China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review

BackgroundLocally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates.MethodsA systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded.ResultsOf the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%.ConclusionA validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.     

基于网络药理学研究黄连解毒汤抗幽门螺杆菌感染作用机制

目的运用网络药理学方法预测黄连解毒汤抗Hp感染的主要有效成分、靶点及信号通路,挖掘其潜在作用机制,为后续实验研究提供依据。方法应用TCMSP筛选黄连解毒汤中黄连、黄芩、黄柏、栀子4味中药的主要有效成分及其潜在作用靶点。通过GeneCards数据库和人类孟德尔遗传数据库(OMIM)筛选Hp感染相关靶点,并取药物和疾病的交集靶点。将交集靶点导入Cytoscape 3.7.2构建有效成分和Hp感染相关靶点网络,并进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用(PPI)网络并进行分析。运用R语言在线检索Bioconductor平台对靶点进行GO功能富集;通过DAVID数据库对靶点进行KEGG通路富集分析。结果黄连解毒汤中共筛选出85个有效成分,主要包括槲皮素、小檗碱、山柰酚、汉黄芩素、黄芩素等。对应靶点112个,疾病相关靶点1960个,药物疾病共同靶点71个。网络中度值最高的有效成分为槲皮素,度值最高的靶点为环加氧酶1(PTGS1)。PPI网络中69个节点中度值较高的靶蛋白包括半胱氨酸蛋白酶3(CASP3)、IL6、MAPK8、原癌基因(MYC)、VEGFA、表皮生长因子受体(EGFR)等。GO功能富集分析共获得89个条目,KEGG通路富集分析共筛选12条存在显著差异的信号通路,其中发挥主要作用的有癌症通路、ErbB信号通路、p53信号通路、凋亡、黏附斑等。结论黄连解毒汤可通过多成分、多靶点、多通路发挥对Hp的治疗作用,可通过抗肿瘤机制调控胃癌进程,本研究可为其有效成分研究和抗Hp机制研究提供依据。     

加拿大问题赌博指数中文版的效度和信度

目的:评估加拿大问题赌博指数中文版(CPGI-C)的效度和信度。方法:选取43例匿名戒赌会成员和202例正常成人为研究对象,将其随机分为两半,分别进行探索性因子分析和验证性因子分析;以赌博相关认知量表(GRCS-C)、Barratt冲动性人格问卷(BIS-11)、抑郁自评量表(SDS)、网络成瘾量表修订版(CIAS-R)和DSM-IV多重反应问卷(DSM-IV-MR)作为效标工具;以受试者工作特征曲线(ROC)评估量表区分问题赌博者的特异度与灵敏度。2周后有5例匿名戒赌会成员和31例正常成人完成重测。结果:CPGI-C的问题赌博指数(PGSI)分量表共9个条目,探索性因子分析得出1个主成分因子,可解释总方差的74.3%;验证性因子分析显示,单因子结构模型的拟合指标良好(χ~2=2.087,CFI=0.926,TLI=0.963,GFI=0.926,IFI=0.978,NFI=0.958, RMSEA=0.094,SRMR=0.032);CPGI总分与各效标量表的总分均呈正相关(r=0.48～0.82,均P<0.001);ROC曲线下面积为0.962,划界分为9.5。CPGI-C的...     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

左、右半结肠癌骨转移病理特征及预后分析

目的:比较左半结肠癌（LSCC）和右半结肠癌（RSCC）骨转移的病理特征和临床预后差异。方法:对漯河市中心医院2007年1月至2015年12月收治的103例结肠癌骨转移病例资料进行回顾性分析，据解剖位置将64例纳入LSCC组，39例纳入RSCC组，对比分析其病理学特征,绘制并分析生存曲线,筛选预后因素。结果:RSCC骨转移相对LSCC表现为:CA199 阳性率高、年龄大、分化程度更差、分期更晚、预后更差。单因素分析结果示原发肿瘤位置、TNM分期、LDH水平、ALP水平是影响结肠癌骨转移3年生存的相关因素。Logistic多因素回归分析显示原发肿瘤位置、TNM分期、ALP水平是结肠癌骨转移的独立危险因素。结论:左、右半结肠癌在病理特点、临床表现、生物学行为、生存预后等方面存在差异，本文为区分左、右半结肠癌骨转移的不同病理特征及预后评价提供了依据。     

