Background: Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers. Objective: To explore the frequency distribution of METTL3 rs1061026, rs1139130, and rs1263801 polymorphisms, and their potential impacts on clinical outcomes and chemotherapy-induced toxicities in a cohort of Chinese pediatric patients diagnosed with primary brain tumors (PBTs). Methods: Genotyping for three investigated SNPs was performed in 107 pediatric patients with PBTs using the Sequenom MassARRAY iPLEX platform. Serum METTL3 levels were determined by Enzyme-Linked Immunosorbent Assay. Serum methotrexate (MTX) concentrations were quantified utilizing fluorescence polarization immunoassay. Results: The three investigated SNPs were not significantly associated with the risks of relapse and metastasis after adjusting all confounders. Compared to individuals with the rs1139130 GG genotype, GA genotype carriers exhibited a significantly higher risk of oral mucositis (adjusted OR: 7.504; 95 % CI, 1.931-29.436; P = 0.004). The rs1139130 GA (adjusted OR: 5.091; 95 % CI, 1.351-19.176; P = 0.016) and AA (adjusted OR: 9.588; 95 % CI, 1.769-51.949; P = 0.009) genotype carriers exhibited a significantly lower risk of fever than GG genotype carriers. The median dose-normalized MTX concentrations at 42 h were lower with borderline significance in children with rs1061026 GT and GG genotypes (0.004 mu mol/L per g/m2) than the TT genotype carriers (0.006 mu mol/L per g/m2, P = 0.048). Patients with the rs1139130 GA genotype had significantly higher median serum METTL3 protein levels (59.91 ng/mL) than GG genotype carriers (44.57 ng/mL, P = 0.015). Conclusion: This study demonstrated the association of the rs1139130 polymorphism with the development of oral mucositis and fever and the rs1061026 polymorphism with MTX exposure.

BACKGROUND:Pediatric brain tumors (PBTs) are the leading type of solid tumors in children, profoundly affecting both survival rates and quality of life. Methotrexate (MTX) is an essential chemotherapy drug for treating these tumors; however, its efficacy and toxicity vary among patients due to genetic factors. OBJECTIVE:This study examined the impact of the intronic rs3780130 polymorphism in the gamma-glutamyl hydrolase (GGH) gene on MTX concentrations and related toxicities in patients with PBTs. METHODS:The GGH rs3780130 T > A polymorphism was genotyped using the Sequenom MassARRAY iPLEX platform in a cohort of 73 PBT patients. RESULTS:We found that children with the AA genotype had significantly higher MTX concentrations compared to those with TT and TA genotypes (P < 0.05). Additionally, the AA genotype was significantly associated with a higher incidence of hepatotoxicity relative to the TT genotype (P < 0.05). It showed a significantly lower occurrence of gastrointestinal toxicities when compared to the TA genotype (P < 0.05). Bioinformatics analysis revealed that the rs3780130 polymorphism had a significant effect on GGH expression across various tissues, suggesting a potential mechanism by which this variant modulated MTX metabolism. CONCLUSION:Our findings highlight the importance of GGH polymorphisms in personalizing MTX therapy for PBT patients and emphasize the necessity for further research to explore the clinical implications of GGH genotypes in larger cohorts, ultimately aiming for more precise therapeutic strategies.

