Uterine cervical neoplasms

宫颈肿瘤
  • 文章类型: Journal Article
    UNASSIGNED: Human papillomavirus (HPV) testing as a method of cervical cancer screening can be performed by healthcare providers or by patients through self-sampling directly in the community, removing several barriers experienced by under screened populations. The objective of this scoping review was to determine which HPV self-sampling implementation and engagement strategies have been used to engage under screened populations (i.e., Indigenous, newcomer, and rural and remote communities) in cervical cancer screening.
    UNASSIGNED: A scoping review was conducted searching MEDLINE, CINAHL, EMBASE, Cochrane Library, and SocINDEX from inception to August 2023. The inclusion criteria were: (1) Indigenous, newcomer, and rural and remote communities; (2) countries identified as members of the Organization for Economic Co-operation and Development; and (3) intervention included HPV self-sampling. The review was registered prior to conducting the search (https://osf.io/zfvp9).
    UNASSIGNED: A total of 26 studies out of 2,741 studies met the inclusion criteria. In-person engagement with trusted community leaders was the most widely used and accepted recruitment and engagement strategy across all three populations. Six out of seven studies with Indigenous communities distributed HPV self-sampling kits to eligible participants in person in a clinical setting for collection on site or at home. Similarly, nine of the identified studies that engaged newcomers recruited participants in person through the community, where eligible participants were either given a kit (n = 7) or received one in the mail (n = 2). Lastly, of the 10 identified studies engaging rural and remote participants in HPV self-sampling, six recruited eligible participants in person at various community locations and four used electronic medical records or registries to identify and mail kits to participants.
    UNASSIGNED: HPV self-sampling through in person kit distribution and mail out of HPV self-sampling kits is an effective way to increase participation rates amongst under screened populations.
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  • 文章类型: Journal Article
    尽管广泛的宫颈癌(CC)筛查计划,低参与导致高发病率和死亡率,尤其是在发展中国家。因为早期CC通常没有症状,需要一种非侵入性和方便的诊断方法来改善疾病检测。在这项研究中,我们开发了一种新的方法来区分CC和宫颈上皮内瘤变(CIN)2/3,一种癌前病变,通过探索CC脂肪酸代谢重编程从健康个体。对公共数据集的分析表明,各种脂肪酸代谢酶在CC组织中的表达水平高于正常组织。相应地,与健康供体样品相比,11个游离脂肪酸(FFA)在CC患者样品中显示出显著不同的血清水平。这11个FFA中有9个在CIN2/3患者中也显示出明显的改变。然后,我们使用这些FFA的组合生成诊断模型,最佳模型包括硬脂酸和二高-γ-亚麻酸。受试者工作特征曲线分析表明,与使用血清鳞状细胞癌抗原水平相比,该诊断模型可以更准确地检测CC和CIN2/3。此外,无论临床分期或组织学类型,使用FFA的诊断模型都能够检测患者.总的来说,在这项研究中开发的血清FFA诊断模型可能是一个强大的新工具,用于非侵入性的早期检测CC和CIN2/3。
    Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.
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  • 文章类型: Journal Article
    巴西的宫颈癌筛查是机会主义的,基于细胞学,为25-64岁的女性提供,覆盖率低(30%),70%的癌症诊断是在晚期完成的,对死亡率没有影响。当前的研究报告了巴西城市基于人群的DNA-HPV检测筛查计划的5年第一轮结果,它旨在成为向更有效程序过渡的模型。程序流程图简单而最新,表明五年后重复进行阴性测试。第一轮(2017年10月至2022年9月)通过DNA-HPV检测筛查了20,551名女性,覆盖率为58.7%,符合该计划的目标年龄范围为99.4%。当排除“大流行期”时,覆盖率增加到77.8%。DNA-HPV检测为87.2%阴性,进行了6.2%的阴道镜转诊和84.8%的阴道镜检查。共有258个高级别前体病变和29个宫颈癌(平均年龄=41.4岁,检测到83%的阶段I)。作为参考,先前计划(2012-2016年)的41,387个细胞学检查检测到36个宫颈癌(平均年龄=52.0岁,p=0.0005),67%处于高级阶段(p<0.0001)。使用DNA-HPV检测组织宫颈癌筛查显示出良好的覆盖率,高年龄和阴道镜检查依从性,并提前10年发现更多的癌前病变和宫颈癌。
    Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25-64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program\'s targeted age range. Coverage increases to 77.8% when excluding the \'pandemic period\'. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012-2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p < 0.0001). Organizing cervical cancer screening using DNA-HPV testing demonstrated good coverage, high age and colposcopy compliance, and detection of more precancerous lesions and cervical cancers 10 years in advance.
