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 evaluate the efficacy and safety of PD-1 inhibitor combined with azacitidine and HAG regimen in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: This study is a prospective, single-arm, phase II clinical trial that included R/R AML patients who met the inclusion criteria and were treated at The First Affiliated Hospital of Soochow University from December 2020 to August 2023. Patients could undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage therapy. The efficacy and safety were evaluated. RESULTS: Twenty patients were enrolled, including 14 males and 6 females, with an average age of (50.7±15.3) years. The overall response rate (ORR) after one cycle of the treatment was 75.0% (15/20), and 35.0% (7/20) of the patients achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after two cycles of the treatment. Eight patients received allo-HSCT. The main adverse events were hematologic toxicities, and no grade 5 adverse events occurred. CONCLUSION The combination of PD-1 inhibitor, azacitidine, and the HAG regimen is a feasible and relatively safe treatment option for R/R AML, thus, to be worth further study.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Azacitidine/administration & dosage* ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; Hematopoietic Stem Cell Transplantation ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Aged

OBJECTIVE: To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy. METHODS: The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type. RESULTS: Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume. CONCLUSION The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Neoplasms/radiotherapy* ; Female

Studies have shown that a variety of diseases such as cardiovascular disease, renal disease and cancer are closely related to trimethylamine oxide (TMAO). Clinically, abnormal elevation of TMAO has been used as an evaluation index of atherosclerosis (AS) prior to imaging. In this study, we investigated the effects of lipid metabolism disorders as well as pharmacological interventions on urinary TMAO using a hyperlipidemic golden gopher model. The study used 48 Syrian golden hamster modeled with a high-fat diet for 2 weeks, and then ezetimibe, simvastatin, ezetimibe and simvastatin groups were administered for 4 consecutive weeks, as well as the clinical trial drug, IMM-H007, for pharmacological intervention. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: SCXK (Beijing) 2021-0011). Urine from rats was analyzed for 2D band selective heteronuclear single quantum coherence (2D bs-HSQC) at week 2 and 4 after drug administration. The results indicated that, in comparison to the control group, the high-fat diet significantly elevated urinary TMAO levels in the model group of hamsters after both 2 and 4 weeks of treatment (P < 0.05). Urinary TMAO levels were significantly reduced (P < 0.05) in the model group after 2 or 4 weeks of intervention with ezetimibe, simvastatin, combination therapy, and IMM-H007, showing a marked decrease even after 2 weeks of treatment. The detection of TMAO could precede the measurement of serum biochemical indicators, facilitating earlier efficacy assessment. This study evaluated the modulatory effects of clinical drugs and clinical trial drugs on TMAO, which provides useful information for clinical drug use and drug research. It also provides a means of TMAO detection based on 2D NMR technology, which is helpful for the clinical application of TMAO detection index.

As an important synthetic antibacterial drug, sulfonamides play an important role in the anti-infection field. Based on the research and development status of sulfonamides, this paper broke the classical structure of sulfanilamide, and designed and synthesized a series of acetyl-contained sulfanilamide tertiary amine thiol azole compounds and sulfanilamide tertiary amine amino azole compounds. The structures were confirmed by ¹H NMR, ¹³C NMR and HRMS. The antimicrobial activity of synthesized compounds in vitro was tested. The antimicrobial activity of amino triazole compound 7a gave stronger activity against Pseudomonas aeruginosa than that of positive control drug norfloxacin, and its inhibitory activity against Staphylococcus aureus was close to that of norfloxacin. The interaction between compound 7a and calf thymus DNA was studied, and the docking experiment between this compound and DNA was also researched.

Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Objective To explore the effect and mechanism of hawthorn leaves flavonoids(HLF)on angiotensin Ⅱ(Ang Ⅱ)-induced myocardial hypertrophy.Methods The H9c2 cells were divided into control group(normal culture),model group(100 nmol·L-1 Ang Ⅱ for 24 h),experimental-L,-M,-H groups(received 100 nmol·L-1 Ang Ⅱ for 24 h,then treated with 25,50 and 100 mg·L-1 HLF for 24 h,respectively),anti-miR-NC and anti-miR-21a-5p groups(transfected with anti-miR-NC and anti-miR-21a-5p,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h),miR-NC+high-dose and miR-21a-5p+high-dose group(transfected with miR-NC and miR-21a-5p mimics,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h+100 mg·L-1 HLF for 24 h).The cell viability was detected by cell counting kit-8.The cell apoptosis was measured by flow cytometry.The expression levels of miR-21a-5p was assessed by quantitative real-time polymerase chain reaction.The expression levels of cyclooxygenase-2(COX2)and prostaglandin E2(PGE2)was measured by Western blot.Results The cell viabilities of control,model group experimental-H groups were 1.03±0.09,0.51±0.05 and 0.93±0.08;cell apoptosis rates were(7.69±0.61)％,(23.04±1.82)％and(9.43±0.71)％;the expression levels of miR-21a-5p were 1.00±0.09,2.43±0.18 and 1.09±0.08;the relative expression levels of COX2 protein were 0.42±0.03,0.85±0.08 and 0.40±0.04;the relative expression levels of PGE2 protein were 0.34±0.03,0.75±0.07 and 0.35±0.03;the differences of above indexes were statistically significant between the model group and the control and experimental-H groups(all P＜0.05).The cell viabilities of anti-miR-NC,anti-miR-21a-5p,miR-NC+high dose and miR-21a-5p+high dose groups were 0.52±0.04,1.12±0.08,0.94±0.09 and 0.57±0.04;the cell apoptosis rates were(23.04±1.82)％,(9.86±0.73)％,(9.47±0.64)％and(24.96±1.94)％;the expression levels of miR-21a-5p were 1.00±0.10,0.43±0.04,1.00±0.09 and 2.12±0.18;the relative expression levels of COX2 protein were 0.86±0.05,0.39±0.04,0.41±0.03 and 0.78±0.07;the relative expression levels of PGE2 protein were 0.74±0.06,0.38±0.07,0.36±0.02 and 0.71±0.05.Compared the anti-miR-21a-5p group with the anti-miR-NC group,compared the miR-21a-5p+high-dose group with the miR-NC+high-dose group,the differences of above indexes were statistically significant(all P＜0.05).Conclusion HLF can inhibit Ang Ⅱ-induced myocardial hypertrophy by regulating the expression of miR-21a-5p and COX2/PGE2 pathway.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective To investigate the effect of endoscopic prebiopsy forceps on the detection rate of polyps in the right semicolon.Method Clinical data of 148 patients diagnosed and treated from March 2022 to December 2022 who were detected as polyps in the right semicolon by general electronic colonoscopy were collected,and clinical data of the patients who underwent endoscopic prebiopsy forceps were re-examined and the patients underwent endoscopic treatment within 1 month.The differences in general data,polyp number detected,polyp size,morphology and pathological diagnosis between the two groups were analyzed and compared.Results 168 polyps were detected in the right semicolon in the general colonoscopy group,and 41 polyps were missed in reexamination using endoscopic prebiopsy forceps,with a missed diagnosis rate of 19.62%.The detection rate of<5 mm polyps was higher in the endoscopic prebiopsy forceps group than that of general colonoscopy group,the difference was statistically significant(P<0.05).The polyps in the two groups were mainly wide-basal type,and the pathological properties were mainly tubular adenoma,there was no statistical significance among all groups(P>0.05).No complications such as bleeding and perforation occurred in the two groups.Conclusion Endoscopic prebiopsy forceps can significantly improve the detection rate of polyps in the right semicolon,in particular,the intraoperative search for disappeared preoperatively identified intestinal polyps,as well as smaller diameter intestinal polyps,which is worthy of further clinical promotion.