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

ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.

ObjectiveTo investigate the therapeutic effect of wall-broken ganoderma lucidum spore powder （GLS） on a mouse model of hepatocellular carcinoma and to explore its underlying mechanism. MethodsFifty 2-week-old C57BL/6J mice were divided into a control group， a model group and low， medium and high-dose GLS groups（0.25， 0.5， 1.0 g/kg ）， with 10 mice in each group. A DEN/CCL₄ mouse hepatocellular carcinoma model was established， and GLS was administered by gavage starting from the 8th week， once a day for 14 weeks. At the end of the final administration， the number of liver nodules was observed ， and the serum alpha-fetoprotein （AFP） was detected using enzyme-linked immunosorbent assay. The content of catalase （CAT） in serum and liver tissue was determined by ammonium molybdate method. The content of reduced glutathione （GSH） in serum and liver tissue was measured by microplate assay. The content of glutathione peroxidase （GSH-PX） in serum and liver tissue was detected by colorimetric method. Immunohistochemistry （IHC-P） was employed to detect the protein expression of proliferating cell nuclear antigen （PCNA）. R eal-time fluorescence quantitative polymerase chain reaction was utilized to detect the relative expression of nuclear factor E2-related factor 2 （Nrf2）， Kelch-like epichlorohydrin-associated protein 1 （Keap1）， NAD（P）H quinone oxidoreductase 1 （Nqo1）， heme oxygenase-1 （Ho-1） and glutamate cysteine ligase catalytic subunit （Gclc） mRNA. ResultsCompared with the control group， the content of serum AFP were significantly higher in the model group （P<0.01）， while the contents of CAT， GSH and GSH-PX in liver and serum were significantly lower in the model group （P<0.01）. The relative expression of Keap1 and Nqo1 mRNA was significantly higher （P<0.01）， the relative expression of Nrf2， Ho-1， Gclc mRNA relative expression was significantly lower （P<0.01）， and the positive expression rate of PCNA was significantly higher （P<0.01）. Compared with the model group， the total number of liver nodules and content of serum AFP in the administered group were significantly lower （P<0.01）， and the contents of CAT， GSH， and GSH-PX in the liver and serum of mice significantly increased （P<0.05 or P<0.01）. The expression of Keap1 and Nqo1 mRNA significantly decreased （P<0.05）. The expression of Nrf2， Ho-1 and Gclc mRNA significantly increased （P<0.05）， and positive expression rate of PCNA significantly decreased （P<0.01）. ConclusionGLS has a significant protective effect on DEN/CCL4 -induced mouse hepatocellular carcinoma model， and the mechanism of action is related to the regulation of oxidative stress in mouse liver.

Objective:To investigate the correlation between carotid-femoral pulse wave velocity(cfPWV)and carotid artery structural,hemodynamic,and cardiac functional parameters.Methods:A total of 420 healthy volunteers who underwent neck ultrasound,cardiac ultrasound,and cfPWV examination at Kailuan General Hospital from June 2022 to February 2023 were selected,and they were divided into two groups based on the atherosclerosis threshold value of cfPWV>10 m/s,which included high cfPWV group(140 cases,cfPWV>10 m/s)and low cfPWV group(280 cases,cfPWV≤10 m/s).The demographic data(age,sex)of 420 persons were collected,and the common carotid artery diameter(CCAD),common carotid artery intima-media thickness(CIMT),plaque status,peak systolic velocity(PSV),end-diastolic velocity(EDV)and mean flow velocity(MFV)were compared between two groups.Then,the differences of interventricular septal thickness(IVST)of heart,left ventricular posterior wall thickness(LVPWT),the ratio of blood flow velocity at early stage to that at advanced stage in mitral valve(E/A)and stroke volume(SV)were analyzed.Multivariate logistic regression was adopted to analyze the independent influence factors of cfPWV enhancement.Results:The average age of high cfPWV group was(61.31±9.66)years old,which was significantly higher than(51.06±10.47)years old of low cfPWV group,and the difference of that was significant(t=-9.56,P<0.01).In the parameters of common carotid artery,63 persons(45.0%)occurred plaque in 140 persons of high cfPWV group,which was significantly lower than 50 persons(17.86%)in 280 persons of low cfPWV group,and the difference of that between two groups was significant(x2=34.97,P<0.05).The differences of CCAD,CIMT,PSV,EDV and MV of common carotid artery at right side of persons between two groups were significant(t=-2.16,-5.40,4.52,5.59,5.04,P<0.05),respectively.The parameters of heart showed that the LVPWT thickness increased(9.35±1.13)mm,and the ratio of E/A<1 increased 77.86%in high cfPWV group,which were significantly related to the increase of cfPWV(r=0.27,0.38,P<0.01).Multivariate logistic regression analysis indicated that age(OR=1.05,95%CI:1.02-1.08),CCAD(OR=1.63,95%CI:1.22-2.16),plaque presence(OR=1.84,95%CI:1.07-3.17),LVPWT(OR=1.35,95%CI:1.05-1.72),and the ratio of E/A<1(OR=2.37,95%CI:1.32-4.26)were independent predictors of cfPWV enhancement.Conclusion:The enhancement of cfPWV is closely related to high age,the reconstruction of common carotid artery(widening of inside diameter,and plaque formation),left ventricular hypertrophy,and diastolic abnormality,which indicates it is possible that atherosclerosis process accompanies by the change of interaction mechanism of blood vessels-heart.

