BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

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 explore the comparison of the predictive value of three risk assessment tools on the chemotherapy-induced nausea and vomiting(CINV)in cancer patients.Methods From January 2022 to December 2022,convenience sampling was used to select 626 cancer patients with Intravenous chemotherapy in the Department of Hepatobiliary Pancreatic Oncology of Zhejiang Cancer Hospital as the research object.CINV risk assessment of patients was performed using George teams acute CINV prediction tool,Dranitsari's CINV risk assessment and CINV nomogram model.Area under curve(AUC),sensitivity,specificity and Youden index were used to compare the predictive value of the three tools.Results Totally 622 patients were ultimately included in the study,with an overall effective rate of 99.36%.There were 51.13%(318/622)patients who experienced CINV.Specifically,patients with grade 2 or higher acute CINV accounted for 18.17%(113/622).When using the three tools for acute CINV risk assessment,the AUC was respectively 0.591,0.616 and 0.558.And Dranitsari's CINV risk assessment has the highest sensitivity,acute and delayed chemotherapy-induced nausea and vomiting prediction tool has the highest specificity.Comparatively,Dranitsari's CINV risk assessment on the Yorden index is better.Conclusion The incidence of CINV in cancer patients is at a high level.The three tools can not effectively predict the risk of acute CINV.We need to develop a localized,multi-disease,standardized CINV risk assessment model for hospital.

Objective:To explore the value of tacrolimus blood concentration and other related indexes in evaluating early postoperative infection in patients with liver transplantation.Methods:Patients with complete medical records who underwent liver transplantation in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2019 were screened. Cohort study was used, and demographic data, laboratory test results, tacrolimus blood concentration and other data of patients with liver transplantation were collected. All patients with postoperative infection were divided into four groups, inculding two to four weeks, five to 12 weeks, 13 to 52 weeks and >52 weeks groups, and uninfected patients in each group were matched 1∶1 according to age ± 3 years old. Independent sample t test and rank sum test were used to analyze the differences in clinical data between postoperative infected and uninfected patients with liver transplantation patients. Logistic regression analysis was used to explore the influencing factors of infection in the early postoperative period (two to four weeks after operation). The relative safe value of tacrolimus blood concentration in the early postoperative period was evaluated by receiver operating characteristic curve. Results:A total of 150 patients with infection after liver transplantation were included, including 65 patients in the two to four weeks group, 31 patients in the five to 12 weeks group, 27 patients in the 13 to 52 weeks group, and 27 patients in the >52 weeks group. There were 52, 30, 32, and 39 uninfected patients in the four groups, respectively. There were 247 males (81.52%) in 303 patients with liver transplantation, and the age ranged from 10 to 78 years old. Hepatitis B cirrhosis and hepatocellular carcinoma were the main primary diseases, accounting for 41.91%(127/303) and 47.52%(144/303), respectively. The tacrolimus blood concentration and alanine aminotransferase in patients with infection in the two to four weeks group were (11.46±4.94) μg/L and 118.20(38.80, 215.80) U/L, respectively, which were both higher than those in the uninfected group ((7.12±2.33) μg/L and 39.40(23.40, 142.70) U/L, respectively). The differences were both statistically significant ( t=6.26, Z=2.66, respectively, both P<0.05). Sputum sources accounted for the largest number of samples, accounting for 61.6%(98/159). A total of 174 pathogens were isolated, of which gram-negative bacteria (55.2%(96/174)) were the majority, mainly Klebsiella pneumoniae (20.1%(35/174)) and Acinetobacter baumannii (13.8%(24/174)). Multivariate analysis showed that tacrolimus blood concentration (odds ratio ( OR)=1.634, 95% confidence interval ( CI) 1.298 to 2.058, P=0.001) was a risk factor for infection at two to four weeks after liver transplantation, while lymphocyte count ( OR=0.165, 95% CI 0.057 to 0.474, P=0.010) was a protective factor. The area under the curve of tacrolimus blood concentration in evaluating the infection at two to four weeks after liver transplantation was 0.817. The cut-off value was 8.7 μg /L ( P<0.05), with the sensitivity of 0.708 and the specificity of 0.846. Conclusions:The main site of infection in patients with liver transplantation is respiratory system. Gram-negative bacilli are the main pathogens. When tacrolimus blood concentration is below 8.7 μg/L at two to four weeks after liver transplantation, the probability of infection in the early postoperative period may be reduced.

Objective:To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models.Methods:The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups.Results:EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference ( P ?