OBJECTIVES:Genetic polymorphisms in FPGS , MTHFR , and ATIC have emerged as important modulators of methotrexate (MTX) metabolism and toxicity. We investigated the distribution of FPGS rs10106, MTHFR rs1801131, and ATIC rs2372536 polymorphisms in children with acute lymphoblastic leukemia (ALL) and assessed their influence on MTX concentrations, toxicity profiles, and clinical outcomes. METHODS:Genotyping of FPGS rs10106 G > A, MTHFR rs1801131 A > C, and ATIC rs2372536 C > G polymorphisms was conducted using the Sequenom MassARRAY iPLEX platform in 145 pediatric ALL patients. RESULTS:Significant ethnic differences were observed in the allelic and genotypic distributions of the three single nucleotide polymorphisms (SNPs) investigated. None of these three SNPs had a significant effect on MTX levels or toxicities. The frequencies of the ATIC rs2372536 CC genotype and C allele in ALL patients (44.8% and 68.6%, respectively) were significantly lower than those in Han Chinese in Beijing, China (58.3% and 78.2%, respectively; P  = 0.036 and 0.019, respectively). Patients carrying the ATIC rs2372536 GG genotype (36.4%, 4/11) had a significantly higher relapse rate than the CC genotype carriers (6.2%, 4/65, P  = 0.013). There, however, were no significant effects on relapse-free survival in Kaplan-Meier and Cox regression analyses for all three candidate SNPs. CONCLUSION:Our findings offer valuable insights into the intricate interplay between genetic polymorphisms, MTX exposure, toxicities, and clinical outcomes in patients with ALL and have the potential to inform precision medicine strategies.

Solute carrier (SLC) transporters play a crucial role in facilitating the cellular uptake of various anticancer drugs, such as methotrexate (MTX). This study aimed to analyze the impact of nonsynonymous single nucleotide polymorphisms (SNPs) in SLC19A1, SLCO1B1, and SLCO1B3 on MTX exposure, toxicities, and prognosis in 148 patients with acute lymphoblastic leukemia (ALL). The SLCO1B3 rs7311358 polymorphism was significantly associated with the median dose-normalized MTX concentrations at 24 h (p < .05). There were significant differences in the proportions of patients with serum MTX levels >40 µmol/L at 24 h among SLC19A1 rs1051266 GG, GA, and AA genotype carriers (29.0, 24.7, and 6.2%, respectively, p < .05). The SLC19A1 rs1051266 G > A polymorphism also displayed significant associations with hematological (p < .05) and hepatic toxicities (p < .01). Our findings indicate that the analysis of SNPs in solute carrier transporters (SCTs) could offer valuable insights into the interpatient variability of MTX pharmacokinetics and toxicities in ALL children.

OBJECTIVE To compare the safety of high-dose methotrexate（HD-MTX） via peripherally inserted central catheter（PICC） and totally implantable venous access port（TIVAP） in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate（MTX）,the incidence of adverse events（including adverse drug reactions and catheter-related complications） and length of stay in hospital.Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study,with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h(C 24h ) in TIVAP group was significantly higher than PICC group [（126.87±61.99） μmol/L vs.（102.45±48.77） μmol/L,P＜0.05). There was no significant difference in blood concentration of MTX at 42 h(C 42h ),compared with PICC group（P＞0.05）. Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C 24h （P＜0.05）. No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups（P＞0.05）. CONCLUSIONS Risk of adverse events is not increased,although the MTX C 24h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.

背景 儿童脉络丛癌(CPC)临床罕见,国内报道较少.目的 探讨儿童CPC的临床特征、治疗及结局.设计 病例系列报告.方法 回顾性分析首都医科大学附属北京世纪坛医院儿科于 2017 年 1 月至 2022 年 10 月收治的手术后病理确诊的CPC患儿,随访截至 2022 年12 月31 日.截取患儿性别、诊断年龄、临床表现、治疗和随访情况,生存数据采用Kaplan-Meier法分析.主要结局指标 总体生存期(OS)和无进展生存期(PFS).结果 12 例 CPC患儿纳入分析,男 4 例,女 8 例;中位诊断年龄 29.7(5.8～119.6)个月,起病年龄＜3 岁 8 例;肿瘤直径≥5cm8 例,＜5 cm 4 例;肿瘤位于幕上 9 例,幕下 3 例;肿瘤位于脑室系统 6 例,脑室外累及脑实质 6 例;起病时发现播散转移 2 例,无转移 10 例.12 例均接受肿瘤切除手术,全切 8 例,近全切 4 例.术后仅行化疗 5 例(42％),联合放射治疗及化疗 7 例(58％).截至末次随访,8 例出现肿瘤复发或进展,其中 4 例因肿瘤进展后死亡.平均 OS(56.7±8.8)个月,1、3、5 年 OS 率分别为(83.3±10.8)％、(66.7±13.6)％和(66.7±13.6)％.平均 PFS(24.3±7.2)个月,1、3 年 PFS 率分别为(41.7±14.2)％和(33.3±13.6)％.Kaplan-Meier单因素分析发现,肿瘤位于幕下 3 年OS低于幕上(χ2 =8.562,P=0.003);单纯化疗 3 年OS低于放化疗联合治疗(χ2=8.488,P=0.004);不同性别、起病年龄(＜3 岁与 3～18 岁)、肿瘤直径(≥5 cm与＜5 cm)、切除程度、有无转移、是否放化疗对 3 年PFS的影响差异均无统计学意义(P均＞0.05).结论 儿童CPC临床罕见,预后差,肿瘤位于幕下及单纯化疗为影响OS的不良预后因素.

