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

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

The prevalence of chronic constipation among the elderly is significant, exerting adverse effects on both their physical and mental health.Presently, pharmacological therapy remains the predominant treatment modality for elderly patients with chronic constipation; however, prolonged use can lead to drug dependence, tolerance, and adverse effects.This article systematically reviews non-pharmacological interventions for chronic constipation in elderly patients, both domestically and internationally, aiming to provide a comprehensive reference for clinical practice.

目的：筛选果蝇Zeste基因增强子同源物2（EZH2）基因上游miRNA及lncRNA，分析其在胃癌细胞中的表达并验证其间的靶向关系，探讨它们对胃癌细胞增殖、迁移和凋亡的影响。方法：通过ENCORI、miRDB和Target Scan数据库查询并分析、筛选EZH2上游miRNA（has-miR-450b-5p），ENCORI数据库和DAINA数据库筛选has-miR-450b-5p上游lncRNA（lncRNA NEAT1），预测hsa-miR-450b-5p、lncRNA NEAT1与EZH2之间的结合位点，双荧光素酶报告基因实验验证hsa-miR-450b-5p与lncRNA NEAT1的结合关系。采用qPCR和WB法检测lncRNA NEAT1和EZH2在正常胃黏膜细胞（GES-1）与胃癌细胞（MGC-803、SGC-7901和MKN-28）中的表达量。按转染物的不同将MGC-803和SGC-7901细胞分为hsa-miR-450b-5p-mimic组、mimic-NC组、si-NEAT1组和si-NC组，转染36~48 h后qPCR法验证过表达及敲减效果；通过qPCR、WB法检测观察过表达hsa-miR-450b-5p对细胞中lncRNA NEAT1和EZH2 mRNA、蛋白表达的影响，以及敲减lncRNA NEAT1对hsa-miR-450b-5p和EZH2 mRNA表达的影响；CCK-8法、划痕愈合实验和流式细胞术分别检测敲减EZH2或敲减lncRNA NEAT1对细胞增殖、迁移和凋亡能力的影响。结果：生物信息学分析筛选获得EZH2上游miRNA和lncRNA为has-miR-450b-5p和lncRNA NEAT1，双荧光素酶报告基因实验验证了两者间存在靶向关系。lncRNA NEAT1和EZH2 mRNA、蛋白在胃癌细胞中均呈高表达（均P<0.05）。与mimic-NC组相比，hsa-miR-450b-5p-mimic组MGC-803、SGC-7901细胞中miR-450b-5p水平均显著升高，而EZH2 mRNA、蛋白和lncRNA NEAT1的表达量均显著降低（P<0.05或P<0.01）；与si-NC组相比，si-NEAT1组MGC-803、SGC-7901细胞中lncRNA NEAT1和EZH2 mRNA的表达量均显著降低（均P<0.01），SGC-7901细胞中hsa-miR-450b-5p表达量显著升高（P<0.05）。敲减EZH2或敲减lncRNA NEAT1后，MGC-803、SGC-7901细胞的增殖、迁移能力均显著降低（均P<0.01）。结论：lncRNA NEAT1 和EZH2在胃癌细胞中均呈高表达，lncRNA NEAT1可通过hsa-miR-450b-5p促进EZH2的表达并提高胃癌MGC-803和SGC-7901细胞的增殖和迁移能力。

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective : To investigate the effect of lncRNA SNHG16 (SNHG16) on the proliferation and migration of gastric cancer cells and its molecular regulatory mechanism. Methods : The expression of SNHG16 in gastric cancer tissue was retrieved based on online database and the downstream target gene of SNHG16 was screened. The interaction between SNHG16 and miR⁃195 ⁃5p was verified by bioinformatics analysis and double luciferase reporter gene experiment. The expression of SNHG16 , miR⁃195 ⁃5p and MYB in gastric cancer cells (HGC⁃27 , MKN⁃28) was detected by real⁃time fluorescent quantitative PCR (qRT⁃PCR) ; SNHG16 was knocked down to detect the expression of miR⁃195 ⁃5p or MYB ; The expression of MYB was detected by overexpression of miR⁃195 ⁃5p;Western blot analysis was used to detect the protein expression level of MYB in each group. Knock down SNHG16 or overexpress miR⁃195 ⁃5p , and the proliferation and migration ability of gastric cancer cells (HGC⁃27 , MKN⁃28) were detected through cell proliferation and scratch test. Results : The expression of LncRNA SNHG16 increased in gastricancer tissues and gastric cancer cells (HGC⁃27 , MKN⁃28 , MKN⁃45 , NCI⁃N87) . The results of double luciferase reporter gene experiment showed that psiCHECK2⁃SNHG16⁃WT and miR⁃195⁃5p mimic were transfected into HGC⁃27 at the same time , significantly inhibiting the luciferase activity of HGC⁃27 cells. The results of qRT PCR and WB experiments showed that knocking down SNHG16 in HGC⁃27 and MKN⁃28 cells upregulated miR⁃195⁃5p and inhibited the expression of MYB at the transcription and translation levels ; Overexpression of miR⁃195 ⁃5p in HGC⁃27 and MKN⁃28 cells inhibited MYB expression. The results of CCK8 proliferation test and cell scratch test showed that knocking down SNHG16 or overexpressing miR⁃195 ⁃5p could inhibit the proliferation and migration of HGC⁃27 and MKN⁃28 cells. Conclusion LncRNA SNHG16 can regulate the expression of MYB in gastric cancer cells through miR⁃195 ⁃5p , and the high expression of SNHG16 can promote the proliferation and migration of gastric cancer cells.

