4例口服复方避孕药致假性库欣综合征病例分析

目的：研究我院收治的4例口服复方避孕药（oral contraceptive pills,OCPs）后致假性库欣综合征病例的临床特征以及复习OCPs影响皮质醇测定的相关文献。方法：回顾性分析4例因月经稀发服用OCPs的育龄期女性患者的临床特点。应用等倍稀释的方法测定OCPs与血总皮质醇之间的交叉反应,并复习相关文献。结果：4例患者在服用OCPs期间均发现血总皮质醇的升高。3例患者均在停用OCPs之后血总皮质醇降至正常。予等倍稀释的方法,在OCPs溶液中测定血总皮质醇,交叉反应小。文献中报道OCPs可能从以下两方面导致假性库欣综合征：OCPs中的雌激素增加皮质醇结合球蛋白的合成而引起血总皮质醇的升高;OCPs可能通过直接刺激下丘脑-垂体-肾上腺轴使血总皮质醇生成增多。结论：OCPs可通过多种机制导致假性库欣综合征,临床上需结合患者的临床表现、体格检查以及其他的实验室结果与库欣综合征进行鉴别,以免误诊、误治。     

溶血尿毒综合征患儿MCP基因突变分析

目的对溶血尿毒综合征（HUS）患儿进行膜辅助蛋白（MCP）基因突变分析。方法对9例HUS患儿提取外周血MCP基因组DNA,应用聚合酶链反应（PCR）扩增MCP基因全部14个外显子及其周围的部分内含子,进行DNA序列测定及基因突变检测。50例尿检正常的南方汉族成年人为对照人群。结果9例HUS患儿未发现MCP基因突变,但2例检测到1个MCP变异（IVS9-78G〉A）,1例为纯合子,另1例为杂合子,50例对照人群基因测序发现同样MCP变异,表明其为MCP基因多态性,但在9例HUS患儿中的等位基因频率与50例对照人群等位基因频率比较,差异有统计学意义（P〈0.05）。结论MCP基因多态性（IVS9-78G〉A）可能是本研究9例HUS患儿发病的易感因素。     

Cotargeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma

Bruton’s tyrosine kinase (BTK) is a proven target in mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma. However, resistance to BTK inhibitors is a major clinical challenge. We here report that MALT1 is one of the top overexpressed genes in ibrutinib-resistant MCL cells, while expression of CARD11, which is upstream of MALT1, is decreased. MALT1 genetic knockout or inhibition produced dramatic defects in MCL cell growth regardless of ibrutinib sensitivity. Conversely, CARD11-knockout cells showed antitumor effects only in ibrutinib-sensitive cells, suggesting that MALT1 overexpression could drive ibrutinib resistance via bypassing BTK/CARD11 signaling. Additionally, BTK knockdown and MALT1 knockout markedly impaired MCL tumor migration and dissemination, and MALT1 pharmacological inhibition decreased MCL cell viability, adhesion, and migration by suppressing NF-κB, PI3K/AKT/mTOR, and integrin signaling. Importantly, cotargeting MALT1 with safimaltib and BTK with pirtobrutinib induced potent anti-MCL activity in ibrutinib-resistant MCL cell lines and patient-derived xenografts. Therefore, we conclude that MALT1 overexpression associates with resistance to BTK inhibitors in MCL, targeting abnormal MALT1 activity could be a promising therapeutic strategy to overcome BTK inhibitor resistance, and cotargeting of MALT1 and BTK should improve MCL treatment efficacy and durability as well as patient outcomes.     