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  • 文章类型: Journal Article
    告知有针对性的干预措施的设计和实施,以减轻德克萨斯州人乳头瘤病毒(HPV)相关癌症的未来负担,有必要检查县和卫生服务地区(HSR)的水平(1)开始并更新HPV疫苗系列的9~17岁儿童和青少年的比例,以及(2)HPV相关癌症发病率(IRs).
    评估德克萨斯州县和HSR水平的HPV疫苗接种开始和最新状态以及HPV相关癌症发病率的时间趋势和地理空间模式。
    这项基于人群的横断面研究使用了德克萨斯州免疫登记处的数据,国家癌症研究所的监测,流行病学,和最终结果程序数据库,和德克萨斯州卫生服务部从2006年到2022年的年度人口统计。在9至17岁的儿童和青少年中进行了HPV疫苗接种率的分析;在20岁及以上的成年人中进行了HPV相关癌症发生率的分析。数据在2023年6月至7月之间提取,并在2024年2月至4月进行统计分析。
    县和HSR水平的HPV疫苗接种开始和最新状态率以及HPV相关癌症IR。
    共32270243名儿童和青少年(65.8%的女性和34.2%的男性)和22490105名20岁及以上的个体(50.7%的女性和49.3%的男性)包括在内。2021年至2022年县级HPV疫苗接种系列的平均起始估计范围为女性的6.3%至69.1%,男性9至17岁的儿童和青少年的7.0%至77.6%。县级疫苗接种的最新估计值通常低于初始估计值,女性为1.6%至30.4%,男性儿童和青少年为2.1%至34.8%。按性别分层的HPV疫苗接种率在县和HSR之间相似。2016年至2020年各县的年龄调整后的年度HPV相关癌症IR,女性个体为0至154.2/100000,男性个体为0至60.1/100000。位于北德克萨斯州的县,HSRs2/3和4/5N,与其他地区相比,女性和男性个体的HPV疫苗接种率较低,HPV相关癌症的IR较高。
    在这项研究中,HPV相关癌症的发病率在德克萨斯州各县和HSR之间差异很大.北德克萨斯州更多的县,HSRs2/3和4/5N,与其他地区相比,HPV相关癌症的IR较高,HPV疫苗接种率的比例较低。设计和实施有针对性的干预措施,以增加HPV疫苗接种率低的县的HPV疫苗接种系列的吸收和完成,可能有助于减轻未来HPV相关癌症的负担。
    UNASSIGNED: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs).
    UNASSIGNED: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas.
    UNASSIGNED: This population-based cross-sectional study used data from the Texas Immunization Registry, the National Cancer Institute\'s Surveillance, Epidemiology, and End Results Program database, and Texas Department of State Health Services annual population counts from 2006 to 2022. The analysis of HPV vaccination rates was conducted among children and teenagers aged 9 to 17 years; the analysis of HPV-related cancer rates was conducted among adults aged 20 years and older. Data were extracted between June and July 2023 and statistical analysis was performed from February to April 2024.
    UNASSIGNED: HPV vaccination initiation and up-to-date status rates and HPV-related cancer IR at county and HSR levels.
    UNASSIGNED: A total of 32 270 243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22 490 105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included. The mean 2021 to 2022 county-level HPV vaccination series initiation estimates ranged from 6.3% to 69.1% for female and from 7.0% to 77.6% for male children and teenagers aged 9 to 17 years. County-level vaccination up-to-date estimates were generally lower compared with those of initiation estimates and ranged from 1.6% to 30.4% for female and from 2.1% to 34.8% for male children and teenagers. The pattern of HPV vaccination rates stratified by sex were similar across counties and HSRs. The age-adjusted annual HPV-related cancer IR by county for years 2016 to 2020 ranged from 0 to 154.2 per 100 000 for female individuals and from 0 to 60.1 per 100 000 for male individuals. The counties located in North Texas, HSRs 2/3 and 4/5N, had lower HPV vaccination rates and higher IRs of HPV-related cancers for both female and male individuals compared with other regions.
