基于长短期记忆网络和Logistic回归的重症监护病房脑卒中患者院内死亡风险预测

目的基于引入注意力机制的长短期记忆网络(long short-term memory，LSTM)和L1正则化的Logistic回归筛选变量，再通过传统的Logistic回归建立重症监护病房(intensive care unit，ICU)脑卒中患者院内死亡风险预测模型并评价模型效果。方法选取重症医学信息数据库(Medical Information Mart for Intensive Care-Ⅳ，MIMIC-Ⅳ)中的脑卒中患者作为研究对象，以是否发生院内死亡作为结局变量，备选预测因子包括人口学特征、合并症、入院48 h内实验室检查和生命体征检查等。将数据根据结局指标以8 ∶2的比例随机进行10次训练集和测试集的划分，在训练集上构建LSTM和L1正则化的Logistic回归模型，在测试集上选取重要程度排名前10的变量的并集纳入Logistic回归建立预测模型，以受试者工作特征曲线下面积(area under curve, AUC)、灵敏度、特异度、预测准确度为指标对模型进行评价，并与未预先进行变量筛选的前进法Logistic回归模型的预测效果进行比较。结果共纳入2 755例脑卒中患者的2 979条ICU入院记录，其中院内死亡记录占17.66%。两个变量筛选模型中，L1正则化的Logistic回归模型的AUC显著优于LSTM模型(0.819±0.031 vs. 0.760±0.018, P < 0.001)，两个模型中重要程度均位于前10的变量包括年龄、血糖和尿素氮。最终预测模型的AUC为0.85，灵敏度为85.98%，特异度为71.74%，预测准确率为74.26%，优于未预先进行变量筛选的前进法Logistic回归模型。结论用引入注意力机制的LSTM和L1正则的Logistic回归筛选出的变量的预测效果较好，具有一定的临床价值。     

术前外周血炎症指标对舌鳞状细胞癌预后预测价值的分析

目的探讨术前外周血炎症指标对舌鳞状细胞癌（TSCC）患者预后的预测价值。方法回顾性分析2010年1月至2017年12月于郑州大学第一附属医院因TSCC行根治性切除术的210例患者的临床病理资料，应用临床诊断性能曲线确定血小板/淋巴细胞比值（PLR）、中性粒细胞/淋巴细胞比值（NLR）的最佳截断值。生存单因素分析应用Kaplan-Meier法和Log-rank检验，多因素分析应用Cox比例风险回归模型，基于Cox回归模型筛选的独立危险因素构建Nomogram模型。结果单因素分析显示，PLR、NLR、肿瘤分化程度、T分期、N分期和TNM分期为影响TSCC预后的危险因素（P<0.05）；多因素分析显示，PLR、N分期和TNM分期为独立危险因素（P<0.05）。Nomogram模型的C指数为0.701（95%CI：0.651~0.752），校准曲线表明Nomogram模型预测无进展生存率与实际无进展生存率具有较好的一致性。结论术前外周血炎症指标对TSCC术后患者的预后可能有一定的预测作用。     

Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension

BackgroundAberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.MethodsFresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E₂) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.ResultsMany circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E₂ strongly regulated it. E₂ decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E₂ reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E₂ and miR‐21‐5p antagonist.ConclusionsmiR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E₂ on MCT‐PH through ERβ.     

一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效分析

目的观察一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损的疗效。方法回顾分析2021年7月—2022年2月符合选择标准的13例采用一次性皮肤拉拢装置治疗的难闭性皮肤软组织缺损患者临床资料。其中男9例，女4例；年龄15～71岁，平均39.8岁。致伤原因：摔伤5例，交通事故伤5例，高处坠落伤3例。皮肤软组织缺损原因：开放骨折4例，伤口感染4例，骨髓炎3例，脱套伤1例，植皮坏死1例。损伤部位：小腿8例，跟骨3例，骨盆1例，足底1例。皮肤软组织缺损范围为5.0 cm×2.0 cm～10.5 cm×6.5 cm。记录伤口情况（包括伤口闭合和伤口愈合）及有无并发症等情况。结果13例患者均获随访，随访时间32～225 d，中位时间164 d。伤口闭合时间5～14 d，平均8.8 d；伤口闭合速度0.7～13.7 cm²/d，平均3.6 cm²/d。所有伤口均甲级愈合，均未发生皮缘损伤、伤口坏死、感染、裂开、水肿等并发症，患者均未诉疼痛不适等，随访时未发现明显瘢痕形成等情况。伤口愈合时间17～28 d，平均21.7 d。其中1例使用该装置后因肺癌病情变化转科，术后17 d随访时伤口未经缝合已直接愈合。 结论一次性皮肤拉拢装置治疗难闭性皮肤软组织缺损疗效确切，伤口闭合时间短，并发症少，操作简便。     

