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

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

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.

Severe acute pancreatitis (SAP) has a mortality rate of up to 30%. Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis with high mortality with poor prognosis. With the rapid development of the concept of minimally invasive surgery,the “step-up” treatment strategy with minimally invasive techniques as the core has improved the prognosis of SAP patients,and surgical intervention is extremely key in this process. This article focuses on the surgical intervention strategies of SAP in the era of minimally invasive surgery,including the application of surgical rescue,the selection of the timing and method in surgical intervention,the early prediction and diagnosis of IPN,and the treatment of residual infection, so as to provide reference for the clinical treatment of SAP. The key to reduce the mortality of SAP patients is to establish an integrated comprehensive treatment platform and properly grasp the timing and method of surgical intervention.

Objective:To investigate the feasibility and therapeutic efficacy of robot-assisted radical resection for hilar cholangiocarcinoma.Methods:This is a retrospective case series study. The clinical data of 29 patients who underwent robot-assisted radical resection for hilar cholangiocarcinoma at the Department of Minimally Invasive Hepatic Surgery,the First Affiliated Hospital of Harbin Medical University from July 2021 to February 2025 were retrospectively collected. There were 16 males and 13 females, aged ( M(IQR)) 68.0 (10.0) years (range:36 to 78 years), and body mass index (24.0±2.9) kg/m 2 (range:17.5 to 29.1 kg/m 2). Bismuth-Corlette classification: 12 cases type Ⅰ, 4 cases type Ⅱ, 6 cases type Ⅲb, and 7 cases type Ⅳ. Preoperative CA19-9 was 161.7(320.9) U/ml (range:7.1 to 1 000.0 U/ml), and carcinoembryonic antigen was 2.8(2.1)μg/L (range:0.3 to 203.1 μg/L). Preoperative total bilirubin was 134.2 (348.9) μmol/L (range:10.4 to 557.9 μmol/L), direct bilirubin was 90.8 (264.1) μmol/L (range:2.5 to 418.7 μmol/L), ALT was 136.4 (134.8) U/L (range:13.0 to 569.9 U/L), AST was 122.2 (119.9) U/L (range:16.0 to 384.0 U/L), and albumin was (34.5±6.3) g/L (range:21.7 to 41.3 g/L). Comparison of quantitative data at different time points using paired t-test or Mann-Whitney U test. Cox univariate analysis was performed for the relevant variables, and Cox multivariate regression analysis was used to screen the independent prognostic factors of patients after robot-assisted radical resection for hilar cholangiocarcinoma. Results:All the 29 patients successfully underwent robot-assisted radical resection of hilar cholangiocarcinoma, and the R0 resection rate was 93.1% (27/29) without conversion to laparotomy. The operation time was 295.0 (87.5) minutes (range:195 to 590 minutes), the intraoperative blood loss was 100.0 (150.0) ml (range:20 to 1 000 ml), the intraoperative blood transfusion rate was 20.1% (6/29), the number of lymph nodes dissected was 10.0 (7.0) pieces (range: 6 to 18 pieces), the first postoperative deflatus time was 3.0 (1.0) days (range:2 to 4 days), The oral feeding time was 5.0 (1.0) days (range: 4 to 7 days), the drainage tube removal time was 8.0 (2.0) days (range: 6 to 26 days), and the postoperative hospital stay time was 10.0 (6.0) days (range:7 to 27 days). The incidence of complications above grade Ⅱ of the Clavien-Dindo complication grading system was 24.1% (7/29), including 3 cases of gastrointestinal bleeding with recurrent high fever, 1 case of delayed gastric emptying, 1 case of bile leakage, and 5 cases of hypoalbuminemia. The total bilirubin was 42.8 (66.8) μmol/L (range:6.8 to 195.9 μmol/L), direct bilirubin was 28.1 (38.5) μmol/L (range:4.3 to 88.6 μmol/L), ALT was 55.8 (56.0) U/L (range:9.9 to 207.1 U/L), AST was 33.9 (17.9) U/L (range:10.6 to 122.7 U/L), and albumin was (32.1±3.8) g/L (range:22.8 to 37.7 g/L), the levels of transaminase and bilirubin in the postoperative liver function indexes were significantly improved compared with those before operation, and the differences were statistically significant (all P<0.05). The mortality rate of patients without perioperative death was 3.4% (1/29) at 90 days after surgery. The results of Cox multivariate regression analysis showed that R0 resection was an independent prognostic factor for survival at 1 year after surgery ( P<0.05). The follow-up time was 15.0 (12.0) months (range:6 to 30 months), 1 of the 29 patients died of intra-abdominal infection 1 week after discharge, and the remaining 28 patients were completely followed up, of which 20 patients had no recurrence and metastasis during the follow-up period, and the tumor-free survival was 15.0 (12.0) months (range:6 to 30 months), the tumor-free survival rate was 65.5% (19/29), the overall survival rate was 68.9% (20/29), and 8 patients with postoperative recurrence and metastasis. One patient with liver metastasis survived after reoperation, and one patient underwent postoperative chemoradiotherapy and died due to recurrence. There were 8 deaths during the follow-up, of which 7 died due to tumor recurrence and metastasis, and 1 died due to previous underlying diseases. Conclusion:Robot-assisted radical resection for hilar cholangiocarcinoma is feasible and effective.

Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.

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.

Objective:To investigate the effect of Gexia Zhuyu decoction on Toll-like receptor 4 (TLR4)/Nuclear factor-kappaB (NF-κB) signaling pathway on ulcerative colitis and intestinal mucosal barrier.Methods:A total of 86 cases of ulcerative colitis admitted to Xi′an Traditional Chinese Medicine (TCM) Hospital from March 2019 to July 2023 were prospectively included and divided into observation group and control group according to random number table method, with 43 cases in each group. The control group was treated with mesalazine enteric-coated tablets; The observation group was treated with mesalazine enteric-coated tablets combined with Gexia Zhuyu decoction for removing stasis. The clinical efficacy of the two groups was compared in terms of TCM syndrome score, intestinal mucosal barrier function index [diamine oxidase (DAO), D-lactic acid (D-LA)], TLR4/NF-κB signaling pathway expression and inflammatory factor index [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] before and after treatment. The occurrence of adverse reactions was also compared.Results:The total effective rate of observation group was higher than that of control group (χ 2=4.074, P=0.044). Before treatment, there was no significant difference in TCM syndrome scores between the two groups (all P>0.05). After treatment, the TCM syndrome scores of both groups were lower than those before treatment (all P<0.05), and the TCM syndrome scores of the observation group were lower than those of the control group (all P<0.05). Before treatment, there were no significant differences in D-LA and DAO levels between the two groups (all P>0.05). After treatment, the levels of D-LA and DAO in both groups were lower than before treatment (all P<0.05), and the levels of D-LA and DAO in the observation group were lower than those in the control group (all P<0.05). After treatment, the mRNA expressions of TLR4 and NF-κB in both groups were decreased compared with those before treatment, and the mRNA expressions of TLR4 and NF-κB in the observation group were lower than those in the control group (all P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were decreased compared with those before treatment (all P<0.05), and the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ 2=2.346, P=0.126). Conclusions:The application of Gexia Zhuyu decoction in the treatment of ulcerative colitis can not only effectively improve the clinical symptoms, signs and intestinal mucosal barrier function, but also improve the inflammatory response by mediating TLR4/NF-κB signaling pathway.

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.

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.