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.     

The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

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...     

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。     

Improving Anti-Coking Properties of Ni/Al2O3 Catalysts via Synergistic Effect of Metallic Nickel and Nickel Phosphides in Dry Methane Reforming

A series of NiP-x/Al₂O₃ catalysts containing different ratio of metallic nickel to nickel phosphides, prepared by varying Ni/P molar ratio of 4, 3, 2 through a co-impregnation method, were employed to investigate the synergistic effect of metallic nickel-nickel phosphides in dry methane reforming reaction. The Ni/Al₂O₃ catalyst indicates good activity along with severe carbon deposition. The presence of phosphorus increases nickel dispersion as well as the interaction between nickel and alumina support, which results in smaller nickel particles. The co-existence of metallic nickel and nickel phosphides species is confirmed at all the P contained catalysts. Due to the relative stronger CO₂ dissociation ability, the NiP-x/Al₂O₃ catalysts indicate obvious higher resistance of carbon deposition. Furthermore, because of good balance between CH₄ dissociation and CO₂ dissociation, NiP-2/Al₂O₃ catalyst exhibits best resistance of carbon deposition, few carbon depositions were formed after 50 h of dry methane reforming.     

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.     

高效液相色谱法测定补骨脂中三种黄酮类成分的含量

目的 :建立补骨脂中三种黄酮类成分含量测定方法。方法 :采用高效液相色谱法分析补骨脂中补骨脂甲素和补骨脂异黄酮的含量。色谱柱 :汉邦 Lichrosphore C1 8(2 5 0 mm× 4.6mm ,5μm) ;流动相 :乙腈 -水 (4∶6) ;流速 1.0 ml/ min;检测波长 :2 79nm(0～ 3 0 min) ,2 47nm (3 0～ 45 min) ;进样量 2 0μl。补骨脂查耳酮 :色谱柱 :汉邦 L ichrosphore C1 8(2 5 0 mm× 4.6mm,5 μm) ;流动相 :甲醇 -水 (85∶ 15 ) ;流速 1.0 ml/ min;检测波长 3 87nm ;进样量 2 0μl。结果 :平均加样回收率为 98.2 % ,RSD为 1.3 % ,0 .0 489～ 0 .3 91μg,r=0 .9999(n=7)。结论 :该方法适合于测定补骨脂中黄酮类成分的含量 ,应用该方法对不同产地的补骨脂中 3种成分含量进行了测定。不同产地中黄酮类成分的含量存在很大差异 ,对补骨脂黄酮类成分进行含量测定应成为补骨脂质量控制的重要环节。