Adoptive transfer of ex vivo expanded regulatory T cells improves immune cell engraftment and therapy-refractory chronic GvHD

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IL12 integrated into the CAR exodomain converts CD8+ T cells to poly-functional NK-like cells with superior killing of antigen-loss tumors

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Identification of cuproptosis‐related subtypes and characterization of the tumor microenvironment landscape in head and neck squamous cell carcinoma

BackgroundCuproptosis is considered a novel copper‐dependent cell death model. In this study, we established a novel scoring system based on 10 cuproptosis‐related genes (CRGs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC).MethodsThe RNA‐seq data of HNSCC patients were downloaded from the GEO and TCGA databases and were merged into a novel HNSCC cohort. Multiomics landscape analyses were conducted, including tumor mutation burden (TMB), copy number variations and the interaction network of CRGs. Patients were then divided into different cuproptosis subtypes based on the expression of 10 CRGs and subsequently regrouped into novel gene clusters referring to differentially expressed genes. A cuproptosis score (CS) system was established using principal component analysis. The CIBERSORT, ssGSEA and ESTIMATE algorithms were used to assess the tumor immune microenvironment. Moreover, the immunotherapeutic and chemotherapeutic responses were assessed.ResultsPatients were divided into three cuproptosis subtypes and subsequently regrouped into three gene clusters, reflecting different immune infiltration. Assessed by the CS system, those with higher CSs exhibited worse prognosis and higher TMB frequency. Nevertheless, the immune‐related analysis revealed patients in the low‐CS group appeared immunosuppressive and easily suffered from immune escape. High CSs possibly show high expression of immune checkpoint genes and enhance chemotherapy sensitivity to cisplatin, docetaxel, and gemcitabine.ConclusionWe established a novel scoring system to predict the prognosis and immune landscape of HNSCC patients. This signature exhibits satisfactory predictive effects and the potential to guide comprehensive treatment for patients.     

STAT3与SOCS3在子宫内膜腺癌中的表达及生物学行为相关性分析

目的探讨STAT3、SOCS3基因蛋白在子宫内膜腺癌中的表达及意义,以期了解这两种蛋白在子宫内膜腺癌癌变过程中的作用。方法收集46例手术切除的子宫内膜腺癌组织标本,同时取30例正常子宫内膜组织作为对照,运用组织芯片技术以及免疫组织化学的方法检测子宫内膜癌组织、正常子宫内膜组织中STAT3、SOCS3蛋白的表达。结果 46例子宫内膜癌组织中STAT3的阳性表达率为76.1%,SOCS3的阳性表达率为19.6%,两者在子宫内膜腺癌与正常子宫内膜组织之间的阳性率表达差异有显著的统计学意义(P<0.05)。二者的阳性表达与子宫内膜腺癌患者的肿瘤分化程度有关,与手术病理分期、肌层浸润及绝经情况等临床特征无相关性(P>0.05)。子宫内膜腺癌中STAT3与SOCS3呈负相关。结论子宫内膜腺癌中STAT3呈高表达,SOCS3呈低表达,提示STAT3促进了子宫内膜腺癌的发生发展,而SOCS3抑制子宫内膜腺癌癌变的作用。     

重组人血管内皮抑制素联合放化疗对晚期头颈部鳞癌患者生存质量的影响

目的探讨重组人血管内皮抑制素联合放化疗对晚期头颈部鳞癌患者生存质量的影响。方法选取我院2016年1月至2018年1月收治的86例晚期头颈部鳞癌患者作为研究对象,按照治疗方式不同将其分为观察组(43例,重组人血管内皮抑制素联合放化疗)和对照组(43例,常规放化疗)。比较两组的疾病控制情况、急性不良反应发生情况、生存质量、希望水平及心理弹性。结果观察组的疾病控制率及缓解率均明显高于对照组(P<0.05)。两组各项急性不良反应发生情况基本相似(P>0.05)。治疗后,观察组的生存质量、HHI、CD-RISC评分均明显高于对照组(P<0.05)。结论重组人血管内皮抑制素联合放化疗能提高晚期头颈部鳞癌患者的疾病控制率及缓解率,改善患者的生存质量。     

Diagnostic and prognostic value of circRNAs expression in head and neck squamous cell carcinoma: A meta‐analysis

