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

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*

OBJECTIVE To prepare a new antibacterial agent triggered by near infrared light to combat bacterial infection and promote wound healing. METHODS The synthesis of antibacterial agengt was supported by the results from transmission electron microscopy, Ultraviolet-visible absorption spectroscopy and Fourier-transform infrared spectroscopy. The antibacterial agent was irradiated under near infrared(NIR) laser with different concentrations to study the photothermal properties. Release of ciprofloxacin from the antibacterial agent was determined under different conditions. Observed antibacterial activity of the agent by spread plate method and bacterial growth curve. The infected wound was made on the back skin of mice, and the mice were treated with different methods to observe the healing process of the wound and study its influence on the wound healing. RESULTS The synthesized antimicrobial agent could be heated repeatedly without attenuation under near-infrared light, and could still reach a high temperature of 45 ℃ at a low concentration of 125 µg·mL-1. At the same time, it could promote the release of loaded antibiotics, and the release rate reached 86%. Compared with 200 µg·mL-1 solution obtained by physical mixing of polydopamine and ciprofloxacin, the synthesized antimicrobial agent combined with near-infrared light showed more excellent antibacterial ability, and the bacteriostatic rate against Escherichia coli and Staphylococcus aureus was 99.9%. Antimicrobial agents with concentrations of only 0.312 5 µg·mL-1 and 1.25 µg·mL-1 combined with near infrared light significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. Through the mouse skin defect model infected by Staphylococcus aureus, it was proved that the synthetic antibacterial agent still had excellent antibacterial effect in practical application, and could accelerate the healing of infected wound. CONCLUSION The synthesized antimicrobial agents have excellent antibacterial effect in vitro, and still have good antibacterial effect and promote wound healing under the conservative power irradiation without causing skin damage in vivo.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an underdiagnosed genetic heart disease worldwide. The management and prognosis of obstructive HCM (HOCM) and non-obstructive HCM (HNCM) are quite different, but it also remains challenging to discriminate these two subtypes. HCM is characterized by dysmetabolism, and myocardial amino acid (AA) metabolism is robustly changed. The present study aimed to delineate plasma AA and derivatives profiles, and identify potential biomarkers for HCM. METHODS: Plasma samples from 166 participants, including 57 cases of HOCM, 52 cases of HNCM, and 57 normal controls (NCs), who first visited the International Cooperation Center for HCM, Xijing Hospital between December 2019 and September 2020, were collected and analyzed by high-performance liquid chromatography-mass spectrometry based on targeted AA metabolomics. Three separate classification algorithms, including random forest, support vector machine, and logistic regression, were applied for the identification of specific AA and derivatives compositions for HCM and the development of screening models to discriminate HCM from NC as well as HOCM from HNCM. RESULTS: The univariate analysis showed that the serine, glycine, proline, citrulline, glutamine, cystine, creatinine, cysteine, choline, and aminoadipic acid levels in the HCM group were significantly different from those in the NC group. Four AAs and derivatives (Panel A; proline, glycine, cysteine, and choline) were screened out by multiple feature selection algorithms for discriminating HCM patients from NCs. The receiver operating characteristic (ROC) analysis in Panel A yielded an area under the ROC curve (AUC) of 0.83 (0.75-0.91) in the training set and 0.79 (0.65-0.94) in the validation set. Moreover, among 10 AAs and derivatives (arginine, phenylalanine, tyrosine, proline, alanine, asparagine, creatine, tryptophan, ornithine, and choline) with statistical significance between HOCM and HNCM, 3 AAs (Panel B; arginine, proline, and ornithine) were selected to differentiate the two subgroups. The AUC values in the training and validation sets for Panel B were 0.83 (0.74-0.93) and 0.82 (0.66-0.98), respectively. CONCLUSIONS The plasma AA and derivatives profiles were distinct between the HCM and NC groups. Based on the differential profiles, the two established screening models have potential value in assisting HCM screening and identifying whether it is obstructive.
Humans ; Amino Acids ; Cysteine ; Cardiomyopathy, Hypertrophic/diagnosis* ; Biomarkers ; Proline ; Arginine ; Ornithine ; Glycine ; Choline

Uncovering conserved 3D protein-ligand binding patterns on the basis of functional groups(FGs)shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions.Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature,large-scale identification and evaluation of FG-based 3D binding motifs are still lacking.Here,we propose a computational method,Automatic FG-based Three-dimensional Motif Extractor(AFTME),for automatic mapping of 3D motifs to different FGs of a specific ligand.Applying our method to 233 naturally-occurring ligands,we define 481 FG-binding motifs that are highly conserved across different ligand-binding pockets.Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs.Combinations of FG-binding motifs facilitate the binding of proteins to a wide spectrum of ligands with various binding affinities.Finally,we show that our FG-motif map can be used to nominate FGs that potentially bind to specific drug targets,thus providing useful insights and guidance for rational design of small-molecule drugs.

