MRI特征评分模型预测增殖型肝细胞癌

目的 观察MRI特征评分模型预测增殖型肝细胞癌(HCC)的价值。方法 回顾性分析241例经病理证实HCC患者,包括90例增殖型HCC、151例非增殖型HCC;采用单因素及多因素logistic回归分析比较组间临床及基于2018版肝脏影像报告和数据系统评估的MRI表现,筛选增殖型HCC的独立预测因素,根据其权重赋分并构建评分模型。绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估模型预测效能;根据评分最佳截断值将患者分为高、低增殖风险亚组,比较组间及亚组间无复发生存(RFS)率和早期RFS率。结果 MRI显示肿瘤晕状强化、动脉期环形高强化、瘤内血管、大量病灶实质低强化及边缘不规则均为增殖型HCC的独立预测因素(OR=3.287、2.362、4.542、2.997、2.379,P均＜0.05),分别赋分7、5、9、7、5分,总分0~33分;以之建立的评分模型预测增殖型HCC的AUC为0.818。以9分为最佳截断值进行判断,高、低增殖风险分别为97例及144例。组间、亚组间RFS率及早期RFS率差异均有统计学意义(P均＜0.05)。结论 MRI特征评分模型可有效预测增殖型HCC。     

表皮生长因子受体酪氨酸激酶抑制剂治疗非小细胞肺癌的耐药机制

表皮生长因子受体酪氨酸激酶抑制剂（ EGFR-TKI）在非小细胞肺癌的治疗中具有重要地位,但有研究发现患者会对EGFR-TKI产生原发性耐药或获得性耐药。目前发现获得性耐药的多种机制最终都导致表皮生长因子受体的下游信号通路被重新激活。肝X受体激动剂对表皮生长因子受体最重要的下游通路PI3K-Akt-NF-κB的多个主要环节均有不同程度的抑制作用,有望逆转EGFR-TKI的继发耐药。     

运用saRNA激活p21基因表达上调对肺癌细胞生长及化疗敏感性的影响

目的:探讨利用针对细胞周期蛋白依赖性激酶抑制蛋白p21WAF1/CIP1(p21)的基因启动子的saRNA (dsp21-322) 特异激活p21基因的表达对肺癌细胞生长及耐药的影响.方法:化学合成针对p21启动子区的saRNA,将其转染非小细胞型肺癌细胞系A549,利用RT-PCR技术及Western blotting技术检测细胞中p21表达情况,进而观察p21表达改变后细胞凋亡情况及对顺铂药物敏感性的影响.结果:在转染dsp21-322的 A549肺癌细胞中,p21的mRNA和蛋白的表达均有所上调.p21表达的上调可引起A549细胞生长的的明显抑制并可增强其对顺铂的化疗敏感性.结论:p21基因在肺癌药物耐药性的过程中发挥了作用,为应用saRNA上调抑癌基因治疗肿瘤提供了新的思路.     

维持性血液透析患者中MIA综合征的临床分析

目的 探讨血液透析患者MIA综合征的发生率、临床表现及与透析的充分性之间的相关性.方法 对142例血透患者进行了营养指标、慢性炎症状况、心血管疾病的横断面调查.结果 142例维持性血透患者普遍存在着营养不良,其发生率为轻中度42.3%(60/142),重度7.0%(10/142),总发生率为49.3%(70/142).142例血CRP为0.33～44(5.55±10.22)mg/L,慢性炎症35例(24.6%)超过正常值(8mg/L).142例有心血管疾病表现的总发生率为52.1%(74/142).提示维持性血透患者存在营养不良、炎症、心血管疾病是较常见的.而兼有营养不良、炎症、心血管疾病即MIA综合征者为19.0%(27/142),但MIA综合征的发生与透析充分性无明显关系.结论 血液透析患者中存在MIA综合征,且营养不良、心血管疾病及炎症之间可能是相互关联的.     

白头翁与蛴螬不同配伍比例体外抗病毒作用研究

目的探究白头翁与蛴螬配伍体外抗病毒效果,筛选最佳抗病毒配伍比例。方法应用水提醇沉法分别得到白头翁与蛴螬水提醇沉液,用大孔树脂法吸附,得到水1部位,将白头翁与蛴螬按1:9、2:8、3:7、4:6、5:5、6:4、7:3、8:2、9:1分别配伍,做体外抗病毒实验。结果白头翁与蛴螬配伍后整体抗EV-71效果优于抗呼吸道合胞病毒效果;其中,当白头翁:蛴螬=8:2时效果最好,TI=68.594。结论当白头翁:蛴螬=8:2时效果最好,TI=68.594,筛选方法最佳。     

PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an alarming mortality rate. The development of novel therapeutic targets or drugs for AML is urgently needed. Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation. Recently, ferroptosis has emerged as a novel method for targeting cancer, including AML. Epigenetic dysregulation is a hallmark of AML, and a growing body of evidence suggests that ferroptosis is subject to epigenetic regulation. Here, we identified protein arginine methyltransferase 1 (PRMT1) as a ferroptosis regulator in AML. The type I PRMT inhibitor GSK3368715 promoted ferroptosis sensitivity in vitro and in vivo. Moreover, PRMT1-knockout cells exhibited significantly increased sensitivity to ferroptosis, suggesting that PRMT1 is the primary target of GSK3368715 in AML. Mechanistically, both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of AML cells following GSK3368715 treatment. Additionally, the GSK3368715 treatment reduced the abundance of H4R3me2a, the main histone methylation modification mediated by PRMT1, in both genome-wide and ACSL1 promoter regions. Overall, our results demonstrated a previously unknown role of the PRMT1/ACSL1 axis in ferroptosis and suggested the potential value and applications of the combination of PRMT1 inhibitor and ferroptosis inducers in AML treatment.     

