BackgroundAutophagy has a critical involvement in the initiation and progression of various cancers, including colorectal cancer (CRC). The feasibility of using autophagy-related genes (ATGs) as prognostic tools for CRC patients is yet to be determined.MethodsRNA sequencing data and clinical information for CRC were obtained from The Cancer Genome Atlas (TCGA) (training set) and Gene Expression Omnibus (GEO) datasets GSE39582 and GSE44076 (validation). ARGs were retrieved from the Human Autophagy Database, and differentially expressed ARGs (DAGs) were identified using the "limma" R package. Prognostic signature DAGs were established via univariate Cox and LASSO Cox regression analyses. The obtained signature was validated through expression analysis, autophagy scoring, survival prediction, and correlation with immune status. Immunohistochemistry assays and in vitro functional experiments in SW480 cells were performed to assess the biological roles of selected DAGs, particularly WIPI2.ResultsWe constructed an 11-gene prognostic signature (CANX, NRG1, WIPI1, EIF2AK3, WDR45, PELP1, ULK1, WIPI2, DAPK1, ULK3, and MAP1LC3C), with high-risk patients showing significantly reduced overall survival compared to low-risk patients. WIPI2, highly expressed in SW480 cells, was selected for functional validation. Knockdown of WIPI2 inhibited cell proliferation, suppressed autophagy (decreased LC3B-II, increased p62), and promoted apoptosis (increased cleaved caspase-3). These findings confirm the pro-survival role of WIPI2 in CRC. The prognostic signature remained independently predictive after adjusting for clinical factors and showed a strong correlation with immune infiltration in TCGA CRC samples.ConclusionThe autophagy-related signature independently predicts CRC prognosis and guides immunotherapy strategies.
Abstract Objective The aim of this study was to establish an ensemble learning model based on clinicopathological parameter and ultrasound radomics for assessing the risk of lateral cervical lymph node with short diameter less than 8 mm (small lymph nodes were used instead) metastasis in patients with papillary thyroid cancer (PTC), thereby guiding the selection of surgical methods. Methods This retrospective analysis was conducted on 454 patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy and lateral neck lymph node dissection or lymph node intraoperative frozen section biopsy at the First Hospital of China Medical University between January 2015 and April 2022. In a ratio of 8:2, 362(80%) patients were assigned to the training set and 92(20%) patients were assigned to the test set. Clinical pathological features and radomics features related to ultrasound imaging were extracted, followed by feature selection using recursive feature elimination (RFE). Based on distinct feature sets, we constructed ensemble learning models comprising random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), gradient boosting decision tree (GBDT), and light gradient boosting machine (Lightgbm) to develop clinical models, radiomics models, and clinical-radiomic models. Through the comparison of performance metrics such as area under curve (AUC), accuracy (ACC), specificity (SPE), precision (PRE), recall rate, F1 score, mean squared error (MSE) etc., we identified the optimal model and visualized its results using shapley additive exPlanations (SHAP). Results In this study, a total of 454 patients were included, among whom 342 PTC patients had small lymph node metastasis in the lateral neck region, while 112 did not have any metastasis. A total of 1035 features were initially considered for inclusion in this study, which were then narrowed down to 10 clinical features, 8 radiomics features, and 17 combined clinical-omics features. Based on these three feature sets, a total of fifteen ensemble learning models were established. In the test set, RF model in the clinical model is outperforms other models (AUC = 0.72, F1 = 0.75, Jaccard = 0.60 and Recall = 0.84), while CatBoost model in the radiomics model is superior to other models (AUC = 0.91, BA = 0.83 and SPE = 0.76). Among the clinical-radiomic models, Catboost exhibits optimal performance (AUC = 0.93, ACC = 0.88, BA = 0.87, F1 = 0.91, SPE = 0.83, PRE = 0.88, Jaccard = 0.83 and Recall = 0.92). Using the SHAP algorithm to visualize the operation process of the clinical-omics CatBoost model, we found that clinical omics features such as central lymph node metastasis (CLNM), Origin_Shape_Sphericity (o_shap_sphericity), LoG-sigma3_first order_ Skewness (log-3_fo_skewness), wavelet-HH_first order_Skewness (w-HH_fo_skewness) and wavelet-HH_first order_Skewness (sqr_gldm_DNUN) had the greatest impact on predicting the presence of lateral cervical small lymph node metastasis in PTC patients. Conclusions (1) In this study, among the ensemble learning models established based on clinicopathological features and radiomics features for predicting PTC lateral small lymph node metastasis, the clinical-radiomic CatBoost model has the best performance. (2) SHAP can visualize how the clinical and radiomics features affect the results and realize the interpretation of the model. (3) The combined CatBoost model can improve the diagnostic accuracy of suspicious lymph nodes with short diameter < 8 mm that are difficult to obtain accurate puncture results. The combined application of radiomics features is more accurate and reasonable than the prediction of clinical data alone, which helps to accurately evaluate the surgical scope and provide support for individual clinical decision making.
