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

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective:To investigate the prevalence and potential classification of symptoms after total knee arthroplasty (TKA) in patients with knee osteoarthritis (KOA), and to analyze the differences in demographic characteristics and surgical data, compare the different potential subgroups, in order to provide a basis for clinical symptom management plans.Methods:This study was a multicenter cross-sectional survey. Through convenience sampling, patients with KOA undergoing TKA in the orthopaedic wards of four tertiary hospitals in Urumqi were selected as the study from November 2023 to February 2024. The study subjects were surveyed using a general information questionnaire, the Visual Analogue Scale (VAS) for pain, the Hospital Anxiety and Depression Scale (HADS), and the Pitts Burgh Sleep Quality Index (PSQI), and the degree of postoperative joint swelling and size of ecchymosis were measured. Latent class analysis was performed using Mplus 8.3 software, and Logistic regression analysis was conducted using SPSS 26.0 software to explore the influencing factors of the latent classes.Results:Totally 337 effective questionnaires were collected, and the recovery rate was 94.7% (337/356), and the age distribution ranged from 47 to 85 (65.19 ± 6.99) years old, with 90 (26.7%) males and 247 (73.3%) females. There were 92.3% (311/337) of TKA patients with postoperative symptom cluster. The symptom cluster of patients with TKA were identified as 3 classes. They were named as "high level pain-psychological disorder group"(12.5%, 39/311), "high bruises-moderate psychological disorders group"(25.4%, 79/311) and "low symptom burden group" (62.1%, 193/311). The results of the unordered multi-class logistic regression analysis showed that age 45-59 years ( OR = 2.367), body mass index 24.0-27.9 kg/m 2 ( OR = 0.207), living with children/parents ( OR = 6.473), and this being the second joint surgery ( OR = 0.040) were the factors influencing the "high level pain-psychological disorders group" (all P<0.05). The factors influencing the "high bruises-moderate psychological disorders group" were living with children/parents ( OR = 4.023), comorbid chronic diseases ( OR = 1.979, 3.842), and intraoperative blood loss ≤100 ml ( OR = 2.342) (all P<0.05). Conclusions:The postoperative symptom cluster of TKA patients have a relatively high incidence, and there is heterogeneity within the symptom cluster, so nurses need to identify at-risk patients early according to the characteristics of different categories and give interventions.

Objective To establish an automatic review plan for coagulation tests with image recognition function,and evaluate the correctness and effectiveness of the plan.Methods Artificial intelligence software and hardware were combined to establish an image recognition system that could automatically determine the characteristics of specimens,blood volume and hematocrit.The correctness of the determination results of specimen character was compared with the visual method,the correctness of the determination results of blood volume was compared with the manual measurement method,and the correctness of hematocrit was compared with the hematology analyzer.According to the flow chart,reference interval,medical decision level,critical value range,relevant literature,work experience and historical data,the autoverification rules of coagulation tests were formulated.The autoverification rules were manually verified,and the autoverification pass rate,true positive rate,true negative rate,false positive rate,and false negative rate were calculated.The change of turnaround time in the laboratory after the implementation of the autoverification scheme was evaluated.Re-sults The accuracy rate of sample trait determination in the image recognition system was 96.72％,and the false negative rate of judging hemolytic,jaundice,and lipoid blood samples as normal samples was 0.04％.The image recognition system was compared with the blood volume data of two groups of specimens measured manually,P=0.4881.The image recognition method was not inferior to the manual measurement method.Comparing the two sets of hematocrit data from the image recognition system and the blood cell analyzer,P=0.1130,the image recognition system was not inferior to the blood cell analyzer.A total of 61 automatic re-view rules for coagulation tests had been established,including numerical abnormalities,logical abnormalities,Delta Check,sample quality abnormalities,reaction curve abnormalities,etc.The automatic review pass rate was 76.19％,true positive rate was 23.77％,true negative rate was 76.19％,false positive rate was 0.04％,and false negative rate was 0.00％.After implementing the automatic audit plan,the turnaround time of sam-ples in each quantile was shortened,with an average shortening time of 13.66 min.Conclusion The applica-tion of image recognition technology in the automatic review of coagulation tests makes the automatic review function more automated and scientific,standardizes specimen quality judgment,improves the accuracy of test results,effectively improves work efficiency and saves manpower.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED). METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points. RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point. CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.