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

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs. Nevertheless, the clinical effectiveness of these treatments is progressively weakened by the emergence of drug resistance, thereby substantially restricting their therapeutic utility. Consequently, there is an imperative need to expedite the discovery of novel antifungal agents. This review seeks to present an exhaustive synthesis of novel antifungal drugs and candidate agents that are either under current clinical investigation or anticipated to progress into clinical evaluation. These emerging compounds exhibit unique benefits concerning their modes of action, antimicrobial spectra, and pharmacokinetic characteristics, potentially leading to improved therapeutic outcomes relative to conventional antifungal regimens. It is anticipated that these novel therapeutic agents will furnish innovative treatment modalities and enhance clinical outcomes in managing invasive fungal infections.

Recently developed three-dimensional echocardiography rendering technology，which includes transillumination imaging and tissue transparency imaging，is based on powerful artificial intelligence algorithm and employs unique visualization methods. This novel technology enables intuitive and realistic visualization of the heart's three-dimensional structure and blood flow images，providing richer and more accurate imaging information for evaluating cardiac anatomy and function. They demonstrate unique value in the diagnosis and treatment of structural heart diseases. This article reviews the applications and prospects of three-dimensional echocardiographic rendering techniques in structural heart disease.

Objective To invegtigate the possible etiology,clinical characteristics,and treatment effects of post tympanoplasty full-frequency bone conduction hearing loss in the operated ear.Methods A retrospective analy-sis was conducted on the possible causes,clinical manifestations,and diagnosis and treatment of 6 cases of full-fre-quency bone conduction hearing loss in the operated ear after tympanoplasty.Results The use of diluted epineph-rine during surgery,controlled hypotension during the operation,ethylene oxide in gelatin sponges,and the exces-sive pro-inflammatory factors produced postoperatively may be associated with the occurrence of full-frequency bone conduction hearing loss in the operated ear after tympanoplasty.Among the six patients,the main initial symptom was dizziness without vertigo or nystagmus.Two cases were ineffectively treated,one case was effectively treated,and three cases were cured.Among the four cases that received timely medication,three were effectively treated.Conclusion Full-frequency bone conduction hearing loss in the operated ear after tympanoplasty is related to various factors,and the clinical manifestations of patients are atypical,often manifesting as dizziness.Timely diagnosis through pure tone audiometry and timely treatment according to the sudden deafness treatment plan often leads to fa-vorable outcomes.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Objective:To explore the effects and mechanisms of Shen-su-yin (SSY) on acute lung injury (ALI) in rats based on untargeted Metabolomics, network pharmacology, and experimental verification.Methods:Untargeted Metabolomics was performed to detect the ingredients of SSY by using ultra-high performance liquid chromatography-Q-exactive orbitrap mass spectrum, and the active ingredients were screened from the detected ingredients. Common targets of the active ingredient targets and ALI targets were utilized to screen hub targets to perform gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Then, key hub targets were selected from the hub targets, and the active ingredients-hub targets network was built to screen core ingredients. Subsequently, molecular docking was performed between the key hub targets and the core ingredients. 48 rats were randomly and equally divided into 4 groups by using a random number table: normal control group, lipopolysaccharide-induced ALI group, ALI+SSY group, and ALI+dexamethasone group. 24 hours after lipopolysaccharide induction, the levels of respiratory rate, blood lactate, lung wet/dry weight ratio, ALI score, inflammatory factors of bronchoalveolar lavage fluid, and oxidative stress mediators of lung tissue in each group were evaluated, and the expression of phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase (GSK) 3β-nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor (NF)-κB signaling pathway was also detected by using Western blot. Finally, one-way analysis of variance, Welch test, or Kruskal-Wallis H test was used to compare data differences among groups. Results:A total of 415 ingredients were detected from the SSY. 66 of the detected ingredients were identified as active ingredients, and 10 of them were selected as core ingredients. The number of common targets, hub targets, and key hub targets was 337, 50, and 10, respectively. Total of 285 biological processes, 32 cellular components, and 51 molecular functions were enriched though GO analysis, and 148 cell signaling pathways such as pathways in cancer and PI3K-AKT signaling pathway were enriched though KEGG analysis. Molecular docking studies revealed that all binding energies between the 10 key hub targets and the 10 core ingredients were less than -5 kcal/mol. Compared with the ALI group, the levels of the respiratory rate, blood lactate, and lung wet/dry weight ratio in ALI+SSY group were significantly decreased (all P<0.01), and the level of ALI score showed a downward trend, but the difference was not statistically significant ( P>0.05). In addition, the levels of interleukin-6, interleukin-1β, and tumor necrosis factor-α in bronchoalveolar lavage fluid and the levels of malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine in lung tissue of rats in ALI+SSY group were significantly decreased in comparison with those in ALI group (all P<0.01). Moreover, compared with the ALI group, the phosphorylation levels of PI3K p85α, AKT1, and GSK3β and the expression level of Nrf2 in lung tissue of ALI+SSY group were significantly up-regulated (PI3K p85α phosphorylation and AKT1 phosphorylation, P<0.01; GSK3β phosphorylation and Nrf2, P<0.05), while the phosphorylation level of NF-κB p65 was significantly down-regulated ( P<0.01). Conclusions:Active ingredients detected from SSY via untargeted Metabolomics can inhibit oxidative stress and inflammation in ALI rats by regulating the PI3K-AKT-GSK3β-Nrf2/NF-κB signaling pathway, thereby alleviating lung lesions.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective To invegtigate the possible etiology,clinical characteristics,and treatment effects of post tympanoplasty full-frequency bone conduction hearing loss in the operated ear.Methods A retrospective analy-sis was conducted on the possible causes,clinical manifestations,and diagnosis and treatment of 6 cases of full-fre-quency bone conduction hearing loss in the operated ear after tympanoplasty.Results The use of diluted epineph-rine during surgery,controlled hypotension during the operation,ethylene oxide in gelatin sponges,and the exces-sive pro-inflammatory factors produced postoperatively may be associated with the occurrence of full-frequency bone conduction hearing loss in the operated ear after tympanoplasty.Among the six patients,the main initial symptom was dizziness without vertigo or nystagmus.Two cases were ineffectively treated,one case was effectively treated,and three cases were cured.Among the four cases that received timely medication,three were effectively treated.Conclusion Full-frequency bone conduction hearing loss in the operated ear after tympanoplasty is related to various factors,and the clinical manifestations of patients are atypical,often manifesting as dizziness.Timely diagnosis through pure tone audiometry and timely treatment according to the sudden deafness treatment plan often leads to fa-vorable outcomes.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Recently developed three-dimensional echocardiography rendering technology，which includes transillumination imaging and tissue transparency imaging，is based on powerful artificial intelligence algorithm and employs unique visualization methods. This novel technology enables intuitive and realistic visualization of the heart's three-dimensional structure and blood flow images，providing richer and more accurate imaging information for evaluating cardiac anatomy and function. They demonstrate unique value in the diagnosis and treatment of structural heart diseases. This article reviews the applications and prospects of three-dimensional echocardiographic rendering techniques in structural heart disease.