Understanding and helping children who have experienced maltreatment

Children who experience maltreatment from within their families can suffer trauma that is devastating to their physical and psychological development. The label developmental trauma has developed to describe this trauma and to guide diagnosis. This has been expanded to describe seven domains of impairment. Together these help the clinician to provide a formulation of a child's difficulties which avoids multiple diagnoses and can guide treatment planning. Dyadic Developmental Psychotherapy and Practice (DDP) is an intervention model that can meet the therapeutic needs of the children alongside the support needs of parents and practitioners caring for them. The attitude of PACE (playfulness, acceptance, curiosity and empathy) is central within DDP interventions, used by therapists, parents and practitioners who together make up the network around the child. Tailoring DDP interventions can be guided by a pyramid of need developed by the author. This helps clinicians develop flexible intervention packages tailored to the needs of the child, family and practitioner. Within the paper these ideas are explored illustrated by the fictional example of Janice. She was maltreated in early childhood and now lives in foster care with Mary and Simeon.     

藤黄酸增强人胃癌SGC7901/DDP细胞对顺铂的敏感性

目的 探讨藤黄酸（GA）对人胃癌SGC7901/DDP细胞顺铂敏感性的影响及其分子机制。方法 采用顺铂（DDP）浓度梯度递增法构建人胃癌顺铂耐药株SGC7901/DDP细胞,采用细胞计数盒-8（CCK-8）法检测藤黄酸和顺铂对SGC7901/DDP细胞的毒性作用,采用Chou-Talalay中效分析法定量评价藤黄酸和顺铂的联合作用效果,采用流式细胞术检测细胞凋亡,采用Western blotting方法检测Bcl-2、Bax、Survivin、多药耐药相关蛋白2（MRP2）、磷酸化氨基末端蛋白激酶（p-JNK）（Thr183/Tyr185）和JNK的蛋白水平。结果 藤黄酸与顺铂各自单独作用48 h的IC₅₀分别为2.94 μmmol/L和39.76 μmmol/L;当抑制率超过20%时,两者联合应用呈协同效应;藤黄酸可协同增强顺铂诱导的细胞凋亡（P<0.05）,下调Survivin和MRP2蛋白水平（P<0.05）,上调Bax蛋白水平（P<0.05）,抑制JNK磷酸化（P<0.05）;JNK特异性抑制剂SP600125可下调MRP2蛋白水平（P<0.05）。结论 藤黄酸可增强人胃癌SGC7901/DDP细胞对顺铂的敏感性,这可能与藤黄酸通过抑制JNK信号通路下调MRP2蛋白表达,以及上调Bax蛋白表达和下调Survivin蛋白表达有关。     

RNA干扰抑制ERCC1/ERCC2表达对非小细胞肺癌化疗敏感性影响观察

目的探讨利用RNA干扰技术沉默非小细胞肺癌A549和A549/顺铂(DDP)细胞株ERCC1和ERCC2的表达对DDP化疗敏感性的影响。方法设计并合成靶向基因siRNA-ERCC1和siRNA-ERCC2,并构建载体,通过前期转染A549/DDP细胞,筛选出沉默ERCC1和ERCC2基因表达最优的小分子RNA片段及最佳的作用时间,再将筛选出来的最优片段通过脂质体LipofectamineTM2000转染入A549细胞,观察其转染效率,使用RT-PCR及细胞免疫组化分别检测转染后基因及蛋白的表达变化;利用MTT法检测转染后细胞IC50,观察其对DDP耐药性的变化;再根据实验结果,从A549和A549/DDP细胞株中选定一株能够被逆转耐药的细胞接种于12只裸鼠皮下,观察裸鼠成瘤时间,并加用DDP局部化疗4次,记录肿瘤体积变化情况。结果通过siRNA-ERCC1和siRNA-ERCC2转染A549细胞株后,其ERCC1mRNA相对表达量为104.097 8±8.551 3,未转染组为128.465 6±12.360 4;ERCC2 mRNA相对表达量为90.415 7±7.882 1,未转染siRNA-ERCC2组为123.310 0±10.999 2。转染组的mRNA相对表达量均小于未转染组,P<0.05。转染A549细胞后,转染组ERCC1和ERCC2蛋白表达量分别为1.982 1±0.518 7和2.087 1±0.655 2,明显低于未转染组ERCC1(4.576 4±1.271 1)和ERCC2(5.680 0±1.416 7),P<0.01;MTT结果提示,siRNA-ERCC1和siRNA-ERCC2转染细胞A549后的IC50分别为(20.322 7±0.452 1)和(20.394 7±0.479 4)μg/mL,与未转染组(21.062 4±0.766 4)μg/mL差异无统计学意义,P>0.05;转染A549细胞后未发现逆转DDP耐药的效果,故筛选出A549/DDP细胞株。siRNA-ERCC1转染组的肿瘤体积为(144.63±7.67)mm3,siRNA-ERCC2转染组为(130.65±8.45)mm3,均明显小于未转染组的(252.35±12.36)mm3,P<0.01。结论高效的特异性siRNA能抑制非小细胞肺癌细胞中ERCC1和ERCC2基因和蛋白的表达,并能使A549/DDP细胞株对DDP的耐药性降低,但不能改变A549细胞株对DDP的耐药性。     

