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

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective: To assess the current situation and related factors of the knowledge, attitude and behavior toward sexual abuse prevention among primary school students in Luzhou City, Sichuan Province, so as to provide a reference basis for the development of sexual abuse prevention education for primary school students. Methods: A total of 4 563 primary school students in Luzhou City were sampled from December 2023 to January 2024 by stratified cluster sampling, and self administered questionnaires were conducted. The binary Logistic regression analysis was used to analyze related factors of the knowledge, attitude and behavior toward sexual abuse prevention. Results: The qualified rates of knowledge, behavior and attitude among primary school students towards sexual abuse prevention in Luzhou were 76.2%, 21.3%, and 90.2 %, respectively. The binary Logistic regression showed that males ( OR=0.66, 95%CI =0.56-0.78), attending rural schools ( OR=0.77, 95%CI =0.64-0.92), left behind status ( OR=0.66, 95%CI =0.53-0.81), and household registration in Lu County ( OR=0.57, 95%CI =0.46-0.70) and Gulin County ( OR=0.70, 95%CI =0.57-0.86) had lower qualified rates of the knowledge of sexual abuse prevention among primary school students ( P < 0.05 ); while qualified knowledge of sexual abuse prevention was positively associated with grade ( OR =3.05-18.81); attending rural schools ( OR=0.82, 95%CI =0.70-0.95) and not having received education on prevention of sexual abuse ( OR=0.55, 95%CI = 0.47-0.64) had lower qualified rates of the behavior of sexual abuse prevention among primary school students ( P <0.05); household registration in Lu County ( OR=0.73, 95%CI =0.58-0.92) and not having received education on prevention of sexual abuse ( OR=0.33, 95%CI =0.26-0.40) had lower qualified rates of the educational attitudes of sexual abuse prevention among primary school students ( P <0.05). Conclusions The qualified rates of knowledge and behavior of sexual abuse prevention among primary school students in Luzhou City needs to be improved. Health education regarding sexual abuse prevention might help enhance primary school students awareness and skills of sexual abuse prevention.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Background::One of the significant challenges for cell therapies, such as chimeric antigen receptor (CAR)-T cell therapy, is the poor infiltration of immune cells into tumor tissues. CAR-monocytes/macrophages (CAR-M) are promising therapies because of their enrichment in the tumor microenvironment. Thus, we constructed a novel CAR-M to facilitate the infiltration of T cells and other immune cells.Methods::The suicide gene inducible caspase-9 ( iCasp9) and anti-erb-b2 receptor tyrosine kinase 2 (HER2) CAR elements were transfected into THP1 (an immortalized human monocyte cell line) by lentivirus. The suicide efficiency and specific anti-tumor efficacy were assessed using flow cytometry, inCucyte, and tumor-bearing BALB/c-nude mouse models. The activation of related signaling pathways in CAR-THP1 activation was explored by transcriptome sequencing. Finally, the synergistic therapeutic efficacy of CAR-THP1 combined with RAK cell treatment was demonstrated in tumor-bearing NOD.CB17-Prkdc scid Il2rg tm1/Bcgen mouse models. Results::We developed a novel CAR-THP1, which incorporated iCasp9, CD3ζ, and CD147 intracellular segments, based on the first-generation HER2-CAR backbone. By constructing and comparing a series of CARs with different permutations, CAR-CD3ζ-CD147-iCasp9-THP1 was selected as the optimal combination. CAR-CD3ζ-CD147-iCasp9-THP1 initiated suicide quickly and efficiently under the control of iCasp9 gene, which enabled us to achieve controlled proliferation of CAR-THP1. CAR-THP1 also exhibited robust specific anti-tumor efficacy independently of T cells in vitro and in vivo. Through transcriptional sequencing, we found that CAR-THP1 tended to differentiate into the M1 phenotype and bridged innate and adaptive immunity. A combination of CAR-THP1 and Retronectin actived killer cells (RAKs) showed better therapeutic efficiency, as the metalloproteinases (MMPs) secreted by CAR-THP1 facilitated the degradation of the dense tumor matrix. This further assisted intratumoral infiltration of T cells and augmented the anti-tumor immune response. Conclusion::CAR-THP1 might be effective against HER2-positive tumor cells and has great potential for combination therapy with other immune cells.