Using nomogram,decision tree,and deep learning models to predict lymph node metastasis in patients with early gastric cancer: a multi-cohort study

The accurate assessment of lymph node metastasis (LNM) in patients with early gastric cancer is critical to the selection of the most appropriate surgical treatment. This study aims to develop an optimal LNM prediction model using different methods, including nomogram, Decision Tree, Naive Bayes, and deep learning methods. In this study, we included two independent datasets: the gastrectomy set (n=3158) and the endoscopic submucosal dissection (ESD) set (n=323). The nomogram, Decision Tree, Naive Bayes, and fully convolutional neural networks (FCNN) models were established based on logistic regression analysis of the development set. The predictive power of the LNM prediction models was revealed by time-dependent receiver operating characteristic (ROC) curves and calibration plots. We then used the ESD set as an external cohort to evaluate the models’ performance. In the gastrectomy set, multivariate analysis showed that gender (P=0.008), year when diagnosed (2006-2010 year, P=0.265; 2011-2015 year, P=0.001; and 2016-2020 year, P<0.001, respectively), tumor size (2-4 cm, P=0.001; and ≥4 cm, P<0.001, respectively), tumor grade (poorly-moderately, P=0.016; moderately, P<0.001; well-moderately, P<0.001; and well, P<0.001, respectively), vascular invasion (P<0.001), and pT stage (P<0.001) were independent risk factors for LNM in early gastric cancer. The area under the curve (AUC) for the validation set using the nomogram, Decision Tree, Naive Bayes, and FCNN models were 0.78, 0.76, 0.77, and 0.79, respectively. In conclusion, our multi-cohort study systematically investigated different LNM prediction methods for patients with early gastric cancer. These models were validated and shown to be reliable with AUC>0.76 for all. Specifically, the FCNN model showed the most accurate prediction of LNM risks in early gastric cancer patients with AUC=0.79. Based on the FCNN model, patients with LNM rates of >4.77% are strong candidates for gastrectomy rather than ESD surgery.     

UBE2C promotes the progression of pancreatic cancer and glycolytic activity via EGFR stabilization-mediated PI3K-Akt pathway activation

BackgroundPancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established.MethodsUBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose.ResultsUBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP.ConclusionsIn conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway.     

MRI、经直肠超声评估直肠癌术前T分期的准确性研究

目的对比MRI、经直肠超声评估直肠癌术前T分期的准确性。方法收集本院2018年1月至2019年1月诊治的63例直肠癌患者的影像学资料,患者均行MRI及经直肠超声检查,以病理学检查结果为"金标准",计算不同检查对直肠癌术前T分期的诊断符合率。结果以病理结果为参照,MRI检查对63例直肠癌患者术前T分期诊断总符合率为92.06%(58/63),与病理学结果相比,两者无统计学意义(P>0.05),其中T1、T2、T3、T4分期诊断符合率依次为92.30%(12/13)、96.55%(28/29)、85.71%(12/14)、85.71%(6/7)。经直肠超声检查对63例直肠癌患者术前T分期诊断总符合率为84.12%(53/63),与MRI结果相比,经直肠超声检查对直肠癌术前T分期诊断总符合率较低(P<0.05),T1、T2、T3、T4分期诊断符合率依次为76.92%(10/13)、93.10%(27/29)、78.57%(11/14)、71.42%(5/7)。结论 MRI、经直肠超声均可有效显示直肠癌图像特征,MRI多序列扫描检查评估直肠癌术前T分期准确性优于经直肠超声。     

克深2 特低渗气藏压裂返排液处理与回用技术

致密气藏采用大排量、大液量加砂压裂改造后返排液的处理一直是业界备受关注的热点问题, 涉及气藏开 发成本与环境保护2 个方面。针对克深2 气田压裂返排液回用技术在现场的应用进行了探讨, 在阐明加重返排液在现场 施工的回用技术、中心站处理工艺及施工流程的基础上, 进行了返排液实验评价, 表明用返排液配制的滑溜水与用清水 配制的滑溜水相比不仅在黏度上二者没有明显差异, 而且能有效降低管路摩阻, 在高排量施工下降阻性能更好, 现场获 得了良好的储层改造效果。该项技术节约了配液用水, 减少了废弃物排放, 实现了节能减排, 是压裂返排液深度环保处 理极其重要的组成部分。