Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To explore clinical effect of reverse shoulder replacement in treating giant irreparable rotator cuff tear complicated with glenohumeral arthritis. METHODS: A retrospective analysis was performed on 18 patients (18 shoulders) with glenohumeral arthritis combined with large irreparable rotator cuff tear admitted from April 2020 to April 2022, including 10 males and 8 females, aged from 60 to 78 years old;7 patients on the left side, 11 patients on the right side;the course of disease ranged from 6 to 21 months;7 patients with grade 3 and 11 patients with grade 4 according to Goutallier grading;8 patients with grade 4b and 10 patients with grade 5 according to Hamada grading. Shoulder joint motion, visual analogue scale (VAS), University of California at Los Angeles (UCLA) score and Constant-Murley shoulder joint function score and complications were compared at the latest follow-up. RESULTS: Eighteen patients were followed up for 24 to 48 months. At the latest follow-up, shoulder joint flexion ranged from 120° to 145°, abduction ranged from 100° to 130°, and rotation ranged from 45° to 60°. VAS ranged from 1 to 3;Constant-Murley score ranged from 80 to 95;and UCLA scores ranged from 27 to 35, and 6 patients obtained excellent result, 11 good and 1 average. Dislocation of shoulder joint occurred in 1 patient at 3 months after operation, but no dislocation occurred after manual reduction. The incision surface infection occurred in 1 patient at 1 week after operation, and the incision healed after anti-infection and cleaning. The other patients did not have complications such as dislocation, infection, prosthesis loosening and peripheral fracture. CONCLUSION Reverse shoulder replacement for the treatment of huge irreparable rotator cuff injury combined with glenohumeral arthritis disease, the clinical effect is good, could significantly improve shoulder joint function and improve quality of life, but still need to strengthen the prevention and treatment of postoperative complications such as dislocation and infection.
Humans ; Male ; Female ; Middle Aged ; Rotator Cuff Injuries/physiopathology* ; Aged ; Retrospective Studies ; Arthroplasty, Replacement, Shoulder/methods* ; Range of Motion, Articular ; Shoulder Joint/physiopathology*

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

【Objective】 To investigate the development of the foot arch and develop a rehabilitation treatment plan for children with spastic diplegia of cerebral palsy gross motor function classification(GMFCS) system grade Ⅰ-Ⅱ. 【Methods】 Fifty children with spastic diplegia and flat exostosis with GMFCS grade Ⅰ-Ⅱ were selected into this study, and were divided into observation group (n=25) and control group (n=25) using the random number table method. The control group received conventional exercise therapy, while the observation group received arch correction exercises additionally. Both groups underwent treatment once a day for 5 days a week. Children in both groups were evaluated before and 6 months after the intervention. The arch index F, electronic plantar pressure measurement index, and the D and E scores of the Gross Motor Function Measure (GMFM-88) were used to assess the severity of clubfoot and the level of motor development. 【Results】 Bofore intervention, there were no significant differences in the arch index F, electronic plantar pressure measurement index, and GMFM-88 score between the observation group and the control group (P>0.05). After 6 months of intervention, the scores of arch index F(t=9.89, 5.35), and GMFM-88 (t=6.59, 3.46) in both groups increased significantly(P<0.05). The scores of foot arch index F (26.08±0.73) and GMFM-88 (30.24±7.94) in the observation group and control group were significantly higher than those in the control group (25.34±0.64, 25.20±7.06) (t=3.81, 2.37, P<0.05). Plantar pressure pictures showed a gradual increase in lateral foot pressure compared to medial pressure, and a decrease in pressure in the midfoot arch area, indicating a decrease in foot valgus and progressive development of the arch. 【Conclusion】 The comprehensive rehabilitation therapy technique incorporating arch correction and gymnastics treatment can promote the arch development in children with GMFCS grade Ⅰ-Ⅱ spastic diplegia, which is important for improving their foot and ankle function and motor development level.

Hypomyelinating leukodystrophies (HLDs) are a group of neurodegenerative diseases characterized by decreased myelination in the central nervous system, with diverse clinical manifestations like psychomotor retardation and dyskinesia.Some HLDs patients have epilepsy, microcephaly and other clinical manifestations.At present, there is no specific treatment of HLDs, and the prognosis is usually poor.At present, with the wide application of gene screening in clinical practice, many pathogenic genes related to HLDs have been found.It is particularly important to clarify the pathogenesis and clinical phenotypic changes of HLDs.

