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

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective To investigate the correlation between baseline plasma soluble triggering receptor expressed on myeloid cell-1(sTREM-1),steroid hormone cortisol and dehydroepiandrosterone(DHEA),immunoendocrine markers,and disease severity in patients with pulmonary tuberculosis(PTB).Methods From March 2020 to May 2022,76 PTB patients and 78 healthy controls were recruited.The plasma sTREM-1 levels were compared between controls and PTB patients.Plasma sTREM-1 and C-reactive protein(CRP),interleukin(IL)-6 and interferon(IFN)-y,erythrocyte sedimentation rate(ESR),steroid hormone cortisol and dehydroepiandrosterone(DHEA)were analyzed to correlate with inflammatory transcripts(IL-6,IFN-γ)in peripheral blood mononuclear cells.Results The sTREM,CRP,ESR,IL-6,IFN-γ,cortisol and cortisol/DHEA were significantly increased(P＜0.05)while DHEA was significantly decreased(P＜0.05)in PTB patients compared with the control group.Futhermore,severe PTB patients had higher sTREM-1 and ESR levels than mild and moderate PTB patients.Spearman correlation analysis showed that sTREM-1 was significantly positively correlated with CRP in all patients(P＜0.05).Only in patients with severe PTB,sTREM-1 was significantly positively correlated with cortisol/DHEA(P＜0.05),and significantly negatively correlated with DHEA(P＜0.05).Conclusions High plasma sTREM-1 levels may be an important factor contributing to the persistence of immunoendocrine imbalance specific to advanced disease in patients with PTB.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective To investigate the correlation between baseline plasma soluble triggering receptor expressed on myeloid cell-1(sTREM-1),steroid hormone cortisol and dehydroepiandrosterone(DHEA),immunoendocrine markers,and disease severity in patients with pulmonary tuberculosis(PTB).Methods From March 2020 to May 2022,76 PTB patients and 78 healthy controls were recruited.The plasma sTREM-1 levels were compared between controls and PTB patients.Plasma sTREM-1 and C-reactive protein(CRP),interleukin(IL)-6 and interferon(IFN)-y,erythrocyte sedimentation rate(ESR),steroid hormone cortisol and dehydroepiandrosterone(DHEA)were analyzed to correlate with inflammatory transcripts(IL-6,IFN-γ)in peripheral blood mononuclear cells.Results The sTREM,CRP,ESR,IL-6,IFN-γ,cortisol and cortisol/DHEA were significantly increased(P＜0.05)while DHEA was significantly decreased(P＜0.05)in PTB patients compared with the control group.Futhermore,severe PTB patients had higher sTREM-1 and ESR levels than mild and moderate PTB patients.Spearman correlation analysis showed that sTREM-1 was significantly positively correlated with CRP in all patients(P＜0.05).Only in patients with severe PTB,sTREM-1 was significantly positively correlated with cortisol/DHEA(P＜0.05),and significantly negatively correlated with DHEA(P＜0.05).Conclusions High plasma sTREM-1 levels may be an important factor contributing to the persistence of immunoendocrine imbalance specific to advanced disease in patients with PTB.

Objective To understand the recognition and coping strategies of ICU nurses on post-ICU syndrome in family members of patients during hospitalisation so as to provide a reference for handling post-ICU syndrome of the family members of patients.Methods A phenomenological approach within qualitative research was adopted.Semi-structured in-depth interviews were conducted with 15 ICU nurses from 3 wards of the Second Affiliated Hospital of South China University.Colaizzi 7-step method was applied to analyse and refine the interview data themes.Results Three main themes and nine sub-themes were identified and they were insufficient cognition of post-ICU syndrome of the family members(limited understanding of post-ICU syndrome in family members,difficulty in recognising or ignoring symptoms,uncertainty about the impact of post-ICU syndrome),active coping with post-ICU syndrome of the family members(coping mainly through listening and explaining,coping mainly through verbal and physical actions,diligent patient care)and various factors hindering nurses'coping with post-ICU syndrome of the family members(compassion fatigue,high ICU work intensity,limited contact time with family members).Conclusion ICU nurses have insufficient understanding of post-ICU syndrome with the family members of patients during hospitalisation.It requires to enhance a comprehensive understanding in ICU nurses about post-ICU syndrome of the family members of patients and to optimise coping strategies to alleviate negative emotions of the family members.Additionally,efforts should be made to overcome factors that hinder nurses'coping with post-ICU syndrome of the family members of patients and to promote a harmonious relationship between medical staff and patients.