Abstract OBJECTIVE: To explore the clinical characteristics and outcome in children with pineoblastoma in Beijing. METHODS: Clinical data of 18 pediatric patients with newly diagnosed pineoblastoma admitted to Beijing Shijitan Hospital between January 2014 and November 2021 were retrospectively analyzed. The diagnoses were confirmed by pathology. RESULTS: Male/female ratio=8:1. The median age at diagnosis was 4.7 (range, 0.2-12.6) years, with 2 cases in infancy, and 13 cases ≥ 3 years. The symptoms at diagnosis included headache (31%), vomiting (29%), convulsions (9%), strabismus (9%), nausea (6%), etc. Four patients experienced metastasis at diagnosis. Ki-67 index was under 30% in 5 cases, 30-80% and ≥80% in 10 and 2 cases, respectively. All were treated with surgery, and 12 children underwent gross total resection (GTR). Seventeen cases were administered both radiotherapy and chemotherapy, with one case only radiotherapy followed by surgery. Median follow-up time was 54 months. Nine patients developed a recurrence and 2 patients died at last follow-up. The 1-year/3-year progression-free survival (PFS) and overall survival (OS) were (77.8±10.5/11.1±10.5)%, and (100/90.9±8.7) %, respectively. The 3-year OS of boys (93.8%) was higher than that of girls (50.0%); and also higher in cases with GTR (91.7%) than STR (83.3%). However, the differences were not significant in the above two groups. The children with Ki-67 index ≥80% had worse 3-year OS than those<80% (χ2=8.000, P=0.005). The median PFS of children treated under the order of craniospinal irradiation followed by chemotherapy was better than that of the inverse order (29m vs 13m, χ2=6.528, P=0.011).CONCLUSION: Pineoblastoma is rare and often fatal, but with better OS in our center, although the PFS is dismal. Boys, GTR resections, and Ki-67 index <80% tends to have better OS, and the order of irradiation followed by chemotherapy tends to have better PFS. Keywords: pineoblastoma; therapy; survival

目的 考察醛氧化酶1(AOX1)在急性淋巴细胞白血病(ALL)中的表达,评估其作为ALL诊断、预后和甲氨蝶呤(MTX)敏感性生物标记物的潜力.方法 基于UCSC数据库下载ALL患者和正常人的RNA测序数据,分析AOX1基因在ALL组与正常组中的表达差异.自TARGET数据集获得ALL患者的总生存期(OS)数据,基于AOX1基因表达水平分为AOX1高表达组与低表达组,分析AOX1基因表达高低对ALL患者预后的影响.基于抗癌药物敏感性基因组学数据库预测MTX半数抑制浓度(IC50),分析AOX1基因表达与MTX敏感性的相关性.根据TARGET数据集的RNA测序数据中AOX1基因与N6-甲基腺嘌呤(m6 A)甲基化修饰基因表达的相关性,分析m6 A修饰在AOX1基因表达调控中的作用.结果 ALL组AOX1基因的阳性表达率93.18％(123例/132例),显著低于正常组98.22％(331例/337例,P<0.01),但2组AOX1基因的中位表达分别为-3.11和-3.05,差异无统计学意义(P=0.43).AOX1高表达组的中位生存时间(26.30个月)显著劣于低表达组(70.30个月,P<0.01).AOX1基因表达与MTX IC50显著负相关(r=-0.29,P<0.01),与多个m6 A修饰基因表达显著正相关.结论 AOX1基因在ALL中低表达,与ALL预后和MTX化疗敏感性显著相关,m6 A修饰可能是ALL中AOX1基因表达调控的机制之一.