    UNASSIGNED: In this study, the incidence of HPV-related cancers varied widely across the counties and HSRs of Texas. More counties in North Texas, HSRs 2/3 and 4/5N, had higher IRs of HPV-related cancers and a lower proportion of HPV vaccination rates than counties in other regions. Designing and implementing targeted interventions to increase uptake and completion of HPV vaccination series across counties with low HPV vaccination rates may help to reduce future the burden of HPV-related cancers.
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  • 文章类型: Journal Article
    背景:小分子荧光探针在不同宫颈病变中甲基化检测的价值分析。
    方法:(1)4组不同病变组织的灰度值差异显著(p<0.05)。两组之间灰度值的比较显示,CA组明显超过LSIL和宫颈炎组,且HSIL组明显高于LSIL组和宫颈炎组(p<0.05);(2)以55.21为中线计算入组受试者的平均灰度值,>55.21为正,≤55.21为负。
    结果:结果显示,宫颈炎组的阳性率为0.00%,LSIL组67.74%,HSIL组83.33%,和CA组100.00%。四组之间的结果明显不同(p<0.05);(3)DAPI之间的比较,探针,明亮,和合并的宫颈炎图像,LSIL,HSIL,和CA表明不同的宫颈病变有相当不同的染色。
    结论:灰度值,阳性率,不同宫颈病变的染色图像明显不同。该小分子荧光探针对宫颈病变具有较好的鉴别价值,可考虑推广应用。
    BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions.
    METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative.
    RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains.
    CONCLUSIONS: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.
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  • 文章类型: Journal Article
    背景:2019年冠状病毒(COVID-19)大流行影响了几个国家的癌症医疗保健,延迟检测和治疗乳腺癌和宫颈癌。本研究的目的是分析和比较筛选,在COVID-19前期和COVID-19期间诊断和治疗乳腺癌和宫颈癌。
    方法:从死亡率信息系统(SIM)收集的次要数据的横断面研究,医院信息系统(SIH)门诊信息系统(SIA)和肿瘤学小组(PO)的乳腺癌通知,包括ICDC50.0至C50.9和子宫颈ICDC53.0至C53.9,大流行之前的分析期为2019年3月1日至10月1日,大流行期间为2020年3月1日至10月1日。2013年至2022年期间也用相同的信息进行了分析,包括诊断的数量,治疗,和死于乳腺癌和宫颈癌。研究人群包括25至70岁的巴西女性。为了比较不同时期的分类变量,卡方或费舍尔精确检验,并且应用了Mann-WhitneyU测试,并应用泊松回归模型对报告的COVID-19病例数和手术量进行建模。
    结果:COVID-19期间乳房X线照片和细胞病理学检查的数量减少,乳腺癌和宫颈癌病例减少。Poisson回归分析显示COVID-19病例数增加导致乳腺细胞病理学检查次数减少,宫颈-阴道细胞病理学检查/微生物区系和筛查,诊断,开始治疗乳腺癌和死于这种疾病。同时,在巴西的一些地区,随着新冠肺炎数量的增加,乳房X光检查和宫颈癌诊断的数量显着增加。
    结论:2020年的COVID-19期显着影响筛查,诊断,治疗乳腺癌和宫颈癌。
    BACKGROUND: The coronavirus 2019 (COVID-19) pandemic impacted cancer health care in several countries, with delays in the detection and treatment of breast and cervical cancer. The objective of this study is to analyze and compare the screening, diagnosis and treatment of breast and cervical cancer in the pre-COVID period and during the COVID-19 period.
    METHODS: Cross-sectional study with secondary data collected from the Mortality Information System (SIM), Hospital Information System (SIH), Ambulatory Information System (SIA) and the Oncology Panel (PO) of breast cancer notifications with ICD C50.0 to C50.9 and cervix ICD C53.0 to C53.9, The analyzed period before the pandemic was from March 1 to October 1, 2019, and during the pandemic from March 1 to October 1, 2020. The period from 2013 to 2022 was also analyzed with the same information, including the number of diagnoses, treatments, and deaths from breast cancer and cervical cancer. The study population consisted of Brazilian women aged 25 to 70 years. In order to compare categorical variables between periods, the Chi-Square or Fisher\'s Exact tests, and Mann-Whitney U tests were applied, and the Poisson Regression model was applied to model the number of reported cases of COVID-19 and the amount of procedures.
