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 evaluate the effectiveness of amplification intervention with hearing aids for restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss. Methods:This study selected 30 patients with normal hearing in one ear and moderate to severe sensorineural hearing loss in the other ear. They were fitted with hearing aids for the worse ear and underwent more than half a year and one year of adaptation training. The Chinese translation of the Twelve-item version of SSQ（C-SSQ12）, angle identification test, speech recognition score（SRS） at different signal-to-noise ratios（SNR=5 and SNR=10） and audiometric thresholds were used to compare the results before and after hearing aid use to evaluate the effectiveness of the unilateral hearing loss intervention. Results:The results of the audiometric thresholds, C-SSQ12 scores, angle identification test, and SRS at SNR=5 and SNR=10 in the worse ear of the unilateral hearing loss patients after hearing aid use were all statistically significant compared to before hearing aid use（P<0.01）. Conclusion:Amplification intervention with hearing aids has significant effects on restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss.
Humans ; Hearing Aids ; Hearing Loss, Unilateral/therapy* ; Middle Aged ; Hearing Loss, Sensorineural/rehabilitation* ; Adult ; Female ; Male ; Auditory Threshold ; Young Adult ; Aged

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To study the prognosis of congenital bile duct cysts following cyst resection, and to analyze the risk factors associated with the development of postoperative biliary calculus.Methods:Clinical data of 149 patients with congenital bile duct cysts undergoing surgery in the First Affiliated Hospital of Nanjing Medical University from May 2004 to January 2022 were retrospectively analyzed, including 59 males and 90 females, with a median age of 32 (21, 47) years old. Patients were divided into two groups: the stone group ( n=51, biliary calculus occurred during the follow-ups after surgery) and non-stone group ( n=98). Clinical data such as gender, age, medical history, cyst type, biliary calculus, anastomotic stenosis and occurrence of cancer were compared. All patients were followed up via telephone consultations. A logistic regression analysis was used to identify the risk factors associated with the occurrence of biliary calculus after surgery. Results:The duration of the follow-ups was 120 (24, 211) months. The observed incidence of postoperative biliary calculus, anastomotic stricture, and cancer in the patients were 34.2% (51/149), 8.7% (13/149), and 4.7% (7/149), respectively. The logistic regression analysis indicated that incomplete cyst resection ( OR=3.332, 95% CI: 1.221-9.094) and postoperative anastomotic stenosis ( OR=13.300, 95% CI: 2.586-68.401) were associated with a higher risk of biliary calculus formation after cystectomy (all P<0.05). Conclusion:Patients with congenital bile duct cysts suffer a high risk of biliary calculus formation after cystectomy. The residual cyst and postoperative anastomotic stenosis are independent risk factors for biliary calculus after surgery.

Objective To investigate whether adjuvant therapy can bring survival benefits to patients with esophageal squamous cell carcinoma (ESCC) who have received neoadjuvant therapy plus esophagectomy. Methods Studies were identified by searching databases including PubMed, EMbase, Web of Science, The Cochrane Library and CNKI from inception to November 2022 to collect studies which conformed to the objective of this study. Clinical outcomes including overall survival (OS) and recurrence-free survival (RFS) were extracted from eligible studies after screening. RevMan 5.4 and Stata 14.0 were used to perform the meta-analysis. Results A total of 9 studies were selected including 1 340 patients. Compared with the neoadjuvant therapy plus surgery (NS) group, the neoadjuvant therapy plus surgery+adjuvant therapy (NS+A) group had no significant benefit in the OS [HR=0.88, 95%CI (0.75, 1.02), P=0.09], but had remarkable benefit in the RFS [HR=0.75, 95%CI (0.58, 0.97), P=0.03]. Subgroup analysis by nodal status showed that adjuvant therapy could improve the RFS of patients with node-positive disease. Prolonged OS was observed in the patients with both positive and negative nodes but not in the patients with only positive nodes. In terms of the subgroup analysis by prescription, it revealed that triple agents exhibited advantages in improving RFS but not OS. However, dual agents did not bring additional survival benefits to the NS+A group compared with the NS group. Subgroup analysis by adjuvant therapy indicated that neither postoperative chemoradiotherapy nor chemotherapy improved OS, whereas postoperative chemoradiation elongated RFS. Conclusion Adjuvant therapy can improve the prognosis of patients with ESCC after neoadjuvant therapy followed by esophagectomy.

Accurately grasping and identifying the ideological characteristics and internal needs of education objects is a prerequisite for implementing "precise ideological and political education".Contemporary medical students,who have grown alongside new media,have formed ideological and behavioral characteristics that are closely integrated with new media and have the characteristics of the times.Colleges and universities should carry out targeted ideological and political education for medical students to improve the effectiveness of their work.Through questionnaire surveys and in-depth interviews,this paper accurately analyzed the characteristics of medical students in the new media environment,such as righteous political attitude,upright and rational concepts,and rich and "internal" online life.It also accurately positioned the challenges that new media posed to the ideological and political education of medical students in aspects such as lifestyle,learning style,communication style.Based on facts,it implemented precise strategies and proposed the strategy of ideological and political education of medical students in the new media environment,which is "integrating explicit education and implicit education to ensure the direction,combining life education with legal education to deepen the connotation,and merging school education with family education to broaden the space."