Study Objective The objective of the present study was to examine the frequency distribution of five single-nucleotide polymorphisms (SNPs; rs1801394 A>G, rs1532268 C>T, rs162036 A>G, rs10380 C>T, and rs9332 C>T) of the methionine synthase reductase (MTRR) gene, their effects on methotrexate (MTX) concentration, and the risk of relapse in a Chinese pediatric population with acute lymphoblastic leukemia (ALL). Design This was a retrospective single-center study, and all analyses were exploratory. Setting Pediatric Department of Beijing Shijitan Hospital, Capital Medical University, Beijing, China. Patients One hundred and forty pediatric patients with ALL. Intervention All patients were treated according to the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol. Measurements and Main Results Serum MTX concentrations were measured using fluorescence polarization immunoassay. Genotyping of five SNPs was performed using the Sequenom MassARRAY iPLEX platform. Chinese children with ALL had a significantly lower frequency of rs1801394 G than European (EUR) and South Asian (SAS) populations; significantly lower frequency of rs1532268 T than American (AMR), EUR, and SAS populations; and significantly lower frequencies of rs162036 G, rs10380 T, and rs9332 T than African and AMR populations (p < 0.01). Seven haplotypes were observed, with the ACACC being the most common haplotype (49.9%) in our study. The median dose-normalized concentrations of MTX in serum at 24 h in children with rs1532268 CT and TT genotypes were significantly higher than those with CC genotype (p = 0.04). Compared with children with AA-CC-AA-CC-CC diplotype, a significantly higher risk of relapse was observed in children with AG-CC-AA-CC-CC and AG-CC-AG-CC-CC diplotypes (p = 0.03 and 0.003, respectively). Conclusions The present study confirmed the ethnic differences in the distribution of MTRR rs1801394, rs1532268, rs162036, rs10380, and rs9332 polymorphisms. The rs1532268 polymorphism had greater effects on MTX disposition. The AG-CC-AA-CC-CC and AG-CC-AG-CC-CC diplotypes were significantly associated with higher risk of relapse of ALL.

目的 分别在大鼠和人混合肝微粒体中考察姜黄素对瑞格列奈代谢的影响,从而考察姜黄素对细胞色素P4502C8(CYP2C8)活性的影响.方法 分别建立大鼠和人肝微粒体体外孵育体系,将姜黄素与瑞格列奈于37℃水浴中共同孵育,用UPLC法测定肝微粒体中瑞格列奈的剩余浓度.在系列浓度的瑞格列奈进行孵育的条件下,绘制米氏曲线,得到瑞格列奈的米氏常数(Km)、最大反应速率(Vmax)和固有清除率(CLint).在系列浓度的姜黄素进行孵育的条件下,测定肝微粒体中瑞格列奈的减少量并计算半数抑制浓度(IC50),考察姜黄素对瑞格列奈代谢的影响.结果 瑞格列奈在大鼠和人肝微粒体中孵育的Km值分别为(51.41±18.29)和(5.66±2.76)μmol·L-1,Vmax分别为(47.29±7.81)和(1.71±0.38)μmol·min-1·mg-1,CLint分别为0.92和3.31 mL-1·min-1·mg-1.姜黄素对瑞格列奈在大鼠和人肝微粒体中均具有明显的抑制作用,IC50值分别为9.87和0.31μmol·L-1.结论 姜黄素可显著抑制瑞格列奈在大鼠和人肝微粒体中的代谢,提示两药合用时具有发生相互作用的风险,且姜黄素与其他经CYP2C8代谢的药物合用时也应谨慎.

