凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

Biomarkers of in vivo limbal stem cell function

PurposeTo evaluate in vivo parameters as biomarkers of limbal stem cell function and to establish an objective system that detects and stage limbal stem cell deficiency (LSCD).MethodsA total of 126 patients (172 eyes) with LSCD and 67 normal subjects (99 eyes) were included in this observational cross-sectional comparative study. Slit-lamp biomicroscopy, in vivo laser scanning confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT) were performed to obtain the following: clinical score, cell morphology score, basal cell density (BCD), central corneal epithelial thickness (CET), limbal epithelial thickness (LET), total corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and tortuosity coefficient. Their potential correlations with the severity of LSCD were investigated, and cutoff values were determined.ResultsAn increase clinical score correlated with a decrease in central cornea BCD, limbal BCD, CET, mean LET, maximum LET, CNFL, CNFD, CNBD, and tortuosity coefficient. Regression analyses showed that central cornea BCD, CET and CNFL were the best parameters to differentiate LSCD from normal eyes (Coef = 3.123, 3.379, and 2.223; all p < 0.05). The rank correlation analysis showed a similar outcome between the clinical scores and the central cornea BCD (ρ = 0.79), CET (ρ = 0.82), and CNFL (ρ = 0.71). A comprehensive LSCD grading formula based on a combination of these parameters was established.ConclusionsA comprehensive staging system combining clinical presentation, central cornea BCD, CET, and CNFL is established to accurately and objectively diagnose LSCD and stage its severity.     

基于肿瘤浸润深度及大小的TTS 评分系统对可切除胃癌患者预后判断的价值

目的:探讨基于肿瘤浸润深度及大小的TTS评分系统对可切除胃癌患者预后判断的价值。方法:选择行根治性切除的234例胃癌患者为研究对象。根据肿瘤浸润深度（T分期）和肿瘤大小构建TTS评分系统，分为TTS 0级、1级、2级，代表肿瘤侵袭性逐渐升高。通过Cox多因素模型分析TTS评分系统作为预后判断工具的可行性。结果:T1-T4期患者肿瘤的平均大小分别为(3.3±2.7)cm、(4.1±3.1)cm、(6.6±3.1)cm、(9.4±4.9)cm。单因素分析显示，肿瘤浸润深度与肿瘤大小、淋巴结转移、TNM分期、淋巴浸润和血管浸润显著相关(P＜0.01)。ROC曲线显示，45 mm为肿瘤大小的最佳界值，可有效区分患者是否存在淋巴结转移，曲线下面积(area under curve,AUC)为0.762。综合肿瘤大小的临界值和肿瘤浸润深度，构建TTS评分系统,TTS 0级、TTS 1级和TTS 2级的患者5年生存率分别为95.6%、83.3%和70.2%，两两比较后发现，不同TTS状态患者的生存率之间均存在显著差异(P＜0.01)。Cox多因素分析发现，TTS评分是影响患者预后的独立性危险因素（P＜0.05）。结论:本研究根据肿瘤浸润深度和大小构建了TTS评分系统，并证明了TTS评分与胃癌患者的预后密切相关。     

Are We Overtreating Patients With T1a HER2+ Breast Cancer? An Analysis of the National Cancer Database

IntroductionThe potential benefit of systemic therapy in patients with T1a HER2+ cancers is not well understood, and no consensus guidelines exist. We sought to investigate practice patterns of chemotherapy use in this population.MethodsFrom the National Cancer Database (2013-2018), we identified female patients with HER2+ cancers staged as cT1aN0 or pT1aN0 and stratified by receipt of chemotherapy. Using univariate and multivariable analyses we assessed the clinicopathologic features associated with the receipt of chemotherapy. We also compared rates of overall survival (OS).ResultsOf 5176 women with cT1aN0 HER2+ cancers, 88 (2%) received neoadjuvant chemotherapy. Younger age and hormone-receptor (HR) negative tumors were factors independently associated with receipt of neoadjuvant chemotherapy (all P < .001). Of 11,688 women with pT1aN0 HER2+ cancers, 5,588 (48%) received adjuvant chemotherapy. Rates of use increased over the analysis period from 39% in 2013 to 53% in 2018 (P < .001). Factors independently associated with receipt of adjuvant chemotherapy included younger age, having a poorly differentiated tumor, exhibiting lymphovascular invasion, undergoing adjuvant radiation (all P < .001). There were no differences in OS when comparing those who did and did not receive chemotherapy in either group.ConclusionsThe use of chemotherapy in patients with HER2+ T1a cancers is increasing over time and is, as expected, more common among patients with unfavorable clinicopathologic features. Since no prognostic algorithm currently exists, more prospective data is needed to understand which of these patients may derive benefit from systemic therapy and which may safely avoid the morbidity of chemotherapy.     