Since the first successful transcatheter aortic valve replacement (TAVR) was performed globally in 2002, the TAVR technology has become increasingly mature. With more than a decade of development in China, its application experience, device research and development, procedural improvements, evidence-based medicine, and guideline updates have continuously progressed, leading to a significant increase in the number of procedures conducted. Compared to traditional surgical operations, TAVR has different postoperative monitoring points and principles for the prevention and management of complications, necessitating the formulation of corresponding monitoring and treatment protocols that align with the technical characteristics of the procedure. This guideline is based on clinical practice and incorporates both domestic and international literature as well as the experiences of Fuwai Hospital. It distills and organizes routine postoperative monitoring practices, process optimization, and complication management for TAVR, establishing a set of practical guidelines for postoperative monitoring in China. These guidelines have strong practical value for optimizing postoperative management strategies and preventing and managing complications, which is beneficial for early functional recovery of patients, shortening hospital stays, and reducing complication rates. They provide guidance and reference for domestic peers and support the standardized development and quality improvement of postoperative management for TAVR in China.

Objective To construct risk models for predicting the occurrence of high altitude de-acclimatization syndrome(HADAS)in the population returning from the plateau to the plain based on different machine learning algorithms and validate the predicting efficiency of these models.Methods Field or online surveys were conducted on the individuals who had ended their high-altitude living and returned to the plain areas from November 2020 to February 2024.Basic information,chronic mountain sickness(CMS),HADAS symptoms and other data were collected.With the inclusion and exclusion criteria,totally 1 095 individuals were subjected and assigned into the modeling group.Positive events were defined as HADAS score>5.Then the modelling group was divided into a training set(n=766)and an internal test set(n=329)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression was used to select independent variables.Risk prediction models for high-altitude adaptation symptoms were built based on 8 machine learning methods,including multiple factor logistic regression(LR),decision tree(DT),random forest(RF),eXtreme gradient boosting(XGB),support vector machine(SVM),K-nearest neighbor(KNN),light gradient boosting(LGB)and na?ve bayes(NB).The models were compared and evaluated using receiver operating characteristic(ROC)curves,calibration curves and confusion matrices in the internal test set.The final model was presented using a nomogram or Shapley additive explanations(SHAP)algorithm.In August 2024,another 132 individuals who returned to the plains and met the same criteria were recruited and served as the external validation group.Results There were 549 individuals(50.14%)out of the 1 095 subjects having HADAS symptoms.LASSO regression identified CMS score,age and duration of high-altitude residence as significant predictors.Among the 8 machine learning algorithms,the LR model was identified as the best,with an area under the curve(AUC)value of 0.819(95%CI:0.789～0.850)and 0.841(95%CI:0.799～0.884),and an F1 score of 0.801 in the internal test set,respectively,and the AUC value and F1 score of the LR model were the largest among the 8 models in the internal test set.Spiegelhalter Z test of the calibration curve of the LR model indicated that its P=0.703 in the training set while P=0.281 in the internal test set.The AUC value of the LR model was 0.867(95%CI:0.765～0.969)in the external validation set.Conclusion The LR model constructed based on indicators including CMS score,age and duration of high-altitude residence has a good overall performance in the internal test set,and good discriminating effect in the external validation set.The constructed nomogram is convenient for application.

