一种预测子宫内膜病变患者内膜病理类型的临床模型＊

目的 开发并评估一种用于预测子宫内膜病变患者内膜病理类型的临床模型；方法 选取2019年11月至2021年11月因妇科B超发现子宫内膜病变并于山东中医药大学附属医院行宫腔镜下内膜活检的患者，结合其病史与最小绝对收缩和选择算子法（Least absolute shrinkage and selection operator，LASSO）筛选影响内膜病变的独立危险因素，列线图（nomogram）函数建立列线图模型，采用ROC曲线下方的面积大小（Area Under Curve， AUC）、C指数（C-index）、拟合优度（Hosmer-Lemeshow）检验、自举法（bootstrap）评估及验证模型，依据列线图对纳入患者进行风险赋分，绘制ROC曲线获取风险评分的截断值，从而划分高低风险的人群；结果 阴道流血、绝经、无流产史、并发高血压、B超内膜厚度增厚、内膜回声不正常，中医证型为虚实夹杂证是发生子宫内膜癌及癌前病变的独立危险因素，评估模型所得AUC值与C-index均>0.9，Hosmer-Lemeshow检验显示P>0.05，bootstrap内部验证法所得C-index亦高于0.9，均说明模型准确度、区分度及可信度良好，当患者的风险评分总和≥177分时，属于高风险人群；结论 本模型可以预测B超提示子宫内膜病变患者的内膜病理类型为癌前或恶变型的概率并识别高风险人群。     

中医药对淋巴管新生与回流功能的作用研究进展＊

淋巴管作为循环系统的重要组成部分之一，具有调节机体体液稳态，协助免疫监视和肠道脂质吸收等重要作用。淋巴管新生是机体生理和病理过程中维持脉管系统结构和功能正常的重要手段，淋巴管新生调控对于防治肿瘤、心血管等诸多疾病有着潜在的临床转化意义；淋巴回流功能则与关节炎症等疾病发病机制关系密切。在循环系统中，相较于中医药调控血管相关疾病的发病机制已取得很大进展，近年来对于淋巴管的研究则明显相对滞后。本文从中医药作用于淋巴管新生及回流功能角度对这一领域的研究进展作一综述，以期为临床上中医药治疗相关疾病提供新的思路与方法。     

Time-varying association of second primary malignancy and long-term survival outcomes in patients with head and neck cancer

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP-HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time-varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP-HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow-up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20-3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP-HNSCC vs regional IP-HNSCC (HR_OS, 3.41; 95% CI: 3.24-3.6 vs HR_OS, 3.18; 95% CI: 3.05-3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.     

住院癌症患者衰弱风险预测模型的构建与验证

目的 调查住院癌症患者发生衰弱的危险因素，构建风险预测模型并检验预测效果。方法 选取广州市2所三级甲等医院住院癌症患者570例，分为建模集422例和验证集148例。采用一般资料调查表、Fried衰弱表型、安德森症状评估量表、医院焦虑抑郁量表、中文版失志量表、营养风险筛查2002、Barthel指数量表进行调查，同期收集患者的白细胞介素-6、C-反应蛋白等实验室指标，应用logistic回归分析筛选衰弱的独立危险因素，构建风险预测模型。结果 住院癌症患者衰弱发生率为33.7%,衰弱的影响因素分别为：造口、营养状况、抑郁、神经心理症状群、消化道症状群、D-二聚体、白细胞介素-6。建模集和验证集ROC曲线下面积为0.788、0.735;Brier得分为0.205,校准斜率为0.625,决策曲线分析表明模型具有一定的临床可用性。结论 住院癌症患者衰弱发生率较高，构建的列线图预测模型具有较好的风险预测价值，可有效识别和筛选住院癌症衰弱高危人群。     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。     

Tumor Mutation Burden,Immune Cell Infiltration,and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors.Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model.Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis.Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635.Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.     

PBL联合PDG在临床医学系高年级医学生中的应用

目的研究以问题为导向的教学方法(PBL)联合问题—讨论—指导(PDG)教学模式在临床医学系高年级医学生培养中的应用效果。方法选取2018年1月—2019年1月临床医学系高年级医学生134例,按随机数字表分为对照组(67例)与研究组(67例),对照组学生采用传统的教学模式,研究组学生采用PBL联合PDG教学模式,比较两组学生理论考试成绩、教学质量与教学效果评分。结果研究组学生的总成绩、教学质量优良率、教学效果各项评分均显著高于对照组(P<0.05)。结论在临床医学系高年级医学生培养中应用PBL联合PDG教学模式,可以有效提高学生对理论知识的掌握与教学效果,提高教学质量。     

Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region

PurposeTo report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol.Materials and MethodsA total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300–500 μm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits.ResultsNine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed.ConclusionsTASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.