Background: Radiomics has been used in the diagnosis of tumor lymph node metastasis (LNM). However, to date, most studies have been based on intratumoral radiomics. Few studies have focused on the use of F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG PET/CT) peritumoral radiomics for the diagnosis of LNM in colorectal cancer (CRC). Purpose: Determining the value of radiomics features extracted from F-18-FDG PET/CT images of the peritumoral region in predicting LNM in patients with CRC. Methods: The clinical data and preoperative F-18-FDG PET/CT images of 244 CRC patients were retrospectively analyzed. Intratumoral and peritumoral radiomics features were screened using the mutual information method, and least absolute shrinkage and selection operator regression. Based on the selected radiomics features, a radiomics score (Rad-score) was calculated, and independent risk factors obtained from univariate and multivariate logistic regression analyses were used to construct clinical and combined (Radiomics + Clinical) models. The performance of these models was evaluated using the DeLong test, while their clinical utility was assessed by decision curve analysis. Finally, a nomogram was constructed to visualize the predictive model. Results: The most optimal set of features retained by the feature filtering process were all peritumoral radiomic features. Carcinoembryonic antigen levels, PET/CT-reported lymph node status and Rad-score were found to be independent risk factors for LNM. All three LNM risk assessment models exhibited good predictive performance, with the combined model showing the best classification results, with areas under the curve of 0.85 and 0.76 in the training and validation groups, respectively. The DeLong test revealed that the performance of the combined model was superior to that of the clinical and radiomics models in both the training and validation groups, although this difference was only statistically significant in the training group. DCA indicated that the combined model displayed better clinical utility. Conclusions: F-18-FDG PET/CT peritumoral radiomics is uniquely suited to predict the presence of LNM in patients with CRC. In particular, the predictive efficacy of LNM for precision therapy and individualized patient management can be improved by using a combination of clinical risk factors.
安罗替尼(AL3818,Anlotinib Hydrochloride)是我国自主研发的新型小分子多靶点酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),治疗靶点包括血管内皮细胞生长因子受体(vascular endothelial cell growth factor receptor,VEGFR)、血小板衍生生长因子受体(patelet-derived growth factor receptor,PDGFR)、成纤维生长因子受体(fibroblast growth factor receptor,FGFR),能够在抑制肿瘤血管生成的同时抑制肿瘤生长,且不良反应发生率较低,患者耐受情况好,可提高患者的生存质量.根据各项临床研究结果,安罗替尼已经获得晚期非小细胞肺癌、小细胞肺癌、软组织肉瘤、食管鳞癌和甲状腺髓样癌的中国临床肿瘤学会(Chinese Society of Clinical Oncology,CSCO)指南推荐,同时在肾癌、肝癌等多个瘤种领域中进行了积极探索.本文就安罗替尼的作用机制、临床研究、安全性等方面的最新临床进展进行综述,为后续的研究提供参考.
