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 discuss the correlation of serum visceraladiposetissue-derived serineproteinase inhibitor(vaspin)and atrial fibrosis biochemical markers in atrial fibrillation(AF)patients.Methods The subjects were selected from inpatients in Shanghai Putuo District People's Hospital during January 2021 to October 2022.Enzyme linked immunosorbent assay(ELISA)was used to determine the levels of serum vaspin,C-terminal propeptide of prollagen type Ⅰ(PⅠCP),matrix metalloproteinase-1(MMP-1),N-terminal type Ⅲ collagen peptide(PⅢNP),tissue matrix metalloproteinase inhibitory factor-1(TIMP-1)of paroxysmal atrial fibrillation(PAF)group,persistent atrial fibrillation(PeAF)group,and control group.The correlation between serum vaspin and the above serum biochemical markers was analyzed.Results ①Levels of serum vaspin(9.51±1.47)ng/ml,PⅠCP(704.83±120.45)ng/ml,MMP-1(5.92±0.73)ng/ml,PⅢNP(63.34±12.24)ng/ml,and TIMP-1(7.56±0.90)ng/ml in PeAF group were significantly higher than those of PAF group and control group(P<0.05);②vaspin was significantly and positively correlated with PⅠCP,MMP-1,PⅢNP,TIMP-1 in PAF group and PeAF group.Conclusion Serum vaspin level of AF patients were significantly high and positively correlated with atrial fibrosis biochemical markers,which indicated that serum vaspin level might be closly related to atrial fibrosis in AF patients.It may be a potential marker to identify the degree of fibrosis in atrial fibrillation.

Objective:To explore the interaction needs between depressed adolescents with non-suicidal self-injury behavior and their parents.Methods:From June to November 2023, purposive sampling was used to select depression adolescents with non-suicidal self-injury behavior and their parents admitted to Huai'an Third People's Hospital as respondents. The semi-structured interview was used to collect data. The paired interview and Colaizzi 7-step analysis methods were used to analyze and summarize interview data.Results:Fifteen pairs of adolescents and their parents were interviewed. The needs of depressed adolescents with non-suicidal self-injury behavior for parental attention were summarized as controlling emotions, empathetic perception, reducing stress, mental dependence, autonomous decision-making, and mutual respect. The needs of parents for depressed adolescents with non-suicidal self-injury behavior were summarized as overcoming depression, restoring education, emotional response, actively seeking help, deep communication, and easing relationships.Conclusions:There are various interactive needs between depressed adolescents with non-suicidal self-injury behavior and their parents, which are closely related but contradictory in coping with the illness. It is recommended that medical and nursing staff conduct research on patients and their parents as a whole and provide personalized and targeted two-way guidance and emotional support through in-depth understanding and careful consideration of the multi-level interaction needs of both parties.

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 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 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 investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Objective:To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation.Methods:The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed.Results:Among 479 B-ALL patients, 34 cases (7.1%) were positive for TP53 gene mutation, and a total of 36 TP53 mutations were detected, including 10 frameshift gene mutations (27.8%) , 23 missense mutations (63.9%) and 3 nonsense mutations (8.3%) . A total of 34 (94.4%) mutations were located in the DNA binding domain (exons 5-8) .The average number of mutated genes in patients with TP53 gene mutation (2.3) and the group without TP53 gene mutation (1.1) were statistically different ( P<0.001) . The proportion of Ph positive and Ph-like positive patients in the TP53 gene mutation negative group was significantly higher than that of the TP53 mutation positive group, and the difference was statistically significant ( P<0.001) . The 3-year OS and EFS rates of the TP53 gene mutation negative group were significantly higher than those of the TP53 gene mutation positive group. The differences in OS and EFS rates between the two groups were statistically significant ( χ2= 4.694, P = 0.030; χ2= 5.080, P= 0.024) . In the multivariate analysis, failure to achieve remission (CR) after one course of induction chemotherapy was an independent adverse prognostic factor affecting OS.Of the 34 patients with TP53 mutation, 16 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the CR 1 state, and 2 patients with recurrence after transplantation obtained CR 2 after infusion of donor-derived anti-CD19 chimeric antigen receptor T (CAR-T) cells. Among the 11 patients with TP53 gene mutation who relapsed during consolidation chemotherapy, 6 received anti-CD19 CAR T cell therapy, 4 patients achieved remission and minimal residual disease (MRD) turned negative, followed by bridging allo-HSCT, and 2 of them sustained CR. Conclusion:Missense mutations are the most common in B-ALL patients with TP53 gene mutation, and the majority of mutations were located in the DNA binding domain. B-ALL patients with TP53 gene mutation should undergo allo-HSCT as soon as possible after CAR-T cell therapy has cleared the MRD after recurrence. B-ALL patients with TP53 gene mutation still have a higher recurrence rate after allo-HSCT, and the infusion of donor-derived CAR-T cells can achieve better sustained remission.

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.