1.Early CD4 + T cell immune reconstitutionas a biomarker for Epstein‑Barr virus control following allogeneic transplantation
Kexin LIN ; Wenwen YANG ; Jiaxiu YIN ; Jing LUO ; Hao ZHOU ; Lanxiang LIU ; Li YANG ; Jie LUO ; Lin LIU ; Junli MOU
Blood Research 2025;60():57-
Purpose:
Achieving high-quality immune reconstitution (IR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is directly associated with the patient’s ability to resist infections, prevent tumor relapses, and suppress graft-versus-host disease (GVHD). The status of CD4 + T cells is critical for reconstituting adaptive immunity after transplantation; however, the patterns of reconstitution and their influencing factors remain unclear.
Methods:
This retrospective cohort study involved 164 patients who underwent myeloablative allo-HSCT from April 2016 to May 2023. Based on the early post-transplantation CD4 + T cell counts, the cohort was divided into two groups: 73 patients with high-quality IR (HIR) and 34 patients with low-quality IR (LIR). LIR was associated with an increased risk of Epstein–Barr virus (EBV) reactivation following transplantation. Plasma EBV viral load was monitored weekly using quantitative PCR for the first 100 days post-transplantation.
Results:
The LIR group had a higher viral load at the time of the first EBV reactivation and a significantly earlier first reactivation compared to the HIR group. No significant differences were observed in overall survival, GVHD incidence, or relapse rates between the groups. A CD4 + T cell count of < 60 cells/μL within 30 days post-transplantation was associated with a higher incidence of EBV viremia compared to the control group.
Conclusion
These findings suggest that early CD4 + T cell counts may serve as a predictive marker for post-transplant EBV infection.
2.SPAG6 promotes proliferation and drug resistance in B-ALL cells through the NF-κB/TNF-α pathway
Shirui PAN ; Jie LUO ; Jing LUO ; Jiaxiu YIN ; Haiqiu ZHAO ; Rong SU ; Lin LIU
Journal of Army Medical University 2024;46(24):2723-2735
Objective To elucidate the underlying mechanisms of sperm-associated antigen 6(SPAG6)in the proliferation and drug resistance of B-cell acute lymphoblastic leukemia(B-ALL).Methods A total of 56 B-ALL patients and 15 iron-deficiency anemia(IDA)patients admitted in the First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023 were recruited and served as the experimental and control groups,respectively.Bone marrow mononuclear cells(BMMNCs)were derived from the bone marrow tissues of the experimental group.According to the results of qRT-PCR for the expression of SPAG6 in the obtained BMMNCs,the B-ALL patients were stratified into newly-diagnosed(New-diag)group,complete remission(CR)group,minimal residual disease Possitive(MRD+)group,and relapse group.Lentiviral vectors were used to construct B-ALL cells with SPAG6 overexpression and knockdown.CCK-8 assay and methylcellulose-based colony formation experiment were employed to assess the survival,proliferation,and clonogenic potential of the cells with varying SPAG6 expression levels.After f B-ALL cells were treated with the chemotherapeutic drugs,daunorubicin(DNR)and methotrexate(MTX),CCK-8 assay,flow cytometry and Western blot analysis were applied to detect cell viability(drug sensitivity andIC50),cell apoptosis,and protein levels of apoptosis-related molecules Bax,Caspase-3 and Bcl-2,respectively.The mRNA-seq profiles of B-ALL patients were obtained from the TARGET database,and gene set enrichment analysis(GSEA)was conducted to explore SPAG6-associated signaling pathways,which were subsequently validated experimentally.After treatment with the NF-κB agonist Phorbol 12-myristate 13-acetate(PMA)and the antagonist BAY-11-7082,cell viability and sensitivity to chemotherapeutic drugs were assessed with CCK-8 assay,and the expression of pathway-related proteins NF-κB P65,p-NF-κB p65,IK Bα,p-IKBα,TNF-α,and EPO was detected by Western blot analysis.A mouse xenograft tumor model was constructed in SPAG6-/+knockdown mice to observe the effect of DNR on tumor growth and the expression of the NF-κB signaling pathway in the tumor tissues with immunohistochemical assay.Results The mRNA level of SPA G6 was significantly higher in the B-ALL patients(P<0.05),and in the MRD group(P=0.001)and R group(P=0.003)than the CR group.SPAG6 overexpression and knockdown in B-ALL cells confirmed that SPAG6 promoted the proliferation(P<0.05)and decreased the sensitivity to DNR and MTX(P<0.05).SPAG6 resisted chemotherapy-induced apoptosis in B-ALL cells by down-regulating pro-apoptotic proteins Bax and Caspase-3(P<0.05),and up-regulating the expression of anti-apoptotic protein Bcl-2(P<0.05).GSEA analysis suggested that the NF-κB pathway was enriched in B-ALL cells,and our experiments confirmed that SPAG6 enhanced the chemoresistance of B-ALL cells to chemotherapy by activating the NF-κB/TNF-α pathway.In in vivo experiments,knocking SPAG6 down significantly reduced the volume of transplanted tumors(P<0.05),and an additional decrease in tumor growth was observed in the DNR-combined treatment group(P<0.05),with reduced levels of NF-κB P65 and p-IKBα by immunohistochemical assay.Conclusion SPAG6 promotes the proliferation of B-ALL cells and reduces their chemosensitivity via the NF-κB/TNF-α pathway,suggesting a close association of SPAG6 with the therapeutic outcomes and prognosis in B-ALL patients.
3.A Multi-center Randomized Double-blind Comparative Clinical Trial of Levocetirizine and Cetirizine for the Treatment of Chronic Idiopathetic Urticaria
Fei HAO ; Hui LI ; Yuangang LU ; Rui YIN ; Jiaxiu CHEN ; Jinjin WU ; Renshan SUN ; Jun DENG
Chinese Journal of Dermatology 1994;0(06):-
Objective To investigate and compare the effect and safety of levocetirizine and cetirizine for the treatment of chronic idiopathetic urticaria (CIU). Methods A multi-center, randomized and double-blind comparative clinical trial was employed. The patients with CIU were divided into levocetirizine group and cetirizine group. Levocetirizine (5mg/day) or cetirizine (10mg/day) were taken once daily for 28 days, and were followed up on the 7th day, 14th day and 28th day after starting treatment. Results One hundred and thirty cases were evaluable for the effect and safety at the end of the study. The effective rates in levocetirizine group and in cetirizine group were 73.44% and 77.27% on the 7th day after treatment, 82.81% and 81.82% on the 14th day, and 89.06% and 81.82% at the end of the therapy respectively. There was no significant difference between the two groups. The drug adverse reaction for levocetirizine group and cetirizine group were 14.06% and 18.18% respectively, which include mouth dryness, dizziness etc. Conclusion Levocetirizine is an effective and safe agent for the treatment of CIU.

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