前列腺癌早期诊断的研究进展北大核心

前列腺癌(prostate cancer, PCa)是中老年男性常见恶性肿瘤之一,目前尚缺乏有效的晚期癌症治疗方法,因此早期诊断对于降低PCa死亡率至关重要。近年来,较多研究开发出多种新型诊断方法以改善对PCa诊断的准确性,同时避免过度诊疗,但其有效性及实用性尚需进一步验证。本文对目前新型生物标志物、联合成像技术及风险预测模型等的早期诊断技术进行总结,以期为临床研究提供指导作用。     

免疫编辑诱导的免疫治疗耐药

近年来，免疫治疗在多种恶性肿瘤治疗中取得突破性进展，为肿瘤患者带来明显生存获益。然而，免疫系统在识别和杀伤肿瘤细胞的同时，出现免疫编辑诱导，导致大多数患者对免疫治疗具有先天或后天的耐药性。肿瘤免疫编辑是免疫系统抑制或促进肿瘤发生发展的过程，肿瘤的发生发展经历了免疫消除、免疫平衡和免疫逃逸三个阶段。在整个过程中，肿瘤的免疫原性被编辑，并获得使疾病进展的各种免疫抑制机制，致使肿瘤细胞逃避免疫系统的监测，导致肿瘤细胞免疫逃逸产生耐药。因此，揭示肿瘤免疫治疗耐药机制及克服耐药至关重要。本文主要从肿瘤免疫编辑过程背后的机制对肿瘤免疫治疗耐药作一具体阐述，为临床中克服免疫耐药取得更好疗效提供参考。     

miR-149与肿瘤关系的研究进展

miRNAs是一类长度约为20~25个核苷酸，参与基因调控表达的内源性非编码RNA。miR-149作为miRNAs的重要成员，在多种肿瘤中表达异常，其表达水平与肿瘤细胞增殖、转移、凋亡、耐药、患者的早期诊断及预后密切相关。因此，miR-149有望成为新一类抗肿瘤治疗的靶点。     

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system

PurposeOver the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma.Material and methodsVarious patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis.ResultsA total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A = 15 patients, score 0–3); (B = 50 patients, score 4–7); (C = 33 patients, score 8–10); and (D = 13 patients, score 11–16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001).ConclusionThere exists a lack of universally acceptable ‘standard-of-care’ salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.     

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

GLP-1类似物在糖尿病肾病患者中的疗效分析

目的观察胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)类似物对2型糖尿病早期肾病患者的肾脏保护作用。方法2017年11月—2019年12月间选取使用GLP-1类似物并参与随访的2型糖尿病早期肾病患者30例,收集患者治疗6个月前后的体重,体质指数(body mass index,BMI),腰围,臀围,血糖,生化指标等,计算胰岛β细胞功能相关指标,进行对比分析。结果治疗后腰围、2 hPG、HbA1c、HOMA-IR、TC、TG、ALB、MA/Cr、UA较治疗前降低,HOMA-β较治疗前升高,差异有统计学意义(P<0.05)。Pearson相关性分析示:HbA1c与MA/Cr呈负相关性(r=-0.421,P<0.05);HOMA-β、TG、TC、UA与MA/Cr呈正相关性(r=0.777,P<0.05;r=0.757,P<0.05;r=0.470,P<0.05;r=0.443,P<0.05)。HbA1c与ALB呈负相关性(r=-0.433,P<0.05);HOMA-β、TG、TC、UA与ALB呈正相关性(r=0.723,P<0.05;r=0.756,P<0.05;r=0.493,P<0.05;r=0.374,P<0.05)。结论GLP-1类似物对2型糖尿病早期肾病患者有较好的降糖、调脂、改善胰岛功能、保护肾脏的作用,而且降血糖、降血脂、改善胰岛功能可能有益于肾脏保护。     

Metabolic syndrome-related sarcopenia is associated with worse prognosis in patients with gastric cancer: A prospective study

