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 understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

Microsimulation model simulates individuals and estimates transition probabilities within the population using individual participant data. This approach could deal with the heterogeneous characteristics among the people or personal history of diseases and may be relevant in addressing cost-effectiveness problems of screening for complex conditions in epidemiology. This paper introduces the general principles, basic steps involved in implementation, analytic methods, and other related issues of the microsimulation model. Based on a practical research case of estimating the cost-effectiveness of microalbuminuria screening for chronic kidney disease in the United States, critical points in applications of the microsimulation model for cost-effectiveness analysis of screening were discussed in detail, including model development, model analysis, and the interpretation of the results. The microsimulation model considers the dynamic nature of complex diseases by estimating a broad range of individual characteristics and increasingly used to provide insights into complex problems that the Markov model does not efficiently address. For better supporting evidence-informed decision-making in public health, future studies should be aware of the accuracy of parameters in the decision-analytic model and the transparency of the models and results, as well as complying with the relevant reporting standards.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

Cost-effectiveness analysis of screening in epidemiology is essential for public health decision-making. This paper describes the general principles, basic steps involved in implementation, analytic methods and other related issues of Markov model. Based on a practical research case of evaluating the cost-effectiveness of primary open-angle glaucoma screening in a Chinese population, key points in applications of Markov model for cost-effectiveness analysis of screening were discussed in detail, including model development, parameters definition, available software, base case analysis, sensitivity analysis and the interpretation of the results. For better supporting evidence-informed decision making in public health, future studies should be aware of the accuracy of parameters in Markov models and the transparency of the models and results, as well as complying with the relevant reporting standards.

Objective To observe the changes of interleukin-18 (IL-18),interleukin-33 (IL-33) and fractional exhaled nitric oxide (FeNO) in children with acute respiratory syncytial virus (RSV) bronchiolitis,and explore the potential mechanism of the transformation from acute RSV bronchiolitis to recurrent wheezing.Methods Fifty-three children with RSV bronchiolitis (RSV bronchiolitis group),32 children with repeated wheeze (repeated wheeze group) and 30 children receiving regular physical examination (healthy control group) from January 2016 to January 2017 in Cangzhou People's Hospital of Hebei Province were selected.The serum IL-18 and IL-33 at the time of inclusion and 2,3 months after inclusion were detected by enzyme linked immunosorbent assay,the FeNO at the same time was detected by multiple breathing technique,and the indexes were compared.The correlation between FeNO and IL-33,IL-18 was analyzed by Spearman method.Results The IL-18 at the time of inclusion and 2,3 months after inclusion in RSV bronchiolitis group and repeated asthmatic group were significantly higher than those in healthy control group:(10.89 ± 1.54) and (14.86 ± 5.54) ng/L vs.(7.26 ± 3.25) ng/L,(13.74 ± 4.16) and (15.45 ± 5.75) ng/L vs.(7.28 ± 3.56) ng/L,(11.38 ± 6.21) and (14.86 ± 5.28) ng/L vs.(7.18 ± 3.41) ng/L,those in repeated asthmatic group were significantly higher than those in RSV bronchiolitis group,and there were statistical differences (P＜0.05).The IL-33 levels at the time of inclusion and 2,3 months after inclusion in RSV bronchiolitis group and repeated asthmatic group were significantly higher than those in healthy control group:(17.68 ± 5.25) and (13.14 ± 5.01) ng/L vs.(3.69 ± 1.61) ng/L,(15.68 ± 4.16) and (15.11 ± 5.24) ng/L vs.(3.28 ± 1.56) ng/L,(13.87 ± 6.21) and (14.11 ± 5.14) ng/L vs.(3.18 ± 1.41) ng/L,IL-33 levels at the time of inclusion in RSV bronchiolitis group were significantly higher than those in repeated asthmatic group,and there were statistical differences (P＜0.05).The FeNO levels at the time of inclusion and 2,3 months after inclusion in repeated asthmatic group were significantly higher than those in RSV bronchiolitis group and healthy control group:(13.14 ± 4.47) ppb vs.(1.89 ± 1.54) and (7.26 ± 4.25) ppb,(14.75 ± 5.15) ppb vs.(7.74 ± 4.16) and (7.28 ± 4.12) ppb,(13.68 ± 5.62) ppb vs.(11.38 ± 6.21) and (7.18 ± 3.41) ppb;compared with that in healthy control group,FeNO at the time of inclusion in RSV bronchiolitis group was significantly decreased,and at 3 months was significantly increased,and there were statistical differences (P＜0.05).Correlation analysis result showed that FeNO at 2 and 3 months after inclusion in RSV bronchiolitis group had positive correlation with IL-18 level at the time of inclusion and 2,3 months after inclusion (P＜0.05),and negative correlation with IL-33 (P＜0.05);FeNO at 2 and 3 months after inclusion in repeated asthmatic group showed positive correlation with IL-18 at the same time (P＜0.05),and was negatively correlated with IL-33 level (P＜0.05);there was no correlation between FeNO and IL-18,IL-33 in healthy control group (P＞0.05).Conclusions IL-18 and IL-33 may be involved in the pathogenesis of acute RSV bronchiolitis and recurrent wheezing,and the concentration of IL-18 and IL-33 is correlated with the level of FeNO.Its potential mechanism needs further study.