    RESULTS: There was a decrease in the number of mammograms and cytopathological exams during COVID-19, as well as a decrease in cases of breast and cervical cancer. The Poisson regression showed that the increase in the number of COVID-19 cases caused a decrease in the number of breast cytopathological examinations, cervical-vaginal cytopathological examinations/microflora and screening, diagnosis, initiation of treatment for breast cancer and deaths from this disease. Meanwhile, in some regions of Brazil, as the number of Covid-19 increased, there was a significantly increase in the number of mammograms performed and cervical cancer diagnoses.
    CONCLUSIONS: The COVID-19 period in 2020 significantly impacted screening, diagnosis, treatment for breast and cervical cancer.
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  • 文章类型: Journal Article
    背景:微RNA(miRNA)是单RNA分子,其在哺乳动物细胞中充当基因表达的全局调节因子,因此在治疗癌症中构成有吸引力的靶标。在这里,我们旨在研究miRNA-141(miR-141)在宫颈癌中的可能参与,并确定其在宫颈癌细胞系中的潜在靶标。
    方法:使用定量实时PCR(qRT-PCR)评估了HeLa和C-33A细胞中miR-141的水平。已经在用GFP标记的CMV启动子载体中进行了新的miR-141构建体。使用微阵列分析,我们在转染的HeLa细胞中鉴定了miR-141可能调控的基因.杀手样受体C1(KLRC1)的蛋白质谱,KLRC3,癌胚抗原相关细胞粘附分子3(CAM3),和CAM6在HeLa细胞中进行了研究,转染了任何一种抑制剂,使用免疫印迹和流式细胞术测定拮抗剂miR-141或miR-141过表达载体。最后,ELISA测定法已用于监测从转染的HeLa细胞产生的细胞因子。
    结果:与正常宫颈HCK1T细胞系相比,miR-141在HeLa和C-33A细胞中的表达显着增加。用抑制剂转染HeLa细胞,拮抗剂miR-141,显示对癌细胞活力的有效影响,与miR-141过表达载体的转染不同。过表达miR-141的HeLa细胞的微阵列数据提供了一百个下调的基因,包括KLRC1、KLRC3、CAM3和CAM6。在miR-141过表达的HeLa细胞中,KLRC1和KLRC3表达谱明显减少,同时白细胞介素8(IL-8)减少,表明miR-141在避免HeLa细胞中程序性细胞死亡中的作用。同样,在miR-141转导的细胞中,CAM3和CAM6表达显着降低,伴随着转化生长因子β(TGF-β)水平的升高,表明miR-141在癌细胞迁移中的影响。使用IntaRNA程序和miRWalk检查miR-141与鉴定的基因之间的直接相互作用和潜在结合位点。基于此,将每个潜在靶标的接种区域克隆到pGL3对照载体中荧光素酶报告基因的上游。有趣的是,miR-141过表达载体预转染HeLa细胞后,构建载体的荧光素酶活性显著降低,而在预转染miR-141特异性抑制剂的细胞中大幅增加。
    结论:一起,这些数据揭示了支持宫颈癌进展的基于miR-141的有效机制,并将miR-141确定为可靠的治疗靶标.
    BACKGROUND: MicroRNAs (miRNAs) are single RNA molecules that act as global regulators of gene expression in mammalian cells and thus constitute attractive targets in treating cancer. Here we aimed to investigate the possible involvement of miRNA-141 (miR-141) in cervical cancer and to identify its potential targets in cervical cancer cell lines.
    METHODS: The level of miR-141 in HeLa and C-33A cells has been assessed using the quantitative real-time PCR (qRT-PCR). A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HeLa cells. The protein profile of killer-like receptor C1 (KLRC1), KLRC3, carcinoembryonic antigen-related cell adhesion molecule 3 (CAM3), and CAM6 was investigated in HeLa cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced cytokines from transfected HeLa cells.
    RESULTS: The expression of miR-141 significantly increased in HeLa and C-33A cells compared to the normal cervical HCK1T cell line. Transfection of HeLa cells with an inhibitor, antagonist miR-141, showed a potent effect on cancer cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HeLa cells overexpressed miR-141 provided a hundred of downregulated genes, including KLRC1, KLRC3, CAM3, and CAM6. KLRC1 and KLRC3 expression profiles markedly depleted in HeLa cells transfected with miR-141 overexpression accompanied by decreasing interleukin 8 (IL-8), indicating the role of miR-141 in avoiding programmed cells death in HeLa cells. Likewise, CAM3 and CAM6 expression reduced markedly in miR-141 transduced cells accompanied by an increasing level of transforming growth factor beta (TGF-β), indicating the impact of miR-141 in cancer cell migration. The IntaRNA program and miRWalk were used to check the direct interaction and potential binding sites between miR-141 and identified genes. Based on this, the seeding regions of each potential target was cloned upstream of the luciferase reporter gene in the pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HeLa cells pre-transfected with miR-141 overexpression vector, while increasing enormously in cells pre-transfected with miR-141 specific inhibitor.
