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.     

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.     

Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology

Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated by a component of the cell cycle apparatus, cyclin D1.

Area covered: The current review is provided to update recent developments in the clinical application of cyclin/CDK inhibitors to breast cancer with a focus on the anti-tumor immune response.

Expert opinion: The cyclin D1 gene encodes the regulatory subunit of a proline-directed serine-threonine kinase that phosphorylates several substrates. CDKs possess phosphorylation site selectivity, with the phosphate-acceptor residue preceding a proline. Several important proteins are substrates including all three retinoblastoma proteins, NRF1, GCN5, and FOXM1. Over 280 cyclin D3/CDK6 substrates have b\een identified. Given the diversity of substrates for cyclin/CDKs, and the altered thresholds for substrate phosphorylation that occurs during the cell cycle, it is exciting that small molecular inhibitors targeting cyclin D/CDK activity have encouraging results in specific tumors.     

等长收缩运动治疗单纯颈伸肌劳损的疗效观察

目的总结等长收缩运动治疗单纯颈伸肌劳损的疗效。方法随机将56例单纯颈伸肌劳损分为两组,一组应用等长收缩运动进行治疗,另一组应用手法治疗,对比两组患者疗效。结果治疗1周后,两组患者的总有效率均为100%（P〉0.05）。结论等长收缩运动治疗单纯颈伸肌劳损的疗效与手法治疗相近,但该法具有更安全、经济、且不受条件、时间限制,更有主动巩固疗效和积极预防的作用。     

三维适形放疗联合肝动脉碘油栓塞化疗并热疗治疗原发性肝癌的疗效研究

目的:探讨原发性肝癌的肝动脉碘油栓塞化疗(TACE)、热疗、三维适形放疗(3DCRT)的综合治疗价值。方法:122例原发性肝癌患者进行前瞻性随机分组研究,综合治疗组64例,行TACE并3DCRT,结合热疗治疗。对照组58例3DCRT治疗,联合TACE。结果:1、2、3年生存率综合治疗组分别为85%、65%、39%,对照组分别为59%、30%、18%(P<0.05)两组毒副作用相似。结论:对于非手术切除的原发性肝癌患者,TA-CE,结合3DCRT并热疗,能明显提高疗效,而毒副作用不增加。     

排粪造影的临床应用

介绍排粪造影方法，报告１６０例造影结果。对照组５２例中２例（３８５％）异常；排粪障碍组１０８例，仅１８例（１６６７％）未见异常，提出了肛直角和肛上距正常测量值。报道主要异常Ｘ线表现。探讨了排粪造影检查对于肛管直肠部及盆底疾病的诊断价值     

HCV的检测方法

从发现丙型肝炎病毒以来 ,丙肝的检测技术发展迅速 ,灵敏度和特异性都有明显的提高 ,方法学在不断改进完善。笔者就近年来丙型肝炎的实验室检测方法作简要的综述     

胆碱酯酶重活化剂PAM类构型、构象问题

本文参考X-衍射数据,采用MNDO程序计算了不同构型、构象PAM类的生成热,结合核磁共振数据讨论了PAM类构象等问题.结果表明,PAM类在水溶液中:顺式体肟基可以自由旋转,任何一种构象都可能成为药效构象;反式体肟基本不可能存在稳定的平面构象,其药效构象只能是优势构象.用MNDO程序中反应途径的计算法,还计算了顺、反式肟基构型相互转变的势垒,为探讨PAM类重活化机理提供了一定的参考.