Expansion of CD3+CD8+PD1+ T lymphocytes and TCR repertoire diversity predict clinical responses to adoptive cell therapy in advanced gastric cancer

The adoptive cell therapy (ACT) and delivery of ex vivo activated cellular products, such as dendritic cells (DCs), NK cells, and T cells, have shown promise for the treatment of gastric cancer (GC). However, it is unknown which cells can improve patient survival. This study was focused on the antitumour activity of a subset of these cellular products and their relationships with clinical outcomes. Nineteen patients were enrolled at the Capital Medical University Cancer Center, Beijing Shijitan Hospital, from June 1, 2013, to May 30, 2016. CD8⁺PD1⁺ T-cell sorting was carried out using flow cytometry, and the T-cell receptor (TCR) repertoire during ex vivo expansion for 15 days was analyzed by next-generation sequencing. After 15 days of culture, the number of CD8⁺ T cells had increased significantly, and the number of CD4⁺ T cells had increased correspondingly. After ex vivo expansion, CD8⁺ T cells exhibited significantly enhanced expression of PD-1, LAG-3, and TIM-3 but not 4-1BB. Survival analysis showed that patients with a pro/pre value of CD8⁺PD-1⁺ T cells >2.4 had significantly favorable overall survival (OS) (median OS time, 248 days versus 96 days, P=0.02) and progression-free survival (PFS) (median PFS time, 183 days vs. 77 days, P=0.002). The sorted CD8⁺PD-1⁺ T cells displayed enhanced antitumor activity and increased IFN-γ secretion after coculture with autologous tumor cell lines. TCR repertoire diversity was decreased after ex vivo expansion, which decreased the Shannon index and increased the clonality value. The prognosis of patients was significantly improved and was associated with the extent of CD8⁺PD-1⁺ T-cell expansion. In summary, this study showed that after ex vivo expansion for 15 days, CD8⁺PD-1⁺ T cells could be identified as tumor-reactive cells in patients treated for GC. Changing TCR species can predict the extent of CD3⁺CD8⁺PD1⁺ T-cell growth and the effect of ACT treatment.     

Does losing money truly hurt? The shared neural bases of monetary loss and pain

Both monetary loss and pain have been studied for decades, but evidence supporting the relationship between them is still lacking. We conducted a meta‐analysis to explore the overlapping brain regions between monetary loss and pain, including physical pain and social pain. Regardless of the type of pain experienced, activation of the anterior insula was a shared neural representation of monetary loss and pain. The network representation pattern of monetary loss was more similar to that of social pain than that of physical pain. In conclusion, our research provided evidence of the common neural correlates of monetary loss and pain.     

Research Progress on Postoperative Minimal/Molecular Residual Disease Detection in Lung Cancer

Lung cancer is the leading cause of cancer‐related deaths worldwide. Approximately 10%–50% of patients experience relapse after radical surgery, which may be attributed to the persistence of minimal/molecular residual disease (MRD). Circulating tumor DNA (ctDNA), a common liquid biopsy approach, has been demonstrated to have significant clinical merit. In this study, we review the evidence supporting the use of ctDNA for MRD detection and discuss the potential clinical applications of postoperative MRD detection, including monitoring recurrence, guiding adjuvant treatment, and driving clinical trials in lung cancer. We will also discuss the problems that prevent the routine application of ctDNA MRD detection. Multi‐analyte methods and identification of specific genetic and molecular alterations, especially methylation, are effective detection strategies and show considerable prospects for future development. Interventional prospective studies based on ctDNA detection are needed to determine whether the application of postoperative MRD detection can improve the clinical outcomes of lung cancer patients, and the accuracy, sensitivity, specificity, and robustness of different detection methods still require optimization and refinement.     

Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accord...     

对照军队医院等级评审谈武警部队医院营养科建设

营养科的建设与发展水平直接关系到患者的康复,也关系到医院的整体医疗质量水平。笔者通过解读《军队三级综合医院等级评审标准和细则》,对医院营养工作的难点进行分析,总结了武警部队营养科建设目前存在的问题,并提出营养科下一步发展对策。     

牛磺酸对大鼠肝缺血再灌注后小肠损伤的保护作用

目的探讨牛磺酸对大鼠肝缺血再灌注(I/R)后小肠损伤的保护作用。方法将大鼠随机分成假手术组,肝I/R组,牛磺酸预处理+肝I/R组;采用阻断肝动脉、门静脉30min后再灌注的方法,制作肝I/R模型。各组于再灌注3,6,24h分别采血,测定二胺氧化酶(DAO)数值,检测小肠功能;同步切取小肠,测定肠道组织中的SOD及MDA含量,评价肠道自由基损伤程度;切片后行苏木素-伊红(HE)染色,观察病理形态学改变;原位末端标记法(TUNEL)测定细胞凋亡;免疫组化法测定caspase-3表达。结果与假手术组比较,肝I/R组SOD水平明显降低(P<0.05),MDA和DAO水平明显升高(P<0.05),小肠病理损伤严重,凋亡指数明显升高(P<0.05),caspase-3阳性率明显增加(P<0.05)。与I/R组同时间点比较,牛磺酸预处理+I/R组各项指标均明显改善(均P<0.05)。结论牛磺酸对肝I/R后小肠损伤具有保护作用。     

