治疗前外周血炎性标志物对EGFR突变阳性晚期非小细胞肺癌患者的预后价值研究

  目的  探讨治疗前外周血炎性标志物在表皮生长因子受体（epidermal growth factor receptor，EGFR）阳性晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）患者中的预后作用。  方法  回顾性分析2015年1月至2018年10月中国人民解放军总医院第五医学中心142例EGFR突变阳性晚期NSCLC患者临床资料。通过受试者工作特征曲线（receiver operating characteristic curve，ROC）确定中性粒细胞与淋巴细胞计数比值（neutrophil-to-lymphocyte ratio，NLR）、血小板与淋巴细胞计数比值（platelet-to-lymphocyte ratio，PLR）、系统免疫炎症指数（systemic immune-inflammation index，SII）和淋巴细胞与单核细胞计数比值（lymphocyte-to-monocyte ratio，LMR）的最佳临界值，应用Kaplan-Meier方法进行生存分析。Cox比例风险模型评估各变量的预测价值。  结果  NLR、PLR、SII和LMR的最佳临界值分别为2.60、167.32、687.39和3.13。根据最佳临界值分别将研究对象分为高值组和低值组，高NLR、PLR和SII组的中位无进展生存期（median progression-free survival，mPFS）及中位总生存期（median overall survival，mOS）均显著低于低值组中相应值，高LMR组mPFS及mOS较低LMR组延长。  结论  治疗前升高的NLR、PLR、SII和降低的LMR可能与接受靶向治疗的EGFR突变阳性晚期NSCLC患者的不良预后相关。      

Comparison of microtransplantation,chemotherapy and allogeneic transplantation in post-remission therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia

Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) have poor prognosis, and the efficacy of chemotherapy plus tyrosine kinase inhibitors (TKIs) followed by mismatched donor stem cell infusion (microtransplantation, MST) has not been determined. We retrospectively summarized 45 patients including 11 undergoing MST with TKIs, 17 receiving allogeneic transplant and 17 undergoing chemotherapy with TKIs. Improved 4-year overall survival rate was observed in the MST group (91%) compared with either transplant group (31%, P = .005) or chemotherapy group (36%, P = .013). The MST group also had higher 2-year and 4-year leukemia-free survival rates (91% and 72%, respectively) compared with either transplant group (33%, P = .005 and 33%, P = .021, respectively) or chemotherapy group (41%, P = .017 and 31%, P = .023, respectively). 2-year and 4-year cumulative incidences of hematologic relapse were lower in the MST group (9% and 28%, respectively) compared with those in the chemotherapy group (56%, P = .025 and 67%, P = .034, respectively). In patients undergoing MST, donor microchimerism was detected (1.07 × 10^-5 to 6.6 × 10^-4 copies from 9 to 1499 days) in 7 patients, and donor/patient-derived HLA*0201/2402⁺WT1⁺CD8⁺ T cells were found from 0.05% to 0.67% in 6 patients. MST may provide a favorable treatment for patients with Ph⁺ ALL.     

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic–immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system. In the chronic inflammation microenvironment, the metabolic activity of tissue cells undergoes extensive changes, which interfere with the normal function of immune cells. Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs, such as the stomach, liver, and colorectum. This metabolic–immune imbalance also corresponds to traditional Chinese medicine (TCM) theories of “yin-yang disharmony” and “disharmony between Ying-nutrients and Wei-defense.” The metabolic–immune imbalance has also been regarded as the key factor supporting “treatment of different diseases with the same method,” in which the same approach is adopted in the treatment of different conditions. In the TCM treatment process, it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function, thereby blocking the progression from inflammation to malignancy. Our study findings deepen the TCM understanding of metabolic–immune dysregulation and the relationship between metabolic–immune dysregulation, pattern identification, and treatment method. They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of “treating different diseases with the same method.     

基于抗肝纤维化生物活性及近红外谱效相关的鳖甲质量评价研究

目的 从鳖甲临床抗肝纤维化功效出发并结合近红外光谱,探索建立关联抗肝纤维化活性的鳖甲质量生物活性评价方法。方法 建立转化生长因子-β1（transforming growth factor-β1,TGF-β1）诱导的LX-2肝纤维化细胞模型,采用qRT-PCR检测鳖甲对I型胶原（type I collagen,COL1）mRNA表达的影响,计算鳖甲对COL1 mRNA相对表达量的抑制率;采用Western blotting检测鳖甲对COL1蛋白表达的影响,以评价鳖甲在细胞模型上的抗肝纤维化生物活性。采集并处理不同批次鳖甲药材的近红外光谱数据,通过谱-效相关分析探究鳖甲药材近红外光谱数据与其抗肝纤维化活性的相关性,筛选活性波段,建立鳖甲的效应近红外谱,以效应近红外谱下面积评价鳖甲药材的质量。结果 体外实验表明,与模型组比较,鳖甲水提物（water extract of Trionycis Carapax,WECT）处理组细胞中COL1 mRNA与蛋白表达水平显著下调（P＜0.05、0.01）;基于谱-效相关分析,共筛选得到R＞0.6、P＜0.05且波数大于8 cm⁻¹的活性波段3个,分别为5226～5235 cm⁻¹、5943～6071 cm⁻¹与6379～6396 cm⁻¹,以3个活性波段下面积为指标,建立鳖甲药材的效应近红外谱,计算各特征波段下面积和,并分析其与生物活性的相关性,两者相关系数R为0.813 53。结论 WECT可抑制LX-2细胞外基质的产生来治疗肝纤维化;效应波谱下面积和（5226～5235 cm⁻¹、5943～6071 cm⁻¹与6379～6396 cm⁻¹）作为鳖甲药材的质量评价系数,用于评价鳖甲药材的质量,可区分不同批次鳖甲药材的抗肝纤维化活性。     