Objective: To establish an experimental model of Turner′s tooth caused by trauma in SD rats and observe its surface by scanning electronic microscopes(SEM) and energy dispersive spectrometry(EDS) was performed. Methods: 40 SD rats aged one day were randomly divided into four groups(n=10). The control group did nothing, The experimental group was exerted different perpendicular forces(per 5 mm2) on the mandibular anterior alveolar process, which was divided into 5 N force group, 10 N force group and 15 N force group. The SD rats were killed at 30 days old to observe the enamel development of their mandibular central incisors. Meanwhile, SEM and EDS were used to observe normal enamel area and enamel hypoplasia area. Results: The control group: all teeth erupted; all enamels developed well. 5 N force group: all teeth erupted; the occurrence rate of enamel hypoplasia was 10%(2 teeth had enamel discoloration). 10 N force group: 1 tooth unerupted; the occurrence rate of enamel hypoplasia was 80%(12 teeth had enamel discoloration and 4 had enamel defects). 15 N force group: 7 teeth unerupted, the occurrence rate of enamel hypoplasia was 60%(3 teeth had enamel discoloration and 9 had enamel defects). There was a statistic difference in the number of unerupted teeth between group 10 N force group and 15 N force group(P<0.05). Under SEM, cracks and rough appeared on the surface of enamel. EDS showed that the Ca and P content in enamel hypoplasia was lower than that in the normal enamel area(P<0.05). Conclusion Tooth trauma can lead to enamel hypoplasia and unerupted teeth. The force of 10 N per 5 mm2is better to establish an experimental model of Turner′s tooth caused by trauma in SD rats. The surface enamel of Turner′s tooth caused by trauma is rough, uneven and the content of calcium and phosphorus decreases.

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (

Objective:To establish a dental fluorosis model of SD rats with various degrees, to observe the microstructures of enamel samples under scanning electron microscope and to clarify the changes of enamel microstructures with various degrees of dental fluorosis, so as to provide clinical reference for the treatment of patients with moderate and severe dental fluorosis.Methods:Thirty male SD rats (6 weeks of age) were randomly divided into 3 groups with 10 rats in each group. The control group was fed with deionized water without fluoride, the low fluoride group was fed with 50 mg/L NaF deionized water and the high fluoride group was fed with 100 mg/L NaF deionized water in order to establish the dental fluorosis model of rats. After feeding for 6 weeks, the rats were sacrificed and the mandibular incisor teeth were collected and recorded. The surface and sagittal plane of each tooth were observed by scanning electron microscopy and the enamel thickness was measured.Results:In the control group, the enamel color was brown yellow. Enamel color discoloration occurred both in low-fluoride group and high-fluoride group. The enamel color in low-fluoride group was mostly yellow and white striped while in high-fluoride group was mostly chalky white. Under electronic microscope, the enamel rods were alternately arranged and their structure was clear and plump in the control group. The enamel rods of moderate fluorosis were arranged in a straight orientation like tips of bamboo shoots. The enamel rods of severe fluorosis, however, became thinner and the tips of rods were broken. In the control group, sagittal images of enamel turned out to be a dense outer structure with clear boundaries among the inner. The structure of the middle layer was reticulated showing a clear boundary with middle and outer layers. The structure of enamel rods in the inner layers was arranged vertically and horizontally. In the moderate fluorosis group, the outer layer of the enamel became thinner and the middle layer disappeared although the boundary between the outer and middle layers was still clear. In the inner layer, the vertically arranged enamel rods seemed still clear, however the horizontal enamel rods disappeared. In the severe fluorosis group, the outer layer could not be traced. The middle layer was exposed to the air and the inner enamel rods contracted. The inner layers of the enamel had gradually become thinner with the development of the dental fluorosis. The thicknesses of inner layers in control, moderate and the severe groups were (180.71 ±7.01), (157.10 ±11.04) and (121.10 ±12.56) μm respectively. As for the thicknesses of the full layers in the above mentioned three groups, the same trend was observed. The thicknesses, in order of the severity of dental fluorosis, were (241.54 ±7.76), (207.42 ±14.36) and (143.79 ±14.60) μm. Conclusions:With the development of dental fluorosis, the outer enamel layers became thinner or disappeared and the inner enamel layers became thinner or lost its normal structure as well. It is highly recommended that the resin penetration could be used for the proper treatment of moderate and severe dental fluorosis and the strong bleaching and the micro-grinding should be used cautiously.