基因调节受损是许多疾病的核心,包括发育系统疾病和癌症.N6甲基腺苷的可调节的甲基化是哺乳动物RNA修饰的重要组成部分,已被越来越多的研究证明其在各种生物学过程及癌症发病机制中发挥重要作用.这种RNA化学标记可由"writers"蛋白(甲基转移酶)产生,并可由"ereasers"蛋白(去甲基酶)逆转,这些化学修饰可以由"readers"蛋白(甲基化阅读蛋白)识别,并依此来调节下游分子机制.RNA m6 A修饰在重要的生物学过程中起着重要作用,有研究表明,m6 A在NSCLC的发生、转移及侵袭方面至关重要,m6 A的研究也为NSCLC治疗提供了新的思路,本文就m6 A在NSCLC中的病因、发展、耐药等方面进行一一论述,目的是从表观遗传学方面进一步挖掘肺癌发生发展的生物学机制,为NSCLC的靶向治疗提供研究思路.
目的:探讨分析优质护理干预联合参一胶囊对急性高危白血病患者异基因外周血干细胞移植术后免疫功能重建及并发症发生率的影响及其临床应用价值.方法:纳入2015年1月至2017年12月间在我院接受异基因外周血干细胞移植术的急性高危白血病患者110例,按随机数字表法分为对照组(54例)和观察组(56例),对照组给予常规护理干预联合参一胶囊治疗,观察组给予优质护理干预联合参一胶囊治疗,对比两组患者经护理干预后免疫功能重建状况、并发症发生率、心理状况及护理满意度.结果:两组患者异基因外周血干细胞移植术后1个月免疫细胞恢复状况差异无统计学意义(P>0.05);观察组异基因外周血干细胞移植术后18个月免疫细胞恢复状况显著优于对照组(P<0.05);观察组异基因外周血干细胞移植术后并发症发生率显著低于对照组(P<0.05);观察组焦虑、抑郁评分显著低于对照组(P<0.05);观察组护理满意度高于对照组(P<0.05).结论:优质护理干预联合参一胶囊能改善急性高危白血病患者异基因外周血干细胞移植术后免疫功能的重建状况,减少并发症的发生,值得临床推广.
小细胞肺癌是肺癌中恶性程度最高的一类亚型,其生物学特点为恶性程度高,预后差.小细胞肺癌目前缺少有效治疗靶点,临床中迫切需要找到新的治疗靶点,改善小细胞肺癌的疗效.趋化因子12(C X C L12)/趋化因子受体4(CXCR4)轴在肿瘤的发生发展中,发挥着重要的作用.CXCR4拮抗剂在小细胞肺癌治疗中显示了一定潜力.本文对CXCR4在小细胞肺癌中的作用及相应靶向药物的研发进行综述.
BACKGROUND:To assess the value of characteristic computed tomography (CT) findings in predicting the survival of patients with pulmonary B-cell non-Hodgkin's lymphoma (NHL). METHODS:Eighty-four patients who were histopathologically confirmed with pulmonary B-cell NHL between 2004 and 2018 were retrospectively enrolled. All patients underwent chest CT scan at the time of initial diagnosis in our hospital. Characteristic CT findings and clinicopathological features of the patients were analyzed, and Cox regression models were used to determine the relationship of CT findings with overall survival (OS) and progression-free survival (PFS). RESULTS:Air bronchogram occurred more frequently in patients with early-stage disease, primary pulmonary lymphoma (PPL) and the indolent histological type of lymphoma than in patients with advanced-stage disease, secondary pulmonary lymphoma (SPL), and the aggressive histological type (all P<0.05). The halo sign was observed most in the SPL group (19/48, 40%; P=0.004), while the presence of cross-lobe sign was higher in patients with PPL (13/36, 36%; P=0.010). Pleural involvement and hilar/mediastinal lymphadenopathy were observed more in patients with SPL and the aggressive histological type (33/48 and 27/48; 31/46 and 26/46, respectively; all P<0.05). Survival analyses showed that the number of lung lesions, cross-lobe sign, and pleural involvement were independent prognostic factors for PFS, while the halo sign and pleural involvement were significantly correlated with OS (all P<0.05). More aggressive, advanced-stage cases and male patients showed worse outcomes. CONCLUSIONS:The halo sign and pleural involvement are independent prognostic factors for OS, while the number of lung lesions, cross-lobe sign, and pleural involvement are correlated with PFS.
