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

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

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*

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

Objective To investigate the efficacy of Bifidobacterium triple live bacteria enteric-coated capsules in the adjuvant treatment of patientys with gestational diabetes mellitus(GDM)complicated with depression,and its effect on intestinal flora and inflammatory indicators.Methods A total of 168 patients with GDM complicated with depression were selected and randomly divided into the control group(81 cases,treated with psychological counseling,dietary control and appropriate exercise)and the observation group(87 cases,treated with Bifidobacterium trilactis enteric-coated capsules on the basis of the control group,2 capsules each time,twice a day).Both groups were treated for 1 month continuously.The therapeutic effects were evaluated after treatment.The depression degree of patients was evaluated by Self-Rating Depression Scale(SDS)before treatment and one month after treatment.The fasting blood glucose(FBG)and 2-hour postprandial blood glucose(2 hPG)of patients were detected.The intestinal flora was detected by fluorescence quantitative PCR.The inflammatory indicators serum tumor necrosis factor-α(TNF-α)and serum C-reactive protein(CRP)were detected by enzyme-linked immunosorbent assay and immunoturbidimetry.The neutrophil and lymphocyte counts in peripheral venous blood were detected by automatic blood analyzer,and the neutrophil-to-lymphocyte ratio(NLR)was calculated.The adverse drug reactions were recorded.Results The total effective rate was 96.55%in the observation group,which was higher than that of the control group(87.65%,P＜0.05).After 1 month of treatment,the SDS score,FBG,2 hPG,serum TNF-α,CRP and NLR were decreased in both groups,and those of the observation group were lower than the control group(P＜0.05).One month after treatment,there was no significant difference in the number of intestinal flora compared with that before treatment in the control group.The number of Lactobacillus and Bifidobacterium in the observation group was increased compared with that before treatment,while the number of Escherichia coli and Bacteroides fragilis decreased.After 1 month of treatment,the number of Lactobacillus and Bifidobacterium in the observation group was higher than that in the control group,while the number of Escherichia coli and Bacteroides fragilis was lower than that in the control group(P＜0.01).The adverse reaction rate of the observation group was 3.45%,and there was no significant difference compared with 1.23%of the control group.Conclusion Bifidobacterium triple live bacteria enteric-coated capsules has a good clinical effect in the adjuvant treatment of GDM with depression,which can effectively control blood glucose level,improve intestinal flora,reduce inflammatory reaction and has good safety.

Objective To investigate the efficacy of Bifidobacterium triple live bacteria enteric-coated capsules in the adjuvant treatment of patientys with gestational diabetes mellitus(GDM)complicated with depression,and its effect on intestinal flora and inflammatory indicators.Methods A total of 168 patients with GDM complicated with depression were selected and randomly divided into the control group(81 cases,treated with psychological counseling,dietary control and appropriate exercise)and the observation group(87 cases,treated with Bifidobacterium trilactis enteric-coated capsules on the basis of the control group,2 capsules each time,twice a day).Both groups were treated for 1 month continuously.The therapeutic effects were evaluated after treatment.The depression degree of patients was evaluated by Self-Rating Depression Scale(SDS)before treatment and one month after treatment.The fasting blood glucose(FBG)and 2-hour postprandial blood glucose(2 hPG)of patients were detected.The intestinal flora was detected by fluorescence quantitative PCR.The inflammatory indicators serum tumor necrosis factor-α(TNF-α)and serum C-reactive protein(CRP)were detected by enzyme-linked immunosorbent assay and immunoturbidimetry.The neutrophil and lymphocyte counts in peripheral venous blood were detected by automatic blood analyzer,and the neutrophil-to-lymphocyte ratio(NLR)was calculated.The adverse drug reactions were recorded.Results The total effective rate was 96.55%in the observation group,which was higher than that of the control group(87.65%,P＜0.05).After 1 month of treatment,the SDS score,FBG,2 hPG,serum TNF-α,CRP and NLR were decreased in both groups,and those of the observation group were lower than the control group(P＜0.05).One month after treatment,there was no significant difference in the number of intestinal flora compared with that before treatment in the control group.The number of Lactobacillus and Bifidobacterium in the observation group was increased compared with that before treatment,while the number of Escherichia coli and Bacteroides fragilis decreased.After 1 month of treatment,the number of Lactobacillus and Bifidobacterium in the observation group was higher than that in the control group,while the number of Escherichia coli and Bacteroides fragilis was lower than that in the control group(P＜0.01).The adverse reaction rate of the observation group was 3.45%,and there was no significant difference compared with 1.23%of the control group.Conclusion Bifidobacterium triple live bacteria enteric-coated capsules has a good clinical effect in the adjuvant treatment of GDM with depression,which can effectively control blood glucose level,improve intestinal flora,reduce inflammatory reaction and has good safety.

