples were taken on the 7th and 14th day after the operation. Micro-CT and HE staining were used to evaluate bone regeneration. Tissue proteins in the modeled area were collected, and Western blotting analysis (WB) was used to detect the protein expression levels of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). BMSC were isolated from WT and Ckap4 -/- mice. The expression of surface markers CD29, Sca-1, CD44, CD45, CD34, and CD11b was detected by flow cytometry, and cell proliferation ability was detected by 5-ethynyl-2'-deoxyuridine (EdU). After 7 days of osteogenic induction, real-time fluorescence quantitative PCR (RT-qPCR) and WB were used to detect the expression levels of RUXN2, ALP, OCN, protein kinase B (AKT), and phosphorylated protein kinase B (p-AKT). After 21 days, alizarin red staining and cetyl pyridine chloride quantification were used to detect the differences in mineralized nodule formation in each group. In CKAP4 gene knockout BMSC, the small-molecule AKT agonist sc79 (4 μg/ml) was added as the intervention group (Ckap4 -/- +sc79), and dimethyl sulfoxide (DMSO) treatment was used as the control group (Ckap4 -/- +DMSO). After osteogenic induction, RT-qPCR, WB, and alizarin red staining were used to compare the osteogenic differentiation differences between the two groups of cells. Results:The micro-CT results showed that at 7 days and 14 days after surgery, the new bone volume in the Ckap4 -/- group [(0.070±0.010) and (0.146±0.019) mm 3] was significantly lower than that in the WT group [(0.094±0.006) and (0.196±0.013) mm 3] (both P<0.01). HE-stained histological sections showed that the area of new bone tissue in the Ckap4 -/- group at 7 days and 14 days after surgery [(0.101±0.008) and (0.158±0.010) mm 2] was also significantly lower than that in the WT group [(0.116±0.005) and (0.183±0.008) mm 2] (both P<0.05). WB was used to detect the tissue proteins in the maxillary modeling area of mice in the two groups 7 days after surgery. The results showed that the expression levels of ALP, RUNX2 and OCN in the Ckap4 -/- group were significantly lower than those in the WT group. BMSC from wild-type mice and CKAP4 knockout mice were both positively expressed for CD29, CD44, and Sca-1, and basically not expressed for CD45, CD34, and CD11b. EdU assay showed that there was no significant difference in the proliferation ability of cells in the two groups. After 21 days of osteogenic induction of BMSC, alizarin red staining results showed that the number of mineralized nodules in the Ckap4 -/- group was significantly less than that in the WT group. After adding sc79, the number of mineralized nodules increased significantly, which was consistent with the results of cetyl pyridine chloride quantification. After 7 days of osteogenic induction, It was found that the expression levels of ALP, RUNX2, and OCN in the CKAP4 -/-group (0.751±0.066, 0.484±0.040, 0.679±0.063) were significantly lower than those in the WT group (1.000±0.113, 1.000±0.081, 1.000±0.113) (all P<0.001). The results of WB were consistent with those of RT-qPCR. At the same time, the WB results showed that the level of p-AKT protein in the CKAP4 -/-group (0.518±0.114) was significantly lower than that in the WT group (1.000±0.234) ( P<0.05). After treatment with sc79 for 7 days of osteogenic induction, RT-qPCR was used to detect the gene expression levels of ALP, RUNX2, and OCN. The results showed that the expression levels in the CKAP4 -/-+sc79 group (2.755±0.353, 4.800±0.990, 2.524±0.137) were significantly higher than those in the CKAP4 -/-+DMSO group (1.000±0.078, 1.000±0.247, 1.000±0.175) (all P<0.001). Conclusions:CKAP4 knockout inhibits the osteogenic differentiation of BMSC by reducing the activity of the PI3K/AKT signaling pathway, thereby suppressing osteogenesis in maxillary expansion.

Objective:To explore the association between sleep and myopia among students aged 6-15 years in Tianjin.Methods:A cross-sectional study was conducted.A total of 218 864 primary and secondary school students aged 6-15 years in Tianjin were recruited from January 2023 to May 2023.Basic information and responses to the Children's Sleep Habits Questionnaire (CSHQ) were collected.Logistic regression models were used to assess the association between myopia and sleep.The study followed the Declaration of Helsinki, and the research protocol was approved by the Medical Ethics Committee of Tianjin Medical University Eye Hospital (No.ChiCTR2200065710). All questionnaires and demographic information were collected with parental consent.Results:It was found that 68 121(31.12%) students were myopic and 178 514(81.56%) had sleep disorders.The prevalence of myopia among students with average daily sleep durations of ≤8 hours, >8-9 hours, >9-10 hours, and >10 hours was 52.17%(9 288/17 803), 35.35%(31 037/87 787), 25.18%(24 481/97 216), and 20.64% (3 315/16 058), respectively, and the difference was statistically significant ( χ2=6 835.649, P<0.001). After adjusting for sex, age, body mass index, and potential confounding factors, compared with students with average daily sleep duration of >10 hours, students with average daily sleep durations of ≤8 hours ( OR=1.496, 95% CI: 1.415-1.581, P<0.001), >8-9 hours ( OR=1.364, 95% CI: 1.383-1.447, P<0.001), and >9-10 hours ( OR=1.257, 95% CI: 1.202-1.316, P<0.001) had a higher risk of myopia.Students with sleep disorders, bedtime resistance, sleep-onset delay, irregular sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness were more likely to be myopic. Conclusions:Sleep is a key factor influencing myopia among schoolchildren aged 6-15 years in Tianjin.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

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.

Blueberry muffin baby refers to the newborn with extensive purple and purplish-red round or oval macules, papules and nodules, and is the phenotype of various diseases. However, the symptoms of neonatal diseases are atypical, the condition changes rapidly, and the diagnosis is very challenging. To date, there have been very few research publications on blueberry muffin baby in China and other countries. This review summarizes the diseases that can manifest as blueberry muffin-like lesions, aiming to assist clinical practice and scientific research.