Objective To design an assisted patient conveying and vibration damping system to solve the problems of operator fatigue and patient bump during casualty evacuation.Methods The assisted patient conveying and vibration damping system was composed of several conveying straps and a vibration damping mechanism.The conveying straps were made up of a waist strap,two shoulder straps,a chest strap,adhesive straps and joint components,and the joint components included adjusting buckles,big buckles,small buckles,connecting buckles and hook mechanisms;the vibration damping mechanism adopted the technical form of extension handle combined with vibration absorber,in which the extension handle was made of rigid material and the vibration absorber was equipped with a scissor guiding mechanism.Tests were carried out on the system to record the operating time of the operators and to analyze the system's vibration damping characteristics.Results The system developed extended the operating time of the stretcher conveyers while reduced the vibration during casualty transport,with a maximum vibration reduction of 71.73％.Conclusion The system developed gains advantages in low vibration and low workload,and can be used for casualty conveying in poor road conditions.[Chinese Medical Equipment Journal,2024,45(1):15-24]

Objective:To analyze the risk factors of secondary epileptic seizures in children with febrile seizures and to construct a nomogram prediction model.Methods:A total of 235 children with febrile seizures who were admitted to Enshi State Hospital for Nationalities from August 2018 to September 2021 were selected. According to whether the children had secondary epileptic seizures during the 6-month follow-up, the children were divided into the seizure group (62 cases) and no-seizure group (173 cases). The best cut-off value of each factor were obtained by the receiver operating characteristic (ROC). Multivariate Cox regression analysis was used to analyze the independent risk factors of secondary seizures in children with febrile seizures. The R software "rms" package was constructed to predict secondary seizures in children with febrile seizures. High-risk nomogram models, calibration curves was used for internal validation of nomogram models, and decision curves to assess the predictive power of nomogram models.Results:The age of the patients in the seizure group was lower than that in the no-seizure group: (14.45 ± 1.54) months vs. (21.47 ± 2.18) months; and the proportion of family history of epilepsy, the proportion of perinatal (abnormal), the proportion of seizure type (comprehensive), the proportion of electroencephalogram (EEG) (abnormal), the number of seizures, the duration of seizure, the tumor necrosis factor-alpha (TNF-α) level in the seizure group were higher than those in the no-seizure group: 56.45%(35/62) vs. 35.84%(62/173), 59.68% (37/62) vs. 15.61%(27/173), 70.97%(44/62) vs. 36.99% (64/173), 74.19% (46/62) vs. 20.81% (36/173), (5.45 ± 2.32) times vs. (2.04 ± 1.02) times, (18.89 ± 4.29) min vs. (12.62 ± 2.34) min, (25.65 ± 5.32) ng/L vs.(18.21 ± 2.29) ng/L, there were statistical differences ( P<0.05). The area under the curve (ACU) of age, number of convulsions, duration of convulsion, and TNF-α were 0.906, 0.913, 0.899, and 0.890, respectively; the best cut-off values were 3 years, 4 times, 15 min, 21 ng/L; age (≤3 years), family history of epilepsy (yes), type of seizures (generalized), perinatal period (abnormal), number of seizures (≥4 times), duration of seizures (≥15 min) were febrile seizures independent risk factors for secondary epileptic seizures in children ( P<0.05), the C-index of this nomogram prediction model was 0.744 (0.567-0.932); the decision curve showed that when the risk threshold was greater than 0.11, the clinical net benefit provided by this prediction model. The benefits were all higher than individual independent risk factors and provided a significant additional net clinical benefit in predicting a high risk of seizures secondary to febrile seizures in children with febrile seizures. Conclusions:This study constructed a nomogram model of the risk of secondary seizures in children with febrile seizures based on age, family history of epilepsy, type of seizures, perinatal period, number of seizures, and duration of seizures. Important strategic guidance.

Objective To explore the differential diagnostic indicators of adult-onset Still's disease(AOSD)from other fever of unknown origin(FUO).Methods The clinical data and laboratory indicators of 177 AOSD patients and 163 FUO patients who were hospitalized in the First Affiliated Hospital of Army Medical University from January 2010 to May 2021 were collected,and the patients were randomly divided into training group and verification group.Statistically significant variables were extracted from univariate analysis for receiver operating characteristic(ROC)curve analysis and the best cut-off value of the variables was obtained.The differential diagnostic indicators were extracted by multivariate logistic regression analysis and nomogram model was constructed.ROC curve,calibration curve,and decision curve analysis were used to evaluate the accuracy and stability of nomogram.Results Univariate analysis revealed that there were significant differences in 4 clinical features(arthralgia,rash,pharyngeal pain,myalgia)and 14 laboratory parameters[white blood cell count(WBC),monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,C-reactive protein,interleukin-6(IL-6),ferritin,globulin,immunoglobulin A,and immunoglobulin G(IgG),creatine kinase,creatinine and complement C3].Multivariate analysis suggested that arthralgia,WBC≥9.995×109/L,IL-6≥98.13 ng/L,ferritin≥507.37 ng/ml,globulin≤36.58g/L,IgG≤13.59g/L,complement C3≥1.27 g/L were related with AOSD.The area under curve(AUC)values of training group and verification group were 0.917(95%CI 0.883-0.951)and 0.869(95%CI 0.802-0.936),respectively.The calibration curves showed good consistency.The decision curve analysis showed that training group and verification group had a large positive rate of return in the wide risk range of 5%-85%and 10%-85%,respectively.Conclusions This study has established a relatively accurate AOSD differential diagnosis model.The combination of arthralgia,WBC,IL-6,ferritin,globulin,IgG and complement C3 may help to distinguish AOSD from other causes of FUO.