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

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

ObjectiveTo observe the effectiveness and safety of the Chinese herbal medicine Mingshi Granules （明视方颗粒） for low myopia in children with heart yang insufficiency. MethodsA multicentre， prospective， double-blind randomised controlled study was conducted， in which 290 children with low myopia from 8 centres were randomly divided into 145 cases in the treatment group and 145 cases in the control group， and the treatment group was given education， dispensing glasses， and Chinese herbal medicine Mingshi Granules， while the control group was given education， dispensing glasses， and granules placebo. Both Mingshi Granules and placebo granules were taken orally， 1 bag each time， twice daily， 4 weeks of oral intake and 2 weeks of rest as 1 course of treatment， a total of 4 courses of treatment （24 weeks）. Equivalent spherical lenses， best naked-eye distance visual acuity， ocular axis， corneal curvature K1， adjustment amplitude， traditional Chinese medicine （TCM） symptom scores， calculate the amount of progression of equivalent spherical lenses， were observed at the 12th and the 24th week of treatment， at the 36th week and 48th week of follow-up， resectively， the control rate of myopia progression was evaluated at the 24th week， and safety indexes were observed before treatment. ResultsThe amount of progression of equivalent spherical lenses was lower in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The control rate of myopia progression at 24 weeks after treatment in the treatment group was higher （57.60%， 72/125） than that in the control group （44.63%， 54/121） （P＜0.05）. The best naked-eye distance visual acuity at 36-week follow-up in the treatment group was higher than that in the control group （P＜0.05）. Equivalent spherical lenses were significantly lower in both groups at all observation time points compared with pre-treatment （P＜0.05）， and were higher in the treatment group than in the control group at the 48-week follow-up （P＜0.05）. The ocular axes of both groups were significantly higher at each observation time point after treatment and at follow-up compared with before treatment （P＜0.05）. The amount of eye axis growth in the treatment group was lower than that in the control group at 24 weeks after treatment and at the 48-week follow-up （P＜0.05）. Corneal curvature K1 was significantly lower in the treatment group at the 24th week of treatment compared to pre-treatment （P＜0.05）. The magnitude of adjustment in the treatment group was significantly higher at the 36-week follow-up and at the 48-week follow-up than before treatment （P＜0.05）. The scores of white/dark complexion， white coating thin pulse， fatigue and total TCM symptom scores of children in both groups at the 12th， 24th， 36th and 48th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； the scores of blurred vision at the 24th and 36th weeks of follow-up were significantly lower than those before treatment （P＜0.05）； and the scores of blurred vision in the treatment group at the 48th week of follow-up were signi-ficantly lower than those before treatment （P＜0.05）. In the treatment group， the score of fatigue was higher than that of the control group at the 36-week follow-up， and the score of blurred vision was lower than that of the control group at the 48-week follow-up （P＜0.05）. No adverse reactions or obvious abnormalities of the safety indexes were observed of the two groups during the treatment. ConclusionChinese herbal medicine Mingshi Granules showed the effect of controlling the progression of low myopia， improving the best naked eye distance visual acuity， slowing down the growth of the eye axis， improving some of the TCM symptoms， with good safety.

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.

