Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*

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

Bone morphogenetic proteins (BMPs) are multifunctional growth factors of the transforming growth factor β (TGF-β) superfamily. They regulate steroid secretion from mammalian granulosa cells, promote granulosa cell survival and proliferation, and inhibit follicular atresia, luteinization, and granulosa cell apoptosis, thereby promoting the development and maturation of mammalian follicles. At the same time, BMPs play an important role in embryonic morphogenesis, induction of uterine receptivity, and blastocyst attachment. This paper describes the effects of BMPs on mammalian follicular and embryonic development and the roles of BMPs in female reproduction, focusing on the process in which BMPs promote follicular maturation by regulating steroid secretion from granulosa cells during mammalian oocyte maturation. This review aims to provide a reference for further research on mammalian oocyte culture and improvement of reproductive efficiency in female animals.
Animals ; Embryonic Development/drug effects* ; Female ; Bone Morphogenetic Proteins/pharmacology* ; Reproduction/physiology* ; Humans ; Granulosa Cells/cytology* ; Oocytes

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 ⁺ or Vgat ⁺neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

Objective To establish a UPLC-MS/MS method to measure the content of monoester-alkaloids(benzoylmesaconine,benzoylaconine,benzoylhypaconine)and diester-alkaloids(mesaconitine,hyp-aconitine,aconitine)in Fengshiantai tablets.To provide a basis for quality control by conducting chemometric analysis and risk assessment on the measurement results.Methods The components were separated on Waters BEH C18 column(2.1 mm×100 mm,1.7 μm)with methanol and 0.1%formicacid aqueous solution as the mobile phase by gradient elution at a flow rate of 0.3 mL·min-1.The column temperature was set at 35℃.The injection volume was 1 μL.The detection was carried out by electrospray ionization(ESI),and electron spray ionization source was adopted in positiveion detection with multiple reaction monitoring mode(MRM).Results Six components showed good linear relationships within their own ranges(r≥0.9990),whose average recovery rate of samples were 90.3%-107.6%with the RSD of 0.9%-1.8%.In 23 batches of tested samples,the diester-alkaloids contents ranged from 1.35 to 19.49 μg per tablet,which indicated low risk of drug safety;the monoester-alkaloids contents ranged from 20.17-99.55 μg per tablet.The results of chemometrics showed that 23 batches of samples were classify into four categories,and there were certain differences in sample quality among different production enterprises.Conclusion The established method is stable and reliable,and can be used for quality control of Fengshi Antai tablets.

Epigallocatechin gallate (EGCG), the predominant polyphenol in green tea, exerts a spectrum of physiological activities, including antioxidant, anticancer, and anti-inflammatory effects. Emerging research underscores the significance of EGCG in modulating oocyte aging. EGCG can enhance antioxidant defenses, improve mitochondrial functions, and inhibit apoptotic pathways, thereby retarding the aging of oocytes. This review delineates the main molecular features of EGCG and expounds its regulatory mechanisms concerning oocyte aging, enriching the knowledge on the role of EGCG in the amelioration of oocyte aging.
Catechin/pharmacology* ; Oocytes/metabolism* ; Humans ; Animals ; Antioxidants/pharmacology* ; Female ; Cellular Senescence/drug effects* ; Tea/chemistry* ; Apoptosis/drug effects*

Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

Objective:To understand the distribution and drug resistance of pathogens isolated from acquired immunodeficiency syndrome (AIDS) inpatients in Beijing area in recent years.Methods:The data on strain identification and antimicrobial susceptibility tests of clinical isolates of pathogens from AIDS inpatients in Beijing Ditan Hospital, Capital Medical University between January 2015 and December 2020 were collected and analyzed descriptively and retrospectively.Results:A total of 728 strains of pathogens were included in the analysis, mainly isolated from blood samples (292 strains, 40.1%), bronchial lavage fluid samples (116 strains, 15.9%), sputum samples (114 strains, 15.7%), urine samples (83 strains, 11.4%), bone marrow samples (26 strains, 3.6%), cerebrospinal fluid samples (24 strains, 3.3%), and pleural effusion samples (24 strains, 3.3%). Among the 728 pathogenic strains, 235 (32.3%) were Gram-negative bacilli, mainly including Pseudomonas aeruginosa, Escherichia coli, Salmonella spp., and Acinetobacter baumannii; 162 (22.3%) were Gram-positive cocci (22.3%), mainly including coagulase negative staphylococci and Staphylococcus aureus; 139 (19.1%) were mycobacteria, including Mycobacterium tuberculosis and nontuberculous mycobacteria; 108(14.8%) were fungi, mainly including Cryptococcus neoformans and Talaromyces marneffei; 84 (11.5%) were other pathogenic strains. According to the calculation of single strain, the top 5 pathogens were Mycobacterium tuberculosis, coagulase negative staphylococcus, nontuberculous mycobacteria, Pseudomonas aeruginosa, and Escherichia coli suceesively. In comparison with the distribution of pathogens isolated from AIDS patients in the same hospital in 2009-2014, the proportion of Gram-negative bacilli decreased (40.73% from 2009 to 2014), and the proportions of Gram-positive cocci, fungi, and Mycobacterium tuberculosis were similar (19.15%, 14.02%, and 9.27% respectively in 2009-2014), and the proportion of non tuberculosis mycobacteria increased significantly (it was not calculated separately and classified into 'others’ because of the relatively low proportion, and the proportion of others was 6.34% in 2009-2014) successively. Gram-negative bacilli were mostly isolated from respiratory samples (47.2%, 111/235), followed by urine samples (20.4%, 48/235); Gram-positive cocci were mostly isolated from blood samples (45.7%, 74/162), followed by bone marrow samples (13.0%, 21/162); mycobacteria were mainly isolated from blood samples (72.7%, 101/139), followed by respiratory samples (26.6%, 37/139); fungi were mainly isolated from blood samples (44.4%, 48/108), followed by respiratory samples (19.5%, 21/108) and cerebrospinal fluid samples (17.6%, 19/108). The results of antimicrobial susceptibility tests showed that the resistance rate of Gram-positive cocci decreased and the rate of the Gram-negative bacilli increased obviously in 2015-2020, compared to those in 2009-2014 in clinical isolates from AIDS patients in the same hospital respectively. Conclusion:In recent years, the proportion of Gram-negative bacilli decreases, the proportion of nontuberculous mycobacteria increases significantly, and the drug resistance rate of most Gram-negative bacilli increases significantly in clinical isolates from AIDS inpatients in Beijing.