全身型幼年特发性关节炎患儿合并巨噬细胞活化综合征早期预警量表建立的研究

目的　总结全身型幼年特发性关节炎（sJIA）合并巨噬细胞活化综合征（MAS）的早期临床特征、实验室及辅助检查特点，筛选对诊断MAS有预警作用的检测指标，并量化形成量表，以达到快速对疾病“早识别，早治疗，降低病死率”的目的。方法　回顾性分析2006年1月至2016年1月，北京儿童医院风湿免疫科收治sJIA合并MAS患儿的病例资料，在临床及辅助检查观测指标中筛选出对早期诊断MAS有评估意义的候选指标；通过ROC曲线的方法选择最佳的诊断界限值（Cut-off值）；采用多因素Logistic回归分析MAS独立危险因素，效果以优势比（OR）表示，计算95％置信区间；经过同行评议对上述因素进行权重分值量化并最终形成积分表。结果　390例sJIA患儿，其中141例合并MAS。临床表现全部患儿均有高热、肝脾和（或）淋巴结进行性增大、血液系统受累，中枢神经系统受累患儿19例。单因素Logistic回归及ROC曲线分析结果显示，MAS组和重症sJIA组比较，10个变量存在显著差异（P<0.05）。Logistic回归分析结果显示，Fib ≤3.11g/L、WBC≤11.0×109/L、SF/ESR≥99.4及PLT≤260×109/L为MAS的独立危险因素。绘制模型ROC曲线，灵敏度和特异度分别为92.42%、81.20%。经过30位同行专家评议并投票，分别对上述患儿进行MAS诊断，并对各项临床表现及检验检查项目进行权重值评分，形成早期预警量表。结论　临床表现结合辅助检查结果，利用积分量表的形式，快速判断重症sJIA是否合并早期MAS，对诊断窗口提前，提高MAS诊断率，降低漏诊及前瞻性研究提供参考。     

整形保乳术与常规保乳术治疗早期乳腺癌的效果比较

目的:比较整形保乳术与常规保乳术在早期乳腺癌治疗中的应用效果。方法:将新疆医科大学附属肿瘤医院乳腺外科2016年1月至2017年9月收治的66例早期乳腺癌患者纳入本次研究，按照随机双盲法将其分为两组，将采取整形保乳术治疗的33例患者设为研究组，将常规保乳术治疗的33例患者设为对照组，对比两组患者的乳房美容效果、手术情况、住院时间、肿瘤转移复发情况和并发症的发生率。结果:研究组患者乳房美容优良率（97.0%）明显高于对照组（78.8%），手术时间明显长于对照组，术中出血量明显少于对照组，住院时间明显短于对照组，组间比较P＜0.05；两组患者肿瘤转移和复发比率、并发症发生率均无明显差异，组间比较P＞0.05。结论:整形保乳术与常规保乳术在治疗早期乳腺癌中均具有较好的疗效，且并发症发生率均较低，但整形保乳术的乳房美容效果更好，手术创伤更小，术后恢复更快，更值得在临床中推广应用。     

多细胞过继性免疫治疗治疗晚期恶性肿瘤的近期疗效及安全性分析

目的:初步观察DC、CIK、γδT、CD3AK及NK细胞多细胞过继性免疫治疗对晚期恶性肿瘤患者的近期临床疗效及安全性分析。方法:对我院在2014年10月至2015年10月收治的162例次晚期恶性肿瘤患者进行多细胞过继性细胞免疫治疗，血细胞分离机单采自体外周血单个核细胞（peripheral blood mononuclear cells，PBMC)，体外培养扩增DC、CIK、γδT、CD3AK及NK细胞，采用FCM法检测各细胞表型，并按计划序贯回输给患者进行治疗。结果:69例（43%）患者临床症状有不同程度改善，尤其是精神、食欲及睡眠质量改善最为明显，安全性分析显示主要不良反应为发热，占15%，28例完成3疗程免疫治疗患者瘤体变化为部分缓解（partial remission，PR）2例，疾病稳定（stable disease，SD）16例，疾病控制率（disease control rate，DCR）为64%。结论:DC、CIK、γδT、CD3AK及NK细胞过继性免疫治疗对晚期恶性肿瘤安全有效，可明显改善其生活质量，具有一定的临床应用前景。     

