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

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.

Objective To investigate the impact of nucleophosmin 1-mutated(NPM1m)subtypes,variant allele frequency(VAF)and co-mutations on the survival outcomes of patients with acute myeloid leukemia(AML).Methods Clinical data,mutation status,and outcomes of 86 NPM1m-AML patients admitted in Department of Hematology,First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed.Spearman correlation analysis,Kaplan-Meier curve analysis,Log-rank test,and Cox regression analysis was applied for correlation analysis,survival analysis,and factors affecting survival.Results The overall survival(OS)was significantly shorter in the Rares subtype of NPM1m than the ABD subtype(median OS:164 d vs 416 d,P=0.043).The VAF of NPM1m was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase(LDH)level(P<0.05).OS was reduced when VAF was≥0.37(median OS:164 d vs 730 d,P=0.003).The presence of myelodysplasia-related gene(MR)mutations was associated with a poorer prognosis when compared to the MR wild-type(median OS:45 d vs 395 d,P<0.001).The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)and DNMT3A also indicated a worse prognosis than the non-triple mutation(median OS:173 d vs 483 d,P=0.007).The presence of PTPN11 mutations was associated with improved OS(median OS:395 d vs 240 d,P=0.027),while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients(median OS:662 d vs 189 d)though no statistical significance(P=0.070).Multivariate analysis revealed that LDH(HR=1.002,95%CI:1.000～1.003,P=0.005),NPM1m VAF(HR=2.415,95%CI:1.208～4.829,P=0.013),Rares subtype(HR=3.037,95%CI:1.134～8.136,P=0.027),and MR mutations(HR=5.283,95%CI:1.991～14.017,P<0.001)were independent risk factors associated with OS in the patients.Conclusion Molecular heterogeneity of NPM1m should be taken into account in prognostic stratification of NPM1m-AML.Factors including the Rares subtype,VAF≥0.37,coexistence of FLT3-ITD and DNMT3A mutations,and MR mutations are associated with poor prognosis of NPM1m-AML.The presence of PTPN11 mutations improves the prognosis,while the presence of N/KRAS mutations shows a trend toward better prognosis.LDH,NPM1m VAF,Rares subtype,and MR mutations are independent risk factors affecting OS of patients with NPM1m-AML.

Near infrared spectroscopy(NIRS)technology has been widely applied in quantitative analysis of pharmaceuticals,food,and chemical industries.In this study,a NIRS quantitative analysis model(MDCSpecNet)based on a multi-scale dilated convolutional neural network was proposed.The model consisted of a one-dimensional convolutional layer,a batch normalization layer,a max-pooling layer,a multi-scale dilated convolutional neural network,and a full-connected layer.Among which,the one-dimensional convolutional layer and the max-pooling layer performed preliminary featured extraction and dimensionality reduction on the original spectra,the batch normalization layer accelerated the convergence of the model,the multi-scale dilated convolutional neural network extracted and fused spectral features,and the fully-connected layer linearly represented the feature information,enhancing the model's prediction accuracy and generalization ability.MDCSpecNet prediction models were established using publicly available NIRS datasets of pharmaceuticals,grains,wheat,milk,and gasoline.The prediction results were compared and analyzed with those of one dimensional convolution neural network(1D-CNN),partial least squares(PLS),support vector regression(SVR),and extreme learning machine regression(ELM)modeling methods.The results showed that,in prediction of the content of active pharmaceutical ingredient(API)in pharmaceuticals,the glucose content in grains,the lactate content in grains,the moisture content in grains,the protein content in wheat,the octane number in gasoline and the cloud point of melamine,the accuracy of the MDCSpecNet model increased by 16%,36.7%,25.1%,22.6%,34.2%,15.2%and 22.6%compared to 1D-CNN,46.9%,66.7%,73.2%,65.8%,16.6%,15.9%and 13.7%compared to PLS,68.1%,70.6%,81.7%,73.9%,69.2%,77.9%and 56%compared to SVR,and 62%,20.4%,48.9%,85.6%,50.4%,13%and 44.6%compared to ELM,respectively.The MDCSpecNet model based on the multi-scale dilated convolutional neural network addressed the issues of low accuracy and poor generalization ability of traditional NIRS modeling methods,and it was feasible to use the MDCSpecNet model for quantitative analysis of NIRS of various substances.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Thyroid hormone（TH）plays an important role in human development and is involved in gene and protein expression in almost all tissues，especially in the development of the central nervous system.TH requires a TH transporter to enter the cell，and three families of TH transporter proteins are known，namely monocarboxylate transporters（MCTs），organic anion transporting polypeptides（OATPs）and L-type amino acid transporter（LAT）.MCT8 has been found to be a specific TH transporter，and OATP1C1 also plays an important role.Deficiency of TH transporters may lead to different degrees of dysfunction in the nervous system and endocrine system.Currently，more studies have been conducted on MCT8 deficiency，which presents with characteristic psychomotor retardation and TH abnormalities，and there are no specific treatment options.In this paper，we summarize the research progress on clinical phenotype，pathogenic mechanism，and treatment of thyroid hormone transporter defects related diseases to provide reference for clinical research.

Objective To evaluate the value of combined detection of serum fibrinogen/albumin ratio(FAR)and milk fat globule epidermal growth factor 8(MFG-E8)in predicting the fetal protection outcome of threatened abortion patients.Methods From May 2022 to May 2023,a total of 89 patients with threatened abortion who received fetal protection treatment in Jianli People's Hospital were regarded as the observation group.They were grouped into a miscarriage group(19 cases)and a successful group(70 cases)based on the fetal protection outcomes.89 normal pregnant women who underwent prenatal examinations were regarded as the control group.Enzyme-linked immunosorbent assay was applied to detect the levels of serum fibrinogen,albumin and MFG-E8.Multivariate Logistic regression was applied to analyze the influencing factors on the fe-tal protection outcome of patients with threatened abortion.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum FAR and MFG-E8 level on the fetal protection outcome of patients with threatened abortion.Results Compared with the control group,serum FAR was higher in the observation group(P<0.05)and serum MFG-E8 level was lower(P<0.05).The proportion of thyroid dys-function,serum C-reactive protein(CRP),and FAR in the miscarriage group were higher than those in the successful group(P<0.05),while serum MFG-E8 level was lower than that in the successful group(P<0.05).Serum FAR,CRP and thyroid dysfunction were risk factors for fetal protection outcome of patients with threatened abortion,while serum MFG-E8 was a protective factor for fetal protection outcome of patients with threatened abortion(P<0.05).The area under the curve(AUC)of serum FAR,MFG-E8,and their combination in predicting the fetal protection outcome of patients with threatened abortion was 0.787,0.853,and 0.954,respectively,and the efficacy of combination of the two in predicting the fetal protection outcome of patients with threatened abortion was better than that of serum FAR and MFG-E8 alone(Zcombination-FAR=2.805,Zcombination-MFG-E8=2.076,P=0.005,0.038),with sensitivity and specificity of 94.74%and 88.57%,re-spectively.Conclusion Serum FAR increases and MFG-E8 level decreases of patients with threatened abor-tion,and the combination of the two has higher predictive value for the fetal protection outcome of patients with threatened abortion.

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.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.