ObjectiveTo evaluate the efficacy of three screening questionnaires for COPD in the community residents of Songjiang District， Shanghai， and to provide a basis for selecting COPD screening questionnaire and process that are more suitable. MethodsCommunity residents aged 40 years or over were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for the study with screening questionnaires and spirometry. Questionnaires included the COPD screening questionnaire （COPD-SQ）， the COPD population screener （COPD-PS） and the revised COPD diagnostic questionnaire （revised-CDQ）. Evaluation of the efficacy of these questionnaires was based on the area under the receiver operating characteristic curve （AUC） of the subjects. DeLong test was used to compare the accuracy of different questionnaires； Z test was used to compare the accuracy of different cut-off values for the same questionnaire. ResultsAmong 3 184 community residents， a total of 259 （8.1%） COPD patients were screened by spirometry. AUC values of these 3 screening questionnaires were >0.7 indicating that they were reliable COPD screening tools. The sensitivity and specificity of the questionnaires at the recommended cut-off values were COPD-SQ （63.7% and 72.2%）， COPD-PS （12.0% and 96.1%）， and revised CDQ （78.8% and 52.7%）， with the COPD-SQ having the highest screening accuracy （AUC=0.754）. The optimal and recommended cut-off values for the three questionnaires differed in this population， but the difference in accuracy was statistically significant only for COPD-PS. The optimal cut-off values for the three questionnaires differed between male and female， and the sensitivity and accuracy of COPD-SQ and COPD-PS improved when lower cut-off values were used for women. The AUC was greater when two questionnaires were utilized simultaneously for screening， but the differences were not statistically significant. ConclusionThe COPD-SQ is recommended for primary COPD screening； a lower cut-off value for women should be considered. The COPD screening questionnaire needs to be further improved for the early diagnosis and treatment of COPD patients.

Objective To analyze the hot spots and trends of digital intelligence technology research in intensive care unit(ICU).Methods ICU digital intelligence technology related literature collected in Web of Science core database,China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP Chinese Journal Service Platform were searched,and the retrieval period is from the establishment of the database to December 12,2023,and visualized analysis was performed by CiteSpace software.Results 700 Chinese literatures and 1705 English literatures were included.Conclusion A total of 18 clusters were formed in Chinese literature,including smart phones,data mining,ventricular premature beats,sepsis,etc.A total of 17 clusters were formed in English literature,including deep learning,expert systems,natural language processing,physiological characteristics,etc.Among them,risk prediction model and clinical decision support are the trends of future research.Conclusion By broadening the scope of diseases and populations,joint artificial intelligence research and development of wearable devices and intelligent detection cloud systems,robots,etc.,is the development trend of the future application field of ICU digital intelligence technology.

Psoriasis is a common immune-mediated inflammatory skin disease with multiple genetic and environmental risk factors.Abnormal vascular hyperplasia,excessive proliferation of keratinocytes and infiltration of various immune cells are the main pathological features.MAPK signaling pathway is involved in the pathogenesis of psoriasis,and SPRED1 has been proved to be a ma-jor negative regulator of MAPK signaling pathway in many diseases.This article reviews the possible role of SPRED1 in the pathogene-sis of psoriasis,in order to provide new insights into the pathogenesis of psoriasis and new directions for the treatment.