PURPOSE:Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play an important role in the response to methotrexate (MTX). In this study, we investigated the frequency distribution of three splicing-regulatory polymorphisms in ABC transporters (ABCC2 rs2273697 G>A, ABCG2 rs2231142 G>T, and ABCB1 rs1128503 A>G) and their effects on MTX concentrations and the clinical outcome in a Chinese pediatric population with acute lymphoblastic leukemia (ALL). METHODS:A fluorescence polarization immunoassay was used to measure the serum MTX concentrations in 24 h (C24h) and 42 h (C42h). The Sequenom MassARRAY system was used for single-nucleotide polymorphism (SNP) genotyping. RESULTS:The study population had significantly lower frequencies of ABCC2 rs2273697 A, ABCG2 rs2231142 G, and ABCB1 rs1128503 G than African and European samples (P < 0.05). The dose-normalized MTX concentrations after 24 h and the proportion of C42h > 0.5 µmol/L were significantly lower in patients with the ABCG2 rs2231142 GG genotype than in patients with the GT or TT genotype (P = 0.01 and 0.006, respectively). No significant effects on MTX pharmacokinetics were observed for ABCC2 rs2273697 and ABCB1 rs1128503 polymorphisms. Bioinformatics analysis suggested that the three SNPs overlapped with the putative binding sites of several splicing factors. CONCLUSION:In conclusion, our study confirmed the ethnicity-based differences in the distribution of the three investigated SNPs. The ABCG2 rs2231142 polymorphism exerted a significant effect on the level of MTX exposure. These findings may help explain the variability in MTX responses and optimize MTX treatment in pediatric patients with ALL.

儿童肾移植受者术后需终身服用免疫抑制剂来维持治疗。而用药依从性直接影响儿童肾移植受者的长期预后。现将对儿童肾移植受者用药依从性的现状、评估方法、影响因素及干预措施进行综述，以期为临床提供参考。

目的 测定帕拉米韦给药后不同时间人血浆中的药物浓度,观察病人用药后安全性及疗效,为临床使用帕拉米韦提供依据.方法 高效液相色谱(HPLC)法测定帕拉米韦的血药浓度,以5 mmol/L磷酸二氢钾溶液(0.1％三乙胺)-乙腈为流动相,磷酸调pH 5.0;检测波长210 nm;流速1.0 mL/min;用药后对病人进行安全性随访.结果 血浆中无干扰测定的内源性物质,线性范围为1～50μg/mL,最低定量限(LLOQ)为1μg/mL,回收率102.5％～110.4％,日间精密度及稳定性均良好,5例病人不同时间血浆中的帕拉米韦均可检出;5例病人的发热缓解时间分别为33、26、26、48、54 h,流感症状缓解时间分别为89、>120、28、48、54 h,发生1例不良反应.结论 HPLC检测方法可靠,适用于人血浆中帕拉米韦的测定.帕拉米韦能快速缓解流感症状,虽然出现的不良事件为轻度,但也要监测其不良反应,以保证用药安全性及有效性.

目的 系统评价阿帕替尼联合替吉奥对比替吉奥单药治疗二线及二线以上进展期胃癌的有效性和安全性,以期为临床合理用药提供依据.方法 系统检索Embase、Cochrane Library、PubMed/Medline、中国知网、万方数据库、维普中文科技期刊全文数据库,收集阿帕替尼联合替吉奥(试验组)和替吉奥(对照组)治疗晚期胃癌的随机对照试验(RCT),筛选文献、提取数据并采用Cochrane系统评价员手册5.1.0提供的偏倚风险评估工具对纳入研究的质量进行评价,采用RevMan 5.3软件进行meta分析.结果 共纳入15项RCT,合计1121例患者.Meta分析结果显示,与对照组比较,试验组总体缓解率和疾病控制率显著高于对照组,差异有统计学意义[OR=0.33,95％CI(0.25,0.44),P<0.00001;OR=0.37,95％CI(0.28,0.50),P<0.00001].安全性方面,试验组手足综合征、高血压和蛋白尿的发生率显著高于对照组[OR=2.11,95％CI(1.09,4.08),P=0.03;OR=0.13,95％CI(0.06,0.28),P<0.00001;OR=0.26,95％CI(0.13,0.51),P<0.00001],两组恶心呕吐、腹泻、乏力和血小板减少等其他不良反应发生率的差异均无统计学意义(P>0.05).结论 替吉奥联合阿帕替尼提高了晚期胃癌患者的总体缓解率和疾病控制率,但要警惕手足综合征、高血压和蛋白尿等不良反应的发生.

