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

Although the incidence of each type of rare tumor is extremely low, the cumulative patient population is large due to the wide variety of such tumors. The diagnosis and treatment of rare tumors in China are currently faced with numerous challenges, such as diagnostic difficulties and limited therapeutic options: traditional histopathological diagnosis has certain limitations, and most treatment regimens still rely on conventional approaches including surgery, radiotherapy and chemotherapy. With the advancement of molecular diagnostic technologies and precision medicine, especially the application of next-generation sequencing, liquid biopsy and artificial intelligence technologies, the diagnostic accuracy of rare tumors has been significantly improved. Meanwhile, innovative therapies such as bispecific antibodies, antibody-drug conjugates, and gene and cell therapies have brought new hope for patients. In the future, China needs to establish a hierarchical diagnosis and treatment network for rare tumors, strengthen drug development and clinical trial exploration, improve relevant medical insurance policies, and build a prevention, diagnosis and treatment system with Chinese characteristics for rare tumors, so as to provide better diagnosis and treatment services for patients.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

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.

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

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

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective:To explore the impacts of remimazolam(REM)on the proliferation,migration,and invasion of hepatocellular carcinoma cells by regulating sphingosine kinase 1/sphingosine 1-phosphate/sphingosine 1-phosphate receptor 3(SPHK1/S1P/S1PR3)signaling pathway.Methods:Human hepatocellular carcinoma cell line HepG2 was treated with REM at concentrations of 0,20,40,80,160,and 320 μmol/L respectively.Cell survival rate was measured,and drug concentrations were screened.Based on the results of cell survival rate,the logarithmic phase cells were di-vided into five groups:Control group,low,medium,and high concentrations of remifentanil groups(REM-L,REM-M,REM-H groups;20,40 and 80 μmol/L),and high concentrations of remifentanil+SPHK1 activator group(REM-H+K6PC-5 group).MTT assay was used to detect the survival rate of HepG2 cells.Plate cloning experiment was performed to de-tect cell proliferation ability.Scratch experiment was performed to detect cell migration ability.Transwell chamber method was performed to detect cell invasion ability.Flow cytometry was used to detect cell apoptosis.Western blot was used to detect the SPHK1,S1P,S1PR3,Bax,and Bcl-2 proteins in cells.Results:For the Control group,the REM-L,REM-M,and REM-H groups showed that the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins gradually decreased with increasing REM concentration,while the apoptosis rate and Bax,E-cadherin proteins showed an opposite trend(P<0.05).For the REM-H group,the REM-H+K6PC-5 group showed a clear increase in the number of HepG2 cell clones,scratch healing rate,invasion rate,Bcl-2,SPHK1,S1P,S1PR3,and N-cadherin proteins,and a clear decrease in the apoptosis rate and Bax,E-cadherin proteins(P<0.05).Conclusion:REM may inhibit the proliferation,migration,and invasion of hepatocellular carcinoma cells and promote cell apoptosis by suppressing SPHK1/S1P/S1PR3 signaling pathway.

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.