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

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:Measure the global longitudinal strain (GLS) of the left ventricle in trauma patients by beside speckle tracking echocardiography to explore the role of STE -GLS in evaluating left ventricular systolic function in trauma patients, and then explore the clinical value of GLS in judging the prognosis of trauma patients.Methods:Trauma patients admitted to intensive care unit from September 1, 2020 to April 1, 2021 with an Injury Severity Score (ISS) of ≥ 16 points. were consecutively enrolled. Moreover, those patients who met the following criteria were selected as the research subjects: aged between 18 and 80 years old, had no serious underlying diseases in the past, the time from trauma onset to admission was within 24 hours, and were able to complete an echocardiogram examination within 24 hours after the onset of the disease. Exclude patients who are unable to complete the ultrasound examination within 24 hours after the onset of the disease, or those with poor image quality, or those complicated with severe heart diseases and systemic comorbidities. The left ventricular global longitudinal strain (GLS) was measured by bedside speckle tracking echocardiography. According to the GLS values they were divided into abnormal group (GLS> -15%) and normal group (GLS≤ -15%). Independent sample t-tests and chi-square tests were applied to conduct a comparative analysis of the clinical characteristics between the two groups of patients. Furthermore, multiple linear regression analysis was conducted to explore the correlation between STE-GLS and the duration of intensive care unit stay.Results:A total of 32 trauma patients were eligible for this study. One patient was found to have abnormal left ventricular systolic function (LVEF<50%) detected by conventional echocardiography, however speckle tracking echocardiography detected decreased left ventricular systolic function (GLS> -15%) in 13 Patients. Multiple linear regression analysis showed that the global longitudinal strain of left ventricle and serum high sensitivity troponin I were independent risk factors affecting the time of intensive care in trauma patients.Conclusions:Speckle tracking echocardiography (STE) is more sensitive than traditional echocardiography and can detect left ventricular systolic dysfunction early. STE-GLS is an independent risk factor affecting hospitalization time of trauma patients in intensive care unit. Clinically, STE-GLS and serum Hs-TnI can be combined to determine the prognosis of trauma patients.

Objective To compare the application value of coronary computed tomography angiography(CCTA)based plaque characteristics and computed tomography(CT)derived parameters in predicting future major adverse cardiovascular events(MACE)between patients with and without diabetes mellitus.Methods A total of 425 patients who underwent CCTA in Shunde Hospital Affiliated to Southern Medical University from June 2016 to November 2016 were retrospectively analyzed.Patients were divided into DM group(n=120)and non-DM group(n=305)for follow-up.According to the occurrence of MACE during follow-up,patients were divided into DM group(n=81),DM+MACE group(n=39),non-DM group(n=39),non-DM group(n=244)and non-DM+MACE group(n=61).The differences in general characteristics,biochemical index and parameters in imaging were compared among the four groups.Cox proportional hazards regression analysis was used to analyze the influencing factors for MACE in the two populations.The receiver operating characteristic(ROC)curve was used to analyze the difference in the predictive value of different plaque characteristics and CT-derived parameters for MACE.Results The levels of coronary artery calcification score(CACS),and the proportion of low-attenuation plaque(LAP)were higher in the DM+MACE group than in the DM group(P<0.05).The levels of positive reconstruction(PR),the proportion of antihypertensive drugs,CAD-RADS,CACS,residual cholesterol and apolipoprotein B were higher in the non-DM+MACE group than in the non-DM group(P<0.05).Cox proportional hazards regression analysis showed that CACS≥100(HR 2.151,95%CI 1.128～4.102,P=0.020)and LAP(HR 2.337,95%CI 1.032～5.290,P=0.042)were the influencing factors for MACE in patients with DM.PR(HR 124.305,95%CI 42.883～360.326,P<0.001)was the influencing factor for MACE in patients without DM.ROC curve analysis showed that the AUC of CACS combined with LAP were 0.606,0.609 and 0.660 for predicting MACE in DM patients within 1,3 and 5 years respectively.The AUC of PR for predicting MACE were 0.862,0.927,and 0.806 in the non-DM population within 1,3,and 5 years respectively.The predictive value of CACS and LAP for MACE in the DM patients was stable during the 5 years,while the predictive value of PR for MACE in the non-DM population decreased significantly after 4 years.Conclusions The predictive values of different plaque characteristics and CT derived parameters for future MACE are different between population with and without diabetes.The combination of CACS and low-attenuation plaques can effectively evaluate the risk of MACE in diabetic patients,while PR has a higher predictive value for MACE in non-diabetic patients.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Objective:To investigate the use of targeted next generation sequencing (tNGS) for the detection of drug resistance in mycoplasma pneumoniae pneumonia (MPP) and analyze the clinical characteristics of MPP.Methods:The clinical data of patients with MPP who underwent bronchoalveolar lavage fluid tNGS at the Department of Respiratory and Critical Care Medicine, The Third People's Hospital of Hubei Province, Jianghan University from February 2022 to February 2024 were collected. According to inclusion and exclusion criteria, 80 patients with MPP were included in this study. The clinical data of the patients were retrospectively analyzed. tNGS of bronchoalveolar lavage fluid was performed to assess drug resistance in MPP. These patients were divided into a drug resistance group ( n = 55) and a non-drug resistance group ( n = 25) based on the presence or absence of the 23SrRNA:A2063G drug resistance mutation. Patient's clinical characteristics were compared between the two groups. The significant indicators from the univariate analysis were introduced into a binary logistic regression model to analyze the independent predictors of drug resistance and their predictive values. Results:The median age of patients with MPP was 38 years, with 53.75% (43/80) being female. Among the patients, 62.50% (50/80) had no underlying diseases, and 68.75% (55/80) exhibited drug resistance, while 42.50% (34/80) had mixed infections. The three most common clinical symptoms were cough (92.50%, 74/80), fever (62.50%, 50/80), and dyspnea (31.25%, 25/80). The most common imaging findings in MPP included patchy shadows (48.75%, 39/80) and consolidation shadows (42.50%, 34/80). Nodular shadows (7.50%, 6/80), tree-in-bud signs (5.00%, 4/80), ground-glass opacities (11.25%, 9/80), bronchial wall thickening (3.75%, 3/80), and pleural effusions (5.00%, 4/80) were not common. Bilateral lesions were present in 40.00% (32/80) of cases. In laboratory examinations, the median levels of inflammatory markers C-reactive protein (39.45 mg/L), procalcitonin (0.08 g/L), and serum amyloid A (168.31 mg/L) were increased. The median or mean levels of other indicators were within the normal range. There were no significant differences between the drug resistance and non-drug resistance groups in terms of gender, age, underlying diseases, clinical symptoms, length of hospital stay, mixed infection rate, mycoplasma pneumoniae (MP)-IgG positivity, MP-IgM level > 300 AU/mL, MP-DNA positivity, percentage of lymphocytes, platelet count, number of lymphocytes, and procalcitonin, D-dimer, prealbumin, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and albumin levels as well as imaging findings (all P > 0.05). In the drug resistance group, the number of fever days, sequence number, white blood cell count, percentage of neutrophils, C-reactive protein level, and serum amyloid A level were as follows: 4 (0, 7), 24464.00 (2754.00, 43457.00), 7.35 (6.09, 9.84), 73.70 (67.20, 73.70), 39.82 (20.82, 70.40), and 205.40 (81.08, 338.30), respectively. These values were significantly higher than those in the non-drug resistance group [2 (0, 4.50), 658.00 (323.00, 7593.00), 6.12 (5.04, 7.20), 64.45 (58.58, 76.33), 35.63 (4.94, 57.36), 81.30 (12.51, 243.76), Z = -2.43, -4.67, -2.72, -2.36, -2.04, -2.37]. The albumin level in the drug resistance group was 41.50 (38.10, 44.30), which was significantly lower than that in the non-drug resistance group [43.55 (40.03, 46.05), Z = -2.07, P < 0.05]. In the binary logistic regression analysis, the sequence number was identified as an independent predictor of drug resistance. When the sequence number exceeded 1001, the area under the curve value was 0.827, with a sensitivity of 94.5% and specificity of 68.0%. Conclusions:The clinical manifestations of MPP are similar in both the macrolide-resistant and the non-resistant groups. However, the drug-resistant group exhibits a greater number of fever days, higher sequence numbers, and more severe inflammatory responses. The sequence number of MPP can be used to predict drug resistance. When the sequence number exceeds 1001, its predictive value for drug resistance is significantly higher.