Objective:To understand the distribution and drug resistance of pathogens isolated from acquired immunodeficiency syndrome (AIDS) inpatients in Beijing area in recent years.Methods:The data on strain identification and antimicrobial susceptibility tests of clinical isolates of pathogens from AIDS inpatients in Beijing Ditan Hospital, Capital Medical University between January 2015 and December 2020 were collected and analyzed descriptively and retrospectively.Results:A total of 728 strains of pathogens were included in the analysis, mainly isolated from blood samples (292 strains, 40.1%), bronchial lavage fluid samples (116 strains, 15.9%), sputum samples (114 strains, 15.7%), urine samples (83 strains, 11.4%), bone marrow samples (26 strains, 3.6%), cerebrospinal fluid samples (24 strains, 3.3%), and pleural effusion samples (24 strains, 3.3%). Among the 728 pathogenic strains, 235 (32.3%) were Gram-negative bacilli, mainly including Pseudomonas aeruginosa, Escherichia coli, Salmonella spp., and Acinetobacter baumannii; 162 (22.3%) were Gram-positive cocci (22.3%), mainly including coagulase negative staphylococci and Staphylococcus aureus; 139 (19.1%) were mycobacteria, including Mycobacterium tuberculosis and nontuberculous mycobacteria; 108(14.8%) were fungi, mainly including Cryptococcus neoformans and Talaromyces marneffei; 84 (11.5%) were other pathogenic strains. According to the calculation of single strain, the top 5 pathogens were Mycobacterium tuberculosis, coagulase negative staphylococcus, nontuberculous mycobacteria, Pseudomonas aeruginosa, and Escherichia coli suceesively. In comparison with the distribution of pathogens isolated from AIDS patients in the same hospital in 2009-2014, the proportion of Gram-negative bacilli decreased (40.73% from 2009 to 2014), and the proportions of Gram-positive cocci, fungi, and Mycobacterium tuberculosis were similar (19.15%, 14.02%, and 9.27% respectively in 2009-2014), and the proportion of non tuberculosis mycobacteria increased significantly (it was not calculated separately and classified into 'others’ because of the relatively low proportion, and the proportion of others was 6.34% in 2009-2014) successively. Gram-negative bacilli were mostly isolated from respiratory samples (47.2%, 111/235), followed by urine samples (20.4%, 48/235); Gram-positive cocci were mostly isolated from blood samples (45.7%, 74/162), followed by bone marrow samples (13.0%, 21/162); mycobacteria were mainly isolated from blood samples (72.7%, 101/139), followed by respiratory samples (26.6%, 37/139); fungi were mainly isolated from blood samples (44.4%, 48/108), followed by respiratory samples (19.5%, 21/108) and cerebrospinal fluid samples (17.6%, 19/108). The results of antimicrobial susceptibility tests showed that the resistance rate of Gram-positive cocci decreased and the rate of the Gram-negative bacilli increased obviously in 2015-2020, compared to those in 2009-2014 in clinical isolates from AIDS patients in the same hospital respectively. Conclusion:In recent years, the proportion of Gram-negative bacilli decreases, the proportion of nontuberculous mycobacteria increases significantly, and the drug resistance rate of most Gram-negative bacilli increases significantly in clinical isolates from AIDS inpatients in Beijing.

Objective To study the detection rate of pathogens from sputum , blood, and bronchoalveolar lavage fluid ( BALF ) samples in acquired immunodeficiency syndrome ( AIDS ) patients complicated with pulmonary infection.Methods Seventy-three hospitalized AIDS patients complicated with pulmonary infection in Beijing Ditan Hospital , Capital Medical University were enrolled from February 2018 to September 2018.Blood, sputum and BALF samples were collected.Blood samples were cultured to detect anaerobic bacteria, aerobic bacteria, fungi and mycobacteria.Antigen agglutination method was applied in blood samples to detect cryptococcus neoformans.The sputum samples were tested for Mycobacterium tuberculosis by acid-fast staining and were cultured to detect bacteria and fungi.The sputum samples were observed under microscope for sporotrichosis and fungal spores.The BALF samples were cultured to detect bacteria and fungi. The BALF samples were tested for Mycobacterium tuberculosis by polymerase chain reaction amplification and acid-fast staining.Pneumocystis were detected in BALF samples by methenamine silver staining method .The BALF samples were observed under a microscope for sporotrichosis and fungal spores .The detection rate of pathogens from blood, sputum and BALF samples were compared.Chi-square test was conducted for statistical analysis.Results In 73 AIDS patients complicated with pulmonary infection , the pathogen detection rates in blood, sputum and BALF samples were 8 (11.0%), 23 ( 31.5%) and 48 (65.8%), respectively.The difference was statistically significant ( F ＝48.513, P ＜0.01 ).The detection rate in BALF samples was significantly higher than that in blood or sputum samples ( χ2 ＝43.349 and 17.136, respectively, both P＜0.01).The detection rate in sputum samples was significantly higher than that in blood (χ2 ＝9.215, P＜0.05). The highest detection rates of pathogens in blood , sputum and BALF samples were Talaromyces marneffei 4.1%(3), viridans group streptococci 16.4%(12) and 35.6%(26), respectively.Conclusions The detection rate of pathogens in BALF samples from AIDS patients complicated with pulmonary infection is the highest , followed by sputum and blood samples.