INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy (HCM) families.Methods:A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affiliated Hospital of Air Force Medical University (Xijing Hospital) from February 2014 to July 2018, and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands. The probands carrying the MYH7-R453C mutation were screened out, and their family members carrying the mutation were verified using Sanger sequencing. Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls. Clinical data such as echocardiography, 12-lead electrocardiogram, and cardiac magnetic resonance imaging of the probands and their family members were collected, and the correlation between patient genotype and clinical phenotype was analyzed. Endpoint or key events were recorded through hospital re-examination or telephone follow-up.Results:The MYH7-R453C mutation was detected in 5 HCM probands, and clinical data and genetic results of 20 family members, including probands, were collected. Among them, 13 carried the MYH7-R453C mutation, of which 12 were diagnosed with HCM, and one child (F1Ⅲ 5) experienced early changes of HCM. The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms. Among the 12 patients diagnosed with HCM, 2 experienced (F2Ⅱ 7, F5Ⅰ 2) sudden cardiac death, 2 experienced (F1Ⅲ 1, F3Ⅲ 3) events of sudden cardiac death survival, 2(F1Ⅱ 2, F3Ⅱ 1) died from heart failure during the follow-up period. Combined with the initial visit and follow-up, 4 families (F1, F2, F3, F5) had a family history of sudden death, among which 3 families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival. Conclusions:In the five families with HCM carrying MYH7-R453C mutations, genotype is highly correlated with clinical phenotype, and patients have a high risk of sudden death and poor prognosis. Early diagnosis of individuals carrying the MYH7-R453C gene mutation, both within the patient′s family and in the patients themselves, is crucial for initiating early treatment, preventing sudden death, and assessing prognosis.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

Objective To observe the effect of immersion virtual reality (IVR) training combined with occupational therapy (OT) in the treatment of stroke patients with unilateral neglect. Methods Fifty stroke patients with unilateral neglect in Shanghai Fourth Rehabilitation Hospital were randomly divided into IVR plus OT group and OT group, with 25 cases in each group. The OT group received conventional OT for unilateral neglect, and the IVR plus OT group received IVR training and OT. Both groups were treated for 4 weeks. Before and after treatment, the Catherine Bergego Scale (CBS), line cancellation test, star cancellation test, and drawing clock test were used to evaluate unilateral neglect symptoms; the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Barthel index (BI) were used to evaluate motor function of upper extremity and activities of daily living. Results After treatment, the results of CBS, line cancellation test, star cancellation test, drawing clock test, FMA-UE and BI scores were significantly improved when compared with those before treatment in both groups, and the improvement effects in the IVR plus OT group were significantly better than those in the OT group (P < 0.05 or P < 0.01). Conclusion IVR training combined with OT can improve unilateral neglect symptoms, motor function of affected upper extremity, and activities of daily living in stroke patients.

Objective:To determine the relative correction factor of pre-vitamin D and simplify the calculation method of vitamin D assay.Methods:By studying the calculation method of vitamin D content in drug standards of various countries,HPLC was used to determine the relative correction factor of pre-vitamin D,and the influencing factors of determination were investigated.Results:The relative correction factors of pre-vitamin D at 254 nm and 265nm wavelength were determined by statistical analysis of 7 laboratories in China.Conclusion:Using the pre-vi-tamin D relative correction factor method to calculate the total amount of vitamin D simplified the experimental steps can be simplified by the pre-vitamin D relative correction factor method to calculate the total amount of vitamin D and the random operating errors can be avoided.The method is rapid and accurate,and lay a solid foundation for further improving the standard of vitamin D preparations.

Objective:To explore the influence of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) on tumor markers and quality of life after breast-conserving surgery for breast cancer.Methods:Patients after breast-conserving surgery for breast cancer in the Third People' s Hospital of Chengdu were selected from June 2015 to June 2018 as the study subjects. Fifty-five cases with conventional radiotherapy (CRT) were selected and included in control group, and 49 cases with SIB-IMRT were enrolled as observation group. The radiotherapy time and radiotherapy-related adverse reactions, serum tumor markers (β2-microglobulin (β2-MG), carbohydrate antigen 125 (CA125), tissue polypeptide specific antigen (TPS), carbohydrate antigen 153 (CA153)) before radiotherapy and at 6 months after radiotherapy, short-term solid tumor treatment effect at 6 months after radiotherapy and quality of life (progression-free survival (PFS), overall survival (OS)) after 5 years of follow-up were collected in both groups of patients. Measurement data were presented as xˉ± s by t test. Enumeration data were analyzed by χ2 test or Fisher test. Nonparametric rank sum test was used to compare the distribution of ranked data between groups. Results:The radiotherapy time in observation group was shorter than that in control group ((37.46±6.74) d vs (43.63±7.26) d), and the incidence of radiotherapy-related adverse reactions was lower than that in control group (14.29% (7/49) vs 32.73% (18/55))(Statistical values were 4.47 and 4.83, P values were <0.001 and 0.028). At 6 months after radiotherapy, the levels of β2-MG, CA125, TPS and CA153 in observation group were lower compared to control group ((1.25±0.21) mg/L vs (1.86±0.37) mg/L, (15.17±2.56) kU/L vs (18.81±3.13) kU/L, (9.43±1.58) μg/L vs (13.49±2.51) μg/L, (11.75±1.63) kU/L vs (15.46±3.07) kU/L) ( t=10.17, 6.44, 9.73, 7.56; all P<0.01), but there was no statistical significance in disease control rate between the two groups ( P>0.05). The observation group had higher objective remission rate (53.06%(26/49) vs 32.73%(18/55)), and the difference was statistically significant( χ2=4.39, P=0.036). After a 5-year follow-up, 44 patients in the observation group survived (89.80%, 44/49), with an OS of (57.92±11.21) months; 42 patients in the control group survived (76.36%, 42/55), with an OS of (54.05±10.14) months. There was no statistically significant difference between the two groups (both P>0.05). The PFS of the observation group patients was higher than that of the control group ((54.93±10.07) months compared to (50.76±9.95) months), and the difference was statistically significant ( t=2.12, P=0.036). Conclusion:Simultaneous integrated boost intensity-modulated radiation therapy for breast cancer patients undergoing breast-conserving surgery can reduce the levels of serum tumor markers, improve the breast aesthetics, and enhance the short-term and long-term quality of life of patients.

Brain-computer interfaces (BCIs) have become one of the cutting-edge technologies in the world, and have been mainly applicated in medicine. In this article, we sorted out the development history and important scenarios of BCIs in medical application, analyzed the research progress, technology development, clinical transformation and product market through qualitative and quantitative analysis, and looked forward to the future trends. The results showed that the research hotspots included the processing and interpretation of electroencephalogram (EEG) signals, the development and application of machine learning algorithms, and the detection and treatment of neurological diseases. The technological key points included hardware development such as new electrodes, software development such as algorithms for EEG signal processing, and various medical applications such as rehabilitation and training in stroke patients. Currently, several invasive and non-invasive BCIs are in research. The R&D level of BCIs in China and the United State is leading the world, and have approved a number of non-invasive BCIs. In the future, BCIs will be applied to a wider range of medical fields. Related products will develop shift from a single mode to a combined mode. EEG signal acquisition devices will be miniaturized and wireless. The information flow and interaction between brain and machine will give birth to brain-machine fusion intelligence. Last but not least, the safety and ethical issues of BCIs will be taken seriously, and the relevant regulations and standards will be further improved.
Humans ; Brain-Computer Interfaces ; Medicine ; Algorithms ; Artificial Intelligence ; Brain