BackgroundCircular RNAs (circRNAs) have been found to have potential biological applications against tumors in humans. This study aimed to evaluate the diagnostic, prognostic, and clinicopathological value of circRNAs in head and neck squamous cell carcinoma (HNSCC).MethodsThe PubMed, Web of Science, EMBASE, and the Cochrane Library were comprehensively searched for the relevant studies before October 20, 2021. Statistical analysis was performed based on STATA 15.0, Meta‐DiSc 1.4, and RevMan 5.3 software.ResultsA total of 55 reports regarding 56 kinds of circRNA were studied in this meta‐analysis, including 23, 38, and 26 articles on diagnosis, prognosis, and clinicopathological features, respectively. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver‐operating characteristic curve (SROC) were 0.78, 0.84, and 0.87, respectively. Besides, the upregulation of oncogenic circRNAs was significantly associated with poorer overall survival (OS) (HR=2.25, p < 0.05) and disease‐free interval (DFS) (HR=1.92, p < 0.05). In contrast, the elevated expression of tumor suppressor circRNAs was associated with a favorable prognosis (HR=0.50, p < 0.05). In addition, the high expression of oncogenic circRNAs was associated with the tumor size (OR=3.59, p < 0.05), degree of differentiation (OR=1.89, p < 0.05), TNM stage (OR=2.35, p < 0.05), lymph node metastasis (OR=1.85, p < 0.05), and distant metastasis (OR=3.42, p < 0.05). Moreover, the expression of tumor suppressor circRNAs was associated with improved clinicopathological features (lymph node metastasis: OR=0.25, p < 0.05).ConclusionsCircRNAs could serve as potential predictive indicators and be useful for the diagnosis, prognosis, and identification of clinicopathological features in HNSCC.     

倾向性评分匹配分析口咽癌PD-L1的表达与HPV感染及预后的相关性研究

目的探讨口咽鳞癌中程序性细胞死亡配体1(PD-L1)与HPV感染状态及患者预后的相关性。方法采用倾向性评分匹配,纳入HPV阳性及HPV阴性口咽癌各50例,对患者进行长期随访,通过免疫荧光检测PD-L1的表达,分析其与HPV感染状态及临床预后的相关性。结果 HPV阳性组及HPV阴性组5年总生存率分别为66%和40%(P=0.003),5年疾病特异性生存率分别为73%和44%(P=0.001)。PD-L1表达率在HPV阳性组较HPV阴性组明显升高(70%vs 42%,P=0.005)。PD-L1与除年龄(P=0.020)外的其他临床病理特征无明显相关性,PDL1阳性为口咽癌独立良好预后因素(DSS,P<0.001;OS,P<0.001)。进一步预后分析提示HPV+/PD-L1+患者较HPV+/PD-L1-者(DSS,P<0.001;OS,P=0.004),HPV-/PD-L1+者(DSS,P=0.010;OS,P=0.047)以及HPV-/PD-L1-者(DSS,P<0.001;OS,P<0.001)具有显著的预后优势。结论 HPV阳性口咽癌患者预后较好,PD-L1在HPV阳性口咽癌中的表达升高,PD-L1阳性可能与HPV阳性口咽癌患者较好的临床预后相关。     

The expression profile and clinical application value of hsa_circ_0016148 in head and neck squamous cell carcinoma

BackgroundDysregulated circular RNAs (circRNAs) are involved in human cancers and may be used as biomarkers with the potential of clinical application. However, little is known regarding the mechanism of circRNAs and their clinical application value in head and neck squamous cell carcinoma (HNSCC).MethodsIn the current study, we established the profile of circRNAs in HNSCC using microarray and then measured the expression of hsa_circ_0016148 in 137 paired HNSCC tissues by qRT‐PCR technique, analyzed the relationship between hsa_circ_0016148 and clinicopathological data, and investigated its diagnostic and prognostic value. The hsa_circ_0016148‐miRNA‐mRNA interaction network was predicted and constructed by Cytoscape.ResultsOur study showed a circRNA expression profile and confirmed downregulated hsa_circ_0016148 in HNSCC tissues (p = 2.64E‐35). The hsa_circ_0016148 expression is remarkably correlated with lymph node metastasis (p = 0.001) and clinical stage (p = 0.029). Then, the area under the receiver characteristic curve (AUC) was 0.912 with 92% of sensitivity and 86.9% specificity, respectively. Besides, our study demonstrated that lower‐expressed hsa_circ_0016148 could independently predict poorer overall survival of HNSCC patients (hazard ratio [HR] = 0.456; 95% confidence interval [CI] = 0.265–0.784; p = 0.005). The hsa_circ_0016148‐miRNA‐mRNA interaction network was constructed, which included a total of nine targeted miRNAs.ConclusionTaken together, our results revealed that hsa_circ_0016148 might play a critical role in HNSCC tumorigenesis and may serve as an indicator with the potential of diagnosis and prognosis for HNSCC.     

