TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

Correlation between cow’s milk protein allergy and otitis media: a systematic review

ObjectivesTo review the evidence pertaining to the association between cow’s milk protein allergy and recurrent acute otitis media and otitis media with effusion.MethodsThe CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched.ResultsFour studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow’s milk protein allergy, 10.7% of cow’s milk protein allergy in 242 children who underwent ENT procedures, 40% of cow’s milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow’s milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p < 0.1).ConclusionConsidering the characteristics and methodological variations of the identified studies, it is not possible to state that there is reliable evidence of an association between cow’s milk protein allergy and otitis media.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction

PurposeTo compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS.Materials and MethodsThis study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures.ResultsTechnical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%–63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73–21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46–13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92–111.81).ConclusionsThe technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.     

Clinicopathological Profile of Myelomatous Pleural Effusion: Single-center Real-world Experience and Review of Literature

Background

Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.

CML Case Studies: Impact of Comorbidities

Clinicians have the choice of five approved tyrosine kinase inhibitors (TKI) to select from for chronic phase CML patients. The best frontline drug for each patient and decisions about if and when to change to another TKI or to stop therapy need to be considered in the context of the comorbidities present. These issues are explored in three illustrative cases. The predominant toxicity issue for all of the TKIs except imatinib is vascular occlusive events, so a systematic approach to assessing

Discussion

The excellent long-term outcomes achieved in most CML patients has led to a revision of the goals of therapy.¹³ While preventing progression to blast crisis remains an important goal, avoiding organ toxicity may be equally important, since deaths from causes other than CML are much more common than CML-related deaths. Patients most at risk of organ toxicity are those patients with comorbidities, particularly those patients with comorbidities that increase their risk of vascular events.

References

• 1.Saußele S, Krauß MP, Hehlmann R, Lauseker M, Proetel U et al, Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV. Blood. 2015;126:42-49.
• 2.Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim D-W et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016; 30:1044–1054.
• 3.Castagnetti F, Gugliotta G, Breccia M,

     

主观疗效评价在恶性肿瘤中医药研究中的应用现状及进展

循证医学模式的引入使得恶性肿瘤中医治疗的有效性有了新的阐述途径,同时也对中医疗效评价体系提出了更高的要求。基于患者的自身感受,医师望闻问切四诊等得到的主观信息是主观疗效评价的重要组成方面,一直以来都是中医疗效评价的重要手段,其由单一的症状是否好转的评价发展至多重症状是否改善、整体生活质量是否提高等的评价方式,主观疗效评价的方式越来越丰富,也越来越规范,文章就目前主观疗效评价在中医药领域的研究现状及进展展开综述。