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.     

Positive correlation between miR-570 and prognosis of colon cancer: inhibition of cell proliferation and invasion

Clinical and Experimental Medicine - Colon cancer is one of most common cancers. The progression of various cancers is driven by miRNA-570. The role of miRNA-570 in the progression of colon cancer...     

Dectin-2受体介导宿主抵抗烟曲霉菌感染的研究

目的探讨C型凝集素受体Dectin-2在烟曲霉菌感染中的作用及机制。方法用紫外线灭活的烟曲霉菌膨胀态分生孢子刺激野生型(wild type, WT)和Dectin-2缺失(Clec4n-/-)小鼠骨髓来源的巨噬细胞(bone marrow derived macrophages, BMDMs)。刺激20min及40min后，利用Western印迹法检测BMDMs中脾酪氨酸激酶(spleen tyrosine kinase, Syk)和核转录因子κB抑制因子(inhibitor-κB, IκBα)的磷酸化水平。刺激16h后，利用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测BMDMs细胞上清液中IL-6、TNF-α和IL-12p40的水平。另一方面，利用压舌感染的方法在WT和Clec4n-/-小鼠中构建烟曲霉菌肺部感染模型。感染2d后，统计小鼠整个肺脏荷菌量，并检测肺脏匀浆液中IL-6和IL-12p40水平。结果体外试验提示，烟曲霉菌刺激后，Dectin-2缺失的BMDMs中Syk和IκBα的磷酸化水平及IL-6、TNF-α和IL-12p40水平显著下降(P＜0.05)。体内试验发现，烟曲霉菌感染后，Dectin-2缺失小鼠中肺脏荷菌量显著升高(P＜0.05)，肺脏匀浆液内IL-6、IL-12p40水平显著降低(P＜0.05)。结论C型凝集素受体Dectin-2激活烟曲霉菌诱导的NF-κB信号通路并介导促炎细胞因子的产生，可在小鼠肺烟曲霉菌病动物模型中发挥保护性作用。     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.     

A Priori Subcell Limiting Approach for the FR/CPR Method on Unstructured Meshes

A priori subcell limiting approach is developed for high-order flux reconstruction/correction procedure via reconstruction (FR/CPR) methods on two-dimensional unstructured quadrilateral meshes. Firstly, a modified indicator based on modal energy coefficients is proposed to detect troubled cells, where discontinuities exist. Then, troubled cells are decomposed into nonuniform subcells and each subcell has one solution point. A second-order finite difference shock-capturing scheme based on nonuniform nonlinear weighted (NNW) interpolation is constructed to perform the calculation on troubled cells while smooth cells are calculated by the CPR method. Numerical investigations show that the proposed subcell limiting strategy on unstructured quadrilateral meshes is robust in shock-capturing.     

Radiomics model based on preoperative gadoxetic acid-enhanced MRI for predicting liver failure

BACKGROUND Postoperative liver failure is the most severe complication in cirrhotic patients with hepatocellular carcinoma(HCC) after major hepatectomy. Current available clinical indexes predicting postoperative residual liver function are not sufficiently accurate.AIM To determine a radiomics model based on preoperative gadoxetic acid-enhanced magnetic resonance imaging for predicting liver failure in cirrhotic patients with HCC after major hepatectomy.METHODS For this retrospective study, a radiomics-based model was developed based on preoperative hepatobiliary phase gadoxetic acid-enhanced magnetic resonance images in 101 patients with HCC between June 2012 and June 2018. Sixty-one radiomic features were extracted from hepatobiliary phase images and selected by the least absolute shrinkage and selection operator method to construct a radiomics signature. A clinical prediction model, and radiomics-based model incorporating significant clinical indexes and radiomics signature were built using multivariable logistic regression analysis. The integrated radiomics-based model was presented as a radiomics nomogram. The performances of clinical prediction model, radiomics signature, and radiomics-based model for predicting post-operative liver failure were determined using receiver operating characteristics curve, calibration curve, and decision curve analyses.RESULTS Five radiomics features from hepatobiliary phase images were selected to construct the radiomics signature. The clinical prediction model, radiomics signature, and radiomics-based model incorporating indocyanine green clearance rate at 15 min and radiomics signature showed favorable performance for predicting postoperative liver failure(area under the curve: 0.809-0.894). The radiomics-based model achieved the highest performance for predicting liver failure(area under the curve: 0.894; 95%CI: 0.823-0.964). The integrated discrimination improvement analysis showed a significant improvement in the accuracy of liver failure prediction when radiomics signature was added to the clinical prediction model(integrated discrimination improvement = 0.117, P =0.002). The calibration curve and an insignificant Hosmer-Lemeshow test statistic(P = 0.841) demonstrated good calibration of the radiomics-based model. The decision curve analysis showed that patients would benefit more from a radiomics-based prediction model than from a clinical prediction model and radiomics signature alone.CONCLUSION A radiomics-based model of preoperative gadoxetic acid–enhanced MRI can be used to predict liver failure in cirrhotic patients with HCC after major hepatectomy.     

可弯曲胸腔镜和硬质胸腔镜诊断不明原因胸腔积液的对比临床研究

目的对比可弯曲胸腔镜和硬质胸腔镜在不明原因胸腔积液诊断中的准确性和安全性。方法采用前瞻性随机对照研究,连续筛选四川大学华西医院2012年3月至2014年3月期间不明原因胸腔积液住院患者,患者年龄18~75岁。经知情同意后,患者随机进入可弯曲胸腔镜组或硬质胸腔镜组进行检查。结果可弯曲胸腔镜组入组49例患者,硬质胸腔镜组入组48例患者。两组共有44例患者通过胸腔镜检查确诊为恶性疾病,48例确诊为良性疾病。两组诊断不明原因胸腔积液总体准确性分别为93.9%和95.8%,可弯曲胸腔镜组诊断肿瘤的敏感性为96.0%,硬质胸腔镜组诊断肿瘤的敏感性为95.2%,两组诊断肿瘤的特异性均为100.0%,两组之间差异无统计学意义。两种胸腔镜技术并发症多数轻微,患者均耐受良好。结论对于不明原因胸腔积液,可弯曲胸腔镜诊断的准确性与硬质胸腔镜相当。尽管可弯曲胸腔镜取材组织小,但是通过多点多次取材,所获得的组织标本能满足病理科医生进行包括免疫组织化学检测在内的疾病诊断。