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

Renal tubular injury has emerged as a critical factor in the progression of diabetic kidney disease (DKD). Given renal tubules' high mitochondrial density and susceptibility to mitochondrial dysregulation and ferroptosis, targeting these pathways could offer therapeutic potential. Metformin (MET), a first-line therapy for type 2 diabetes mellitus (T2DM), exerts reno-protective effects by improving mitochondrial function and attenuating fibrosis; however, its role in regulating ferroptosis in DKD remains unclear. This study aimed to investigate the role of MET in modulating mitophagy and ferroptosis in diabetic kidneys. In diabetic mouse models, MET notably alleviated tubular injury by promoting mitophagy and reducing ferroptosis, as shown by increasing levels of phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and Parkin, while decreased levels of malondialdehyde (MDA) and iron content. Mechanistically, MET downregulated the hypoxia-inducible factor-1alpha (HIF-1α)/myo-inositol oxygenase (MIOX) signaling axis in renal tubular epithelial cells (RTECs), thereby restoring mitophagy and inhibiting ferroptosis. These findings demonstrate that MET mitigates diabetic renal injury by promoting mitophagy and countering ferroptosis via suppressing the HIF-1α/MIOX pathway, highlighting its potential as a therapeutic intervention for halting DKD progression.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To observe factors influencing the risk of urinary tract infection (UTI) after cerebral hemorrhage (ICH).Methods:A total of 77 ICH patients undergoing rehabilitation between August 2015 and August 2017 were studied. Among them, 24 were diagnosed with a UTI according to clinical manifestations and urine routine tests and urine culture. They formed the UTI group. The other 53 were the non-UTI group. Complete clinical evaluations were available for all 77, and those data were used to identify risk factors for UTI using univariate and multivariate logistic regression analysis.Results:The univariate analysis showed that age, side of paralysis, consciousness dysfunction, Brunnstrom staging of the lower extremity, tracheotomy, indwelling catheter, lung infection, white blood cell count, neutrophil percentage, serum natrium, uric acid, D-dimer level and fibrinogen were all significant predictors of UTI. The multivariate analysis identified age, right side hemiplegia and D-dimer level as useful predictors.Conclusions:Advanced age and a high D-dimer level are independent risk factors for UTI after ICH, while hemiplegia on the right side is a protective factor.

Stargardt disease (STGD) is one of the most prevalent inherited macular dystrophy, and most often occurs in child or adolescence. Irreversible vision loss is observed in almost all cases. Type 1 (STGD1) is one of the most common type. It is an autosomal recessive condition, caused by mutations in the Abca4 gene. In recent years, encouraging progress has been made in the treatment of STGD1. C20-D3-retinyl acetate (ALK- 001), fenretinide and ICR-14967 (A1120) as visual cycle modulators, StarGen as gene supplementation therapies, and the stem cell transplantation of human embryonic stem cell-derived retinal pigment epithelium cells are the most promising therapies. With the development of studies and clinical trials, the clinical application of various treatments of STGD1 are expected in the near feature, which are expected to save the vision of most patients.

Objective To investigate the expression of MPZL1 in gastric cancer tissues, its relation with the prognosis, and its effects on proliferation and colony formation of gastric cancer. Methods GEPIA and UALCAN databases were used to analyze the expression of MPZL1 in various malignant tumors. The KM Plotter database and UALCAN database were used to analyze the effect of MPZL1 on the overall survival of gastric cancer patients. The expression of MPZL1 protein and the changes of apoptosis-related proteins in gastric cancer cells were detected by Western blot, and the effects of MPZL1 expression on cell proliferation and colony formation were detected by CCK-8 and colony formation assay, respectively. Results MPZL1 was found to be highly expressed in various malignant tumors by GEPIA database. The results of UALCAN and KM Plotter databases analysis showed that MPZL1 was highly expressed in gastric cancer tissues, and might be correlated with the overall survival of gastric cancer patients. The results of CCK-8 and colony formation assay showed that the overexpression of MPZL1 promoted the proliferation and colony formation ability of gastric cancer cells (P < 0.05). Western blot results showed that compared with control group, the expression levels of pro-apoptotic proteins Bad and Caspase-7 in the overexpression group were significantly lower while those in knockdown group were higher. Conclusion MPZL is highly expressed in gastric cancer tissues and promotes the proliferation and colony formation of gastric cancer cells, which may be related to the inhibition of apoptosis.