内镜活检胃癌组织中MUC3A,MUC13表达及与病理参数和预后的关系

目的:探讨内镜活检胃癌组织中黏蛋白3A(MUC3A)、黏蛋白13(MUC13)表达及与病理参数和预后的关系。方法:选取2013年1月至2014年12月南阳市中心医院肿瘤科收治的接受内镜活检的116例患者胃癌组织和癌旁正常组织进行分析,采用免疫组织化学法检测所有组织样本中MUC3A,MUC13表达,观察二者表达情况,并分析二者与临床病理参数及预后的关系。结果:胃癌患者组织MUC3A,MUC13阳性率分别为68.97%和66.38%,高于正常组织的32.76%和7.76%(P<0.05);胃癌组织中MUC3A,MUC13表达与年龄、性别、肿瘤大小无关(P>0.05),与组织分化、浸润深度、TNM分期、淋巴结转移有关(P<0.05);随访5年结果显示:胃癌组织中MUC3A阳性患者中位生存时间为(40.50±1.95)个月,低于阴性患者的(48.67±2.51)个月(P<0.05),MUC3A阳性患者预后5年生存率为32.50%,低于阴性患者的55.56%(P<0.05);MUC13阳性患者中位生存时间为(38.52±1.92)个月,低于阴性患者的(49.06±2.71)个月(P<0.05),MUC13阳性患者预后5年生存率为30.00%,低于阴性患者的61.11%(P<0.05);COX多因素回归分析显示:TNM分期,淋巴结转移,MUC3A,MUC13是影响胃癌预后的独立危险因素(P<0.05)。结论:MUC3A,MUC13在胃癌组织中呈高表达,且与临床病理参数及预后密切相关,二者均有望作为判定胃癌发生发展及预后评估的参考指标。     

光滑念珠菌生物膜形成机制及其抗性研究

光滑念珠菌是亚洲第三或第四种最常见的侵袭性念珠菌病的病原体，占念珠菌血流感染的29%，其形成生物膜的能力被认为是最重要的毒力因子之一。光滑念珠菌生物膜的形成与医院感染的发病率和病死率高度相关。但是，对光滑念珠菌生物膜的研究少且分散。为此，本文将从环境因素、基因调控、抗性和抗性机制等多方面对光滑念珠菌生物膜进行综述。     

Periodontal diseases and adverse pregnancy outcomes: Mechanisms

Adverse pregnancy outcomes (APOs) have been defined as (a) pre-term birth, when there is a delivery before 37 completed weeks (<259 days); (b) pre-eclampsia, which is a multisystem disorder of pregnancy characterized by maternal hypertension and proteinuria after the 20th gestational week; (c) low and very low birthweight, depending on whether the weight of the baby is less of 2500 g or <1500 g and (d) the spontaneous death of the fetus with <20 weeks (miscarriage) or between 20 and 36 weeks (stillbirth). In 2012, during the Consensus Report from the Joint EFP/AAP workshop on periodontitis and systematic diseases the role of periodontal diseases on APOs was reviewed. Some years later, this evidence has grown, and an update on the literature regarding the mechanisms related to this potential association (APOs and periodontal diseases) needs to be presented. The two major pathways (direct and indirect) already accepted in 2012 are still valid nowadays. Most evidence published in the last 5 years deals with a strong and solid evidence coming from the direct pathway while there is as scarce new evidence regarding indirect pathway. In this direct pathway, the haematological dissemination of oral microorganisms and their products, would later induce an inflammatory/Immune response in the foetal-placental unit. The most plausible route for this direct pathway is the hematogenous transmission through dental bacteremia, although not many new studies dealing with bacteremia has been performed lately.