Objective To compare the application value of coronary computed tomography angiography(CCTA)based plaque characteristics and computed tomography(CT)derived parameters in predicting future major adverse cardiovascular events(MACE)between patients with and without diabetes mellitus.Methods A total of 425 patients who underwent CCTA in Shunde Hospital Affiliated to Southern Medical University from June 2016 to November 2016 were retrospectively analyzed.Patients were divided into DM group(n=120)and non-DM group(n=305)for follow-up.According to the occurrence of MACE during follow-up,patients were divided into DM group(n=81),DM+MACE group(n=39),non-DM group(n=39),non-DM group(n=244)and non-DM+MACE group(n=61).The differences in general characteristics,biochemical index and parameters in imaging were compared among the four groups.Cox proportional hazards regression analysis was used to analyze the influencing factors for MACE in the two populations.The receiver operating characteristic(ROC)curve was used to analyze the difference in the predictive value of different plaque characteristics and CT-derived parameters for MACE.Results The levels of coronary artery calcification score(CACS),and the proportion of low-attenuation plaque(LAP)were higher in the DM+MACE group than in the DM group(P<0.05).The levels of positive reconstruction(PR),the proportion of antihypertensive drugs,CAD-RADS,CACS,residual cholesterol and apolipoprotein B were higher in the non-DM+MACE group than in the non-DM group(P<0.05).Cox proportional hazards regression analysis showed that CACS≥100(HR 2.151,95%CI 1.128～4.102,P=0.020)and LAP(HR 2.337,95%CI 1.032～5.290,P=0.042)were the influencing factors for MACE in patients with DM.PR(HR 124.305,95%CI 42.883～360.326,P<0.001)was the influencing factor for MACE in patients without DM.ROC curve analysis showed that the AUC of CACS combined with LAP were 0.606,0.609 and 0.660 for predicting MACE in DM patients within 1,3 and 5 years respectively.The AUC of PR for predicting MACE were 0.862,0.927,and 0.806 in the non-DM population within 1,3,and 5 years respectively.The predictive value of CACS and LAP for MACE in the DM patients was stable during the 5 years,while the predictive value of PR for MACE in the non-DM population decreased significantly after 4 years.Conclusions The predictive values of different plaque characteristics and CT derived parameters for future MACE are different between population with and without diabetes.The combination of CACS and low-attenuation plaques can effectively evaluate the risk of MACE in diabetic patients,while PR has a higher predictive value for MACE in non-diabetic patients.