EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

酒精使用障碍严重程度的影响因素及风险预测模型构建

背景 酒精使用障碍（AUD）是常见的慢性复发性精神疾病,对于重度AUD,需早期快速识别并及时妥善处理,以避免不可逆的伤害发生。目前,对AUD严重程度的评估主要基于临床医师对患者的精神检查,关于AUD严重程度影响因素及预测模型的研究有限。目的 分析AUD患者疾病严重程度的影响因素,构建风险预测模型,为评估AUD患者的疾病严重程度提供参考。方法 回顾性选取2017年1月1日—2022年12月31日南宁市第五人民医院收治的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）AUD诊断标准的1 358例首次住院患者为研究对象,收集其基本资料,根据疾病严重程度分为轻中度组（n=330）和重度组（n=1 028）。按7∶3将患者分为训练集和测试集,在训练集样本中构建Logistic回归模型,在测试集样本中采用受试者工作特征（ROC）曲线分析该模型对AUD严重程度的预测价值。结果 与轻中度组相比,重度组居住地在城市（χ²=7.804）、农民（χ²=17.991）、饮酒频率高于1~2次/天（χ²=35.267）的比例更高,初次饮酒年龄更大（t=-3.858）,合并躯体疾病数量更多（Z=-22.782）,γ-谷氨酰胺转移酶（χ²=259.940）和总胆红素异常（χ²=148.552）的比例更高（P均<0.01）。在训练集中进行的Logistic分析结果表明,农民（OR=2.024,95% CI：1.352~3.029）、初次饮酒年龄较大（OR=1.075,95% CI：1.025~1.129）、用餐时间外也饮酒（OR=3.988,95% CI：2.408~6.606）、总胆红素水平异常（OR=1.034,95% CI：1.000~1.069）、合并更多的躯体疾病（OR=4.386,95% CI：2.636~7.298）是AUD更严重的危险因素。该模型在测试集中的ROC曲线下面积（AUC）为0.906。结论 在精神专科医院中,农民、初次饮酒年龄较大、用餐时间外也饮酒、总胆红素水平异常、合并更多的躯体疾病可能是重度AUD的危险因素。     

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I–IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4–5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3–5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3–5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3–5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3–5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.     

葛根研究进展

葛根为豆科植物野葛或干葛藤的干燥根,干葛藤又可称为粉葛。葛根为常用中药,始载于《神农本草经》,被列为中品。具有发表解肌、开阳透疹、解热生津等作用,对心血管系统、免疫系统等疾病有较好的治疗效果。本文就其在药代动力学、药理作用、药剂学及不良反应等方面的近期研究进展作一概述。     

五味沙棘散对卵清蛋白诱导的过敏性支气管哮喘大鼠的保护作用及机制

目的 探究五味沙棘散对卵清蛋白（ovalbumin,OVA）诱导的过敏性哮喘大鼠的保护作用及机制。方法 SD大鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组和五味沙棘散（0.5、2.0 g/kg）组,建立OVA诱导的大鼠早期支气管哮喘模型,苏木素-伊红（HE）和Masson染色观察支气管病理情况及纤维化程度;免疫组化检测支气管间隙连接蛋白43（connexin 43,Cx43）的表达和分布;ELISA检测血清中免疫球蛋白E（immunoglobulin E,IgE）和白细胞介素-13（interleukin-13,IL-13）水平;亚甲基蓝法和WSP-1荧光探针法测定血清中硫化氢（hydrogen sulfide,H₂S）水平。建立CdCl₂诱导的支气管上皮BEAS-2B细胞损伤模型,MTT法检测细胞活性;Hoechest 33342染色法观察细胞核形态变化;MitoSOX染色检测细胞线粒体活性氧（mitochondrial reactive oxygen species,mtROS）水平;Western blotting检测半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3,Caspase-3）、核因子红细胞系2相关因子（nuclear factor erythroid 2-related factor,Nrf2）和Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1,Keap1）蛋白表达。结果 五味沙棘散能够减少支气管黏膜上皮细胞脱落和黏液分泌（P＜0.001）,降低胶原纤维的沉积和Cx43的表达及分布（P＜0.05、0.01、0.001）,降低血清中IgE、IL-13水平（P＜0.05）,升高血清中H₂S水平（P＜0.05、0.01）。五味沙棘散含药血清呈剂量相关性地抑制CdCl₂诱导的BEAS-2B细胞凋亡及mtROS水平（P＜0.01、0.001）,上调Caspase-3和Nrf2蛋白表达（P＜0.05、0.01）,下调Keap1蛋白表达（P＜0.01）。结论 五味沙棘散对OVA诱导的哮喘大鼠和CdCl₂诱导的支气管上皮细胞凋亡均具有保护作用,其机制可能与调控Nrf2/Keap1信号通路有关。     

IL‐27 improves adoptive CD8+ T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation

IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8⁺ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8⁺ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8⁺ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8⁺ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8⁺ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8⁺ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.     