    CONCLUSIONS: Together, these data uncover an efficient miR-141-based mechanism that supports cervical cancer progression and identifies miR-141 as a credible therapeutic target.
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  • 文章类型: Journal Article
    背景:作为营养状况的评估工具,控制营养状况(CONUT)和改良控制营养状况(mCONUT)评分与各种癌症的生存率相关.我们旨在研究CONUT/mCONUT评分的预后价值与放疗治疗的IIB-IIIB期宫颈癌患者生存时间之间的关系。
    方法:在这项回顾性研究中,对2013年9月至2015年9月的165例患者进行分析,和最佳CONUT/mCONUT得分截止值使用受试者工作特征曲线确定。使用倾向评分匹配(PSM)来最小化选择偏差。使用Kaplan-Meier方法和Cox比例风险模型评估CONUT/mCONUT评分与生存时间相关的预测值。创建两个列线图来预测总生存期(OS)和无进展生存期(PFS)。
    结果:CONUT和mCONUT评分的临界值均为2。低CONUT评分组的五年OS和PFS率高于高CONUT评分组(OS:81.1%vs.53.8%,分别,P<0.001;PFS:76.4%vs.48.2%,分别;P<0.001)。高CONUT评分与OS(风险比(HR)2.93,95%CI1.54-5.56;P=0.001)和PFS(HR2.77,95%CI1.52-5.04;P<0.001)降低相关。高CONUT评分影响PSM队列中的OS。在Cox回归分析中,高mCONUT评分与OS和PFS降低无关。
    结论:CONUT评分是预测接受放疗的宫颈癌患者生存的一个有前景的指标。
    BACKGROUND: As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score\'s prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy.
    METHODS: In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score\'s predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS).
    RESULTS: The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis.
    CONCLUSIONS: The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.
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  • 文章类型: Journal Article
    宫颈癌(CC)是全球女性中第四大常见恶性肿瘤,是发展中国家女性癌症相关死亡的主要原因。CC的早期症状往往不明显,诊断通常是在晚期阶段进行的,导致不良的临床预后。近年来,大量研究表明,肥大细胞(MCs)与肿瘤的发生发展有着密切的关系。然而,目前对MC在CC中所起作用的研究还非常有限。因此,这项研究对人类CC细胞进行了单细胞多组学分析,目的探讨MC与CC中肿瘤微环境相互作用的机制。目的是为预防提供科学依据,诊断,和CC的治疗,希望改善患者预后和生活质量。
    本研究从ArrayExpress数据库中的十个CC肿瘤样品获得单细胞RNA测序数据。弹弓和AUCcell用于推断和评估MC亚群的分化轨迹和细胞可塑性。CC中MCs亚群的差异表达分析,采用基因本体论,基因集富集分析,和基因集变异分析。应用CellChat软件包预测MC亚群与CC细胞之间的细胞通讯。细胞功能实验验证了HeLa和Caski细胞系中TNFRSF12A的功能。此外,建立了一个风险评分模型来评估临床特征的差异,预后,免疫浸润,免疫检查点,以及各种风险评分的功能丰富。使用拷贝数变异的推断来计算拷贝数变异水平。
    将获得的93,524个高质量细胞分为十种细胞类型,包括T_NK细胞,内皮细胞,成纤维细胞,平滑肌细胞,上皮细胞,B细胞,浆细胞,MC,中性粒细胞,和骨髓细胞。此外,总共1392个MC被细分为七个亚群:C0CTSG+MC,C1CALR+MC,C2ALOX5+MC,C3ANXA2+MC,C4MGP+MC,C5IL32+MC,和C6ADGRL4+MC。值得注意的是,C2亚群与肿瘤相关的MC密切相关,弹弓结果表明C2亚群位于分化的中晚期,可能代表CC良性至恶性转化的关键过渡点。CNVscore和批量分析结果进一步证实了C2亚群的转化状态。CellChat分析显示TNFRSF12A是参与C2ALOX5+MC作用的关键受体。此外,体外实验表明下调TNFRSF12A基因可能部分抑制CC的发展。此外,基于C2亚群标记基因的预后模型和免疫浸润分析为患者预后和临床干预策略提供了有价值的指导.
