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| 1 | 基于TLR4/MyD88信号通路探究miR-326对抑郁模型脑组织的保护作用显示文摘目的探究抑郁模型脑组织的可能保护机制。方法通过不同类型的胁迫建立大鼠慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,通过侧脑室注射miR-326 agomiR以上调miR-326的表达水平。蔗糖偏好测试(sucrose preference test,SPT)、旷场测试(open field test,OFT)、强迫游泳测试(forced swim test,FST)、高架十字迷宫(elevated plus maze,EPM)实验被用来检测动物的行为学及抑郁状态。通过ELISA试剂盒检测大鼠血清中去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)、5-羟色胺(5-hydroxytryptamine,5-HT)水平,采取Western blot法检测大鼠海马组织TLR4、MyD88蛋白水平。结果CUMS组大鼠体重、蔗糖消耗量、OFT中心区域停留时间及张开手臂时间低于对照组,FST静止时间明显高于对照组(P<0.05)。CUMS组大鼠海马组织中miR-326表达显著低于对照组,CUMS+agomiR 326组大鼠海马组织中miR-326表达高于CUMS+agomiR NC组(P<0.05)。CUMS+agomiR 326组大鼠体重、蔗糖消耗量、OFT中心区域停留时间及开放臂停留时间显著高于CUMS+agomiR NC组,FST静止时间明显低于CUMS+agomiR NC组(P<0.05)。CUMS组NE、DA和5-HT水平显著低于对照组,CUMS+agomiR 326组NE、DA和5-HT水平显著高于CUMS+agomiR NC组(P<0.05)。CUMS组大鼠TLR4蛋白和MyD88蛋白水平显著高于对照组,CUMS+agomiR 326组大鼠TLR4蛋白和MyD88蛋白水平显著降低(P<0.05)。结论在CUMS抑郁模型中,miR-326可能通过调控TLR4/MyD88信号通路参与脑组织的保护作用。 | 刘威 | 2023 | 河北医科大学学报2023，44，10： | 0 |
| 2 | Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy显示文摘BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden. | Ning Wang Fei-Li Chen Lu Pan Yan Teng Xiao-Juan Wei Han-Guo Guo Xin-Miao Jiang Ling Huang Si-Chu Liu Zhan-Li Liang Wen-Yu Li | 2023 | World Journal of Clinical Oncology2023，14，12： | 0 |
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