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

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.

Objective:To explore the characteristics of nutrition self-management of home-based elderly chronic obstructive pulmonary disease (COPD) patients based on user persona, in order to provide reference for accurate home nutrition management.Methods:From July to December 2023, home-based elderly COPD patients in the Department of Respiratory and Critical Care Medicine of General Hospital of Ningxia Medical University were selected by convenience sampling method. The Mini Nutritional Assessment, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Physical Activity Rating Scale-3, COPD Patients Self-Management Scale were used to conduct questionnaire survey. The SPSS 26.0 software was used to analyze the influencing factors of patients′ self-management of nutrition. Attributes with statistical significance ( P<0.05) were extracted as labels, and the visualization of patients′ self-management of nutrition portraits was completed in the form of pictures combined with labels. Results:A total of 320 questionnaires were distributed, and 309 valid questionnaires were collected. Among 309 home-based elderly COPD patients, there were 210 males and 99 females with an age of (69.14 ± 6.84) years old. According to the data analysis results, three dimensions of natural attributes, social attributes, and behavioral tracks were artificially extracted to construct three types of nutritional self-management user persona for home-based elderly COPD patients, respectively namely blind management type, independent attempt type, and powerless type.Conclusions:There are great differences in the nutritional status and self-management of home-based elderly patients with COPD. Accurate management measures can be developed based on user persona analysis to improve their nutritional status.

Objective To explore the factors affecting the coefficient of variation(CV)of glucose in type 2 diabetes mellitus(T2DM)patients based on real-time dynamic glucose monitoring system.Methods A total of 354 patients with T2DM hospitalized in the Department of Endocrinology of Jiangsu Shengze Hospital were enrolled in this study from March 2023 to March 2024 and divided into two groups:the glycemic variability(GV,CV>36%)group(n=118)and the glucose stable(GS,CV≤36%)group(n=236).The clinical data of the two groups were compared,and the influencing factors for CV>36%were analyzed.Results The DM duration and HbA1c were higher(P<0.05),while BMI,visceral fat area,subcutaneous fat area(SFA),FC-P,serum uric acid(SUA),and TG were lower in the GV group than in the GS group(P<0.05).Spearman correlation analysis showed that CV was positively correlated with diabetes duration and HbA1c(P<0.05),and negatively correlated with FC-P,SFA and SUA(P<0.05).Logistic regression analysis showed that DM duration,HbA1c,SFA,FC-P and SUA were the influencing factors for GV.Scatter plot analysis showed that there was a linear trend between CV level and log HbA1c and log SFA in T2DM patients.CV level increased with the increase of log HbA1c,and decreased with the increase of log SFA.ROC curve analysis showed that the area under the curve(AUC)of FC-P was 0.703(95%CI:0.640～0.765,P<0.001)for predicting GV in T2DM patients,and the cut-off value was 1.095 ng/ml.The AUC of SUA was 0.622(95%CI:0.555～0.688,P<0.001)for predicting GV,and the cut-off value was 280.5 μmol/L.Conclusions The DM duration,HbA1c,SFA,FC-P and SUA are important factors for GV,and FC-P and SUA have predictive value for GV.

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.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective To investigate how miR-30b regulates mitophagy independently of the PINK1/Parkin pathway by targeting ubiquitin specific peptidase 14(USP14)in neuronal oxygen-glucose deprivation/reoxygenation(OGD/R)injury,and to provide new insights for the treatment of neonatal hypoxic-ischemic encephalopathy.Methods Fetal rat cortical neurons were isolated and an OGD/R model was established.Experiments were conducted in two parts.In part 1,cells were randomized into control,OGD/R,OGD/R+microRNA(miR)-negative control(NC),OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+oe-NC,and OGD/R+miR-30b mimic+oe-USP14 groups.In part 2,cells were randomized into control,OGD/R,OGD/R+miR-NC,OGD/R+miR-30b mimic,OGD/R+miR-30b mimic+si-NC,OGD/R+miR-30b mimic+si-Parkin,and OGD/R+miR-30b mimic+si-Drp1(dynamin-related protein 1)groups.miR-30b and USP14 mRNA levels were measured by real-time quantitative PCR.Cell viability was assessed using the CCK-8 assay and cell death by propidium iodide staining.Protein levels of USP14,microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3 Ⅰ,translocase of outer mitochondrial membrane 20(TOMM20),PINK1,Parkin,and Drp1 were determined by Western blot.MitoTracker Green staining was used to evaluate mitochondrial morphology,and mitochondrial reactive oxygen species(ROS)were measured using the MitoSOX Red probe.AGO2-RNA immunoprecipitation and dual-luciferase reporter assays were performed to validate the targeting relationship between miR-30b and USP14.Results Compared with the OGD/R group,the OGD/R+miR-30b mimic group showed higher cell viability,miR-30b expression,LC3 Ⅱ/LC3 Ⅰ ratio,and Drp1 protein expression(P<0.05),and lower PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).PINK1 and Parkin protein levels did not differ significantly between these two groups(P>0.05).Compared with the OGD/R+miR-30b mimic+oe-NC group,the OGD/R+miR-30b mimic+oe-USP14 group exhibited reduced cell viability,miR-30b expression,and LC3 Ⅱ/LC3 Ⅰ ratio(P<0.05),and increased PI positivity,mitochondrial ROS,USP14 mRNA and protein expression,TOMM20 protein expression,mitochondrial fragmentation index,and mitochondrial volume(P<0.05).miR-30b was confirmed to target USP14.In addition,no significant differences were observed between the OGD/R+miR-30b mimic+si-NC and OGD/R+miR-30b mimic+si-Parkin groups in LC3 Ⅱ/LC3 Ⅰ ratio,fragmentation index,or average mitochondrial volume(P>0.05).Compared with the OGD/R+miR-30b mimic+si-NC group,the OGD/R+miR-30b mimic+si-Drp1 group showed a decreased LC3 Ⅱ/LC3 Ⅰ ratio and increased fragmentation index and average mitochondrial volume(P<0.05).Conclusions miR-30b regulates mitophagy by targeting USP14 independently of the PINK1/Parkin pathway,and confers protection against neuronal OGD/R injury.

Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Anti-leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis is an autoimmune encephalitis mediated by LGI1 antibodies, which can occur in both adults and children. Its common clinical manifestations include epileptic seizures, cognitive and psychiatric disorders; rare symptoms include sleep disorders and autonomic disorders; and its characteristic manifestations are faciobrachial dystonic seizures and refractory hyponatremia. Since anti-LGI1 antibody-associated encephalitis is relatively rare in clinical practice, this article reviews the disease in terms of etiology and pathogenesis, clinical manifestations, auxiliary examinations, diagnosis and differential diagnosis, treatment, recurrence and prognosis. It aims to improve clinicians′ understanding of this disease, provide references for its early diagnosis and treatment, and thereby improve patients′ prognosis.