Objective:To explore the influencing factors and the impact of artificial liver treatment on the prognosis and survival of patients with acute-on-chronic liver failure (ACLF).Methods:Clinical data from 201 cases with ACLF from January 2016 to December 2019 was retrospectively analyzed. The survival rate was calculated by the Kaplan-Meier method, the log-rank test of univariate analysis, and the multivariate analysis of the stepwise Cox regression forward method.Results:The median survival time of patients was 6 months, and the survival rates at 6, 9, and 12 months were 51.2%, 38.3%, and 29.9%, respectively. In univariate analysis, age, presence or absence of hypertension and upper gastrointestinal bleeding, treatment method, model for end-stage liver disease (MELD) score, and cholinesterase were associated with prognosis ( P < 0.05). Multivariate regression analysis results showed that MELD score was the main factor affecting the 1-year prognosis of ACLF patients ( P = 0.002). Artificial liver treatment was beneficial for the 1-year prognosis of ACLF patients aged < 50 years or with a MELD score of ≥20 ( P < 0.05 ). The relative risk ratio (RR) of mortality was 2.55 times higher in patients with advanced age (≥50 years old) than that of younger patients ( P < 0.001). Regression analysis was performed using age as a stratification factor, and upper gastrointestinal bleeding was related to the prognosis of younger patients, while choline esterase was related to the prognosis of advanced age. Regression analysis after stratified MELD score showed that age and hypertension were related to the prognosis of patients with MELD score < 20, and treatment method and age were related to the prognosis of patients with MELD score≥20. Conclusion:Artificial liver treatment is beneficial for the 1-year prognosis of ACLF patients. Age, MELD score, hypertension, and upper gastrointestinal bleeding are independent risk factors affecting the prognosis of ACLF patients.

Humans ; Hypothermia ; Perioperative Care ; Intraoperative Complications ; Patients ; Body Temperature

Objective: To evaluate the effectiveness of different laboratory methods for the supplementary diagnosis of pulmonary tuberculosis（PTB）and provide reference data for the early diagnosis of PTB. Methods: A total of 298 suspected PTB patients, who were diagnosed and treated in the outpatient department of Shanghai Tongren Hospital from January 2016 to December 2018, were divided into 3 groups: active PTB (138 cases)，inactive PTB (43 cases) and non-PTB (117 cases) group. Sputum acid-fast staining, MGIT liquid culture system and Xpert MTB/RIF test were performed to detect the sputum specimens. The sensitivity and specificity were compared by Chi-square test. Results: The three methods showed certain significance for distinguishing active PTB, inactive PTB combined with non-PTB (χ 2 values were 89.08, 138.94 and 137.12 respectively, all P＜0.01). There was no significant difference for the positive rate of the three methods between inactive PTB and non-PTB. The sensitivities of acid-fast staining, MGIT liquid culture, Xpert MTB/RIF test and the combination of three methods in the diagnosis of active PTB were 45.7% (63/138), 63.8% (88/138), 65.4% (87/133) and 78.2% (104/133) respectively. The sensitivities of MGIT culture and Xpert MTB/RIF test were significantly higher than that of acid-fast staining (χ 2 was 35.79 and 11.26 respectively，all P＜0.01). There was no significant difference for the sensitivities between MGIT liquid culture and Xpert MTB/RIF test（χ 2 was 29.87, P＞0.05) . The sensitivity of combined detection was higher than that of single detection（χ 2 was 30.84, 64.62, 70.14, respectively, all P＜0.01）. The diagnostic specificities of the three methods and their combination were 99.1%（116/117), 98.3%（115/116）, 99.1%（113/114) and 97.3%（110/113）respectively. There was no significant difference for the specificities of the three methods. Conclusion High sensitivities of MGIT liquid culture and Xpert MTB/RIF test were shown in PTB diagnosis. Combined detection of the three methods may improve the sensitivity of detection.