ObjectivesSarcopenia and metabolic syndrome (MetS) are associated with the prognosis from malignant tumors. However, evidence of the relationship between sarcopenia and MetS among gastric cancer (GC) patients following radical gastrectomy is lacking. This study assessed the association between preoperative sarcopenia and MetS among GC patients and analyzed the prognosis of patients with different malnutrition statuses.MethodsWe prospectively assessed the preoperative statuses of sarcopenia and MetS among patients who underwent radical gastrectomy from July 2014 to December 2017. We combined sarcopenia and MetS to generate four groups: MetS-related sarcopenia group (MSS), sarcopenia group (S), MetS group (MS), and normal group (N).ResultsA total of 749 patients with resectable GC were included in this study. Preoperative MetS was associated with sarcopenia (p < 0.001). Multivariate logistic regression presented that MetS-related sarcopenia (OR = 2.445; p = 0.010) and sarcopenia alone (OR = 2.117; p = 0.001) were independent predictors of grade Ⅱ and above complications, while MetS alone was not (p = 0.342). Cox regression analysis revealed that MetS-related sarcopenia led to the worst prognosis in the four groups (MSS vs MS: HR = 3.555, p < 0.001; MSS vs N: HR = 2.020, p = 0.003; MSS vs S: HR = 1.763, p = 0.021). However, the MetS group had better prognosis than the normal group (MS vs N: HR = 0.568, p = 0.048).ConclusionPreoperative MetS was associated with sarcopenia among GC patients. MetS-related sarcopenia resulted in a significantly worse prognosis. The long-term prognoses of patients with sarcopenia were impaired by preoperative MetS, while patients without sarcopenia benefited. Thus, patients with both sarcopenia and MetS require more medical interventions.     

腹腔镜胆总管探查术中T管、双J管引流与单纯一期缝合的应用比较

背景与目的 腹腔镜胆总管探查术（LCBDE）以“创伤小、恢复快”的临床优势成为临床治疗胆总管结石的主要手段，甚至是一线推荐方案。但LCBDE后是否需引流胆汁及不同胆汁引流方式的选择仍存在诸多争议，如传统的LCBDE+胆道外引流管（T管）引流适应证的探讨、单纯一期缝合（PDC）是否导致高术后并发症发生率、胆道内引流是否优于外引流等。针对以上问题，本文采取回顾性研究，比较T管、胆道内引流管（双J管）与PDC在LCBDE中的临床应用，并就其相应适应证进行探讨。方法 回顾性收集2015年3月—2018年5月昆明医科大学第二附属医院363例行LCBDE患者的临床资料，根据治疗方式不同分为T管组（128例）、双J管组（115例）和PDC组（120例）。比较三组术前一般资料（性别、肝功能、胆总管直径、结石直径）；围手术期相关资料（手术时间、住院时间、住院费用）及术后并发症（胆源性胰腺炎、胆汁漏、胆管狭窄、引流管脱落、残余结石）发生率等。结果 三组患者术前一般资料差异无统计学意义（均P>0.05）。PDC组平均手术时间（75.5 min）明显短于T管组（98.5 min）与双J管组（90.5 min），PDC组与双J管组的平均住院时间（4.8 d与5.4 d）均少于T管组（7.8 d），PDC组与双J管组平均住院费用（18 489 元与20 157元）均低于T管组（24 034 元），差异均有统计学意义（均P<0.05）。三组术后总并发症发生率差异无统计学意义（P=0.521）；PDC组胆汁漏发生率（3.3%）高于另两组（均P<0.05），且患者均为多发胆管结石（>1枚），其中3例结石嵌顿于Oddi括约肌，2例胆管直径<10 mm；双J管组术后胆源性胰腺炎发生率（4.3%）明显高于另两组（均P<0.05），其中2例患者由于结石嵌顿致十二指肠乳头水肿，2例十二指肠乳头旁憩室，1例乳头炎性狭窄。结论 虽然PDC在住院时间及住院花费方面有优势，但术后并发症发生率较高，T管引流与双J管引流也有各自优势与适应证。是否需要引流及引流方式的选择，应根据患者经济情况，结合术前检查，术中腹腔镜及胆道镜对胆道情况的评估进行综合判断，“个体化”选择，以期尽量减少术后并发症，提高患者满意度。