阿帕替尼通过抑制HMGA2增强顺铂对胃癌的抗瘤作用

目的：探讨阿帕替尼（apatinib，APA）联合顺铂（cisplatin，DDP）对胃癌（gastric carcinoma，GC）细胞增殖、侵袭和迁移 能力的影响及其分子机制。方法：收集2016年1月到2019年6月武威市人民医院手术切除的50例GC患者的癌及癌旁组织标 本，以及GC细胞系MGC803和SGC7901， 用qPCR检测组织中HMGA2和细胞中增殖、迁移及侵袭相关mRNA的表达水平。采 用脂质体转染技术， 将pcHMGA2转染MGC803和SGC7901细胞，经分别用不同浓度的DDP和APA处理，分为NC、pcHMGA2、 pcHMGA2+DDP及pcHMGA2+DDP+APA组， 用Western blotting检测GC细胞中HMGA2蛋白的表达水平，MTT、Transwell小室 法分别检测细胞的增殖、迁移和侵袭能力。结果：HMGA2 mRNA在GC组织中表达水平高于癌旁组织（P<0.05），且高表达组 GC患者的生存率显著降低（P<0.01）。DDP 显著抑制 MGC803 和 SGC7901 细胞的增殖、侵袭和迁移能力（均P<0.01）； DDP+APA组MGC803和SGC7901细胞的增殖、侵袭和迁移能力显著低于DDP组（均P<0.01）；APA显著增强DDP对GC细胞 HMGA2表达的抑制作用（均P<0.01）；APA通过下调HMGA2表达增强DDP对GC的抗肿瘤性。结论：APA能促进DDP对GC的 抗瘤作用，其分子机制可能是增强DDP对HMGA2表达的抑制作用有关。     

中药单体逆转卵巢癌顺铂耐药机制的研究进展

卵巢癌的早期症状不典型并且缺乏有效的筛查方法,多数患者确诊时已是晚期,严重危害当代妇女健康。肿瘤减灭术后以铂类药物为主的化疗是晚期卵巢癌和复发性卵巢癌患者的首选,但几乎所有的复发性卵巢癌患者最终都会发展为铂耐药。因此寻找天然、安全、有效的化疗增敏剂已成为卵巢癌研究中迫切而又重要的课题。随着中药在癌症治疗中的应用日益广泛,人们对中药单体的研究也日渐深入,中药单体干预卵巢癌顺铂(DDP)耐药的机制也愈发清晰。基于中药单体研究现状,通过查阅多个中英文数据库中中药单体相关实验研究,发现中药单体在多方面参与了逆转卵巢癌DDP耐药,其机制可以概括为以下6个方面:增加胞内药物浓度、逆转凋亡受阻、逆转胞内信号通路异常、增加DNA损伤和抑制DNA修复、调控胞内自噬、抑制上皮间质转化(EMT)。中药单体从多靶点减轻了卵巢癌DDP耐药,增加了DDP对卵巢癌体外细胞和体内移植瘤的毒性作用,因此中药单体有望成为卵巢癌DDP化疗的天然增敏剂。然而中药单体目前的研究还存在实验类型单一、机制尚不完全明确、不良反应不明等不足,从实验室到临床,中药单体增敏DDP化疗的应用未来还需要多靶点、多水平的实验研究及大规模的临床研究的验证。     