An imbalance of netrin-1 and DCC during nigral degeneration in experimental models and patients with Parkinson's disease

Aims

Multiple guidance cues, such as netrin-1 (NTN-1)/deleted in colorectal carcinoma (DCC), control the guidance of axons and help establish functional neural circuits during development. However, the function of these guidance molecules during the neurodegenerative process is unclear.

Methods

To access the alterations of NTN-1 and DCC during the onset and progression of PD, we first established two subacute and one chronic PD model. Then, we investigated the relationship between the NTN-1/DCC pathway and cell death in SH-SY5Y cells. Finally, we conducted correlation studies between plasma NTN-1 and parkinsonian symptoms in patients to understand how this pathway contributes to PD.

Results

We found that the imbalance of NTN-1 and DCC was a common feature of nigral DA neuron injury in PD mouse models. We investigated that MPP+ inhibited NTN-1 expression and increased DCC expression in a concentration- and time-dependent manner. We further discovered a significant decrease in plasma NTN-1 levels and a positive correlation with UPDRS scores in PD patients.

Conclusion

Our findings confirmed the imbalance of NTN-1/DCC signaling during nigral degeneration in experimental PD models and found for the first time a correlation of plasma NTN-1 with PD symptoms in patients.     

电针联合推拿健患侧治疗缺血性中风后遗症29例临床观察

目的:电针联合推拿健患侧治疗缺血性中风后遗症29例临床观察。方法:依据患者来门诊先后顺序随机分为对照组和观察组(电针刺配按导推拿),每组29例。对照组针刺穴位并通电治疗,观察组采用针刺结合按导推拿法治疗3个疗程,患者在家里每天练习导引上肢、下肢运动,将两组的临床治疗效果进行比较。结果:经不同方法治疗后,观察组各项指标的改善程度优于对照组,神经功能缺损、Barthel指数、肌张力指标变化均优于对照组,治疗后两组疗效差异具有统计学意义(P<0.05)。结论:针刺配按导推拿健患侧治疗缺血性中风后遗症临床效果显著,具有广泛临床应用价值。     

Single-cell atlas of the immune microenvironment reveals macrophage reprogramming and the potential dual macrophage-targeted strategy in multiple myeloma

The tumour microenvironment (TME) plays a critical role in disease progression in multiple myeloma (MM). This study aimed to present an atlas of MM-TME in disease progression and explore TME-directed therapeutic strategies. We performed single-cell RNA sequencing (scRNAseq) in samples from different disease stages. We validated the findings by bulk RNAseq, flow cytometry (FCM) and in vitro and in vivo functional experiments. We delineated a compromised TME during disease progression, characterized by enrichment of exhausted NK cells and CD8⁺ T cells and reprogramming of macrophages (MPs). The reprogrammed tumour-associated MPs (TAMs) displayed a mixed phenotype showing both M1 and M2 features, with two TAM clusters exclusively present in the MM stage showing higher M2 scores. We validated the mixed M1/M2 phenotype in TAMs in a clinical cohort and verified phagocytic dysfunction in reprogrammed TAMs. Cellular interaction analysis identified two enriched ligand–receptor pairs between MPs and malignant plasma cells (PCs), including the SIRPA-CD47 pathway suppressing phagocytosis and the CD74–MIF (macrophage inhibitory factor) reshaping the phenotype of MPs. The expression of CD47 and MIF correlated with disease progression and adverse outcomes. We designed a dual-MP-targeted strategy by combining an anti-CD47 antibody and MIF inhibitor to activate phagocytosis and repolarize MP to a functional phenotype and proved its potent antitumour effect in vitro and in vivo. We drafted alterations in MM-TME during disease progression and unravelled TAM's reprogramming. The dual MP-targeted approach blocking both CD47 and MIF showed potent antitumour effects.     

龙虎交战法针刺风池穴的临床新用

龙虎交战法是针刺补泻的一种手法 ,在《金针赋》《针灸大成》等古医籍中均有记载。笔者通过十余年的临床 ,发现用此手法针刺风池穴治疗足跟痛、震颤麻痹、失眠等亦颇有效。兹举例说明如下。1　足跟痛孙某 ,男 ,46岁 ,教师。 1 993年 9月 1 0日诊。 3天前因站立行走过久 ,突感右足跟疼痛 ,行走不便 ,动辄痛甚。查右足跟压痛 ,X片检查未见异常。治疗时嘱其取坐位 ,以 2 8号 1 .5寸毫针刺右风池穴 ,针刺方向是穴位对侧眼眶口之内下角 ,深约 0 .5～ 1寸。待得气后 ,行龙虎交战手法 ,左右反复快速捻转 1 0～ 2 0次 ,留针 45分钟 ,其间每隔 1 0…