前列地尔联合甲泼尼龙针改善血栓前状态治疗AECOPD临床分析

目的观察前列地尔联合甲泼尼龙对AECOPD炎症以及血栓前状态的影响,并分析其临床疗效。方法选取2011年8月~2013年8月于舟山市妇幼保健院进行治疗的AECOPD患者100例,随机分成甲泼尼龙治疗对照组和前列地尔联合甲泼尼龙治疗观察组,每组50例。IL-6、TNF-α表达的检测使用ELISA法。比较两组的全血高切黏度、全血低切黏度、血浆黏度等血液流变指标,以及临床疗效和不良反应发生率。结果治疗前对照组和观察组全血高切黏度、全血低切黏度、血浆黏度差异无统计学意义(P>0.05)。治疗后两组均出现显著减低(P<0.05),但观察组的减低效应显著优于对照组(P<0.05)。治疗前观察组和对照组IL-6、TNF-α表达水平差异无统计学意义(P>0.05),治疗后IL-6和TNF-α均显著减低(P<0.05和P<0.01),但治疗后IL-6、TNF-α表达水平在观察组显著低于对照组(P<0.05)。对照组咳嗽缓解时间、呼吸困难消失时间、啰音消失时间以及住院时间分别为5.74±1.62、3.68±0.76、5.27±1.24、9.74±2.28天,显著长于观察组的3.76±1.03、2.53±0.58、3.36±0.88、7.22±1.69天(P<0.05)。观察组临床治疗有效率为90.0%,显著优于对照组的76.0%(P<0.05)。结论前列地尔联合甲泼尼龙治疗AECOPD,可以显著改善患者的血栓前状态,抑制炎性反应,临床安全、有效,值得推广使用。     

热缺血对兔肾表面微循环的影响

作者用10只家兔.观察了不同时限热缺血对兔肾表面微循环的影响。将动物分四组。A组为手术对照,不阻断肾动脉。其余B、C、D组分别阻断左肾血流10min、30min和60min。在阻断前和恢复血流10min后,分别用显微镜观察肾表面微循环。行右肾切除。动物观察14天。结果表明,10min缺血组动物仅有轻度毛细血管收缩。30min以上热缺血.不仅引起更明显的微血管收缩,还可引起不同程度的血管扩张和血流淤滞现象。微循环紊乱尤其是血流淤滞的程度.与术后肾功能及组织学检查结果一致。提示缺血后肾皮质微循环状况与肾功能恢复密切相关。肾保存时,保存液中加入适当保护剂保护肾脏微循环,对于移植后肾功能的恢复具有重要意义。     

单针超滤浓缩回输术治疗肝硬化顽固性腹水180例分析

目的探讨单针腹水超滤浓缩回输术治疗肝硬化顽固性腹水的疗效。方法180例均为我院收治的患者,经内科保守治疗效果不佳者。其中男142例,女38例。本次出现腹水2个月至3年不等,伴有肝肾综合征82例,原发性腹膜炎27例,胆道感染16例,肠道感染10例,胸水或胸水感染者6例,消化道出血者12例,应用日本东丽血液净化机、国产负压吸引器及一次性血路管、中空纤维滤器及带有侧孔平头空心套管针对患者实行超滤浓缩术,一次可超滤腹水3000～13000ml,迅速改善多种临床症状及体征。结果腹水缓解并维持3个月以上视为显效。腹水缓解其后再次出现,但使用利尿剂重新敏感视为有效。近期腹水回到原来水平视为无效。结果:显效60例(33.3%),有效90例(50%),无效30例(16.6%),总有效率为83.3%。操作过程中患者仅有3例出现一过性血压下降,2例腹部轻微疼痛,9例腹部针刺部位瘀癍,3例穿刺部位有渗出。结论单针腹水超滤浓缩术操作简便易行,副反应小,能迅速缓解顽固性腹水患者的痛苦,是治疗肝硬化顽固性腹水的一种安全有效的方法。     

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats

BackgroundThis study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats.MethodsA total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg·d). After modeling or treatment, the value of E/A and E/e'' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot.ResultsCompared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e'') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e'' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05).ConclusionsKangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function.