Objective:To explore the clinical efficacy of removal of large and medium-sized meningiomas in the sellar region via neuroendoscope assisted supraorbital keyhole approach.Methods:The clinical data of 13 patients with large and medium-sized meningiomas in the sellar region accepted surgery via neuroendoscope assisted supraorbital keyhole approach in our hospital from March 2017 to March 2019 were analyzed retrospectively. The surgical efficacies of these patients were analyzed.Results:Total removal was achieved in all 13 patients: 2 were with Simpson I resection, and 11 with Simpson II resection. The vision was improved in all patients. After surgery, scalp hydrops appeared in 2 patients, transient diabetes insipidus in 2 patients, and recurrent hyponatremia and hypokalemia in one patient; these symptoms were relieved gradually for 2 weeks. No olfactory disturbance was noted in these 13 patients. Follow up for 3-18 months showed no recurrence, and Karnofsky performance status scores were≥80.Conclusion:Surgery via supraorbital keyhole approach is suitable for large and medium sized meningiomas in the sellar region, with advantages of beauty, minimal invasion, few postoperative complications and quick recovery.

Objective To retrospectively analyze the clinical efficacy and safety of VCD (bortezomib/cyclophosphamide/dexamethason) in the treatment of multiple myeloma (MM) patients. Methods Fifty-five consecutive patients with newly diagnosed or relapsed MM were enrolled in the study retrospectively from June 2012 to June 2017. We collected and analyzed the clinical information of all patients treated with VCD.Results Firstly, the patients received therapy of VCD for median 4 cycles (Range : 2 ～8). The overall response rate (ORR) was 85.5％ (45/55). The complete response/near complete response rate (CR/nCR) , very good partial response rate (VGPR) and partial response rate (PR) were 27.3％, 23.6％ and 34.6％, respectively. The ORR of10 patients with renal inadequacy was 80.0％, while 45 cases with normal renal function was 82.2％ (P=0.627).Secondly, with a median follow-up of 13.5 months, the median progression free survival (PFS) , the median duration of response (DOR) and the median overall survival (OS) were 27 (1～61) months, 18 (1～50) months and 49 (1～64) months, respectively. Univariate prognostic analysis showed that abnormal ISS stage Ⅲ, relapse, renal dysfunction and response inferior to VGPR were negative prognostic factors for PFS, while abnormal ISS stageⅢ and renal dysfunction were negative prognostic factors for OS. Moreover, the multivariate prognostic analysis showed that abnormal ISS stage Ⅲ and response inferior to VGPR were independent prognostic factors for PFS, while ISS stage Ⅲ was independent prognostic factors for OS. Thirdly, the VCD treatment is effective and safe.The adverse events were evaluated according to International Myeloma Working Group Uniform Response Criteria.The results showed that the most common grade 3 ～4 non-hematology adverse events (AEs) were infection (20.0％) , peripheral neuropathy (5.5％) and hypertension (5.5％). The most common grade 3～4 hematology AEs were thrombocytopenia (10.9％) , neutropenia (9.0％) and anemia (5.5％). A total of 2 patients (3.6％) discontinued VCD because of serious peripheral neuropathy and 2 cases (3.65％) died of respiratory failure because of serious infection. Conclusions The VCD regimen is effective and safe in the treatment of newly diagnosed or relapsed/refractory MM patients in China. VCD is safe in patients with renal dysfunction.

Objective To study the pinoresinol diglucoside (PDG) on gene regulation role of ESF-1 cells in collagen secretion, to reveal PDG repair mechanisms on scalded skin.Methods The cells cultured in vitro were divided into the control group, the estradiol group and the three different PDG doses groups. The concentration of the high, medium and low dose groups were 100, 10, 1μmol/L, and that of estradiol group were 10-3μmol/L. The activity of proliferation was detected by MTT. Then collagen type I (Col I), collagen typeⅢ (ColⅢ), tissue inhibitors of metalloproteinase 1 (TIMP-1), tissue inhibitors of metalloproteinase 2 (TIMP-2) and matrix metalloproteinase 1 (MMP-1) expression levels of mRNA after administration of cells were detected by RT-PCR.Results Compared with the control group, the proliferation of ESF-1 cells (0.559 ± 0.027, 0.552 ± 0.034vs. 0.489 ± 0.027,P<0.05) in the estradiol and medium-dose PDG was significantly higher. The expression level of mRNA of ColⅠ(0.958 ± 0.021, 0.929 ± 0.031, 0.916 ± 0.015vs. 0.844 ± 0.022), ColⅢ (0.783 ± 0.038, 0.918 ± 0.021, 0.855 ± 0.017vs. 0.678 ± 0.024), TIMP-1 (0.939 ± 0.025, 0.889 ± 0.036, 0.853 ±  0.015 vs. 0.780 ± 0.023), TIMP-2 (0.507 ± 0.024, 0.655 ± 0.037, 0.572 ± 0.025vs. 0.405 ± 0.062) in the estradiol, low-, medium-dose PDG groups were significantly higher than those in the control group (P<0.05 or P<0.01). Besides, the MMP-1 (0.343 ± 0.038, 0.407 ± 0.046, 0.435 ± 0.037vs.0.519 ± 0.041) mRNA expression level in the middle and low dose PDG groups significantly decrease (P<0.05 orP<0.01). Conclusions The PDG could enhance the activity of ESF-1 cell proliferation, increase the expression of related collagen and tissue inhibitor of metalloproteinases and inhibit that of matrix metalloproteinases to repair scalded skin.