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.

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases. Biliary stricture is a rare but serious long-term complication of acute pancreatitis, which can induce cholangitis, progressive liver function impairment, and secondary biliary cirrhosis. Due to the clinical symptoms of acute pancreatitis that can mask biliary system diseases, some patients may not receive timely diagnosis and treatment for concurrent biliary issues during the onset of acute pancreatitis, which can be life-threatening in severe cases. Currently, the ideal treatment strategy for biliary system complications secondary to acute pancreatitis remains unclear, lacking definitive guidelines or consensus. This article integrates recent research developments from both domestic and international studies to elucidate the pathogenesis, diagnosis, and treatment strategies for biliary system complications secondary to acute pancreatitis.

Acute pancreatitis is a common surgical emergency characterized by severe local or systemic complications during its progression. Diseases of the biliary system are among the serious local complications of acute pancreatitis, primarily including acute acalculous cholecystitis (AAC) and biliary stricture. AAC often occurs in the later stages of acute pancreatitis, exacerbating systemic inflammation and leading to organ failure and life-threatening conditions in severe cases. Biliary stricture is a rare but serious long-term complication of acute pancreatitis, which can induce cholangitis, progressive liver function impairment, and secondary biliary cirrhosis. Due to the clinical symptoms of acute pancreatitis that can mask biliary system diseases, some patients may not receive timely diagnosis and treatment for concurrent biliary issues during the onset of acute pancreatitis, which can be life-threatening in severe cases. Currently, the ideal treatment strategy for biliary system complications secondary to acute pancreatitis remains unclear, lacking definitive guidelines or consensus. This article integrates recent research developments from both domestic and international studies to elucidate the pathogenesis, diagnosis, and treatment strategies for biliary system complications secondary to acute pancreatitis.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

Objective:To observe the incidence of early blood eosinophils (Eos) elevation in patients with peritoneal dialysis (PD), analyze its related factors, and its relationship with early-onset peritonitis in PD patients.Methods:This study was a retrospective observational cohort study. Patients who underwent PD catheterization in Peking University People's Hospital from January 2012 to December 2022 were included. After surgery, PD treatment was started immediately and followed up regularly ≥12 months. The general information and laboratory indexes collected 1 week before catheterization, and at 1, 3, 6 and 12 months after catheterization were recorded. The occurrence of elevated blood Eos (≥0.5×10 9/L) during the early stage of PD, the related factors of Eos elevation (≥0.5×10 9/L) and the relationship with early-onset peritonitis (within 12 months after PD initiation) were analyzed. Results:(1) A total of 235 patients were enrolled, with an age of (57.9.±13.9) years, including 136 males (57.9%). The primary diseases were predominantly chronic glomerulonephritis (111/235, 42.7%) and diabetic nephropathy (83/235, 35.3%). During the 12-month follow-up period, 73 patients had elevated blood Eos (31.1%), of which 37 cases (50.7%) occurred within 1 month after PD catheterization, 21 cases (28.7%) occurred 2-3 months after PD catheterization, 12 cases (16.4%) occurred 4-6 months after PD catheterization, and 3 cases (4.1%) occurred 7-12 months after PD catheterization. In 73 patients with elevated Eos, 69 cases (94.5%) were mildly elevated, 4 cases (5.5%) were moderately elevated. As for the duration of elevated blood Eos, 28 cases (38.4%) lasted less than 1 month, 27 cases (37.0%) lasted 1-3 months, and 18 cases (24.7%) lasted more than 3 months. (2) In patients with elevated blood Eos, the proportion of male patients (71.4% vs. 52.1%, χ 2=7.515, P=0.006), the proportion of diabetes mellitus (55.7% vs. 41.2%, χ 2=4.168, P=0.046), and the proportion of combined vascular disease (32.9% vs. 18.2%, χ 2=6.060, P=0.017) were significantly higher than those patients in normal blood Eos group. (3) Multivariate Logistic regression analysis showed that male was an independent related factor for elevated blood Eos (≥0.5×10 9/L) in the early stages of PD ( OR=2.044, 95% CI 1.101- 3.794, P=0.023). (4) Diabetes mellitus ( OR=3.363, 95% CI 1.087-10.405, P=0.035), lower baseline hemoglobin level ( OR=0.941, 95% CI 0.903-0.980, P=0.004) and elevated blood Eos (with serum Eos<0.5×10 9/L as reference, OR=2.917, 95% CI 1.022-8.326, P=0.045) were the independent related factors of early-onset peritonitis. Conclusion:Blood Eos elevations are common in early stage of PD patients , mainly occuring within 6 months after PD catheterization, and most of them are slightly increased and last less than 3 months. Male sex is an independent related factor for the elevation of blood Eos in the early stage of PD. Elevated blood Eos is an independent related factor for early-onset peritonitis.

Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.

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.

To fully exploit Transformer for accurate registration,self-similarity context is used as a feature extractor to extract the semantic information of the voxel neighborhood context,using symmetric multi-scale discrete optimization with diffusion regularization to find smooth transformations for quickly calculating the point-by-point distance between descriptors.In addition,a spatial-channel Transformer based on window attention network is proposed,which combines channel,spatial attention and self-attention scheme based on(moving)window,and makes full use of the complementary advantages of these 3 attention mechanisms,enabling the network to utilize global statistical information and have strong local fitting ability.The results of comprehensive experiments on 3D brain MRI datasets of LPBA40,IXI and OASIS shows that the proposed method is superior to the commonly used registration methods(SyN,VoxelMorph,CycleMorph,ViT-V-Net and TransMorph)on several evaluation indicators,proving its effectiveness in deformable medical image registration.