Objective:To investigate the trajectories of intrinsic capacity in older adults and explore the impact of leisure activities on the decline of intrinsic capacity.Methods:This study is a prospective cohort study conducted in a community in Beijing, China.A convenience sampling method was used to select 284 cases of older adults from November to December 2020.The purpose of the study was to gather information on the general conditions, intrinsic abilities(including cognitive, vitality, motor, psychological, and sensory dimensions), and participation in leisure activities of older adults.A 2.5-year follow-up of the respondents was conducted.Results:A total of 243(85.6%, 243/284)respondents completed the 2.5-year follow-up.The follow-up intrinsic capacity score decreased from a baseline level of 4(3, 4)to 3(3, 4)( Z=-4.667, P<0.001).Among the respondents, 113(46.5%, 113/243)older adults showed a decrease in intrinsic capacity, with more significant decreases observed in the locomotor and psychometric dimensions( χ2=16.953, 23.510, both P<0.001).The number of declines in intrinsic ability was higher in the low group of leisure activities compared to the high group[62.2%(56/90) vs.37.3%(57/153), χ2=14.199, P<0.001].There was a positive correlation between leisure activity scores and the follow-up intrinsic capacity score( r=0.200, P=0.002), as well as with the value of change in the score of intrinsic capacity( r=0.146, P=0.023).The results of Logistic regression analysis indicated that leisure activities( OR=0.644, 95% CI: 0.507 to 0.818, P<0.001), physical leisure activities( OR=0.565, 95% CI: 0.395 to 0.809, P=0.002), and intellectual leisure activities( OR=0.742, 95% CI: 0.555 to 0.992, P=0.044)independently influenced the decline of intrinsic ability in the elderly, even after accounting for demographic information, number of diseases, and type of medicine taken. Conclusions:The decline in intrinsic abilities is a common occurrence among the elderly population.Engaging in leisure activities has been found to be effective in reducing this decline.It is important to emphasize the impact of leisure activities on the overall health of older individuals.

Objective:To investigate age-related characteristics of gait parameters in the elderly.Methods:From February 2023 to August 2023, a convenient sampling method was used to investigate the elderly over 60 years old in communities in Beijing.General characteristics and anthropometric data were collected.Gait parameters of the subjects during normal speed walking were measured using a wearable gait analyzer.Comparisons were made of the basic characteristics, physical status and gait parameters in different age groups.Linear regression analysis was used to evaluate the changes of physical status and gait parameters with age, with the 60-69-year-old group as the baseline standard.Results:A total of 670 elderly people were included, including 324(48.4%)aged 60-69 years, 285(42.5%)aged 70-79 years, and 61(9.1%)aged ≥80 years.Linear regression analysis showed that after adjusting for confounding factors, with increasing age, skeletal muscle mass index(SMI)( β=-0.018, 95% CI: -0.029--0.007), calf circumference( β=-0.096, 95% CI: -0.142--0.051), upper limb flexibility( β=-0.200, 95%, 95% CI: -0.355--0.046), lower limb flexibility( β=-0.244, 95% CI: -0.377--0.111), grip strength( β=-0.397, 95% CI: -0.491--0.303), the Short Physical Performance Battery(SPPB)( β=-0.080, 95% CI: -0.100--0.060)decreased( P<0.05), and the gait parameter such as speed( β=-0.010, 95% CI: -0.014--0.007), cadence( β=-0.398, 95% CI: -0.634--0.162), step length/height( β=-0.002, 95% CI: -0.003--0.002), stride length( β=-0.009, 95% CI: -0.011--0.007), swing power( β=-0.009, 95% CI: -0.012--0.006), ground impact( β=-0.020, 95% CI: -0.026--0.014), foot fall( β=-0.050, 95% CI: -0.064--0.036), pre-swing angle( β=-0.545, 95% CI: -0.714--0.377)all decreased( P<0.05), while stride time( β=0.005, 95% CI: 0.001-0.009), single limb support time( β=1.566, 95% CI: 0.499-2.633), terminal double limb support time( β=0.609, 95% CI: 0.084-1.134), swing duration( β=1.288, 95% CI: 0.024-2.552), single step time( β=2.417, 95% CI: 0.462-4.372)and support phase time( β=1.935, 95% CI: 0.421-3.449)all increased( P<0.05). Conclusions:The walking ability tends to decline with age in older people in the community who walk at a normal walking speed.

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Induction Chemotherapy ; Retrospective Studies ; Neoplasm, Residual ; Prognosis

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective:To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population.Methods:This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR.Results:There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age ( P<0.001), a higher incidence of CVD ( P=0.025), and the highest level of UACR ( P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) ( OR=0.72, 95% CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation ( OR=0.98, 95% CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight ( P=0.003) or overweight ( P=0.001), in those without CVD history ( P=0.001), and in those with impaired estimated glomerular filtration rate ( P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD ( P=0.048). Conclusion:A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.