Searching for prognostic biomarkers for small renal masses in the urinary proteome

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early-stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label-free liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC-SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)-SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC-SRMs (ccRCC-SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC-SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC-SRMs. A two-protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70–0.93) in distinguishing progressive from nonprogressive ccRCC-SRMs. Patients (Stage I–IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10⁻⁶) compared to patients with no alterations. Our in-depth proteomic analysis identified novel biomarkers for early-stage RCC-SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.     

“从肠论治”脓毒症截断扭转防治策略的理论与实践

脓毒症是机体应对感染失控反应所致威胁生命的器官功能障碍,其病死率居高不下,全球大约每年大约有530万患者死亡,故深入探究脓毒症的发病机制和寻找有效的治疗药物是目前医学界的重要课题。中医药治疗脓毒症具有潜在优势,本团队在继承朱良春国医大师、国家非物质文化遗产“顾氏外科”奠基人顾伯华教授学术经验基础上,通过临床实践,首次提出"从肠论治”截断扭转防治脓毒症策略,为中医药治疗脓毒症提供了新的思路。     

扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌临床研究

目的:探讨扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌的效果及对患者免疫功能的影响。方法:选择80例胃癌患者,按随机数字表法分为观察组和对照组各40例。对照组行腹腔镜辅助小切口根治手术治疗,观察组予以扶正抑癌汤联合腹腔镜辅助小切口根治术手术治疗,比较2组患者临床疗效及免疫功能。结果:治疗前,2组中医症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组中医症状评分较治疗前下降(P<0.05),且观察组中医症状评分低于对照组(P<0.05)。治疗前,2组癌胚抗原(CEA)、糖类抗原199 (CA199)、糖类抗原125 (CA125)水平比较,差异无统计学意义(P>0.05)。治疗后,2组CEA、CA199、CA125水平较治疗前下降(P<0.05),且观察组CEA、CA199、CA125水平低于对照组(P<0.05)。治疗前,2组CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异无统计学意义(P>0.05)。治疗后,2组CD4^+、CD8^+、CD4^+/CD8^+水平较治疗前升高(P<0.05),且观察组CD4^+、CD8^+、CD4^+/CD8^+水平高于对照组(P<0.05)。结论:扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌效果显著,可有效降低相关肿瘤标志物水平,并改善患者免疫功能。     

Tadalafil for the treatment of benign prostatic hyperplasia

Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.

Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).

Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function.     

放疗联合安罗替尼对小细胞肺癌患者胱天蛋白酶3、多腺苷二磷酸核糖聚合酶表达的影响研究

目的探讨放疗联合安罗替尼对小细胞肺癌(SCLC)患者胱天蛋白酶3(caspase 3)、多腺苷二磷酸核糖聚合酶(PARP)表达的影响。方法将86例SCLC患者随机分为放疗组(n=42)和联合组(放疗联合安罗替尼,n=44),探索两组1年生存率、不良反应发生情况及对caspase 3、PARP表达的影响。结果治疗前两组患者血清caspase 3、PARP水平比较,差异均无统计学意义(P﹥0.05);治疗后联合组患者血清caspase 3水平明显高于放疗组,PARP水平明显低于放疗组,差异均有统计学意义(P﹤0.01)。两组患者白细胞减少、中性粒细胞减少发生率比较,差异均无统计学意义(P﹥0.05)。联合组患者1年生存率高于放疗组,差异有统计学意义(P﹤0.05)。结论放疗联合安罗替尼可以有效提高SCLC患者血清内caspase 3水平,降低PARP水平,延长患者的生存时间,值得临床进一步研究。     

Long-Term Results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access

PurposeTo report the 5-year results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula (pAVF) Creation for Hemodialysis Access.Materials and MethodsThe retrospective review of 107 intent-to-treat (ITT) patients from the pivotal trial provided a long-term follow-up population (LTP) of 85 patients with a median follow-up duration of 50 months (range, 12–60 months). Data evaluated in the LTP group were fistula maturation and usage, secondary procedures, and complications. The Kaplan-Meier analysis of primary patency, assisted primary patency, cumulative patency, and functional patency (time from 2-needle cannulation to abandonment) were performed for the ITT population.ResultsIn the LTP, 99% (84 of 85) of fistulae were mature, with 99% (78 of 79) of patients requiring hemodialysis using their pAVF. Sustained fistula use (2-needle cannulation at the prescribed rate, 2 of 3 sessions) was achieved in 92% (78 of 85) of patients, with 7 patients not using their pAVF because they were not on dialysis (n = 4), were on peritoneal dialysis (n = 2), and refused to use fistula (n = 1). Fistula maintenance was required in 31.8% (27 of 85) of patients and included fistula dysfunction (21.2%), thrombosis (5.9%), cannulation injury (12.9%), and arm swelling (4.7%). The number of procedures performed per patient per year to maintain function and patency was 0.32 (91 of 288) for years 2–5. The cumulative patency rates were 89.5%, 88.4%, 88.4%, 85.6%, and 82.0% for years 1, 2, 3, 4, and 5, respectively. The functional patency was 91.8% at the end of the study. There were no major complications related to pAVF during the long-term follow-up.ConclusionsPercutaneous fistulae have provided clinically effective and durable access for hemodialysis with low complications. The continued use and evaluation of pAVF are warranted.