VEGF、STAT3在大肠癌组织中的表达及其相关性研究

目的探讨血管内皮生长因子(VEGF)和信号转导子与转录活化子3(STAT3)表达在大肠癌中的变化,以及与大肠癌临床病理的关系,并研究两者的相关性。方法采用免疫组化方法检测大肠癌中VEGF、STAT3的表达情况。结果大肠癌中VEGF、STAT3蛋白表达阳性率分别为66.7%(22/33)和63.6%(21/33),显著高于正常大肠组织的阳性率(P<0.01);VEGF的表达与Duke′s分期及有无淋巴结转移有关(P<0.05);而STAT3的表达与肿瘤的分化程度、Duke′s分期有关及有无淋巴结转移有关(P<0.05)。相关分析表明VEGF和STAT3正相关(P<0.05)。结论大肠癌组织中存在VEGF和STAT3的高表达,VEGF的表达与大肠癌病程的发展及淋巴转移关系相关,而STAT3的表达除与大肠癌病程的发展及淋巴转移相关外,还与大肠癌组织的分化程度有关。另外,大肠癌的发生过程中VEGF可能受STAT3的调控,STAT3可能会成为大肠癌的抗血管生成新的治疗靶点。     

Targeting Lin28 axis enhances glypican-3-CAR T cell efficacy against hepatic tumor initiating cell population

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Small Atypical Cervical Nodes Detected on Sonography in Patients With Squamous Cell Carcinoma of the Head and Neck

Objective. The purpose of this study was to assess the probability of metastasis of small atypical cervical lymph nodes detected on sonography in patients with squamous cell carcinoma (SCC) of the head and neck. Methods. .We reviewed, retrospectively and blindly, sonographic findings of 148 patients (118 men and 30 women; mean age, 58.2 years) who underwent curative neck dissection. Each lymph node was classified by using a 4‐point scale: 1, definitely benign; 2, indeterminate (small [short‐axis diameter <10 mm for levels I and II and <7 mm for levels III–VI] atypical node); 3, definitely metastatic; and 4, large (>3‐cm) metastatic. Lymph nodes were considered atypical if they met at least 1 of the following criteria: a long‐ to short‐axis diameter ratio of less than 2.0, absence of a normal echogenic hilum, and heterogeneous echogenicity of the cortex. These results were verified, on a level‐by‐level basis, with histopathologic findings. Results. Small atypical nodes were found on sonography in 63 cervical levels of 48 patients, of which 18 (28.6%) were proved to have metastatic nodes. The probability of metastasis was significantly higher with than without a large (>3‐cm) ipsilateral metastatic node (0.50 versus 0.20; P = .038) and marginally higher with than without an ipsilateral metastatic node (0.41 versus 0.16; P = .061) but not significantly associated with the T stage of the primary tumor (P = .238) or the presence of an ipsilateral tumor (P = .904). Conclusions. Metastasis was encountered in about 30% of small atypical cervical nodes on sonography in patients with SCC of the head and neck. Our results indicate that small atypical nodes must be interpreted with consideration of metastatic nodes in the ipsilateral neck.     

