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 investigate the correlation between platelet alloantibodies and CD8⁺ T cell with platelet desialylation and apoptosis in platelet transfusion refractoriness(PTR). METHODS: The expression of RCA-1, CD62P and Neu1 on platelets were detected in 135 PTR patients and 260 healthy controls. The ability of PTR patients' sera with anti-HLA antibody, anti-CD36 antibody and antibody-negative groups to induce platelet desialylation and apoptosis, and the potential effect of FcγR inhibitors on desialylation and apoptosis were evaluated. Additionally, the association between CD8⁺ T cells and platelet desialylation in patients was analyzed. RESULTS: The expression of RCA-1 and Neu1 on platelets in PTR patients were significantly higher than those in healthy donors（P < 0.05）, but were not related to platelet alloantibody (P >0.05). The sera of PTR patients generally induced platelet desialylation in vitro （P < 0.05）, with no significant differences among the groups（P >0.05）. However, the sera with anti-CD36 antibodies could induce platelet apoptosis significantly higher than that in the anti-HLA antibody group and antibody-negative group in vitro (P < 0.05). In PTR patients with anti-CD36 antibodies, platelet apoptosis was dependent on FcγR signaling, while desialylation is not. Moreover, CD8⁺ T cells in PTR patients were significantly associated with platelet desialylation (P < 0.05). CONCLUSION Platelet desialylation is a common pathological phenomenon in PTR patients， which involves the participation of CD8⁺ T cell, but isn't associated with platelet alloantibody; while anti-CD36 antibodies have potential clinical significance in predicting platelet apoptosis in PTR patients.
Humans ; Apoptosis ; CD8-Positive T-Lymphocytes/immunology* ; Blood Platelets/metabolism* ; Platelet Transfusion ; Isoantibodies ; Male ; Female ; Middle Aged

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective To evaluate the diagnostic value of transrectal contrast-enhanced ultrasound (CEUS) for rectal cancer with intestinal stenosis caused by tumors. Methods Forty-nine patients with rectal cancer underwent transrectal CEUS and magnetic resonance imaging (MRI) before surgery.Intraoperative tumor localization and postoperative pathological results were taken as the gold standard for diagnosis.The differences in T stage,localization,and tumor length of rectal cancer were compared between the two methods. Results The total accuracy rates of transrectal CEUS and MRI in diagnosing T stage were 75.5% (36/49) and 67.3% (33/49),which had no significant difference (χ²=0.8,P=0.371).The total accuracy rates of transrectal CEUS and MRI in judging tumor localization were 79.5% (39/49) and 77.5% (38/49),which had no significant difference (χ²=0.061,P=0.806).The measurement results of tumor length in pathological examination had no significant difference from the transrectal CEUS results (t=1.42,P=0.162) but a significant difference from the MRI results (t=3.38,P=0.001).Furthermore,transrectal CEUS detected 8 (16.3%) cases of colonic polyps among the 49 patients,while MRI did not detect colon lesions. Conclusions Transrectal CEUS has good consistency with MRI in T staging and localization judgement of rectal cancer with intestinal stenosis,and this method can more accurately evaluate the tumor length and simultaneously evaluate whether there is a lesion in the entire colon at the proximal end of stenosis.It can be used as a supplementary examination before rectal cancer treatment in clinical practice.
Humans ; Rectal Neoplasms/complications* ; Male ; Middle Aged ; Female ; Aged ; Contrast Media ; Ultrasonography ; Adult ; Magnetic Resonance Imaging ; Constriction, Pathologic/diagnostic imaging* ; Aged, 80 and over ; Intestinal Obstruction/etiology*

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.