Objective:To investigate the correlation between clinical outcomes of congenital diaphragmatic hernia (CDH) and chromosomal abnormalities.Methods:This was a retrospective study involving 101 fetuses who underwent invasive prenatal diagnosis and chromosomal analysis for CDH at the Prenatal Diagnosis Center of Guangzhou Medical University Affiliated Women and Children's Medical Center from January 1, 2010, to December 31, 2021. According to ultrasound results, they were divided into the isolated CDH group and the complex CDH group. The results of chromosomal karyotype analysis or chromosomal microarray analysis (CMA) and birth outcomes were analyzed. For live-born children, follow-up results were analyzed. Statistical analysis was performed using t-test or Chi-square (or Fisher's exact) test. Results:(1) The mean age of the mothers of the 101 fetuses was (29.6±5.3) years, ranging from 20 to 47 years, and 16 mothers (15.8%) were over 35 years old. The mean gestational age at invasive prenatal diagnosis was (27.1±5.0) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days; the mean gestational age at first diagnosis of CDH was (26.6±4.8) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days. (2) The 101 fetuses were divided into isolated CDH group (81 cases, 80.2%) and complex CDH group (20 cases, 19.8%) based on whether they had other ultrasound abnormalities. Among the 20 complex cases, 13 had more than two types of malformations, with cardiovascular system malformations being the most common (11 cases, including seven chromosomal abnormalities). The highest proportion of chromosomal abnormalities was found in fetuses with central nervous system malformations (3/4). (3) Among the 101 CDH fetuses, 31 (30.7%) underwent chromosomal karyotype analysis alone, 39 (38.6%) underwent CMA alone, and 31 (30.7%) underwent both tests. The rate of chromosomal abnormalities was 13.9% (14/101). The detection rates of abnormalities by chromosomal karyotype analysis and CMA were 16.1% (10/62) and 14.3% (10/70), respectively. The additional detection rate by CMA was 2.8% (2/70). (4) The gestational age at diagnosis in the complex CDH group was earlier than that in the isolated CDH group [(22.7±4.2) weeks vs. (27.7±4.6) weeks, t=4.47, P<0.001]. The total detection rate, as well as the detection rates by chromosomal karyotype analysis and CMA, were higher in the complex CDH group than those in the isolated CDH group [45.0% (9/20) vs. 6.2% (5/81), χ2=17.13; 7/15 vs. 6.4% (3/47), χ2=10.82; 5/11 vs. 8.8% (5/57), χ2=7.55; all P<0.01]. (5) Among the 101 CDH fetuses, two were lost to follow-up, and 99 (98.0%) were successfully followed up. Among these 99 cases, 48 were terminated, and 51 were live births. The chromosomal abnormality rate in the 48 terminated fetuses was 25.0% (12/48), including 28 isolated cases and 20 complex cases. All 51 live births were isolated cases, with 45 (88.2%) cured by postnatal surgery and six (11.8%) having adverse clinical outcomes (including two preoperative deaths, three postoperative deaths, and one postoperative recurrence). Conclusions:The rate of chromosomal abnormalities in CDH is high, and it is higher in complex CDH than in isolated CDH. When prenatal diagnosis reveals fetal CDH, invasive prenatal diagnosis is recommended to exclude chromosomal karyotype abnormalities, with CMA recommended as the preferred chromosomal testing method.