Objective To investigate the role and possible mechanism of celastrol(Cel)in sodium oxalate(NaOx)-induced acute kidney injury(AKI)and crystal deposition in the kidney tissues in mice.Methods Male C57BL/6 mice(aged 8～12 weeks,weighing 22～24 g)were randomly divided into 3 groups.Saline group(control group,intraperitoneal injection with normal saline and drinking water freely),NaOx group(injured group,intraperitoneal injection of 75 mg/kg NaOx,and drinking water containing 50 μmol/L NaOx),and NaOx+Cel group(treatment group,intraperitoneal injection of 1 mg/kg Cel firstly and then 75 mg/kg NaOx in 24 h later,drinking water containing 50 μmol/L NaOx).All specimens were collected in 24 h after NaOx injection.HK-2 cells were randomly divided into 4 groups:Medium group(no treatment),NaOx group(500 μmol/L NaOx),NaOx+Cel group(400 nmol/L Cel pre-treatment for 2 h followed by 500 μmol/L NaOx treatment),and NaOx+Cel+BA group[8 μmol/L betulinic acid(BA,NF-κB agonist)after the interventions as the NaOx+Cel group].Cells of each group were collected in 24 h after corresponding treatments.Von Koosa and cell adhesion assays were used to observe crystal deposition.HE staining was employed to observe renal histopathology and score the damage.CCK-8 assay was utilized to detect cell viability to obtain the optimal concentrations of NaOx and Cel.Serum urea and creatinine levels were detected.Immunohisotochemical assay was conducted to detect the expression of OPN,CD44,KIM-1,NGAL,p65,IL-1β,BAX,and Caspase-3,and Western blotting was performed for protein levels of OPN,CD44,KIM-1,p65,P-p65 and IL-1β.Results The mice in the NaOx+Cel group showed reduced crystal deposition(P<0.0001),attenuated renal tubular damage(P<0.01),decreased serum urea and creatinine levels(P<0.05),and declined expression levels of the renal adhesion molecules OPN and CD44,the kidney injury molecules KIM-1 and NGAL,the inflammation-associated molecules p65 and IL-1β,and the apoptosis related molecules BAX and Caspase-3 when compared with the NaOx group(P<0.05).In in vitro study,the NaOx+Cel group showed reduced crystal adhesion(P<0.0001),decreased expression of the adhesion molecules OPN and CD44(P<0.05),down-regulation of the inflammatory molecule IL-1β and P-p65/p65 ratio(P<0.05),and down-regulation of the renal injury molecule KIM-1(P<0.05)when compared with the NaOx group.In the NaOx+Cel+BA group,crystal adhesion was significantly increased(P<0.0001),the inflammatory molecule IL-1β and the ratio of P-p65/p65 were increased(P<0.05),and the kidney injury molecule KIM-1 was increased when compared with the NaOx+Cel group(P<0.05).Conclusion Cel may reduce NaOx-induced crystal deposition and AKI by inhibiting NF-κB activation.

Objective:To study the correlation of TCM syndrome elements of large artery atherosclerosis (LAA) cerebral infarction with the new four thrombotic markers and cerebrovascular disease risk factors.Methods:Retrospective analysis was conducted for the baseline data and four diagnosis of 174 patients with LAA cerebral infarction in Department of Neurology, Shanxi Provincial People's Hospital from August 2022 to September 2023. These patients were classified into six TCM syndrome elements: internal wind, qi deficiency, internal fire, blood stasis, yin deficiency, and phlegm-dampness. Thrombomodulin (TM), fibrin-α2 antifibrinolytic inhibitor complex (PIC), thrombin-antithrombinogen complex (TAT), and tissue-type plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) tests were performed in 24 h. Correlation analysis was conducted between the TCM syndrome typing of LAA stroke patients and baseline data, as well as the results of four thrombotic tests.Results:Among the 174 patients with LAA cerebral infarction, 49 (28.16%) were in the internal wind type, 37 (21.26%) in the phlegm-dampness type, 37 (21.26%) in the qi deficiency type, 16 (9.20%) in the internal fire type, 18 (10.35%) in the yin deficiency type, and 17 (9.77%) in the blood stasis type. Comparison of plasma TM ( P=0.003), PIC ( P=0.022), TAT ( P<0.001) and t-PAIC ( P=0.007) levels of each TCM syndrome element showed statistically significant differences ( P<0.05). Logistic regression analysis showed that gender was an influencing factor for the internal wind syndrome element and qi deficiency syndrome element [ OR (95% CI)=0.140 (0.037-0.536)] and blood stasis syndrome element [ OR (95% CI)=0.185 (0.042-0.820)] in TCM; TM was an influencing factor for the internal wind syndrome element and yin deficiency syndrome element [ OR (95% CI)=0.617 (0.423-0.900)], and blood stasis syndrome element [ OR (95% CI)=0.693 (0.496-0.968) ]; TAT was an influencing factor for internal wind syndrome element and phlegm-dampness syndrome element [ OR (95% CI)=2.143 (1.364-3.367)], qi deficiency syndrome element [ OR (95% CI)=1.937 (1.221-3.073)], and internal fire syndrome element [ OR (95% CI)=1.937 (1.221-3.073)], internal fire evidence element [ OR (95% CI)=2.949 (1.796-4.842)], and blood stasis evidence element [ OR (95% CI)=2.118 (1.246-30 600)]; t-PAIC was an influential factor for internal wind syndrome element and qi deficiency syndrome element [ OR (95% CI)=1.140 (1.033-1.258)] ( P<0.05). The ROC curve suggested that a TM level of 8.05 TU/ml had a diagnostic performance of 71.8% for the yin deficiency syndrome; a TAT level of 2.45 ng/L had a diagnostic performance of 71.2% for the internal wind syndrome; a TAT level of 1.65 ng/L had a diagnostic performance of 72.6% for the internal fire syndrome; and a t-PAIC level of 17.55 ng/L had a diagnostic performance of 70.4% for the qi deficiency syndrome. The diagnostic performance of t-PAIC was 70.4% at a t-PAIC level of 17.55 ng/L. Conclusion:Plasma TM, TAT, and t-PAIC levels are independent risk factors for different syndrome elements in patients with LAA cerebral infarction and can be used as markers for early determination of different syndrome elements.