Reversal effect of recombinant human Endostatin on cisplatin resistance in A549/DDP human lung adenocarcinoma cells in vitro

Objective： Recombinant human Endostatin （rh-Endostatin, YH-16） can reverse cisplatin resistance in A549/DDP cells. However, the possible effect of rh-Endostatin in reversing DDP-resistance in A549/DDP cells and the mechanism are needed to be investigated. Methods： Lung adenocarcinoma cell line A549 and its DDP-resistant cell line A549/DDP were treated with DDP and/or recombinant human Endostatin. Difference in drug resistance was analyzed between different regi- mens and between different cell lines after a 72 h-treatment in vitro. And below the non-cytotoxic concentration of rh-End- ostatin, the possibility of rh-Endostatin in reversing DDP-resistance in A549/DDP was evaluated. The resistance protein which was detected in the study included P glycoprotein （P-gp） and topoisomerase II （Topo-II）. Results： Rh-Endostatin below 400 IJg/mL showed no cytotoxicity in either A549 or A549/DDP after 72 h-treatment with it. The inhibited concentration of 50% （IC50） observed for DDP was （0.79 _＋ 0.05） IJg/mL in A549 and （13.2 ＋ 1.1） in A549/DDP respectively. IC50 was reduced to 2.57 ＋ 0.05 #g/mL in A549/DDP treated by rh-Endostatin below the non-cytotoxic concentrations in combination with DDP, with a reversal fold （RF） of 5.14 and a relative reversal rate of 85.6%. Apoptotic rates were 2.01%, 13.47% and 29.26% re- spectively for cells treated with rh-Endostain, DDP, and the combination. The rate of the A549/DDP control group was 0.99%. The expression level of P-gp or Topo-II was higher in A549/DDP cells than in A549 cells. Rh-Endostatin may partially reverse DDP-resistance in A549/DDP cells in vitro, with a probable mechanism related to lowering expression of P-gp and Topo-II. Conclusien： Rh-Endostatin of non-cytotoxic dose partially reversed cisptatin resistance in cisplatin-resistant human lung adenocarcinoma cell line A549/DDP. Rh-Endostatin reversed the resistance of A549/DDP cells to DDP, which may be related to decreased protein expression of P-gp and Topo-II in A549/DDP cells.     

The anti-cancer effect of Huaier aqueous extract with rh-Endostatin and DDP

Objective： The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human Endostatin and DDP in human lung adenocarcinoma A549 cells. We also investigated the reversal effect of Huaier aqueous extract in reversing cisplatin resistance in human lung adenocarcinoma A549/DDP cells. Methods： We treated A549 cells with Huaier aqueous extract and the combination of Huaier aqueous ex- tract and DDP or rh-Endostatin for 24 h, 36 h and 48 h. And then we calculated the inhibition rate through MTT approach and detected the apoptosis rate by flow cytometry. We also treated A549 and A549/DDP cells with DDP, Huaier aqueous extract, DDP and Huaier aqueous extract for 72 h, respectively. Results： Huaier aqueous extract can inhibit the growth of A549 cells and the inhibition rate improved with the increase of the concentration. The inhibition rate of the combination of rh-Endostatin and 4 mg/mL of Huaier aqueous extract in three time points and the combination of rh-Endostatin and 2 mg/mL of Huaier aqueous extract in the time point of 48 h on the growth of A549 cells all improved （P 〈 0.005）. The inhibition rate of the com- bination of DDP and Huaier aqueous extract with the concentration of 2 mg/mL or 4 mg/mL on the growth of A549 cells all improved （P 〈 0.005）. The combination of Huaier aqueous extract and DDP and the combination of Huaier aqueous extract with rh-Endostatin and DDP can improve the inhibition on the growth ofA549 cells （P 〈 0.005）. Conclusion： Huaier aqueous extract has the inhibition and apoptosis-inducing effects on the A549 cells. And the combination of Huaier aqueous extract and rh-Endostatin or DDP has the synergistic effects on the inhibition of A549 cells. The combination of Huaier aqueous extract with rh-Endostatin and DDP has the synergistic effects on the inhibition ofA549 cells. Huaier aqueous extract can reverse the cisplatin resistance in human lung adenocarcinoma A549/DDP cells.     