人乳头状瘤病毒相关头颈颌面部鳞癌的研究进展

头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）发病率占头颈部恶性肿瘤的90%，死亡率为40%~50%，来源于口腔、口咽、鼻咽、下咽及喉。通常认为烟草、酒精的过度使用与HNSCC有关，但越来越多的研究表明，人乳头状瘤病毒（human papillomavirus，HPV）感染与HNSCC的发生发展高度相关，尤其是口咽鳞状细胞癌（oropharyngeal squamous cell carcinoma，OPSCC）。本文对HPV相关HNSCC的分子生物学表现、致病机制、治疗进展、预防策略作一综述，为临床及个体化治疗提供新的思路。     

心肌STAT3蛋白表达对急性心肌梗死患者病情评估价值研究

目的 探讨心肌STAT3蛋白表达对急性心肌梗死患者病情的评估价值.方法 选取自2016年4月至2017年12月北京市和平里医院收治的70例急性心肌梗死患者纳入心梗阻,另同期选取77例非急性心肌梗死受试者纳入正常组.两组受试者均通过冠状动脉导管介入抽吸加H9 c2细胞原代培养的方式获取心肌标本,采用免疫组化法和免疫印迹法测定心肌STAT3蛋白的表达情况.结果 正常组STAT3蛋白棕黄色深染率为3.12％,心梗组STAT3蛋白在发病时,发病后6、12、24 h棕黄色深染率分别为36.00％、22.57％、22.00％、15.14％,组间及组内各时间点比较,差异均有统计学意义(P<0.05).两组受试者STAT3蛋白免疫印迹法检测结果显示,心梗组患者在发病时,发病后6、12、24 h测定蛋白表达量分别与正常组比较,差异均有统计学意义(P<0.05);心梗阻患者各时间段测得的蛋白表达量比较,差异均无统计学意义(P>0.05).结论 STAT3表达量的升高对急性心肌梗死有一定的评估作用.     

Prognostic prediction of head and neck squamous cell carcinoma: Construction of cuproptosis‐related long non‐coding RNA signature

BackgroundRecently, a new type of programmed cell death, cuproptosis, has been identified to play important role in the progression of tumors. We constructed a cuproptosis‐related long non‐coding RNA (lncRNA) signature to predict the prognostic significance for head and neck squamous cell carcinoma (HNSCC).MethodsThe risk model was developed based on differentially expressed lncRNAs associated with cuproptosis. Principal component analysis was used to assess the validity. The Kaplan–Meier curves were analyzed to compare the overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS) values. The multivariate and univariate Cox regression analyses were used to evaluate the prognostic efficiency. Furthermore, the functional enrichment, immune cell infiltration, tumor mutation burden (TMB), and sensitivity toward chemotherapy were also explored.ResultsSix cuproptosis‐related lncRNAs (AL109936.2, CDKN2A‐DT, AC090587.1, KLF3‐AS1, AL133395.1, and LINC01063) were identified to construct the independent prognostic predictor for HNSCC. The area under the curve and C‐index values obtained using the risk model were higher than the values corresponding to the clinical factors. Analysis of Kaplan–Meier curves indicated that the OS, PFS, and DSS time recorded for the patients in the low‐risk group were higher than the corresponding values recorded for the patients belonging to the high‐risk group. By functional enrichment analysis, we observed that differentially expressed genes were enriched in the immune response and tumor‐associated pathways. The patients characterized by a low‐risk score exhibited better immune cell infiltration than the patients belonging to the other group. We also observed that the sensitivity of the individuals belonging to the low‐risk group to chemotherapeutic agents (cisplatin, docetaxel, and paclitaxel) was higher than the sensitivity of those in the other group.ConclusionsA cuproptosis‐related lncRNA‐based signature that functioned as an independent prognosis predictor for HNSCC patients was constructed. The chemosensitivity of individual patients can be potentially predicted using this signature.     

STAT3蛋白在子宫内膜异位症合并不孕患者中的表达及临床意义

目的研究STAT3蛋白在子宫内膜异位症合并不孕患者中的表达及临床意义。方法将2013年4月至2014年5月就诊的卵巢子宫内膜异位症合并不孕患者纳入研究对象,收集异位子宫内膜组织作为异位组,在位子宫内膜组织作为在位组;将同期就诊的子宫肌瘤患者纳入研究,收集子宫内膜组织作为对照组。采用实时聚合酶链反应和免疫印迹试验的方法检测子宫内膜组织中STAT3、p-STAT3、MMP2、MMP9的mRNA和蛋白含量。结果 1MMPs含量:异位组MMP2、MMP9的mRNA和蛋白含量高于在位组和对照组;2STAT3含量:三组间STAT3的mRNA和蛋白含量无差异,异位组p-STAT3的mRNA和蛋白含量高于在位组和对照组;3MMPs和STAT3的相关性:p-STAT3的蛋白含量与MMP2、MMP9的蛋白含量呈正相关。结论异位的子宫内膜组织中p-STAT3呈高表达,且可能通过促进MMP2、MMP9的表达来参与子宫内膜异位症的发生。     

