热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

T3、T4期结直肠癌淋巴结转移危险因素分析

目的探讨T3、T4期结直肠癌患者淋巴结转移危险因素,为临床诊疗提供参考。方法回顾性分析2008年1月至2017年12月在空军军医大学西京消化病医院行结直肠癌根治术的1112例T3、T4期结直肠癌患者的临床病理资料,分析淋巴结转移状态与临床病理因素及肿瘤标志物的相关性,应用logistic多因素回归法分析淋巴结转移的相关危险因素。结果单因素分析结果显示,性别、年龄、肿瘤部位分层的结直肠癌患者间淋巴结转移率差异均无统计学意义(均P>0.05),淋巴结转移率在不同肿瘤长径[<5 cm和≥5 cm分别为37.75%(211/559)、52.26%(289/553),χ^2=23.666,P<0.01]、大体类型[浸润、溃疡、蕈伞、隆起分别为37.04%(20/54)、47.52%(432/909)、34.33%(23/67)、69.51%(57/82),χ^2=13.787,P=0.003]、分化程度[高、中、低分化分别为34.11%(102/299)、49.00%(317/647)、48.80%(81/166),χ^2=19.771,P<0.01]、错配修复缺陷(dMMR)[是和否分别为26.34%(64/243)、50.17%(436/869),χ^2=43.996,P<0.01]、神经侵犯[是和否分别为48.17%(421/874)、33.20%(79/238),χ^2=16.954,P<0.01]、脉管侵犯[是和否分别为79.16%(338/427)、23.65%(162/685),χ^2=327.493,P<0.01]以及术前癌胚抗原(CEA)[阳性(≥5 mg/ml)和阴性(<5 mg/ml)分别为52.87%(249/471)、39.16%(251/641),χ^2=20.162,P<0.01]和CA199[阳性(≥35 U/ml)和阴性(<35 U/ml)分别为59.33%(124/209)、41.64%(376/903),χ^2=21.465,P<0.01]分层患者间差异均有统计学意义。logistic多因素回归分析显示,脉管侵犯和术前CA199阳性是T3、T4期结直肠癌患者淋巴结转移独立危险因素(OR=13.006,95%CI 9.329~17.276,P<0.01;OR=2.194,95%CI 1.513~3.181,P<0.01),dMMR阳性是淋巴结转移的保护性因素(OR=0.279,95%CI 0.190~0.411,P<0.01)。结论脉管侵犯是T3、T4期结直肠癌患者淋巴结转移的主要危险因素。术前肿瘤标志物CA199的检测可以作为预测T3、T4期结直肠癌患者淋巴结转移状态的指标,一定程度上可为诊疗方案的制订提供参考。     

Recipient hypertonic saline infusion prevents cardiac allograft dysfunction

Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Predicting Renal Function Outcomes After Partial and Radical Nephrectomy

Background

Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit.

UPLC-MS/MS测定73例患者血中头孢哌酮与舒巴坦的浓度

目的：建立液相色谱-串联质谱法（UPLC-MS/MS）同时测定人血浆中头孢哌酮与舒巴坦的浓度，分析头孢哌酮/舒巴坦血药浓度监测结果，为临床合理用药提供参考。方法：以氯唑沙宗为内标，采用Waters BEHC₁₈柱（2.1 mm×100 mm，1.7 μm）进行分离，通过串联质谱仪，负离子检测模式下，以多反应监测（MRM）方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果：头孢哌酮与舒巴坦在测定条件下1~200 mg·L^-1范围内线性关系良好，两者日内精密度RSD均<10%，基质效应分别为（72.77±0.99）%与（75.72±0.11）%，提取回收率均>90%。73例患者共监测血药浓度96次，其中不同给药方案2 g，q8 h（43例次）；2 g，q12 h（26例次）；2 g，q6 h（27例次），各组头孢哌酮血药浓度的中位数分别为34.12 mg·L^-1（4.12~177.79 mg·L^-1）、31.23 mg·L^-1（1.89~251.8 mg·L^-1）、59.96 mg·L^-1（1.77~140.58 mg·L^-1），舒巴坦血药浓度的中位数分别为6.3 mg·L^-1（0.61~136.01 mg·L^-1）、28.83 mg·L^-1（0.5~133.69 mg·L^-1）、11.17 mg·L^-1（0.73~143.53 mg·L^-1）。Mann-Whitney U检验显示，头孢哌酮血药浓度结果无统计学差异（P>0.05），舒巴坦有统计学差异（P<0.05）。结论：本检测方法操作简便、快速、重复性好，可满足临床头孢哌酮与舒巴坦浓度的检测；头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关，有必要开展血药浓度监测并依据结果适时调整用药方案，提高治疗效果减少耐药率的发生。     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.