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*

Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective:To evaluate the consistency between architectural distortion（AD）observed on coronal images in three-dimensional ultrasonography（3D-US）and full-field digital mammography（FFDM），and to analyze the influencing factors of the presence of AD on 3D-US coronal images.Methods:A retrospective study was conducted on 96 female patients（97 lesions）with AD identified via FFDM that examined at Affiliated Hangzhou First People's Hospital，School of Medicine，Westlake University from January 2019 to December 2021，all of which with corresponding 3D-US results. Kappa analysis was used to assess the consistency between AD on 3D-US and FFDM.The differences of the lesion characteristics on FFDM（glandular density，presence of calcifications，and degree of distortion），3D-US features（number of lesions，presence of mass or non-mass lesions，and skipping sign in coronal images），clinical pathological characteristics（age，location，and pathology）between groups with AD and without AD in 3D-US were compared. Multivariate Logistic regression was used to identify the influencing factors.Results:Among the FFDM-identified AD lesions，62（63.92%，62/97）lesions showed AD on 3D-US coronal images，including 30 malignant lesions（48.39%，30/62）；35（36.08%，35/97）lesions without AD on 3D-US，in which 4（11.43%，4/35）were malignant. The consistency of distortion degree between FFDM and 3D-US was moderate（Kappa=0.455， P<0.001），with no statistically significant difference（ χ2=2.882， P=0.143）. The probability of malignancy was higher in typical AD compared to atypical AD. The comparisons of age，location，number of lesions，presence of skipping sign in 3D-US，breast density，and presence of calcification in the lesion showed no statistically significant differences between the groups with and without AD（all P >0.05）.The pathological results of malignancy，presence of lesions in 3D-US（mass and non-mass lesions），and the degree of distortion in FFDM showed statistically significant differences（all P < 0.05）. The multivariate Logistic regression analysis indicated that there were no independent risk factors for the appearance of AD in 3D-US（all P > 0.05）. Conclusions:In breast FFDM AD lesions，the incidence of 3D-US coronal plane AD was 63.92%，and the consistency between the degree of distortion in FFDM and 3D-US was moderate. The probability of malignancy is higher with typical AD. Pathological malignancy，presence of lesions in 3D-US（both mass and non-mass lesions），and typical AD in FFDM are more likely to correspond with AD in the coronal.

AIM:Regulatory T cells(Tregs)are a specialized subset of CD4+T cells primarily involved in im-munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen-tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un-explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4+T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+T cells in peripheral blood,alongside a decrease in the proportion of mature CD8+T cells.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/fl mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3+T cell population,particularly the CD8+T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice.CONCLUSION:The populations of mature Tregs,CD8+T cells and eosinophils in various im-mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.

Objective:To investigate the clinical characteristics and risk factors for recurrence of perianal abscess in children.Methods:A retrospective study was conducted on the clinical data of 161 children with perianal abscess who were hospitalized in the Children's Hospital affiliated to Zhengzhou University from January 2015 to December 2022.Based on whether or not recurrence occurred after treatment，the patients were divided into the recurrence group(58 cases) and the simple group(103 cases).The clinical manifestations，laboratory examination indexes，and recurrence risk factors of children with perianal abscess were analyzed.Results:The effective rate of treatment for 161 children with perianal abscess was 64.0% (103/161),and 58 cases had recurrent abscess or fistula formation.The main orientations of the lesions were at the 3 o'clock position in 62 cases (38.5%) and at the 9 o'clock position in 67 cases (41.6%) in the lithotomy site.Bacterial culture of drainage fluid from perianal abscesses was positive in 61 (37.9%) children and the pathogens were Klebsiella pneumoniae in 48 cases,Staphylococcus aureus in 7 cases and Escherichia coli in 6 cases.The recurrence group mainly had underlying diseases including 38 cases of Crohn's disease，15 cases of chronic diarrhoea，and 5 cases of immunodeficiency,while the simple group had 3 cases of Crohn's disease，36 cases of chronic diarrhoea，and 2 cases of immunodeficiency，with 62 cases（60.1%）had no underlying diseases.The recurrence group showed significant statistical differences in gender（ χ2= 4.347， P=0.041），age（ χ2= 4.071， P=0.045），abscess size（ χ2= 6.298， P=0.008），abscess with fistula（ χ2= 10.928， P<0.001），combined with underlying diseases（ χ2= 10.673， P<0.001），fever（ χ2= 6.215， P=0.014），growth retardation（ χ2= 8.273， P=0.004），malnutrition（ χ2=4.521， P=0.038），hospitalization cost（ t=5.581， P=0.021），and hospital stay（ t=5.309， P=0.036）compared to the simple group.Additionally，the recurrence group showed significant statistical differences in white blood cells（ t=6.873， P=0.006），C-reactive protein（ t=7.631， P=0.003），fecal calprotectin（ t=10.073， P<0.001），albumin（ t=4.587， P=0.025），interleukin-6（ t=11.648， P<0.001），tumor necrosis factor-α（ t=7.803， P=0.021），lymphocyte count（ t=8.478， P=0.011），CD4 +/CD8 + ratio（ t=10.674， P<0.001），and IgA（ t=6.437， P=0.002）compared to the simple group.Multivariate Logistic regression analysis showed that abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 + ratio，and high fecal calprotectin were high risk factors for recurrence of perianal abscess in children. Conclusion:Children with perianal abscesses have a high recurrence rate and are prone to fistula formation.Perianal abscess with fistula，Crohn's disease，low IgA，low CD4 +/CD8 +ratio，and high fecal calprotectin are high risk factors for recurrence in children.

Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

This article comprehensively discusses the concept of workplace ostracism, measurement tools, theoretical basis, the current situation of workplace ostracism among nurses, and research on related variables. It proposes targeted strategies to address workplace ostracism among nurses, aiming to reduce the occurrence of workplace ostracism incidents among nurses. This is of great significance for constructing a harmonious work environment and promoting individual mental health.

AIM:Regulatory T cells(Tregs)are a specialized subset of CD4+T cells primarily involved in im-munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen-tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un-explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4+T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4+T cells in peripheral blood,alongside a decrease in the proportion of mature CD8+T cells.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/fl mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3+T cell population,particularly the CD8+T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/fl mice.CONCLUSION:The populations of mature Tregs,CD8+T cells and eosinophils in various im-mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.