综合疗法治疗4~5期慢性肾脏病31例临床观察

目的:观察综合疗法治疗慢性肾脏病(CKD)4~5期脾肾亏虚证的效果。方法:将CKD4~5期脾肾亏虚证患者62例随机分为2组,其中治疗组31例,对照组30例(剔除1例)。对照组予基础治疗合中药、骨化三醇及碳酸钙D3片治疗,治疗组予基础治疗合中药、骨化三醇及益肾泄浊汤保留灌肠治疗,观察时间为4周。比较2组血肌酐(Scr)、肾小球滤过率(e GFR)、尿素氮(BUN)、血钙、血磷、碱性磷酸酶(ALP)、甲状旁腺激素(i PTH)及中医证候疗效。结果:中医证候总有效率治疗组为83.87%(26/31),对照组为73.33%(22/30),组间比较,差异有统计学意义(P<0.05);2组Scr、e GFR、BUN、血磷治疗前后组内比较及治疗后组间比较,差异均有统计学意义(P<0.01或P<0.05);2组血钙、i PTH、ALP治疗前后组内比较,差异均有统计学意义(P<0.01),但治疗后组间比较,差异无统计学意义(P>0.05)。结论:综合疗法治疗慢性肾脏病4~5期脾肾亏虚证效果确切,安全可靠。     

Proposal of a novel subclassification of pN3b for improvement the prognostic discrimination ability of gastric cancer patients

IntroductionIn the recent edition of TNM staging system, pN3b gastric cancer were separated into the staging system for better prognosis accuracy. The definition of pN3b contains a large range of metastasis lymph nodes (mLNs). However, few studies have evaluated the prognosis of pN3b patients and it remains unknown whether these patients were reasonably assigned into the same substage.Materials and methodsA total of 642 pN3b patients from a multi-institutional cohort in China were included. Disease-specific survival (DSS) was estimated using the Kaplan-Meier method and the Cox proportional hazards regression analysis was used to identify the independent prognostic factors. Restricted cubic spine model was used to specify the association between the continuous variables and the logarithm Hazard ratios (HRs). The optimal cut-off value of mLNs for DSS was identified using the X-tile software.ResultsThe 5-year DSS rate of total pN3b cohort was 15.4%. The smooth curves showed a non-linear association between the mLNs and the logarithm HRs. All pN3b gastric cancer patients were divided into two subclassifications (pN3b1: 16-24 mLNs, pN3b2: ≥25 mLNs). Significant survival difference was observed between two subclassifications (P = 0.048). Additionally, more LNs examined could decrease the death risk of pN3b patients and bring survival benefit only in pN3b1 patients, but not in pN3b2 patients.ConclusionsWe proposed a novel subclassification of pN3b patients, which assigned patients into two subclassifications with significant survival difference. Future study should explore the prognosis value based on this novel subclassification in TNM staging system.     

动态对比增强磁共振成像对鼻咽癌临床分期的诊断价值评价

目的:探讨DCE-MRI各项参数对鼻咽癌临床分期的诊断价值。方法:纳入2016年1月至2019年12月确诊的208例NPC初诊患者为研究对象，均行DCE-MRI、DWI检查，分析临床分期不同的患者感兴趣区的转运常数（Ktrans）、血管外细胞外间隙体积百分数（Ve）、速率常数（Kep）、容积分数（fPV）、DWI表观扩散系数（ADC值），考察指标与NPC临床分期的相关性。结果:Ktrans、Ve值随NPC临床分期增加而增大，而ADC值则随之减小，随着T分期增加Ve值增加，Kep、fPV值则在不同分期均未见明显差异（P＞0.05）；相关性结果显示，Ktrans、Ve值与临床分期、T分期呈正相关，而ADC值呈负相关（P均<0.05）；ROC曲线分析结果显示，Ktrans曲线下面积最高，为0.915，而早期（I期、Ⅱ期）、晚期（Ⅲ期与Ⅳ期）的AUC分别为0.906、0.920，均高于DWI ADC（AUC分别为0.824、0.807）。结论:DCE-MRI测量参数可反映不同临床分期NPC的变化，可考虑用于NPC不同分期的诊断、疗效评价。