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

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective:To investigate the effects of pulsed electromagnetic fields(PEMFs)combined with iron oxide nanoparticle paramagnetic gel on muscle strength,mass,and function in elderly patients with degenerative muscle atrophy.Methods:The clinical data of 40 patients with degenerative muscle atrophy who were treated in our hospital from Sep 2024 to Mar 2025 were retrospectively analyzed.According to the treatment method,patients were divided into the PEMFs group and the combined treatment group,with 20 cases in each group.The intervention sites in both groups were the bilateral quadriceps femoris.The PEMFs group received low-frequency alternating PEMFs therapy,while an iron oxide nanoparticle paramagnetic gel was applied locally to the target area prior to each PEMFs session in the combined treatment group.Muscle strength,mass,and functional indicators were assessed in both groups before and after the intervention.Results:After 12 weeks of intervention,the combined treatment group showed greater improvements in maximum voluntary contraction,rectus femoris thickness,and cross-sectional area compared to the PEMFs group(P＜0.05).Additionally,the combined treatment group showed further reductions in timed up and go test(TUGT)and five-repetition sit-to-stand test(5STS)durations,as well as increased walking distance in the 6-minute walk test(6MWT),all of which were better than those observed in the PEMFs group(P＜0.05).The combined therapy also resulted in superior improvements in skeletal muscle mass index and Berg Balance Scale score(P＜0.05).Conclusions:PEMFs have a promotive effect on muscle strength,mass,and functional performance.The combination with iron oxide nanoparticle paramagnetic gel can further enhance its therapeutic efficacy.

Objective:To explore the effects of Baduanjin and brisk walking on the sleep quality among fe-male college students.Methods:Ninety female college students with poor sleep quality[Pittsburgh Sleep Quality Index(PSQI)≥ 8]were recruited randomly assigned to Baduanjin,brisk walking,and control groups,with 30 par-ticipants in each.The Baduanjin and brisk walking groups participated in 10-week intervention(five 45-minute ses-sions per week),while the control group did not receive any intervention.Baseline and post-intervention assessments were conducted using the PSQI,a lung capacity test,echocardiography,and the Fatigue Scale(FS-14).Results:Af-ter 10 weeks,participants in both the Baduanjin and brisk walking groups got significantly lower PSQI and FS-14 total scores compared to baseline(Ps＜0.001).Cardiopulmonary function indicators,including stroke volume(SV),forced expiratory volume in one second(FEV1.0),the vital capacity-to-body mass index(VC/W),and maximum voluntary ventilation per minute(MVV),also significantly improved(Ps＜0.001).Furthermore,the Baduanjin group had significantly lower PSQI and FS-14 scores than both the brisk walking and control groups(P＜0.001),along with superior improvements in cardiopulmonary function(P＜0.001).Conclusion:This study in-dicates that Baduanjin is particularly effective in improving sleep quality,cardiopulmonary function,and reducing fatigue among female college students,showing advantages over brisk walking.

Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective:To investigate the effects of pulsed electromagnetic fields(PEMFs)combined with iron oxide nanoparticle paramagnetic gel on muscle strength,mass,and function in elderly patients with degenerative muscle atrophy.Methods:The clinical data of 40 patients with degenerative muscle atrophy who were treated in our hospital from Sep 2024 to Mar 2025 were retrospectively analyzed.According to the treatment method,patients were divided into the PEMFs group and the combined treatment group,with 20 cases in each group.The intervention sites in both groups were the bilateral quadriceps femoris.The PEMFs group received low-frequency alternating PEMFs therapy,while an iron oxide nanoparticle paramagnetic gel was applied locally to the target area prior to each PEMFs session in the combined treatment group.Muscle strength,mass,and functional indicators were assessed in both groups before and after the intervention.Results:After 12 weeks of intervention,the combined treatment group showed greater improvements in maximum voluntary contraction,rectus femoris thickness,and cross-sectional area compared to the PEMFs group(P＜0.05).Additionally,the combined treatment group showed further reductions in timed up and go test(TUGT)and five-repetition sit-to-stand test(5STS)durations,as well as increased walking distance in the 6-minute walk test(6MWT),all of which were better than those observed in the PEMFs group(P＜0.05).The combined therapy also resulted in superior improvements in skeletal muscle mass index and Berg Balance Scale score(P＜0.05).Conclusions:PEMFs have a promotive effect on muscle strength,mass,and functional performance.The combination with iron oxide nanoparticle paramagnetic gel can further enhance its therapeutic efficacy.

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

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.