淫羊藿醇提物调节M2样巨噬细胞极化减少乳腺癌细胞迁移和集落形成的研究

目的 探讨淫羊藿Epimedium brevicornu醇提物对体外巨噬细胞极化调控机制及对M2样巨噬细胞促进4T1细胞迁移和集落形成的影响。方法 采用CCK-8法检测不同浓度淫羊藿醇提物对骨髓来源巨噬细胞（bonemarrowderived macrophages,BMDM）活力的影响,确定淫羊藿醇提物的安全作用浓度;采用Western blotting和q RT-PCR检测淫羊藿醇提物对M2样巨噬细胞标志物精氨酸酶-1(arginase-1,Arg-1)和CD163表达的影响;采用q RT-PCR检测淫羊藿醇提物对M2-肿瘤相关巨噬细胞（tumor-associated macrophages,TAMs）相关基因炎症区域1(found in inflammatory zone 1,Fizz1)、过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor γ,PPARγ)、几丁质酶3样分子3(chitinase 3-like 3,Ym1)、趋化因子24(C-C motif chemokine ligand 24,CCL24)、巨...     

基于多途径联合效应的甘草防治脓毒血症活性成分筛选及作用机制研究

目的 研究甘草中有效组分对脓毒血症的防治作用及机制。方法 采用小鼠骨髓来源巨噬细胞(bone marrow-derived macrophages,BMDM)构建体外NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体激活模型及H2O2诱导的氧化应激模型筛选出甘草抗炎、抗氧化应激的有效组分,采用ip脂多糖(lipopolysaccharide,LPS,20 mg/kg)诱导C57BL/6小鼠脓毒血症致死模型以及脓毒血症模型,评价致死模型中小鼠的生存率及脓毒血症模型小鼠腹腔灌洗液中巨噬细胞和中性粒细胞在渗出细胞中的占比以及外周血和腹腔灌洗液中白细胞介素-1β(interleukin-1β,IL-1β)及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果 基于BMDM细胞NLRP3炎症小体激活模型筛选出甘草中有效组分刺甘草查耳酮,可显著抑制半胱氨酸天冬氨酸蛋白酶-1(cystein-asparate protease-1,Ca...     

肝脏血管平滑肌脂肪瘤诊断与外科治疗：附19例报告

背景与目的 肝脏血管平滑肌脂肪瘤（HAML）是肝脏少见的一种间叶组织来源的良性肿瘤,影像学检查缺乏特异性,术前诊断率低,容易误诊为肝细胞癌或其他肝良性肿瘤,本文报告19例HAML患者的诊治过程,以期为临床提供参考和借鉴。方法 回顾性分析2011年1月—2019年12月收治的19例HAML患者临床资料,其中女12例,男7例;年龄28~61岁;体检发现无临床症状者14例,表现为上腹部隐痛者3例,间断腹胀者1例,腹痛伴腹泻者1例;1例合并慢性乙型病毒性肝炎及肺脓肿,1例合并乙型肝炎肝硬化代偿期。19例均不伴肾肺等其他脏器血管平滑肌脂肪瘤,均无结节性硬化症。肿瘤直径1.3~12 cm,平均直径（4.6±2.2）cm。AFP、CA19-9、CEA均正常。7例患者术前诊断肝细胞癌（36.8%）,12例术前诊断肝良性肿瘤（63.2%）,分别为7例诊断肝腺瘤,2例诊断炎性假瘤,1例诊断肝海绵状血管瘤,1例诊断肝局灶性结节性增生,1例术前行超声引导下肝脏穿刺活检病理证实HAML。结果 患者均行外科手术治疗,18例行肝切除治疗,1例行超声引导下肝肿瘤穿刺活检术、经皮穿刺肝肿瘤射频消融术。平均手术时间（172.7±80.4）min,术中平均出血量为（456.6±528.1）mL,平均术后住院时间（9.8±2.7）d。19例患者病理检查均证实HAML,其中7例为上皮样血管平滑肌脂肪瘤,免疫组化检查HMB-45、SMA均阳性表达。患者术后恢复良好,所有患者无肝衰竭、腹腔出血、胆汁漏等并发症发生,无死亡病例。全部病例均获随访,均未发现肿瘤复发及转移。术后患者有良好的生活质量。结论 HAML瘤属于良性肿瘤,术前诊断比较困难,一部分患者容易误诊为肝细胞癌,最终诊断依靠病理及免疫组织化学染色,外科手术切除是安全、有效的治疗选择,预后良好。     

我国COVID-19相关临床试验注册特点及存在的伦理学问题

目的：通过对我国新型冠状病毒感染(COVID-19)相关临床试验注册信息多角度分析,探讨其中存在的伦理学问题,以期为新突发传染病等公共卫生事件临床伦理的规范化提供依据。方法：在美国临床试验注册中心(ClinicalTrials.gov)和中国临床试验注册中心(ChiCTR)使用“新型冠状病毒”“COVID-19”等关键词检索2020年1月1日至2022年11月15日注册的COVID-19相关临床试验,归纳分析其注册的时空分布特点、研究类型、干预措施、研究状态及伦理等信息,发现并探讨相关伦理学问题。结果：共纳入1 560项COVID-19相关的临床试验,其中ClinicalTrials.gov注册481项,ChiCTR注册1 079项。临床试验注册高峰期集中在2020年2-4月;根据省级行政区划分湖北省、上海市、北京市临床试验注册量较多。干预性研究(843/1 560,54.00%)在所有注册类型中占比最高,注册内容涉及疫苗(202/843,23.96%)、化学药品(193/843,22.89%)、中医药(153/843,18.15%)及生物制品(90/843,10.68%)等多个方面;...