同型半胱氨酸、维生素D、C、E、B12及叶酸与胃癌关系的研究进展北大核心

胃癌作为临床最常见的肿瘤之一,常因确诊疾病较晚而影响治疗效果,胃镜活检后的病理虽然作为确诊的金标准,但是由于此方式过程痛苦,操作复杂,费用较高,且具有侵入性,可能会导致患者拒绝操作而难普及于临床,因此积极找寻胃癌有效的监测指标十分必要。近年来,很多学者研究维生素与胃癌的相关关系,并试图通过摄取某些维生素降低胃癌发生率,延缓病情及改善预后,也有通过检测血清中维生素的水平给早期胃癌的诊断提供帮助。本文就同型半胱氨酸、维生素D、维生素C、维生素E、维生素B12及叶酸在胃癌中的作用机制,及其在血清中水平与胃癌关系的相关研究进展进行简要综述,为临床胃癌诊疗提供新思路。     

Lymph node micrometastasis of poorly differentiated node-negative gastric cancer risks a worse-than-expected survival outcome under standard management algorithm

BackgroundInvestigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types.Patients and methodsA surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN.ResultsCancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78.ConclusionDefective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.     

Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly. The development of foot ulcer in a diabetic patient has been estimated to be 19%-34% through their lifetime. The pathophysiology of diabetic foot ulcer consist of neuropathy, trauma and, in many patients, additional peripheral arterial disease. In particular, diabetic neuropathy leads to foot deformity, callus formation, and insensitivity to trauma or pressure. The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification, surgical debridement, dressing to facilitate wound healing, off-loading, vascular assessment (status and presence of a chance for interventional vascular correction), and infection and glycemic control. Although especially surgical procedures are sometimes inevitable, they are poor predictive factors for the prognosis of diabetic foot ulcer. Different novel treatment modalities such as nonsurgical debridement agents, oxygen therapies, and negative pressure wound therapy, topical drugs, cellular bioproducts, human growth factors, energy-based therapies, and systematic therapies have been available for patients with diabetic foot ulcer. However, it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials. This review aims at evaluating diabetic foot ulcer with regard to all aspects. We will also focus on conventional and novel adjunctive therapy in diabetic foot management.     

基于iTRAQ技术探讨人胃癌细胞乙酰肝素酶调控的信号通路北大核心

目的:探讨人胃癌细胞中乙酰肝素酶(HPSE)调控的差异蛋白和信号通路,为以HPSE为靶点防治胃癌提供依据。方法:利用siRNA干扰技术,在乙酰肝素酶(HPSE)基因高表达的SGC7901细胞中转入干扰HPSE的慢病毒载体(LV-HPSE-RNAi),通过嘌呤霉素筛选出稳定株,利用qPCR和Western blot分别检测HPSE mRNA和蛋白表达;利用细胞划痕实验和Transwell侵袭实验测定细胞的迁移和侵袭能力;利用同位素标记的相对和绝对定量(iTRAQ)联合二维液相色谱串联质谱(2DLC-MS/MS)技术筛查差异蛋白,并进行生物信息学分析,对差异蛋白PKCa应用Western blot进一步验证。结果:人胃癌SGC7901细胞和沉默HPSE表达的ZSGC7901细胞对比检测出98个差异蛋白,并且富集在157条信号通路上。与肿瘤发生发展关系密切的有6条:细胞外基质和受体相互作用、局灶性黏附、PI3K-Akt信号通路、癌途径、癌中microRNAs、Wnt信号通路。且上调的FAK、ITGA、PKCa等蛋白和下调的PKA、CDK6等蛋白在通路中处于重要的位置。Western blot结果证明PKCa在沉默HPSE的ZSGC7901细胞中表现为上调,差异具有统计学意义(P<0.05),与蛋白质组学筛选结果一致。结论:HPSE在人胃癌细胞中调控的蛋白,参与细胞重要生物学过程、参与重要分子功能及重要信号途径,有望可以成为防治胃癌的新靶点。     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Incidence and risk factors for Chyle leak after pancreatic surgery for cancer: A comprehensive systematic review

BackgroundChyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy.MethodsA systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality.ResultsLiterature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases.ConclusionsThe extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.     

基于肿瘤浸润深度及大小的TTS 评分系统对可切除胃癌患者预后判断的价值

目的:探讨基于肿瘤浸润深度及大小的TTS评分系统对可切除胃癌患者预后判断的价值。方法:选择行根治性切除的234例胃癌患者为研究对象。根据肿瘤浸润深度（T分期）和肿瘤大小构建TTS评分系统，分为TTS 0级、1级、2级，代表肿瘤侵袭性逐渐升高。通过Cox多因素模型分析TTS评分系统作为预后判断工具的可行性。结果:T1-T4期患者肿瘤的平均大小分别为(3.3±2.7)cm、(4.1±3.1)cm、(6.6±3.1)cm、(9.4±4.9)cm。单因素分析显示，肿瘤浸润深度与肿瘤大小、淋巴结转移、TNM分期、淋巴浸润和血管浸润显著相关(P＜0.01)。ROC曲线显示，45 mm为肿瘤大小的最佳界值，可有效区分患者是否存在淋巴结转移，曲线下面积(area under curve,AUC)为0.762。综合肿瘤大小的临界值和肿瘤浸润深度，构建TTS评分系统,TTS 0级、TTS 1级和TTS 2级的患者5年生存率分别为95.6%、83.3%和70.2%，两两比较后发现，不同TTS状态患者的生存率之间均存在显著差异(P＜0.01)。Cox多因素分析发现，TTS评分是影响患者预后的独立性危险因素（P＜0.05）。结论:本研究根据肿瘤浸润深度和大小构建了TTS评分系统，并证明了TTS评分与胃癌患者的预后密切相关。     

Comparison of the effectiveness of i-scan and conventional endoscopy in the detection of the endoscopic signs of atrophic gastritis: A clinical trial

Background and study aimsThis study aimed to determine whether the use of i-scan endoscopy provides additional benefits to conventional endoscopy in the diagnosis of gastric precancerous lesions.Patients and methodsA total of 120 patients with histologically-verified intestinal metaplasia (IM) or atrophic gastritis (AG) were prospectively evaluated by esophagogastroduodenoscopy. Endoscopic examinations were performed using i-scan and high-definition white-light endoscopy (HD-WLE). The diagnostic yields of both techniques and the number of targeted biopsies per patient were compared.ResultsA total of 318 suspicious lesions were detected in 108 patients with i-scan (n = 186) and 81 patients with HD-WLE (n = 132). The diagnostic yields of i-scan and HD-WLE were 81.6% (98/120) versus 77.5% (93/120), respectively (p > 0.05). When only targeted biopsies were taken into account, the diagnostic yields of i-scan and HD-WLE were 89.8% versus 65.4%, respectively (p < 0.05). The mean number of biopsies per patient for i-scan and HD-WLE were 3.27 (393/120) and 7.3 (882/120), respectively (p < 0.05). The mean endoscopic procedure times were 16 and 17 min for i-scan and HD-WLE, respectively (p > 0.05).ConclusionsAlthough targeted biopsies with i-scan were not found to be significantly superior to either targeted or random biopsies with HD-WLE, the number of biopsies required to confirm these lesions was much lower.