荜茇酰胺对人肺癌A549/DDP细胞耐药性的逆转作用

目的:研究荜茇酰胺对人肺癌A549/顺铂(DDP)细胞耐药性的逆转作用。方法:A549/DDP细胞经0、20、30μmol/L荜茇酰胺作用48 h后,用MTS法检测肿瘤细胞抑制率;流式细胞术检测肿瘤细胞凋亡、细胞周期、P-糖蛋白(P-gp)表达和肿瘤细胞内罗丹明Rht123含量的变化;Western blotting法检测多药耐药基因(MDR)1、多药耐药相关蛋白(MRP)1、DNA拓扑异构酶(Top)Ⅱ、谷胱甘肽S-转移酶(GST)-π、凋亡抑制蛋白Survivin、周期蛋白依赖性蛋白激酶(CDK)1和蛋白激酶(PK)Cζ蛋白表达;实时荧光聚合酶链反应(RT-PCR)法检测MDR1、MRP1、Top-II、GST-π、Survivin和CDK1 m RNA表达;酶标仪检测含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-3、8活性。结果:A549/DDP细胞经0、20、30μmol/L荜茇酰胺作用48 h后,DDP对肿瘤细胞增殖的抑制率明显升高;与0μmol/L比较,20、30μmol/L荜茇酰胺作用48 h后,DDP导致的细胞凋亡率和G2期/M期明显升高,P-gp表达明显减弱,Rh-123浓度明显增加,MDR1、MRP1、Top-II、GST-π、Survivin、CDK1和PKCζ蛋白表达明显减弱,MDR1、MRP1、Top-Ⅱ、GST-π、Survivin、CDK m RNA表达明显减弱,Caspase-3、8的活性明显增强。结论:荜茇酰胺可逆转人肺癌A549/DDP细胞DDP耐药性,可能与其调节多药耐药相关基因表达有关。     

SP和FP方案化疗治疗晚期鼻咽癌的疗效比较分析

目的：比较分析SP和FP方案治疗晚期鼻咽癌的疗效。方法48例晚期鼻咽癌随机分为两组,每组24例,分别给予SP和FP方案化疗,治疗结束后评价疗效。结果 SP方案组有效率为58.33%（14/24）, PF方案组有效率为54.17%（13/24）,差异无统计学意义（P〉0.05）。结论 SP和FP方案治疗晚期复发和转移的鼻咽癌疗效均较好。     

灵芝多糖诱导耐药卵巢癌细胞凋亡的实验研究

目的研究灵芝多糖在体外对耐药卵巢癌细胞株SKOV-3/DDP的增值抑制和诱导凋亡的作用,并初步探讨其作用机制。方法 （1）采用MTT法检测灵芝多糖对耐药卵巢癌细胞株SKOV-3/DDP细胞增殖的抑制作用。（2）采用光学显微镜、相差显微镜观察灵芝多糖作用后细胞形态变化。（3）采用DNA片段检测证实细胞凋亡;（4）采用DCFH-DA荧光分光光度法检测细胞内ROS水平。（5）采用Real-time PCR技术检测谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）mRNA的表达,观察细胞内过氧化物的清除情况。结果灵芝多糖可明显抑制SKOV-3/DDP3细胞增殖并诱导其发生凋亡。结论灵芝多糖诱导细胞凋亡的机制可能是通过增加肿瘤细胞内ROS的生成,降低GSH-Px和CAT mRNA的表达,即通过氧化应激途径诱导SKOV-3/DDP细胞发生凋亡。