神经细胞粘附分子1(neural cell adhesion molecule l,NCAM1)是一种非钙依赖性粘附分子,能介导细胞与细胞、细胞与细胞外基质间的相互作用.在神经系统的发育、免疫细胞功能的调节、细胞的识别及转移、肿瘤的浸润与生长等方面发挥重要作用.近年来的研究表明NCAM1可能参与了口腔扁平苔藓(oral lichen planus,OLP)的发生、发展及癌变过程.本文将从NCAM1的结构、功能及调节,NCAM1在OLP中的异常表达,NCAM1在OLP发生、发展中的可能作用及NCAM1与OLP癌变等方面作一综述.
This study aimed to explore the role of small nucleolar RNA host gene 14 (SNHG14) in the pathogenesis of diffuse large-B-cell lymphoma (DLBCL). DLBCL cell lines (OCI-Ly7 and OCI-Ly3) and specimens from patients were collected to evaluate the roles of SNHG14 in DLBCL pathogenesis. The results showed that SNHG14 expression increased and miR-152-3p expression decreased in DLBCL tissues and cell lines, indicating a negative correlation between miR-152-3p and SNHG14 expression. Moreover, SNHG14 was found to promote DLBCL growth, migration, and EMT-like processes in vitro, and directly inhibits miR-152-3p gene expression via sequestration of the miR-152-3p transcripts in DLBCL. Additionally, SNHG14/miR-152-3p inhibits apoptosis and promotes cell proliferation on cytotoxic T lymphocytes (CTLs) in DLBCL via the PD-1/PD-L1 checkpoint. Furthermore, both the immune escape and progression of DLBCL are advanced by SNHG14 expression via its interactions with miR-152-3p. Collective, this suggests that SNHG14 is a potential diagnostic, prognostic, and therapeutic target for DLBCL.
Abstract Rationale: Pyloric gland adenoma (PGA) is often associated with pyloric gland metaplasia. It has high malignant potential but a low clinical diagnosis rate. Therefore, we reported a case of PGA and reviewed the literature to summarize the clinicopathological features of pyloric adenoma. Patient concerns: A 62-year-old female underwent gastroscopy due to intermittent acid regurgitation and heartburn, which revealed a 4×6 mm flat, elevated lesion in the greater curvature of the upper gastric body, with depression in the central region and blood scab attachment. Diagnosis and intervention: Biopsy revealed gastric adenoma with low-grade intraepithelial neoplasia. The patient was treated with ESD, and pathology showed gastric pyloric gland adenoma with low-grade dysplasia. The cells were positive for MUC6 and MUC5AC immunohistochemically. Outcomes: The patient received proton pump inhibitors and gastric mucosal protective agents for one month after ESD. She occasionally presented acid regurgitation and heartburn, with no abdominal pain, abdominal distension, melena, or hematochezia. Follow-up gastroscopy will be reexamined 1 year later. Lessons: PGA has nonspecific performance under endoscopy, and its diagnosis mainly depends on pathology. Clinicians need to increase their ability to recognize such lesions and treat them in time to improve the prognosis.
子宫内膜癌是女性生殖道三大恶性肿瘤之一,近年来其发病率呈上升趋势,且发病年龄逐渐年轻化,但病因及发病机制尚不明确.PAX基因家族通过编码相应的转录因子影响细胞的增殖、分化、迁移和凋亡,参与胚胎发育、多系统组织器官形成等过程.在多种人类肿瘤中,均发现PAX基因可通过多种途径参与肿瘤的发生发展,但其在子宫内膜癌中的作用尚不清楚.因此,研究PAX基因在子宫内膜癌中表达的特性,可能能为子宫内膜癌寻找到有效的肿瘤标志物,进而为肿瘤的诊断、分类、预后及治疗等提供新思路.
microRNA(微小RNA,miRNA)是小的非编码RNA,能够通过靶向信使RNA进行翻译抑制或在较小程度上降解来抑制基因表达.miRNA不受控制的表达与癌症进展相关,并且miRNA上调或下调与癌症中的致癌和肿瘤抑制作用相关.miR-25是miRNA的一员,研究表明miR-25参与非小细胞肺癌的发生、转移侵袭、诊断、介导铂耐药及预后过程.本文主要综述了近年来非小细胞肺癌与miR-25相关研究取得的最新进展.