Clinical Utility of Genomic Assay in Node-Positive Early-Stage Breast Cancer

Breast cancer (BC) is the most common malignancy among women in Canada. Adjuvant treatment in early BC can reduce the risk of BC recurrence. Historically, the decision for adjuvant chemotherapy for early BC was made only based on clinical and tumour characteristics. In recent years, there has been an effort toward developing genomic assays as a predictive and prognostic tool to improve precision in estimating disease recurrence, sensitivity to systemic treatment and ultimately with clinical utility for guidance regarding adjuvant systemic treatment(s). There are various commercial genomic tests available for early-stage ER+/HER-2 negative BC. This paper will review the Oncotype DX 21-gene Recurrence Score (RS), MammaPrint, EndoPredict, Prosigna^®, and Breast Cancer Index (BCI) genomic assays. We will also focus on these genomic assays’ clinical application and utility in node-positive early-stage BC based on the most recent evidence and guidance recommendations.     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

反义miR-21通过调控hTERT表达抑制胶质瘤细胞生长

目的探讨敲低miR-21表达对人胶质瘤细胞系U87细胞功能的影响以及相关作用机制。方法脂质体介导转染miR-21反义寡聚核苷酸（miR-21 inhibitor）敲低U87细胞miR-21的表达。使用实时荧光定量PCR鉴定转染后U87细胞miR-21表达水平;MTT法检测转染后细胞增殖水平,流式法评价转染后细胞周期分布及凋亡变化,并结合Western印迹及RT-PCR验证在U87细胞中miR-21和hTERT间关系。结果体外转染反义miR-21寡聚核苷酸能明显抑制U87细胞生长,诱导其凋亡,并且能够明显下调hTERT表达。结论反义miR-21可能通过下调hTERT表达抑制胶质细胞生长,miR-21可作为胶质瘤基因治疗的靶点。     

胃癌组织中P53及P21蛋白的表达及意义

目的：探讨P53和P21蛋白异常表达在胃癌发生发展中的作用。方法：应用免疫组化技术检测38例胃癌及相应癌旁组织中P53和P21蛋白的表达。结果：胃癌组织P53蛋白表达率84．21％（32／38）,癌旁组织P53蛋白表达均为阴性。胃癌组织P53蛋白表达率明显高于癌旁组织,差别具有显著性（χ^2=55．27,P〈0．05）。胃癌组织P21蛋白阳性表达率52．63％（20／38）,癌旁组织P21蛋白阳性表达率89．73％（34／38）,胃癌组织P21蛋白阳性表达率明显低于癌旁组织,差别有显著性（χ^2=12．546,P〈0．05）。胃癌组织中P21与P53蛋白共同阳性表达率为47．36％,但两者无相关性（P〉0．05）。结论：P53和P21蛋白表达异常与胃癌发生有着密切关系。     

Circ_SAR1A regulates the malignant behavior of lung cancer cells via the miR‐21‐5p/TXNIP axis

BackgroundLung cancer is one of the most common malignancies globally and a significant component of cancer‐related deaths. The lack of early diagnosis accounts for detecting approximately 75% of cancer patients at an intermediate to an advanced stage, with a low 5‐year survival rate. Therefore, a more comprehensive understanding of the molecular mechanisms of lung cancer development is necessary to find reliable and effective therapeutic and diagnostic biomarkers.Methodscirc_SAR1A, miR‐21‐5p, and TXNIP in lung cancer tissues, animal xenografts, and cell lines were validated by qRT‐PCR and western blotting analyses. RNase R digestion and nuclear/cytoplasm fractionation experiments were utilized to determine the stability and localization of circ_SAR1A in lung cancer cells. The binding between miR‐21‐5p and circ_SAR1A or TXNIP was confirmed by luciferase reporter, RNA pull‐down, Spearman''s correlation, and rescue assays. CCK‐8, colony formation, flow cytometry, Transwell, and western blotting were utilized to illustrate the malignant behavior of lung cancer cells.Resultscirc_SAR1A and TXNIP were down‐regulated while miR‐21‐5p was up‐regulated in lung cancer samples and cells. circ_SAR1A was located predominantly in the cytoplasm; it inhibited lung cancer growth in vitro and in vivo by sponging to miR‐21‐5p. miR‐21‐5p silencing suppressed lung cancer malignancy by targeting TXNIP.Conclusionscirc_SAR1A is a critical negative regulator of lung carcinogenesis. circ_SAR1A/miR‐21‐5p/TXNIP attenuation inhibited lung cancer progression, presenting an ideal diagnostic and a potential therapeutic target.     

16th Asian Congress of Surgery and 3rd Chinese Surgical Week

In the case of a previous offspring with trisomy 21, recurrence risk for Down syndrome is about 1%. It may be due to chance, but the possibility of germline mosaicism for trisomy 21 in one of the parents has important implications for the recurrence. Here we report a young healthy mother, who has a second pregnancy of trisomy 21.[第一段]