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

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

With the continuous evolution and refinement of the healthcare insurance system,there arises a heightened de-mand for the standardization and efficacy of healthcare insurance management.This paper takes a prominent public hospital in Guangzhou City as a case study to delve into the establishment and enhancement of an intelligent monitoring system for healthcare insurance.Initially,an analysis is conducted from the perspectives of the national,policy,and institutional levels to underscore the imperative and urgency of constructing an intelligent monitoring system for healthcare insurance.Subsequently,a comprehen-sive review of the current research landscape,both domestically and internationally,is presented,highlighting the challenges faced by domestic intelligent auditing systems in terms of their level of intelligence,the sophistication of hospital-level intelligent monitoring,and the standardization of rule libraries.Following this,the paper elaborates on the practical endeavors undertaken by large public hospitals in Guangzhou City regarding the construction and optimization of the intelligent monitoring system for healthcare insurance.This encompasses aspects such as the structure of the intelligent monitoring system,collaborative manage-ment in operational modes,and the standardization of rule libraries.Finally,the paper concludes by summarizing the positive im-pact of these practices on the regulation of medical service behaviors and the enhancement of efficiency in healthcare insurance quality management,while also offering insights into future research directions.

Objective To investigate the influencing factors for sleep disorder during parachute training in special operations forces from a unit of the army,and to develop and validate a prediction model.Methods A total of 349 special operations officers and soldiers undergoing parachute training from October to November 2022 were recruited as research objects.Self-made questionnaires,Self-Rating Anxiety Scale(SAS)and Pittsburgh Sleep Quality Index(PSQI)Scale were used to collect their baseline data and assess sleep quality.According to their PSQI score,the participants were divided into sleep disorder group and non-sleep disorder group,and then assigned into a training set(n=228)and a validation set(n=97)in a ratio of 7∶3.Based on the training set,univariate analysis and multivariate logistic regression analysis were used to screen out the factors influencing the risk of sleep disorders.Then R language was employed to draw a nomogram model,and receiver operating characteristic(ROC)curve was plotted to evaluate the discrimination of the model.Calibration curve analysis and Hosmer-Lemeshow goodness-of-fit test were applied to evaluate the accuracy of the model,and decision curve analysis(DCA)was conducted to evaluate the validity of the model.The validation set was used for internal validation.Results There were totally 325 participants with valid data,and all of them were male.They had a total PSQI score of 4.26±3.30,and 62 of them(19.1％)had sleep disorders,including 46(14.1％)of mild,14(4.3％)of moderate,and 2(0.6％)of severe sleep disorders.Based on the 228 participants in the training set,the results of univariate and multivariate logistic regression analyses showed the number of parachute jumping(OR=0.390,95％CI:0.185～0.811),smoking(OR=2.980,95％CI:1.352～7.028),anxiety state(OR=3.280,95％CI:1.434～7.570),and chronic pain(OR=4.090,95％CI:1.952～8.690)were independent influencing factors of sleep disorder in these parachute officers and soldiers.A risk prediction model for sleep disorder was constructed,and the area under the curve(AUC)value was 0.778,with an optimal threshold of 0.163,a specificity of 63.6％and a sensitivity of 84.1％,with good discrimination.The quasi-curve and Hosmer-Lemeshow goodness-of-fit test(Chi-sqaure=8.789,P=0.456)showed that the model had good accuracy,and the clinical decision curve indicated that the prediction model had good clinical applicability.The model was confirmed to be valid with internal verification based on the validation set of 97 participants.Conclusion Special operations forces with parachute training have different degrees of sleep disorders.Number of parachute jumping,smoking,anxiety and chronic pain will aggravate sleep disturbances.

Objective To understand the molecular epidemiological characteristics of Norovirus outbreaks and the genome evolution of Norovirus epidemic strains in Hainan Province from 2020 to 2022.Methods The information and samples have been collected from the norovirus outbreaks from 2020 to 2022.Norovirus was detected by using the real-time PCR in these samples,then the detected sequences were amplified the analyzed.The Norovirus se-quences of 8 strains had been amplified and analyzed.Results From 2020 to 2022,39 gastroenteritis outbreaks were reported,and 25 outbreaks caused by Norovirus which mainly occurred in childcare institutions and schools(20/25,80％).The Norovirus outbreaks were mainly concentrated in counties around Haikou(northeast),which including Ding'an(5 cases),Wenchang(4 cases),Chengmai(4 cases),and Lingao(3 cases);following by western regions which included Baisha(2 cases),Ledong(2 cases),and Dongfang(3 cases).1 case was in Wanning in the southeast.Among individuals aged 2-17,the positive proportion of Norovirus in males was higher than that in females.Among individuals aged over 55,the proportion of Norovirus positive in females was higher than that in males.The gender of positive samples among individuals aged 18-40 was related to their profession.According to RT-PCR typing and sequencing,GⅡ group Norovirus were classified in13 outbreaks.There were 4 genotypes detected.GⅡ.2[P1 6]was the main epidemic strain with 60％(9/13),and the other three genotypes were GⅡ.4 Sydney[P31](15.4％,2/13)GⅡ.4 Sydney[P16](7.7％,1/13)and GⅡ.3[P12](7.7％,1/13).Further genic analysis of 8 Norovirus strains showed that all of them were still in the same branch as the previ-ous strain,and all exhibited a certain amount of amino acid variation.Conclusion Norovirus is the main pathogen of gastroenteritis outbreaks in Hainan province,and the main epidemic strain is GⅡ.2[P16].It is necessary to continue to strengthen the monitoring that provides scientific evidence for the prevention and control of norovirus out-breaks in Hainan region.