Objective To use color Doppler ultrasound to measure the hemodynamic indexes,and to es-tablish the diagnostic prediction model of inflammatory fetal distress.Methods A total of 213 pregnant women admitted to the obstetrics department of the First Affiliated Hospital of Air Force Military Medical U-niversity were collected as the research subjects and divided into the control group and case group according to whether or not fetal distress occurred,including 93 cases in the control group and 120 cases in the case group.The predictive value of PI,RI,S/D values of middle cerebral artery,umbilical artery and uterine artery for pre-dicting fetal distress was analyzed The diagnostic model was constructed by logistic regression analysis.The receiver operating characteristic(ROC)curve,calibration curve and clinical decision curve were adopted to an-alyze and evaluate the diagnostic efficiency of the model for adverse perinatal outcome and the clinical benefit of the patients.Results The univariate analysis results showed that MCA-PI,MCA-RI,MCA,S/D and CPR in the case group were lower than those in the control group,while UA-RI,UA,S/D and UtA-RI were higher than those in the control group.The multivariate regression analysis further showed that MCA-PI,MCA-RI and CPR were the independent protective factors for predicting fetal distress,while UA-R1 and UA-S/D served as the independent risk factors affecting the fetal outcome.Based on five independent influencing fac-tors,the risk prediction model was constructed,and the area under the receiver operating characteristic curve was 0.880(95％CI:0.834-0.925).The sensitivity,specificity and accuracy were 0.93,0.70 and 0.83 respec-tively,and the goodness of fit was good.Conclusion The hemodynamic indexes measured by color Doppler ul-trasound have good predictive value for the diagnosis of fetal distress.The risk prediction model established by the combined indexes has a certain reference value for the intervention in advance of pregnant women with fe-tal distress occurence.

Objective To investigate the effect and mechanism of recombinant human CC16 protein(rhCC16)on cigarette smoke extract(CSE)-induced senescence of human bronchial epithelial cells(HBECs).Methods CCK-8 assay was used to evaluate the cell viability in HBECs after treated with 0％,1％,2.5％,5％,7.5％and 10％CSE and/or 0,10,100,250 and 500 ng/mL rhCC16.β-galactosidase staining was used to observe the activity of the enzyme in control,CSE,and CSE+rhCC16 treated HBECs.The mRNA levels of P16 and P21 in above cell groups were detected by real-time fluorescence quantitative PCR(qPCR),and the protein levels of P16,P21,p-P53,P38,p-P38,ERK1/2 and p-ERK1/2 were detected with Western blot in control group,CSE and CSE+rhCC16 groups.Results Compared with the control group,5％CSE stimulation for 72 h or the treatment of 500 ng/mL or lower dose of rhCC16 had no significant effect on cell viability of HBECs.Stimulation 5％CSE for 72 h resulted in significantly higher positive rate to β-galactosidase staining(P＜0.05),elevated mRNA and protein levels of P16 and P21(P＜0.05),and enhanced protein levels of p-P53,p-P38 and p-ERK1/2(P＜0.05)when compared with the control group.Compared with the simple CSE stimulation,250 ng/mL 1hCC16 treatment decreased positive rate to β-galactosidase staining(P＜0.05),reduced mRNA and protein levels of P16 and P21(P＜0.05)and protein levels of p-P53,p-P38 and p-ERK1/2(P＜0.05).Conclusion rhCC16 inhibits CSE-induced cellular senescence of HBECs,which may due to its suppression in P38 MAPK and ERK1/2 signaling pathway.

Atrial fibrillation (AF) is one of the most common arrhythmias. Studies have shown that there is a significant correlation between inflammation and AF. Pathogenic microbial infection has long been considered the most likely factor to trigger and maintain the inflammatory process. In recent years, with the development of molecular biology technology, more and more evidence shows that some bacteria and viruses can cause AF. The research on AF and pathogens has gradually become a hot topic in recent years.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.