    我们首先确定了CC内的转化性肿瘤相关MC亚群C2ALOX5+MC,处于肿瘤分化的关键阶段,并影响CC的进展。体外实验证实了敲低TNFRSF12A基因对CC发展的抑制作用。基于C2ALOX5+MC亚群构建的预后模型显示出优异的预测价值。这些发现为CC的临床决策提供了新的视角。
    UNASSIGNED: Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients\' prognoses and quality of life.
    UNASSIGNED: The present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations.
    UNASSIGNED: The obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies.
    UNASSIGNED: We first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.
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  • 文章类型: Journal Article
    背景:宫颈癌(CC)和乳腺癌(BC)威胁着女性的福祉,受与健康相关的耻辱和缺乏可靠信息的影响,这可能会导致晚期诊断和早期死亡。ChatGPT很可能成为健康信息的关键来源,尽管质量问题也会影响寻求健康的行为。
    方法:这项横断面在线调查比较了ChatGPT对五名专门从事乳房X线照相术的医生和五名专门从事妇科的医生的反应。关于CC和BC的二十个常见问题被问到4月26日和29日,2023年。由七名专家组成的小组评估准确性,一致性,以及使用7点李克特量表的ChatGPT反应的相关性。分析了反应的可读性,可靠性,和效率。ChatGPT的反应被合成,结果以雷达图的形式呈现。
    结果:ChatGPT对CC和BC问题的准确性得分为7.0(范围:6.6-7.0),超过得分最高的医师(P<0.05)。ChatGPT平均花费13.6s(范围:7.6-24.0)来回答所提出的20个问题中的每一个。可读性与所涉及的专家和医生相当,但与医生相比,ChatGPT产生了更多的扩展反应。重复回答的一致性为5.2(范围:3.4-6.7)。结合不同的上下文,总体ChatGPT相关性评分为6.5分(范围:4.8-7.0分).雷达图分析表明精度相当好,效率,在某种程度上,相关性。然而,有明显的不一致之处,可靠性和可读性被认为是不够的。
    结论:ChatGPT有望成为CC和BC的初始信息来源。ChatGPT也具有很高的功能,似乎优于医生,并符合专家共识,尽管可读性还有改进的空间,可靠性,和一致性。未来的工作应该集中在开发先进的ChatGPT模型上,这些模型明确旨在改善医疗实践和对症状有担忧的人。
    BACKGROUND: Cervical cancer (CC) and breast cancer (BC) threaten women\'s well-being, influenced by health-related stigma and a lack of reliable information, which can cause late diagnosis and early death. ChatGPT is likely to become a key source of health information, although quality concerns could also influence health-seeking behaviours.
    METHODS: This cross-sectional online survey compared ChatGPT\'s responses to five physicians specializing in mammography and five specializing in gynaecology. Twenty frequently asked questions about CC and BC were asked on 26th and 29th of April, 2023. A panel of seven experts assessed the accuracy, consistency, and relevance of ChatGPT\'s responses using a 7-point Likert scale. Responses were analyzed for readability, reliability, and efficiency. ChatGPT\'s responses were synthesized, and findings are presented as a radar chart.
    RESULTS: ChatGPT had an accuracy score of 7.0 (range: 6.6-7.0) for CC and BC questions, surpassing the highest-scoring physicians (P < 0.05). ChatGPT took an average of 13.6 s (range: 7.6-24.0) to answer each of the 20 questions presented. Readability was comparable to that of experts and physicians involved, but ChatGPT generated more extended responses compared to physicians. The consistency of repeated answers was 5.2 (range: 3.4-6.7). With different contexts combined, the overall ChatGPT relevance score was 6.5 (range: 4.8-7.0). Radar plot analysis indicated comparably good accuracy, efficiency, and to a certain extent, relevance. However, there were apparent inconsistencies, and the reliability and readability be considered inadequate.
    CONCLUSIONS: ChatGPT shows promise as an initial source of information for CC and BC. ChatGPT is also highly functional and appears to be superior to physicians, and aligns with expert consensus, although there is room for improvement in readability, reliability, and consistency. Future efforts should focus on developing advanced ChatGPT models explicitly designed to improve medical practice and for those with concerns about symptoms.
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