Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

2011—2020年平顶山市 乙型病毒性肝炎流行病学特征分析 时空分布特征及与性别、年龄变化情况

[摘要]　目的　分析河南省平顶山市2011—2020年乙型病毒性肝炎（乙肝）流行病学特征，为调整本市的乙肝防控策略和措施提供科学依据。方法?通过中国疾病预防控制信息系统收集网络直报的平顶山市2011—2020年乙肝病例数据，采用描述性流行病学方法进行分析。结果?2011—2020年平顶山市共报告27 078例乙肝病例，年平均发病率为67.47/10万，2016—2020年期间的年平均发病率（36.95/10万）较2011—2015年期间（98.46/10万）明显下降（χ2=5628.949，P=0.000）；急、慢性乙肝发病率分别为8.50/10万和57.88/10万；0～14岁以下儿童年平均发病率最低，为2.89/10万，随着年龄的增长，乙肝报告发病率呈现逐渐增高的趋势（χ2趋势=4644.258，P=0.000）；男性年平均发病率（71.21/10万）高于女性（63.44/10万）（χ2=89.803，P=0.000）；2016—2020年间发病率居前3位的分别为宝丰县（58.40/10万）、舞钢市（57.83/10万）、石龙区（56.50/10万），均为城郊地区。结论?平顶山市2011—2020年乙肝报告发病率呈下降趋势，尤以0～14岁以下儿童发病率较低。建议进一步加强成人乙肝防控工作，并重点加强宝丰县和舞钢市等高风险地区的防控工作。     

多模态超声对侵袭性前列腺癌的诊断价值及ROC曲线分析研究

目的：探讨多模态超声(MUS)对侵袭性前列腺癌(PCa)的诊断价值及受试者工作特征(ROC)曲线分析。方法：选择2018年01月至2021年02月于本院行手术切除并经病理证实的86例PCa患者作为研究对象,根据病理Gleason评分可分为两组,高侵袭组(Gleason＞4+3,共46例),低-中侵袭组(Gleason≤4+3,共40例)。所有患者术前均行MUS检查,包括经直肠常规超声(TRUS)、剪切波弹性成像(SWE)、超声造影(CEUS)。比较两组之间各参数的差异,采用ROC曲线分析其对高侵袭组PCa的诊断效能。结果：高侵袭组与低-中侵袭组的TRUS表现显著不同(P<0.05),其中高侵袭组中TRUS主要表现为弥漫性。高侵袭组SWE中SR比值(23.86±13.67)显著高于低-中侵袭组(12.82±11.95),差异具有统计学意义(P<0.05)。高侵袭组的CEUS参数中初始强度、峰值强度显著高于低-中侵袭组(P<0.05),而两组达峰时间、峰值减半时间无显著差异(P>0.05)。MUS对高侵袭组PCa诊断的ROC曲线下面积最大,敏感度、特异度也最高(P<0.05)。结论：MUS对高侵袭性PCa具有更高的诊断价值,有助于指导临床对治疗方案的选择。     

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.     

Maternal consumption of ɷ3 attenuates metabolic disruption elicited by saturated fatty acids-enriched diet in offspring rats

Background and aimsHigh-fat diet (HFD) intake during gestation and lactation has been associated with an increased risk of developing cardiometabolic disorders in adult offspring. We investigated whether metabolic alterations resulting from the maternal consumption of HFD are prevented by the addition of omega-3 (?3) in the diet.Methods and resultsWistar rat dams were fed a control (C: 19% of lipids and ?6:?3 = 12), HF (HF: 33% lipids and ?6:?3 = 21), or HF enriched with ?3 (HFω3: 33% lipids and ?6:?3 = 9) diet during gestation and lactation, and their offspring food consumption, murinometric measurements, serum levels of metabolic markers, insulin and pyruvate sensitivity tests were evaluated. The maternal HFD increased body weight at birth, dyslipidemia, and elevated fasting glucose levels in the HF group. The enrichment of ?3 in the maternal HFD led to lower birth weight and improved lipid, glycemic, and transaminase biochemical profile of the HFω3 group until the beginning of adulthood. However, at later adulthood of the offspring, there was no improvement in these biochemical parameters.ConclusionOur findings show the maternal consumption of high-fat ?3-rich diet is able to attenuate or prevent metabolic disruption elicited by HFD in offspring until 90 days old, but not in the long term, as observed at 300 days old of the offspring.     

主动脉出口血压对左心室血流特性的影响

采用Mimics对心脏进行三维重构，用3-matic进行模型优化以及模型误差分析，对左心室室壁运动做速度分布假设，基于UDF宏文件对左心室室壁运动编写程序，将血液视为非牛顿流体，采用动网格技术研究不同血压对左心室血液流动的影响。模拟发现当左心室收缩时，压力梯度明显，内部压力减小。当左心室舒张时，内部压力逐渐增高。二尖瓣口处的速率先增大后减小。血压升高，左心室内剪切应力持续增大，极易破坏红细胞结构，产生溶血现象，导致心脏功能紊乱。     

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.     

程序性死亡受体1和程序性死亡受体配体1在非小细胞肺癌组织中的表达情况及临床意义

目的探讨程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法选择150例NSCLC患者的NSCLC组织及其癌旁组织,采用实时荧光定量聚合酶链反应(PCR)检测两种组织中PD-1 mRNA和PD-L1 mRNA的相对表达量。采用免疫组织化学染色法检测NSCLC组织中PD-1和PD-L1的表达情况,分析PD-1和PD-L1表达情况与患者临床特征的关系。采用流式细胞术检测NSCLC组织和癌旁组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平。结果NSCLC组织中PD-1 mRNA和PD-L1 mRNA的相对表达量分别为(5.03±1.92)和(4.95±1.09),分别高于癌旁组织的(1.72±0.81)和(1.25±0.24),差异均有统计学意义(P﹤0.05)。TNM分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移、有远处转移的NSCLC患者NSCLC组织中PD-1和PD-L1的高表达率均明显高于TNM分期为Ⅰ~Ⅱ期、高+中分化、无淋巴结转移、无远处转移的患者,差异均有统计学意义(P﹤0.01)。NSCLC组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平均明显高于癌旁组织,差异均有统计学意义(P﹤0.01)。结论PD-1和PD-L1在NSCLC组织中高表达,可能成为一种新的生物标志物,PD-1/PD-L1信号通路可能参与了NSCLC的免疫逃逸过程,对其逃逸机制进行研究可以为NSCLC患者的临床治疗提供新靶点。     

薄层色谱法在当前中药质量标准中的应用探讨

薄层色谱鉴别在历版《中国药典》中的应用经历了从无到有、从少到多的过程；而薄层扫描含量测定在最近几版《中国药典》中的应用比例逐渐降低。随着对中药质量标准体系要求的进一步提高，薄层色谱法的不足之处陆续显现，如仪器普及率低、设备并不简单、结果重复性和稳定性较差、鉴别速度及准确性不及高效液相色谱法、展开剂毒性大等，逐渐不合时宜。在制定中药质量标准时，研究者不应该墨守成规，薄层色谱鉴别也不应该是雷打不动的定性鉴别必备选项。高效液相色谱法具备完全取代薄层色谱法的可行性，薄层色谱法可作为高效液相色谱法的补充。为充分降低检测成本、缩短检测周期、提高鉴别效率，笔者建议中药质量标准体系应该大幅减少薄层色谱鉴别方法的应用，增加高效液相特征图谱鉴定，尽量做到“一个条件，一张图谱”；除非确有必要，《中国药典》等国家质量标准体系应将薄层色谱鉴别作为推荐方法，而非强制标准。