目的 研究瑞格列奈在大鼠肝微粒体中的酶促反应动力学,并考察氯沙坦钾对其在大鼠肝微粒体中代谢的影响.方法 建立大鼠肝微粒体体外孵育体系对瑞格列奈的代谢进行研究;以洛伐他汀为内标,应用UPLC测定大鼠肝微粒体中瑞格列奈的浓度.采用底物减少法,通过GraphPad Prism 5.0软件计算瑞格列奈的酶促反应动力学常数Vmax和Km;分别以系列浓度氯沙坦钾(2.5～50 μmol·L-1)与瑞格列奈(44 μmol·L-1)于37℃水浴中共同孵育,并测定肝微粒体中瑞格列奈的减少量,考察氯沙坦钾对瑞格列奈的抑制作用.结果 瑞格列奈在大鼠肝微粒体的最佳孵育时间为40 min,最佳蛋白质量浓度为l mg·mL-1;瑞格列奈酶促反应动力学参数Vmax=47.29 μmol·min-1·(mg·protein)-1,Km=51.41 μmol·L-1;氯沙坦钾对瑞格列奈在体外肝微粒体抑制作用的IC50值为17.89 μmol·L-1.结论 氯沙坦钾对瑞格列奈在大鼠肝微粒体中的代谢具有较强的抑制作用,两药联合应用可能发生相互作用,具有诱发低血糖的风险.

目的 分析参麦注射液的临床使用情况和安全性.方法 收集2009年9月至2013年6月全国26家医院30 012例使用参麦注射液的患者数据,使用SPSS 15.0软件对人口学特征、诊断信息和具体使用情况进行统计分析.结果 使用参麦注射液的患者中男性15 742例(52.45％),女性14 270例(47.55％);45～60岁8 218例(27.38％),61～75岁10 452例(34.83％).临床中主要用于肿瘤患者化疗的辅助治疗,使用最多的3种肿瘤分别是肺癌(1 533,5.11％)、乳腺癌(1 509,5.03％)和胃癌(847,2.82％);其次是用于冠心病的治疗(5 703,19.00％).单次给药剂量50 mL 占比最大(14 406,48.00％),其次是100 mL(10 804,36.00％)和200 mL(600,2.00％).18 902例(62.98％)在注射时使用了溶媒,最多(84.64％)采用的是5％葡萄糖注射液.总不良反应发生率为0.15％,57.78％的不良反应发生在输液后24小时内.不良反应最常表现为心血管系统的损害,其次分别是血液系统和呼吸系统.结论 真实世界中参麦注射液应用范围广、可治疗疾病多,不良反应的出现多与超说明书使用有关.

