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.

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 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.

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.

Primary seminal vesicle adenocarcinoma is a rare malignant tumor of reproductive system. A 21-year-old patient with primary seminal vesicle adenocarcinoma was treated in our hospital in August 2014. Without surgical treatment, the patient survived for 4.5 years after 6 cycles of chemotherapy and pelvic radiotherapy. Local recurrence was found in February 2019 and laparoscopic radical prostatectomy was performed. There was no local recurrence and metastasis after follow-up for 10 months.

Objective To compare the clinical feasibility of different methods for detecting Clostridium difficile (CD) .Methods The stool samples were collected from the patients with suspected antibiotic-related diarrhea during 2016 ,and the enzyme linked immunosorbent assay (ELISA) and identification medium culture method were used for detection .Then the sensitivity ,specificity and consistency were compared between the two methods .Results 29 cases of antigen-positive specimens were measured by ELISA ,including 25 cases of toxin-positive and 4 cases of toxin negative ;29 suspected strains were cultured by the selective identification medium ,which were identified by the mass spectrometry as 28 strains of Clostridium difficile and 1 strain of undetected species ;the sensitivity and specificity of ELISA method and identification culture medium method were 97% ,100% and 93% ,95% respectively ,both methods showed extremely good consistency (Kappa=0 .92) .Conclusion The ELISA method has the characteristics of fastness ,high efficiency ,time saving ,simple operation ,easy interpretation and so on ,and can rapidly and accurately screen CD related diarrhea diseases ;the medium culture method has a good specificity and can rapidly obtain the infectious strain ;their combined use can greatly increase the CD detection rate and has great help for late treatment .

Objective To investigate the relationship and clinical significance between the concentration of 25-hydroxy vitamin D3 [25-(OH)D3 ]in the serum and community-acquired pneumonia(CAP)in infants.Methods The study recruited 98 infants.There were 68 cases of mild pneumonia and 30 cases of severe pneumonia.The con-centration of 25-(OH)D3 in serum,IgA and alkaline phosphatase(AKP)were measured.33 infants who accepted physical examination in the outpatient department were selected as control group at the same time.Results The serum 25-(OH)D3 concentration of severe pneumonia was (21.09 ±7.32)ng/mL,mild pneumonia was (25.77 ± 8.06)ng/mL and the control group was (37.13 ±6.94)ng/mL.The differences among the three groups had statisti-cally significant differences(t =9.18,3.72,5.34,all P <0.05).The differences of serum IgA concentration among the three groups had statistically significant differences (t =5.42,3.96,8.92,all P <0.05).But serum AKP concen-tration among the three groups had no statistically significant differences(t =0.86,0.58,0.47,all P >0.05).The prevalence of Vitamin D deficiency was 40.0%,which was higher than mild pneumonia patients(20.6%)and the healthy children(9.1%)(χ2 =8.43,17.55,all P <0.05).Conclusion The serum 25-(OH)D3 concentration and IgA of CAP patients were lower than healthy children,especially in severe pneumonia cases.The prevalence of Vita-min D deficiency was significantly higher than healthy children.There were no relevance between the serum concentra-tion of 25-(OH)D3 ,IgA and AKP.25-(OH)D3 plays an important role in the development of CAP.The low level of serum 25-(OH)D3 concentration may be one of the risk factors and has correlation to the severity of pneumonia.