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。     

3D打印模型在儿童先天性脊柱侧凸治疗中的应用研究

目的探讨3D打印模型在儿童先天性脊柱侧凸治疗中的应用疗效。方法回顾性分析2015年12月至2016年12月于首都医科大学附属北京儿童医院接受手术治疗的83例先天性脊柱侧凸患儿临床及影像学资料,根据是否使用3D打印模型分为试验组(n=44)和对照组(n=39),比较两组手术时间、术中透视次数、置钉准确性、矫形效果及并发症情况。结果本研究共纳入83例先天性脊柱侧凸患儿,其中男童47例,女童36例,平均手术年龄5.98 (1.5~13)岁。行半椎体切除术40例,Ponte截骨术31例,经椎弓根截骨术8例,全脊椎切除术4例。随访时间24~35个月。试验组患儿手术时间短于对照组[(180.92±16.74) min (201.51±27.60) min],差异有统计学意义(t=2.798,P<0.05),试验组术中出血量[(340.23±89.52) mL vs.(392.64±100.41) mL]及术中透视次数(4.36±0.89 6.05±1.28)明显少于对照组,差异有统计学意义(P<0.05);试验组置钉准确率高于对照组(93.55%vs 79.91%)(X^2=218.00,P<0.05),平均置钉时间明显短于对照组[(4.24±1.05) min vs.(8.35±2.29) min],差异有统计学意义(t=10.71,P<0.05)。两组患儿矫形率无明显差异(t=-1.135,P=0.272)。试验组与对照组患儿术后胸膜损伤、硬膜损伤发生率无明显差异(P>0.05)。结论 3D打印模型能清晰、直观显示先天性脊柱侧凸患儿的脊柱结构及形态,为制定手术计划及手术置钉提供帮助,从而提高置钉准确率,减少术中透视次数,缩短手术时间,减少术中出血量。     

Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

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.

Genetic characterization and diversity of porcine circovirus type 2 in non‐vaccinated South African swine herds

The porcine circovirus type 2 (PCV2) is a swine infectious viral pathogen of great significance in global swine herds. It was recently detected at another Province of South Africa sequel to the first detection of North American‐like strain (PCV2a) at Gauteng about two decades ago, but there is a dearth of information about the genomic features and diversity of the viral strains in circulation within the country and the entire sub‐Saharan Africa region. To date, only one complete genome of the virus from South Africa is available on global data base. This current effort is therefore geared towards the full‐genome characterization of the circulating PCV2 strains in the pigs of Eastern Cape Province. With the use of conventional polymerase chain reaction method, fifteen complete PCV2 genomes were successfully amplified, sequenced and assembled from field samples obtained from non‐vaccinated pigs in the region. Neighbor Joining and Maximum Likelihood phylogenetic analyses of the ORF2 gene and full genomes unanimously showed that most of the assembled genomes (11) belong to genotype PCV2b. Furthermore, three of the characterized sequences formed clade with other reference mutant PCV2b and PCV2b subtype 1C (i.e. PCV2d) strains from the USA, China and South Korea. The last sequence, however, clustered with other reference strains belonging to PCV2 intermediate clade 2 (PCV2‐IM2), recently identified in a global PCV2 strains phylogenetic analysis. This study reports the first complete genome sequences of PCV2b, PCV2d and PCV2‐IM2 in pigs from South Africa, and it gives a possible insight into the genetic characteristics and variability of the viral strains presently in circulation within the country. It further emphasizes the need for more stringent measures in curtailing the introduction and spread of transboundary swine pathogens in the country and entire Southern African region.     

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.