Objective:To assess the association between short-term ambient air pollution exposure and arterial stiffness and whether obesity modifies these associations.Methods:A cross-sectional study was conducted based on Fangshan family cohort in Beijing. The 24 hours average air pollutant levels on the day cohort participants took baseline survey were calculated as short-term air pollution. A generalized additive model (GAM) with Gaussian links was used to estimate changes in typical carotid artery intima-media thickness (CIMT), brachial-ankle pulse wave velocity (BAPWV), pulse pressure (PP) and ankle-branchial index (ABI) after short-term exposure to each air pollution (PM 2.5, PM 10, SO 2, NO 2, CO). The cross-product terms of each air pollution, body mass index (BMI), and waist-to-hip ratio were included in the GAM model to test the interaction. Further, they conducted a stratified analysis to test their effects on the relationship between short-term exposure to each air pollution and the arterial stiffness indicators. Results:A total of 4 211 individuals were included in the analysis. Individuals' age was (58.9±8.7) years, of which 2 268 (53.9%) were female. Several covariates, including sociodemographic factors, lifestyle behaviors, and history of drugs, were included in the analysis. The results of the GAM analysis showed that an increase in PM 2.5 ( β=2.912×10 -4, 95% CI: 1.424×10 -4-4.400×10 -4, P<0.001), CO ( β=0.027, 95% CI: 0.011-0.043, P<0.001), SO 2 ( β=2.070×10 -3, 95% CI: 7.060×10 -4-3.430×10 -3, P=0.003), and NO 2 ( β=3.650×10 -4, 95% CI: 2.340×10 -5-7.060×10 -4, P=0.036) were associated with an increase in CIMT, while an increase in PM 10 ( β=0.018, 95% CI: 0.002-0.033, P=0.028) was associated with an increase in PP in the study population. Besides, the waist-to-hip ratio had an effect-modification on the correlation of short-term exposure of PM 2.5 (interaction P=0.015), NO 2 (interaction P=0.008), and CO (interaction P=0.044) with CIMT, and the correlation between short-term exposure of PM 2.5 (interaction P=0.002), NO 2 (interaction P=0.010), CO (interaction P=0.029), PM 10 (interaction P<0.001) with PP. The significant association between CIMT, PP, and air pollution concentrations was more visible in people with lower waist-to-hip ratios. Conclusions:Short-term ambient air pollution exposure was associated with arterial stiffness indicators, and there was an effect modification of waist-to-hip ratio on these associations, and lower waist-to-hip ratios may enhance the association between air pollution exposure and indicators.

Objective To explore the effect and mechanism of berberine combined with curcumin on ath-erosclerosis(AS)by mediating M1 macrophages polarization.Methods M1-type macrophages were obtained from mouse mononuclear macrophages(RAW264.7)induced by lipopolysaccharide(LPS,100 ng/mL)and interferon(IFN)-γ(20 ng/mL).A cell model was established.The cells were divided into a control group,model group,berberine group,curcumin group and berberine plus curcumin group.Concentrations of berberine and curcumin were detected by CCK-8 assay.The expression levels of M1-type macrophage markers iNOS,TNF-α,CXCL9 and p-STAT6/STAT6 in macrophage supernatant were detected by ELISA.Levels of iNOS,TNF-α and CXCL9 mRNA were detected by RT-PCR.Levels of iNOS,STAT6 and p-STAT6 proteins in each group were detected by Western blot.After down-regulation of STAT6 level by siRNA technology,expression of p-STAT6 protein was detected by Western blot.Expression levels of iNOS,TNF-α,CXCL9 and p-STAT6 were detected by ELISA.Results In the polarization of M1 macrophages induced by LPS and IFN-γ,berberine(25 μmol/L)and curcumin(20 μmol/L)were the best concentrations as compared with other drug concentration groups,and neither alone nor combined use could significantly inhibit the viability of RAW264.7 cells(P<0.05).As compared with the normal group,iNOS,TNF-α and CXCL9 mRNA and protein levels were increased in the model group,while P-STAT6/STAT6 levels were decreased,with statistical differences(P<0.05).As compared with the model group,iNOS,TNF-α and CXCL9 mRNA and protein levels in the berberine group,curcumin group,and berberine plus curcumin group were decreased,while P-STAT6/STAT6 levels were increased,and the changes were more obvious in berberine plus curcumin group,with statistical difference(P<0.05).After transfection of STAT6 siRNA in M1 macrophages in the berberine plus curcumin group,P-STAT6 levels were down-regulated,while expressions of iNOS,TNF-α and CXCL9 were up-regulated,with statistical differences(P<0.05).Conclusions Both berberine and curcumin can inhibit the activity of M1-type macrophages and reduce inflammatory response.The action of berberine combined with curcumin is more advantageous than that of either drug alone,which may be the main mechanism of action through activation of STAT6.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.