Objective To explore the establishment of a new model of informational drug treatment pathway management.Methods The orthopedic drug treatment pathways was developed through multidisciplinary diagnosis and treatment(MDT),and the pathway management was implemented with the help of an information systems to implement refined control rules.Cases before the implementation of the management pathway(January to May 2022)were selected as the control group,and cases after the implementation of the management pathway(June to December 2022)were selected as the improvement group to evaluate the management effectiveness.Results After establishing drug treatment pathways for 8 major types of surgeries,maintaining 990 medical prescriptions for recommended drugs in the HIS system,and 176 control rules in the MINDS system.There was a significant improvement in the orthopaedic department's indexes of antimicrobial drug use rate,antibacterial drug use intensity,average inpatient medication cost,and percentage of the amount of basic medication after applying a new model of drug treatment pathway management.According to the case analysis before and after the implementation of the pathway,the rational rate of using orthopedic antibiotics,analgesics,fluid replacement and volume expansion drugs,acid inhibiting and stomach protecting drugs,blood activating and swelling-reducing proprietary Chinese medicines were increased by 21.6%,12.7%,23.3%,32.1% and 27.1%,respectively.The average drug costs was reduced by 111.51 yuan,15.33 yuan,49.84 yuan,42.29 yuan and 14.23 yuan,respectively.Conclusion The management mode of drug treatment pathway based on MDT established by our hospital is practical and effective,and the relevant experience may provide valuable insights for pharmaceutical peers.

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 investigate the correlation between clinical outcomes of congenital diaphragmatic hernia (CDH) and chromosomal abnormalities.Methods:This was a retrospective study involving 101 fetuses who underwent invasive prenatal diagnosis and chromosomal analysis for CDH at the Prenatal Diagnosis Center of Guangzhou Medical University Affiliated Women and Children's Medical Center from January 1, 2010, to December 31, 2021. According to ultrasound results, they were divided into the isolated CDH group and the complex CDH group. The results of chromosomal karyotype analysis or chromosomal microarray analysis (CMA) and birth outcomes were analyzed. For live-born children, follow-up results were analyzed. Statistical analysis was performed using t-test or Chi-square (or Fisher's exact) test. Results:(1) The mean age of the mothers of the 101 fetuses was (29.6±5.3) years, ranging from 20 to 47 years, and 16 mothers (15.8%) were over 35 years old. The mean gestational age at invasive prenatal diagnosis was (27.1±5.0) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days; the mean gestational age at first diagnosis of CDH was (26.6±4.8) weeks, ranging from 13 weeks and 3 days to 38 weeks and 3 days. (2) The 101 fetuses were divided into isolated CDH group (81 cases, 80.2%) and complex CDH group (20 cases, 19.8%) based on whether they had other ultrasound abnormalities. Among the 20 complex cases, 13 had more than two types of malformations, with cardiovascular system malformations being the most common (11 cases, including seven chromosomal abnormalities). The highest proportion of chromosomal abnormalities was found in fetuses with central nervous system malformations (3/4). (3) Among the 101 CDH fetuses, 31 (30.7%) underwent chromosomal karyotype analysis alone, 39 (38.6%) underwent CMA alone, and 31 (30.7%) underwent both tests. The rate of chromosomal abnormalities was 13.9% (14/101). The detection rates of abnormalities by chromosomal karyotype analysis and CMA were 16.1% (10/62) and 14.3% (10/70), respectively. The additional detection rate by CMA was 2.8% (2/70). (4) The gestational age at diagnosis in the complex CDH group was earlier than that in the isolated CDH group [(22.7±4.2) weeks vs. (27.7±4.6) weeks, t=4.47, P<0.001]. The total detection rate, as well as the detection rates by chromosomal karyotype analysis and CMA, were higher in the complex CDH group than those in the isolated CDH group [45.0% (9/20) vs. 6.2% (5/81), χ2=17.13; 7/15 vs. 6.4% (3/47), χ2=10.82; 5/11 vs. 8.8% (5/57), χ2=7.55; all P<0.01]. (5) Among the 101 CDH fetuses, two were lost to follow-up, and 99 (98.0%) were successfully followed up. Among these 99 cases, 48 were terminated, and 51 were live births. The chromosomal abnormality rate in the 48 terminated fetuses was 25.0% (12/48), including 28 isolated cases and 20 complex cases. All 51 live births were isolated cases, with 45 (88.2%) cured by postnatal surgery and six (11.8%) having adverse clinical outcomes (including two preoperative deaths, three postoperative deaths, and one postoperative recurrence). Conclusions:The rate of chromosomal abnormalities in CDH is high, and it is higher in complex CDH than in isolated CDH. When prenatal diagnosis reveals fetal CDH, invasive prenatal diagnosis is recommended to exclude chromosomal karyotype abnormalities, with CMA recommended as the preferred chromosomal testing method.