细胞因子在分化型甲状腺癌诊疗中的应用进展北大核心

甲状腺癌是内分泌系统常见的恶性肿瘤之一,其发病率呈逐年上升趋势。甲状腺癌以分化型甲状腺癌(differentiated thyroid carcinoma, DTC)为主,尽管多数DTC患者经规范化治疗后预后良好,但由于部分肿瘤的病理类型侵袭性较高或肿瘤组织分化程度较低,病情进展迅速导致患者总生存时间显著缩短。近年来,有关炎症与肿瘤之间相关性的研究越来越多,炎性微环境的改变在肿瘤发病机制中的作用逐渐被证实,更多的证据表明细胞因子可作为肿瘤的良恶性鉴别、预后判断提示及诊疗方案选择等的重要参考依据。本文就部分细胞因子在DTC诊疗中的应用进展进行论述,旨在为DTC的诊疗与预后判断等提供参考依据。     

Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics

The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.     

Clinical characteristics and surgical outcomes of resectable acinar cell carcinoma of the pancreas-propensity score matching analysis with pancreatic ductal adenocarcinoma

BackgroundSurgical resection is recommended for patients with resectable acinar cell carcinoma (ACC). The aim of this study was to investigate the clinical characteristics and surgical outcomes of resectable ACC in comparison to pancreatic ductal adenocarcinoma (PDAC).MethodA retrospective analysis was performed on all patients who consecutively underwent radical resection with pathologically confirmed ACC and PDAC from December 2011 to December 2018. Clinicopathologic characteristics and follow-up information were analyzed. A 1:3 propensity score matching (PSM) method was used to minimize the bias between ACC and PDAC.ResultsA total of 26 patients with ACC and 1351 with PDAC were included. Compared to PDAC, ACC tended to be larger (4.5 vs. 3.0 cm; p < 0.001) and more frequently located in the pancreatic body/tail (61.5% vs. 36.6%, p = 0.009), with lower total bilirubin levels, lower neutrophil lymphocyte ratio (NLR) levels and lower carbohydrate antigen 19-9 (CA19-9) levels and carcinoembryonic antigen (CEA) levels. There was no difference in postoperative morbidities in patients with ACC and PDAC. The median OS and RFS were longer in ACC when compared to PDAC (OS: 43.5 mo vs. 19.0 mo, p = 0.004; RFS: 24.5 mo vs. 11.6 mo, p = 0.023). After the 1:3 PSM, ACC remained to be a better histological type for OS (p = 0.024), but had comparable RFS with PDAC (p = 0.164).ConclusionPatients with ACC after radical resection had better OS than that with PDAC. However, ACC is also an aggressive tumor with a similar trend of RFS with PDAC after the matching, necessitating the multidisciplinary treatment for resectable ACC disease.     

原发灶不明骨髓转移癌25例临床分析北大核心

目的:探讨原发灶不明骨髓转移癌的病例特点、治疗情况及预后。方法:对纳入的25例患者进行回顾性分析其各自的临床特点、治疗过程以及生存情况。结果:25例患者中位总生存期为6个月。初诊时是否伴有血液学症状、病理类型、治疗方式以及接受治疗时间对患者生存有显著差异。治疗方式、家庭支持强度是影响预后的独立因素。结论:原发灶不明骨髓转移癌是临床少见的疾病,给予积极的综合治疗,加强社会家庭的支持强度可能会改善其预后。     

C反应蛋白和白蛋白比值预测单发小肝癌患者微血管侵犯的价值研究

背景 既往对肝癌微血管侵犯病理诊断的重要性重视不够，目前国内外缺乏对微血管侵犯统一的病理诊断标准，也未将微血管侵犯列为病理常规诊断指标。C反应蛋白/白蛋白比值（CAR）作为新型系统性炎性因子，与肝癌的增殖、侵袭转移等恶性生物学行为密切相关。 目的 探讨CAR预测单发小肝癌患者微血管侵犯的价值。 方法 选择2017年6月至2021年6月在新疆医科大学第一附属医院行肝切除术的单个、肿瘤直径≤5 cm的术后病理检查证实为肝癌的患者346例为研究对象。收集患者一般资料，并计算CAR。绘制CAR预测单发小肝癌患者微血管侵犯的受试者工作特征（ROC）曲线，并计算CAR的最佳诊断截点，根据CAR最佳诊断截点将患者进行分组，采用1∶1最近邻居倾向性评分匹配（PSM）法将Logistic模型估计的倾向性评分相近患者进行配对，得到两组间各临床特征比较均衡性较高的样本。比较匹配后两组患者微血管侵犯率，采用Logistic回归分析评估匹配前、后CAR对单发小肝癌患者微血管侵犯的预测价值。 结果 346例患者中微血管侵犯阳性131例（37.9%），微血管侵犯阴性215例（62.1%）。ROC曲线分析结果显示，CAR预测单发小肝癌患者微血管侵犯的灵敏度为82.9%，特异度为76.4%，ROC曲线下面积为0.787〔95%CI（0.697，0.877）〕，最佳诊断截点为0.03。根据CAR最佳诊断截点，将患者分为CAR<0.03组（A组，n=145）和CAR≥0.03组（B组，n=201）。采用1∶1最近邻居PSM法，共92对匹配成功，匹配后两组临床资料均衡。匹配后，B组患者微血管侵犯发生率〔43.5%（40/92）〕高于A组〔13.0%（12/92）〕（χ2=6.314，P=0.013）。采用3种Logistic回归分析结果显示，匹配前、后CAR均为单发小肝癌患者微血管侵犯的独立影响因素（P<0.05）。 结论 CAR作为新型系统性炎症指标，可用于预测单发小肝癌微血管侵犯，当CAR≥0.03时提示单发小肝癌微血管侵犯发生率较高。     

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study

BackgroundDuring the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands.MethodsWe estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence.ResultsWith a decrease in numbers of sex partners of 15–25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred.ConclusionsDespite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

LINC00649通过miR-424-5p/IGF1R轴调控内质网应激介导的宫颈癌细胞凋亡

目的探讨LINC00649/miR-424-5p/IGF1R对内质网应激(ERs)介导的宫颈癌(CC)细胞凋亡的影响。方法从GEO数据库中获取CC相关的数据,并分析差异表达的miRNAs。利用生物信息学数据库预测miR-424-5p的上、下游靶点,将LINC00649和IGF1R纳入研究,随后双荧光素酶实验进一步验证靶向关系。qRT-PCR检测LINC00649、miR-424-5p和IGF1R在CC组织和细胞中的表达水平。CCK-8和流式细胞术分别评估CC细胞增殖和凋亡变化。Western blot检测ERs相关蛋白GRP78、CHOP和Caspase-12的表达。结果与癌旁组织和H8细胞相比,LINC00649和IGF1R在CC组织和细胞中表达上调,而miR-424-5p下调(均P<0.05)。LINC00649的异常高表达与CC患者的预后不良有关,敲减LINC00649可通过促进ERs来抑制CC细胞活力,诱导细胞凋亡(均P<0.05)。LINC00649吸附miR-424-5p上调IGF1R的表达。miR-424-5p抑制剂或过表达IGF1R均可部分逆转敲减LINC00649对CC细胞的影响(均P<0.05)。结论 LINC00649能够通过miR-424-5p/IGF1R抑制CC细胞的ERs过程进而减少细胞凋亡,提高细胞活力。