OBJECTIVE: To explore the feasibility of remote monitoring of neonatal jaundice in newborns with ABO hemolytic disease. METHODS: Forty six neonates of gestational age >35 weeks with ABO hemolytic disease admitted to Women's Hospital, Zhejiang University School of Medicine from January 20th, 2020 to February 29th, 2020 were enrolled in the study (study group). The newborns were followed up at home after discharge, the transcutaneous bilirubin (TCB) levels were measured by parents using the provided device and the results were sent to the doctor by smart phone using the installed APP. Fifty six newborns with ABO hemolytic disease admitted in 2018 who received conventional outpatient follow-up after discharge served as the control group. The demographic characteristics, total serum bilirubin (TSB) level during hospitalization, number of outpatient visit and rate of re-admission due to rebound hyperbilirubinemia were compared between the two groups. RESULTS: There were no significant differences between the two groups in gestational age, birth weight, delivery mode, gender, length of the first hospitalization, TSB level before phototherapy and before discharge, and the managements during the first hospitalization (all CONCLUSIONS The remote follow-up for neonatal jaundice at home can effectively reduce the number of outpatient visits without increasing the risk of readmission and severe neonatal hyperbilirubinemia for newborns with ABO hemolytic disease.
Bilirubin ; Erythroblastosis, Fetal/diagnosis* ; Female ; Humans ; Hyperbilirubinemia, Neonatal/diagnosis* ; Infant, Newborn ; Jaundice, Neonatal/diagnosis* ; Monitoring, Physiologic/methods* ; Phototherapy

Objective:To observe risk factors for lung infection (LI) after cerebral hemorrhage (ICH).Methods:A total of 118 patients with ICH were retrospectively analyzed. Among them, 63 were diagnosed with an LI according to clinical manifestations and X-ray or CT on admission. They were selected into an LI group, while the rest formed the non-LI group. Gender, age, duration of disease, side of paralysis, position and type of ICH, complications, cognitive disorders, consciousness, dysphagia, motor function, and serum levels of albumin, sodium, potassium, calcium and magnesium were recorded on the second day after admission. The risk factors for LI were analyzed using univariate and multivariate logistic regression analysis.Results:Age, duration of disease, side of paralysis, position and type of ICH, tracheotomy, urinary tract infection, cognitive impairment, dysphagia, motor function, and serum levels of albumin, sodium, calcium, and magnesium were all significant predictors of LI after an ICH. Multivariate logistic regression analysis showed that right side hemiplegia, bilateral paralysis, subarachnoid hemorrhage, urinary tract infection, and serum magnesium are all significant predictors.Conclusions:Right or bilateral paralysis, subarachnoid hemorrhage and urinary tract infection are independent risk factors for LI after an ICH. High serum magnesium within the normal range can reduce the incidence of LI.

Objective:To explore the factors related to cognitive dysfunction after traumatic brain injury.Methods:A total of 55 patients with traumatic brain injury were analyzed retrospectively. The clinical information about the patients, including age, gender, paralyzed side, course of the disease, type of injury, degree of injury, treatment, speech function (grades of Boston aphasia severity), swallowing function (7-level evaluation method), limb motor function (Brunnstrom stages of the upper limb, hand and lower limb), complications (tracheotomy, lung infection, urinary tract infection, pressure sores, electrolyte imbalance and hypoproteinemia), whether the patient received rehabilitation therapy, and D-dimer and coagulation examination results were recorded. Univariate analysis and ordered multi-class logistic regression analysis were conducted to screen the related factors using Rancho Los Amigos cognitive function grades as the dependent variable.Results:The results of the univariate analysis showed that consciousness, aphasia severity, swallowing ability, Brunnstrom stages, having received a tracheotomy, urinary tract infection, hypoproteinemia, fibrinogen and D-dimer all significantly predicted Rancho Los Amigos cognitive function grades. The logistic regression analysis showed that disordered consciousness, aphasia severity, Brunnstrom stage of the upper limbs, and urinary tract infection were significant predictors.Conclusions:Disordered consciousness, aphasia severity, Brunnstrom stage of the upper limbs, and urinary tract infection are factors related to cognitive dysfunction after traumatic brain injury.

Objective: To explore the effect of distance education in the teaching mode of medical clinical skills, and to provide theoretical and practical basis for finding a better teaching mode to promote the combination of theory and practice. Methods: A total of 172 trainees of clinical skill training in the training center were divided into the control group and the observation group (the observation group was divided into pre-class long-distance group, in-class long-distance group, after-class long-distance group). There were 43 trainees in each group. The control group adopted traditional teaching methods in clinical basic skills courses, and the observation group adopted mixed teaching mode under long-distance education. The satisfaction of teachers and students under the two teaching modes were investigated, and the performance of each group of students in skills, human-computer dialogue, and team first aid comprehensive test were compared. Results: There were significant differences in teacher satisfaction between the control group and the pre-class and in-class distance groups (χ² = 15.315, P = 0.000). There were significant differences in student satisfaction between the control group and the pre-class and in-class distance groups in terms of interactive participation, liveliness, interesting training skills and teaching level (χ²=4.497-17.153, P = 0.000-0.034). The results of each group reached the expected teaching goals. There were significant differences between the skill test score control group and the pre-class and in-class remote groups (t=25.357, 14.712, all P =0.000). There were significant differences between the human-machine dialogue test control group and the three observation groups (t=14.561, 19.420, 3.821, all P =0.000). There were significant differences between the team emergency comprehensive test control group and the three observation groups (t=14.561, 19.420, 3.821, all P=0.000). Conclusions Distance education has flexible in the mixed teaching mode of clinical skills, especially in pre-class and in-class. It can rapidly improve the basic clinical skills, theoretical knowledge and team mobilization ability of students. It is one of the best bridges to communicate their clinical theory and practice.