The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals

This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Objective:To investigate the safety and efficacy of intravascular intervention in ruptured intracranial vertebral artery dissecting aneurysm (IVADA).Methods:A retrospective analysis was performed; 25 patients with ruptured IVADA (25 aneurysms) admitted to Department of Neurosurgery, First Affiliated Hospital of University of Science and Technology of China from January 2020 to June 2023, were chosen. Aneurysm and parent artery occlusion or stent-assisted spring coil embolization were performed according to location of the aneurysms, degrees of aneurysm immediate embolization were evaluated by Raymond grading, and perioperative adverse events were recorded. The patients were followed up for 6-48 months, and aneurysm recurrence was determined according to DSA results; prognoses were assessed by modified Rankin Scale (mRS), with scores of 0-2 as good prognosis and scores of 3-6 as poor prognosis.Results:All 25 patients had unilateral ruptured IVADA, 10 (40%) received aneurysm and parent artery occlusion (occlusion of dissection segment) and 15 (60%) received stent-assisted embolization. Immediately after surgery, 19 patients (76%) had grading I embolization, 4 (16%) grading II embolization, and 2 (8%) grading III embolization. No aneurysm rupture or stent related thrombosis was observed during procedure; 3 patients (12%) died after procedure, with postoperative rebleeding in 1, postoperative cerebellar infarction with respiratory failure in 1, and severe pneumonia in 1. In the 22 survivals, 18 had good prognosis and 4 had poor prognosis. In the 5 relapsed patients (all accepted stent-assisted embolization), 4 underwent re-intervention, and one with visualization at aneurysm neck was relatively stable on re-examination and accepted regular follow up.Conclusion:Aneurysm and parent artery occlusion can be used for non-dominant vertebral artery aneurysms not involving posterior inferior cerebellar artery, whose recurrence rate is lower than that of stent-assisted coil embolization.

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action， so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group， model group， carbamazepine group （0.06 g·kg^-1·d^-1）， high-dose Lutongning group （2.70 g·kg^-1·d^-1）， and low-dose Lutongning group （1.35 g·kg^-1·d^-1） according to the stratified basic mechanical pain thresholds， with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg^-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin （HE） staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors interleukin （IL）-1， IL-6， IL-8， tumor necrosis factor （TNF）-α， neuropeptide substance P， and β-endorphins （β-EP） in the serum of rats， and Western blot was used to detect the protein expression levels of IL-1β， purinergic receptor P2X7 （P2X7R）， and phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）. ResultCompared with that in the normal group， the pain threshold of rats in the model group was significantly lower （P<0.01）. The absolute value of neutrophils （NEUT#） and the percentage of neutrophils （NEUT） were significantly improved， and the percentage of lymphocytes （LYMPH） was significantly reduced （P<0.01）. The serum levels of IL-1， IL-6， IL-8， and TNF-α were significantly increased （P<0.01）. SP content in brain tissue was significantly increased， and β-EP content was significantly decreased （P<0.01）. The relative protein expression of IL-1β， P2X7R， and p-p38 MAPK was significantly increased （P<0.05）. HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration， mild proliferation of microglial cells， reduction in the number of myelinated nerves， and obvious demyelination. The trigeminal nerve fibers of rats were disarranged， and some nerve fibers showed vacuolization. Axons were swollen， and Schwann cells proliferated. Demyelination was observed. Compared with the model group， each administration group significantly increased the pain threshold of rats （P<0.05， P<0.01）， reduced NEUT# and NEUT， and elevated LYMPH （P<0.05， P<0.01）. The administration group significantly decreased the levels of IL-1， IL-6， IL-8， and TNF-α in serum and SP in brain tissue （P<0.01） and increased the level of β-EP （P<0.01）. They significantly down-regulated the protein expression of IL-1β， P2X7R， and p-p38 MAPK（P<0.05， P<0.01） and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats， and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

