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 analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans ; Female ; Breast Neoplasms/diagnostic imaging* ; Middle Aged ; Lymphatic Metastasis/diagnostic imaging* ; Axilla ; Retrospective Studies ; Nomograms ; Ultrasonography ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging* ; Risk Factors ; Ki-67 Antigen

Objective To investigate the mechanism of Chonghe soft extract on ulcer wound healing in diabetic rats through protein kinase B(Akt)/mammalian Sirolimus target protein(mTOR)-mediated nucleotides binding oligomeric acid domain-like receptor protein 3(NLRP3)inflammasome inactivation.Methods Thirty six SD rats with diabetic ulcer,which were established by feeding with high glucose and high fat diet and injecting intraperitoneally with streptozocin(STZ)combined with skin defect,were randomly divided into model group,Chonghe soft extract group and growth factor group,with twelve rats in each group.Another twelve SD rats were injected an equal dose of citric acid-sodium citrate buffer solution and used as blank group.The blank group and the model group were not received drug intervention,but the Chonghe soft extract group and the growth factor group were externally applied Chonghe soft extract and growth factor gel,respectively.The wound healing of each group was observed and recorded.After 7 days and 14 days of treatment,the histopathology of wound were observed by HE staining and the number of fibroblasts were counted.The levels of IL-1β,IL-18 and TNF-α in serum were detected by ELISA.The expression of autophagy-related protein Beclin-1 and LC3Ⅱ in granulation tissue was detected by immunohistochemistry.The expression of NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),Caspase1,Pro-Caspase1 and Akt/mTOR autophagy pathway-related proteins Akt,p-Akt,mTOR and p-mTOR were detected by Western Blot.Results Compared with the blank control group,the pathological wound repair of the model group was delayed on the 7th day and 14th day,the number of fibroblasts per unit area was decreased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were increased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 were increased in the wound tissues(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were decreased in the wound tissues(P<0.01).Compared with the model group,the pathological injury in Chonghe soft extract group and growth factor group was significantly improved on the 7th day and 14th day.The number of fibroblasts per unit area was significantly increased(P<0.01).The levels of IL-1β,IL-18 and TNF-α were significantly decreased(P<0.01).The expression levels of ASC,Pro-Caspase1,Caspase1,and NLRP3 in the wound tissues were decreased(P<0.01),while the expression levels of Beclin-1,LC3-Ⅱ,mTOR,p-mTOR,Akt and p-Akt were increased(P<0.01,P<0.05).Conclusion Chonghe soft extract can reduce inflammatory reaction,promote the generation of fibro,regulate the Akt/mTOR-mediated NLRP3 inflammasome inactivation,improve the level of autophagy in wound,and promote ulcer wound healing in diabetic rats.

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

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 explore the effect of sinomenine(SIN)on LPS-induced apoptosis and autophagy of lung epithelial cells through the JNK/c-Jun signaling pathway.Methods:MLE-12 lung epithelial cells were cultured,and the toxicity of SIN was detected by CCK-8.Apoptosis was detected by flow cytometry,the number of autophagosomes was detected by immunofluorescence,and the expression levels of apoptosis,autophagy and JNK/c-Jun signaling pathway-related proteins were detected by Western blot.Results:After LPS modeling,apoptosis rate and the number of autophagosomes were increased,the protein levels of Cleaved caspase-3,Bax,and Beclin-1,and LC3Ⅱ/LC3Ⅰ,p-JNK/JNK and p-c-Jun/c-Jun were increased(P<0.05);Bcl-2 and P62 protein levels were decreased(P<0.05).SIN treatment can significantly improve the effects of LPS on apoptosis and autophagy,as well as the regulation of the JNK/c-Jun signaling pathway(P<0.05).Treatment with the autophagy inhibitor 3-MA or the JNK agonist ANISO could partially reverse the protective effect of SIN on LPS-induced lung epithelial cells(P<0.05).Conclusion:SIN may increase autophagy and pro-tect lung epithelial cells damaged by LPS by regulating proteins related to the JNK/c-Jun signaling pathway.

Objective:To identify the genetic mutation of coagulation factor Ⅶ(F7)gene in a pedigree with coagulation factor Ⅶ(FⅦ)deficiency and explore the molecular pathogenesis.Methods:The prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),D-dimer(DD),fibrin degradation products(FDP)and coagulation factor Ⅶ activity(FⅧ:C)of the proband and her family members were detected by Sysmex-CS5100 analyzer.All exons and exon-intron boundaries of the F7 gene were amplified by PCR followed by direct sequencing.The detected mutation was confirmed by reverse sequencing.The ClustalW software was used to analyze the conservatism of the mutant site.Pathogenicity of the mutation was assessed with Mutation Taster and PolyPhen-2 online bioinformatics software.Structure of the mutant protein was analyzed using Swiss-PdbViewer software.Results:The results of routine coagulation tests showed that PT of the proband was markedly extended to 42.5 s,and her FⅦ:C significantly reduced to 2％.The FⅦ:C of her grandmother,mother and sister had slightly reduced to 49％,51％,and 42％,respectively.These coagulant parameters of her father were within the normal range.Genetic analysis reveled a heterozygous G＞A change at cDNA 646 in exon 6 of F7 gene in the proband,resulting in a replacement of glycine at 156 of FⅦ catalytic region with serine(p.Gly156Ser).The sequencing results of other exons and exon-intron boundaries of her F7 gene were normal.The proband's grandmother,mother and sister were all the carriers of this missense mutation except her father.Bioinformatics analysis showed that the p.Gly156Ser mutation caused polarity change of the amino acid at this site and formation of side chains,leading to increase of protein instability,which may affect catalytic activity of structural domain.Meanwhile,both Mutation Taster and PolyPhen-2 online bioinformatics software also predicted the pathogenicity of this missense mutation with high scores.Conclusion:The heterozygous p.Gly 156Ser mutation is the direct cause of the reduced FⅦ in this proband.