Development and Primary Application of an Indirect ELISA Based on Rep Protein to Analyze Antibodies against Porcine Cocirvirus-like Virus (PCLV)

Porcine circovirus-like virus (PCLV) is a member of circovirus that contains a single-strand DNA genome, which may be one of the pathogens that causes diarrheal symptoms in pigs. The Rep protein encoded by the genome of PCLV may be responsible for viral genome replication. The development of serological detection methods for PCLV is of great necessity for clinical diagnosis, as well as epidemiological investigations. Therefore, this study attempted to build an indirect enzyme-linked immunosorbent assay (ELISA) to examine antibodies against PCLV based on the His-tagged recombinant Rep protein. Full-length PCLV Rep protein was induced and expressed in E. coli and was purified as an antigen to establish an ELISA detection kit. The purified Rep protein was used to inject into mice to produce specific antibodies. There was no cross-reaction of Rep-based ELISA with antisera against other porcine viruses. The intra-assay and inter-assay coefficient variations (CVs) were 0.644–8.211% and 0.859–7.246%, respectively, indicating good repeatability. The non-cross-reaction with TGEV, PRRSV and PCV2 testing showed high sensitivity and high specificity for this ELISA assay. A total of 1593 serum samples collected from different pig farms in Jiangxi Province were tested for anti-PCLV Rep antibodies, and 284 (17.83%) of the 1593 samples were Rep antibody positive. Altogether, the indirect ELISA detection tool developed in this study could be applied to examine serum of PCLV antibodies with good repeatability, high sensitivity and high specificity. In addition, field sample detection results suggested that the PCLV antibody has a low prevalence in pig populations in Jiangxi Province of China.     

法舒地尔对脓毒症所致急性肺损伤及肺组织中HMGB1表达的影响

目的观察法舒地尔对小鼠脓毒症所致急性肺损伤的影响及其使用与否对肺组织中HMGB1表达量的影响。方法将48只BALB-C小鼠随机分为对照组、盲肠结扎穿刺（CLP）组、法舒地尔预处理组,在6、24 h时间点取血、肺泡灌洗液及鼠肺用于结果分析。结果在6、24 h时间点,法舒地尔可以显著降低CLP所致的小鼠血清中TNF-α及HMGB1和肺泡灌洗液中蛋白浓度的增加。除此之外,法舒地尔预处理还可以逆转CLP诱导的小鼠肺组织病理形态改变。同时,法舒地尔能减少CLP所致小鼠肺组织中HMGB1 mRNA表达量的增加。结论法舒地尔能减轻CLP小鼠所致的肺损伤并降低肺组织中HMGB1的表达。     

Proviewer一次性使用软组织阻隔装置在颅内手术操作有效性及安全性的随机对照临床研究

目的评价Proviewer一次性使用软组织阻隔装置在颅内手术操作过程中的有效性和安全性,为推广应用提供科学依据。方法采用前瞻性随机对照的临床研究方法,以应用Proviewer一次性使用软组织阻隔装置为试验组,以传统脑压板手术为对照,比较两组手术间临床疗效及手术安全性的差异。结果从2011年06月至2011年12月,共有19例患者纳入全分析集(FAS),其中试验组10例,对照组9例。因为年龄违反入选标准而排除2例,故符合方案集(PPS)共有17例,其中试验组9例,对照组8例。纳入安全性分析集的19例,其中试验组10例,对照组9例。以临床效果综合计分作为主要疗效指标。试验组和对照组比较,在FAS和PPS的差异均具有统计学意义(P<0.05),试验组优于对照组。进一步对视野观察计分和主述性观察计分指标进行比较,表现出相同的结果,即在FAS和PPS的差异均具有统计学意义(P<0.05),试验组优于对照组。以不良事件作为安全性评价指标。试验组共出现1人(10.00%),对照组共出现1人(11.11%)。两组不良事件发生率差别无统计学意义(P>0.05)。所有不良事件均与治疗器械无关,且在病人出院前消除。结论Proviewer一次性使用软组织阻隔装置与传统脑压板相比,在颅内手术操作过程中能为手术者提供更好的观察视野、便利的手术操作,减少术中出血量;且未产生与医疗器械有关的不良反应,有较高的临床应用价值,值得临床推广使用。     

中性粒细胞相关载脂蛋白表达与胃癌进展、转移及预后的关系

目的:探讨中性粒细胞相关载脂蛋白(NGAL)在胃癌组织中的表达及与胃癌进展、转移及预后的关系.方法:应用免疫组化法检测NGAL在102例胃癌、32例正常胃组织中的表达,分析其与胃癌临床病理特征及预后的关系.结果:NGAL在胃癌组织中的阳性表达率为56.9%,明显高于在正常胃组织中的21.9%(χ2>=11.938,P<0.01),不同胃癌组织学分型患者NGAL阳性表达差异有统计学意义(χ=10.180,P<0.05),胃癌患者NGAL表达与浆膜侵犯、TNM分期、淋巴结转移以及T分期呈正相关(r,分别为0.307、0.211、0.220、0.201,P<0.05或P<0.01). NGAL表达阳性组和阴性组5年累积生存率分别为24.3%和43.7%,差异有统计学意义(P=0.018).结论:NGAL在胃癌中表达上调,与胃癌进展和淋巴结转移显著相关,提示预后不良,可作为评价胃癌预后新的生物学指标.