Objective To observe the clinical efficacy of citicoline sodium tablets combined with huperzine A tablets in the treatment of patients with cognitive impairment after stroke,and to explore the influence on neurological function and serum levels of vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF).Methods Patients with cognitive impairment after stroke were classified into control group and treatment group according to cohort method.The control group was given oral administration of huperzine A tablets 0.1-0.2 mg for twice a day,while the treatment group was given 0.2 g citicoline sodium tablets orally for three times a day on the basis of the control group.Both groups of patients were treated for 12 weeks.The clinical efficacy,cognitive function[Mini-Mental State Examination(MMSE),National Institute of Health stroke scale,Barthel index],neurological function and daily living ability and serum vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)levels were compared and safety was evaluated.Results One hundred patients were enrolled in the experimental group and the control group.After treatment,the total effective rates in treatment group and control group were 92.00％(92 cases/100 cases)and 75.00％(75 cases/100 cases)with significant difference(P＜0.05).The MMSE scores in treatment group and control group after treatment were(23.40±2.43)and(19.35±2.51)points;the scores of National Institutes of Health Stroke Scale were(12.25±1.24)and(15.84±1.61)points;the Barthel Index scores were(71.14±8.60)and(64.26±8.33)points;VEGF levels were(191.52±14.80)and(125.73±11.48)pg·mL-1;BDNF levels were(9.47±1.59)and(8.01±1.35)ng·mL-1.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).The adverse drug reactions in the treatment group were mainly dizziness and nausea,and the adverse drug reactions in the control group were mainly dizziness and nausea.The incidence rates of adverse drug reactions in treatment group and control group were 8.00％(8 cases/100 cases)and 5.00％(5 cases/100 cases)(P＞0.05).Conclusion Citicoline sodium tablets combined with huperzine A tablets have a definite efficacy in the treatment of patients with cognitive impairment after stroke,and it has a significant improvement effect on cognitive function and neurological function of patients,with good safety.

Objective:To explore the application value of multimodal MRI imaging in early neurological deterioration (END) and clinical prognosis prediction of acute ischemic stroke (AIS).Methods:A total of 200 AIS patients admitted to the Chengde Central Hospital from October 2019 to October 2022 were selected as the study subjects. Based on whether END occurred within 7 days of enrollment, there were 40 cases in the occurrence group and 160 cases in the non occurrence group. The influencing factors of END occurrence in AIS patients and the predictive value of multimodal magnetic resonance imaging (MRI) parameters on END were analyzed; According to the modified Rankin (mRS) score, patients were divided into good prognosis and poor prognosis groups, and the impact of multimodal MRI imaging parameters on the risk of poor prognosis in AIS patients was analyzed.Results:There were statistically significant differences in the apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and their differences before and after thrombolysis in multimodal MRI imaging parameters between the END group and the non END group, as well as in the National Institutes of Health Stroke Scale (NIHSS) score at admission, age, and time from onset to admission (all P<0.05). The difference between ADC and CBF before and after thrombolysis, time from onset to admission, NIHSS score at admission, and age were all independent influencing factors for the occurrence of END in AIS patients (all P<0.05). The area under the curve (AUC) of the combined prediction of the difference between ADC and CBF before and after thrombolysis for the occurrence of END in AIS patients was 0.924, which was higher than that predicted by a single indicator ( P<0.05). The incidence of poor prognosis in patients with END was significantly higher than that in patients without END ( P<0.05). The risk of poor prognosis in AIS patients with a difference of less than <45.83×10 -9 mm 2/s before and after ADC thrombolysis was 3.136 times higher than that in patients with ≥45.83×10 -6 mm 2/s. The risk of poor prognosis in AIS patients with a difference of less than 10.52 ml/(min·100 g) before and after ADC thrombolysis was 2.640 times higher than that in patients with ≥10.52 ml/(min·100 g). Conclusions:Multimodal MRI imaging can be used for END evaluation in AIS patients and can provide reference for clinical prognosis evaluation.

Familial hyperaldosteronism type Ⅲ(FH-Ⅲ) is extremely rare, and there are no reported cases in China. Herein, we reported two cases with FH Ⅲ, both of which presented with severe hypertension and hypokalemia in their early childhood. One patient had significantly enlarged adrenal glands and developed clinical manifestations of Cushing′s syndrome at the age of 20. Complete relief of symptoms was achieved after bilateral adrenalectomy. The other case had normal adrenal imaging, and with spironolactone treatment, blood pressure and potassium levels were well-controlled. Both cases had germline mutation of KCNJ5 gene which were c. 433G>C(p.Glu145Gln) and c. 452G>A(p.Gly151Glu), respectively.