高危型人乳头瘤病毒(HPV)的持续性感染是宫颈癌的主要危险因素,天然免疫系统通过模式识别受体(PRR)诱导促炎症细胞因子及Ⅰ型干扰素释放,在抵御外源微生物过程中发挥重要作用.天然免疫系统障碍使HPV不能被有效清除,HPV持续性感染,最终导致宫颈癌的发生.PRR在HPV感染过程中发挥重要作用,并且其异常表达参与宫颈癌的发生发展过程.此外,调节PRR的表达可以增强宫颈癌细胞的凋亡,在宫颈癌的治疗中具有潜在的临床意义,有望成为宫颈癌治疗的新途径.
目的 探讨基于行为改变理论制定的护理模式在结直肠癌造口患者中的应用效果.方法 将2019年1月入院的46例患者设为对照组,2019年2月人院的48例患者设为观察组.对照组患者给予常规结直肠造口的护理措施,观察组患者给予依据行为改变理论制定的护理模式进行干预.分别于手术前1d、出院后第3个月末,采用肠造口患者自我管理问卷和知信行量表评价干预的效果.结果 在出院后第3个月末,观察组肠造口患者自我管理问卷总分及各维度得分均高于对照组,差异有统计学意义(P<0.05);观察组患者知信行量表总分及各维度得分均高于对照组,差异有统计学意义(P<0.05).结论 基于行为改变理论的干预模式可以提高肠造口术后患者的自我管理能力和知信行水平.
Leukemia is amalignant clonal disease that originates from hematopoietic stem cells. As in-depth research examines the molecular biology and immunology of the hematopoietic system, leukemia treatment has evolved from a single cytotoxic drug to treatments that inducing differentiation and apoptosis. Meanwhile, autophagy has become a growing concern as a new form of cell death. The immune response, hematopoietic stem cell differentiation, and drug resistance of tumor cells are all potentially affected by autophagy. Regulating autophagy may become one of the promising directions in the field of targeted therapy.
G蛋白偶联受体81(GPR81)属于G蛋白偶联受体家族(GPCR),是在脂肪和肌肉细胞中发现的乳酸受体,GPR81也称为羟基羧酸受体1(HCAR1).随着对GPR81研究的深入,发现其与肿瘤的发生、发展密切相关.GPR81在不同类型的肿瘤组织中发挥不同的生物学作用,GPR81在肺癌、胰腺癌、胆管腺癌、乳腺癌等组织中作为促癌受体,而在结肠组织中GPR81可通过调节肠道中的炎症反应,从而抑制炎症相关的结肠癌的发展.本文主要阐述了GPR81和GPCR的特点,并对GPR81在肿瘤中的研究进展作一综述.
OBJECTIVE:To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation.METHODS:A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed.RESULTS:Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P<0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P<0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P<0.05).CONCLUSION:Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.
目的:评估基质金属蛋白酶-13(MMP-13)在慢性牙周炎患者经过牙周基础治疗前后的非刺激性全唾液、龈沟液及血清中的表达水平.方法:纳入20名慢性牙周炎患者和20名牙周健康者,采用ELISA分别检测慢性牙周炎患者治疗前、后及健康人非刺激性全唾液、龈沟液及血清中MMP-13的水平,检测患者牙周临床指标BI、PD和CAL,并进行组间比较.结果:患者除非刺激性唾液外,患者治疗后的龈沟液和血清中MMP-13水平显著降低(P<0.05),并且MMP-13水平与健康对照组无显著差异(P>0.05).患者治疗后龈沟液中BI和PD也明显降低,并与MMP-13水平相关(P<0.05).结论:龈沟液中MMP-13的表达水平可能成为慢性牙周炎的检测指标之一.