背景 婴儿期起病的中枢神经系统(CNS)肿瘤临床罕见,国内少见报道.目的 探讨婴儿期起病的CNS肿瘤患儿的临床特征、病理类型、治疗结局及预后的影响因素.设计回顾性队列研究.方法 以2011年6月至2019年12月婴儿原发CNS肿瘤病例为队列起点,采用多学科诊疗模式手术联合化疗,以2020年3月31日为随访终点,采集性别、起病年龄、有无转移、肿瘤部位、肿瘤级别、肿瘤直径、切除程度、是否化疗作为生存率(OS)和无事件生存率(EFS)的预后影响因素.主要结局指标OS和EFS的预后影响因素.结果 52例初诊婴儿原发CNS肿瘤进入本文分析,男36例,女16例;诊断时中位年龄6.7(0～12)个月,起病年龄<6月龄18例,其中新生儿期起病2例.幕上33例,幕下17例,脊髓2例;肿瘤直径<5 cm 26例,≥5 cm 19例,不详7例.行手术治疗44例中,全切/次全切39例(89％),部分切除4例,非开颅活检1例,起病即转移4例.经临床和影像学诊断,评估手术风险高和经济原因等未手术治疗8例,于诊断后0.9(0～1.24)个月死亡.低级别肿瘤24例,高级别肿瘤20例.脉络丛肿瘤17例,胶质瘤11例,胚胎性肿瘤13例,非成熟畸胎瘤2例,先天性造釉细胞型颅咽管瘤1例.手术后化疗24例,复发或进展11例(其中死亡10例),EFS 13例,其中有事件存活1例.手术后未化疗20例,1例复发或进展后死亡,EFS 19例.COX回归分析显示,肿瘤非全切较肿瘤全切/次全切OS和EFS的HR分别为5.7(95％CI:1.408～23.115)和5.1(95％CI:1.260～20.731);高级别肿瘤较低级别肿瘤婴儿OS和EFS的HR分别为18.0(95％CI:2.222～146.5897)和8.3(95％CI:1.687～40.530);肿瘤部位幕下较幕上婴儿OS和EFS的HR分别为4.2(95％CI:1.563～11.291)和4.9(95％CI:1.996～12.216).结论 婴儿原发CNS肿瘤低级别肿瘤预后良好,高级别肿瘤如非典型畸胎瘤/横纹肌样瘤、伴多层菊形团胚胎性肿瘤及松果体母细胞瘤预后差,肿瘤非全切、高级别肿瘤和幕下肿瘤为影响OS和EFS的不良预后因素.

目的 建立老年综合科管饲给药标准操作流程,评估其对用药错误和管饲并发症发生率的影响.方法 以2019年1月至6月老年科的管饲患者为对照组,2019年7月至12月的管饲患者为试验组.通过建立管饲药物的给药标准、管饲标准给药流程、管饲冲管流程、降低管饲腹泻措施、出现腹泻后的处理流程,并对医护人员进行同质化培训,对试验组患者进行干预,比较干预前后的不合理医嘱百分比、堵管率和腹泻率.结果 老年综合科管饲给药不合理医嘱百分比由干预前的19.35％显著降至7.89％(P<0.05);临床堵管率由干预前的14.55％显著降至5.77％(P<0.05);腹泻率由之前的11.82％显著降至3.85％(P<0.05).结论 建立管饲给药、堵管、腹泻的标准化处理流程有利于减少用药错误的发生,同时显著降低管饲喂养并发症的发生率.

目的:对聚乙二醇-二硬脂酰磷脂酰乙醇胺(PEG-DSPE)胶束在单层上皮细胞的转运过程进行研究.方法:采用薄膜水化法制备包载荧光探针香豆素6的PEG-DSPE胶束,建立测定香豆素6含量的荧光分析法,考察马丁达比犬肾单层上皮细胞(Madin Darby canine kindey,MDCK)对香豆素6胶束的摄取和吸附作用,考察温度、不同内吞抑制剂对胶束在单层MDCK细胞跨膜转运的影响.结果:香豆素6 PEG-DSPE胶束可以很快被细胞吸附和摄取,随时间增加,吸附和摄取达动态平衡.胶束在单层细胞上的跨膜转运受温度的影响,4℃下,跨膜转运受到明显抑制;甲基-β-环糊精、高渗蔗糖、氯丙嗪及制霉菌素对胶束的内吞均有明显抑制作用,其中甲基-β-环糊精的抑制率高达88％.阿米洛利对胶束的内吞无影响.结论:胶束在MDCK单层细胞上的跨膜转运是主动的、能量依赖性的过程,跨膜转运机制是多因素的,包括了小窝蛋白介导的内吞过程和网格蛋白介导的内吞过程.

The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of CYP450 enzymes.Zhenyuan capsule and simvastatin may interact with each other through CYP3A4 mediation,then affect the efficacy and even produce adverse reactions.However,no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites.In this study,liquid chromatography-electrospray ionization-mass spectrometry (LC-MS/MS) was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats.Compared with the simvastatin alone,the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in A UCo-24 and A UCo-∞,and they were decreased in varying degrees (P＜0.05).It appeared that the Zhenyuan capsule might increase the activity of CYP3A4 to some extent.