Exploration of a predictive model based on genes associated with fatty acid metabolism and clinical treatment for head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumors of the head and neck and presents high risks of recurrence and poor prognosis postoperatively. The aim of this study was to establish a predictive model based on fatty acid metabolism (FAM) genes to forecast the prognosis of HNSCC patients and the subsequent treatment strategies.MethodsWe accessed the TCGA and GEO databases for HNSCC genes and clinical data. The FAM risk score model was created and validated using a combination of univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Combining risk scores and clinical characteristics, a nomogram was established and assessed. Subsequently, the function, gene mutation, immune difference, and chemotherapeutic drug sensitivity of the groups with high‐ and low‐risk scores were analyzed. Consequently, the mode''s validity was evaluated comprehensively by combining single gene analysis.ResultsThe FAM risk score model for predicting HNSCC prognosis had certain validity. Patients in the high‐ and low‐risk groups had genetic mutations, and the prognosis was the poorest for the high‐risk groups with high genetic mutations. The patients with low‐risk scores were suitable for immunotherapy since they had increased infiltration of immune cells. In contrast, the patients in the other groups were more suitable for chemotherapy.ConclusionThe results of this study demonstrated that the FAM risk score model may predict the prognosis of HSNCC and has a certain therapeutic guidance value.     

西妥昔单抗联合同步放化疗治疗局部头颈部鳞癌的疗效及对患者睡眠质量的影响

目的:研究西妥昔单抗联合同步放化疗治疗局部头颈部鳞癌的疗效及对患者睡眠质量的影响.方法:选取珠海市第二中医院收治的局部头颈部鳞癌患者100例作为研究对象,按治疗方案分为观察组和对照组,每组50例.观察组行西妥昔单抗联合同步放化疗,对照组行单一同步放化疗,分析比较2组患者临床疗效.结果:观察组治疗总有效率比对照组高,治疗...     

Satraplatin联合放疗对鼻咽癌裸鼠STAT3及NF-κB表达的影响

目的观察并分析Satraplatin(赛特铂)联合放疗对鼻咽癌裸鼠信号传导及转录激活因子(STAT3)及核因子κB(NF-κB)表达的影响。方法取健康裸鼠120只,按照随机数字表法将其分为对照组和观察组,每组60只。所有裸鼠均鼻咽癌造模成功(经过低分化鼻咽癌CNE-2细胞接种)。对照组裸鼠又随机分为未处理组、处理后1周组(放疗)、处理后3周组(放疗),每组20只。观察组裸鼠又随机分为未处理组、处理后1周组(放疗+Satraplatin)、处理后3周组(放疗+Satraplatin),每组20只。观察两组裸鼠处理前、处理后1周、处理后3周肿瘤凋亡率、瘤体重量、STAT3、NF-κB相对表达量。结果两组裸鼠处理前后肿瘤凋亡率差异显著(P <0. 05),两组裸鼠处理前肿瘤凋亡率比较无显著差异(P>0. 05),随着处理后时间的延长,两组裸鼠肿瘤凋亡率显著升高,但观察组裸鼠处理1周、3周肿瘤凋亡率显著高于对照组(P <0. 05)。两组裸鼠处理前后瘤体重量差异显著(P <0. 05),两组裸鼠处理前瘤体重量比较无显著差异(P>0. 05),处理后,两组裸鼠瘤体重量显著降低(P <0. 05),处理1周、3周瘤体重量显著低于对照组(P<0. 05)。两组裸鼠处理前后STAT3、NF-κB水平差异显著(P <0. 05),两组裸鼠处理前STAT3、NF-κB水平比较无显著差异(P>0. 05),处理后,两组裸鼠STAT3、NF-κB水平显著降低(P <0. 05),处理1周、3周观察组裸鼠STAT3、NF-κB水平明显低于对照组(P <0. 05)。结论 Satraplatin联合放疗能有效降低鼻咽癌裸鼠STAT3及NF-κB表达,增加鼻咽癌裸鼠肿瘤细胞凋亡,减轻瘤体重量。