Objective:To investigate the clinical characteristics, risk stratification, thrombolytic effects and prognosis of 110 patients with acute pulmonary embolism (PE) treated with thrombolysis.Methods:The clinical data of 110 patients with PE admitted to Beijing University People's Hospital from May 2009 to March 2019 were retrospective analyzed. The clinical data including general information, symptoms and signs, blood pressure, artery blood gas, coaglulation, and radiography were collected. Inclusion criteria: high-risk and intermediate high-risk group. Exclusion criteria: intermediate low-risk and low-risk group. According to the prognosis and risk stratification, the patients were divided into survival group and non-survival group, high-risk group and intermediate high-risk group. The indicators above were compared between with χ 2 test, t test or nonparametric test where appropriate. Results:Of the 110 patients with PE, 49 patients were male and 61 female with an average age of 65±16 years old; and 12 patients were in the high-risk group and 98 in the intermediate high-risk group. The respiratory rate of the high-risk group was higher, and blood pressure, PO 2, SaO 2 before thrombolysis were more lower than the intermediate high-risk group ( P<0.05). One hundred and nine patients were treated with systemic recombinant tissue plasminogen activator (rtPA), 70 patients with 50 mg, and 39 patients with 100 mg. One patient, who was contraindicated to systemic thrombolysis (with active vagina bleeding), was treated with interventional local thrombolysis; another 5 patients treated with interventional local thrombolysis because the clinical symptom were not improved markedly. One hundred and two patients survived and 8 patients died, among which, 3 patients were in the high-risk group and 5 in the intermediate high-risk group. The age, heart rate, respiration rate of the non-survival group were higher than those in the survival group, and the PO 2 before thrombolysis, PCO 2 after thrombolysis were lower ( P<0.05). Bleeding complication were occurred in 22 patients: 18 patients with minor bleeding, such as bleeding gums, skin ecchymosis, and 4 patients with moderate-severe bleeding, such as cerebral hemorrhage, abdominal bleeding, gastrointestinal bleeding, and vagina bleeding. Thirteen of 70 patients in the 50 mg group and 9 of 39 patients in the 100 mg group occurred bleeding complication. The bleeding complication of the low dose group was lower than that of the standard dose group ( P<0.05). Conclusions:Thrombolysis is first-line therapy to high-risk PE. Thrombolysis is safe and effective in the intermediate high-risk group with a lower incidence rate of bleeding complication.

Objective To investigate the clinical characteristics and prognosis of patients with acute aortic dissection (AAD) and hypertension,and explore other related prognostic factors in AAD.Methods The present study enrolled consecutive patients diagnosed with AAD who were admitted to Peking University People's Hospital between January 2000 to December 2015.Patients diagnosed with AAD by CT angiography,aortography or magnetic resonance imaging within 14 days of onset were included.Patients with infectious diseases,haematological diseases,malignancies,autoimmune diseases and patients without clearly clinical diagnosis or incomplete data were excluded.The patients were initially divided into two groups based on their history of hypertension,and their clinical characteristics were compared and analyzed.We further divided AAD patients into survival group and death group according to their in-patient outcomes,and factors related to their prognoses were analyzed.Logistic regression analysis was applied to analyze the independent risk factors related to hospital death in AAD patients with P＜0.05 as the significant value.Results The hypertensive group contained 237/346 cases included (68.45％),patients in this group were generally older than their non-hypertensive counterparts,accompanied by increased prevalence of comorbidities (coronary heart diseases or diabetes) and a statistical significant elevated admission blood pressures (systolic and diastolic,P＜0.05).No significant difference were found between the groups in terms of white blood cell and platelet count,D-dimer,neutrophil to lymphocyte ratio(NLR),fibrinogen,serum creatinine and serum lipid profiles (P＞0.05).Hypertensive patients were less likely to receive surgical treatment compared with those without hypertension(P＜0.05),with increased risk of in-hospital mortality (P＞0.05).Further logistic regression analysis revealed the presence of hypertension did not independently predict in-hospital mortality of AAD patients.Factors such as age,Stanford classification of the AAD,NLR and platelet counts were found to have independent predictive values for in-hospital mortality (P＜0.05).Conclusion AAD patients with hypertension are generally older,have more comorbidities such as coronary heart diseases and diabetes.The presence of hypertension itself is not directly associated with in-hospital mortality in AAD patients,while the Stanford classification,age,NLR and platelet counts are independent risk predictors.