针刺联合化痰通络汤治疗痰瘀互结型卒中相关性肺炎的疗效及对T淋巴细胞亚群的影响

目的：观察针刺联合化痰通络汤治疗痰瘀互结型卒中相关性肺炎(SAP)的疗效及对T淋巴细胞亚群的影响。方法：选取2017年12月-2019年8月在佛山市中医院神经内科就诊的痰瘀互结型卒中相关性肺炎(SAP)患者共84例为研究对象,随机分为观察组和对照组,每组各42例。对照组予西医常规治疗,包括抗感染、化痰、改善氧供及其他相关对症治疗,观察组在对照组基础上予普通针刺联合化痰通络汤口服,其中针刺每日1次,一周治疗6天,化痰通络汤每日口服1剂,两组均连续治疗2周。比较两组患者治疗前后中医证候积分,观察两组患者临床疗效,血清肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP)、降钙素原(PCT) ,T淋巴细胞亚群(CD3_⁺、CD4_⁺、CD8_⁺、CD4_⁺/ CD8_⁺比值)的水平。结果：治疗后,观察组总有效率为92.86%,与对照组78.57%相比,具有显著差异(P＜0.05)；观察组中医证候积分较治疗前及对照组均显著降低(P＜0.05)；观察组患者TNF-α、hs-CRP、PCT水平较治疗前及对照组均明显降低,具有显著差异(P＜0.05)；CD3_⁺、CD4_⁺、CD4_⁺/CD8_⁺比值较治疗前及对照组均明显升高,CD8_⁺水平明显降低,均具有显著差异(P＜0.05)。结论：针刺联合化痰通络汤,针药结合治疗痰瘀互结型SAP患者,可以明显改善相关症状,提高临床疗效,减轻炎症因子水平,增强患者机体免疫功能。     

复方半枝莲汤治疗失代偿期乙型肝炎肝硬化的临床效果及患者血清T细胞亚群分析

目的:探讨复方半枝莲汤治疗失代偿期乙型肝炎肝硬化的临床效果。方法:选取2016年1月-2018年1月于通辽市传染病医院进行治疗的失代偿期乙型肝炎肝硬化患者60例,按照随机方式分为两组,对照组为恩替卡韦^+保肝对症的常规治疗;研究组在对照组治疗方式的基础上联合使用复方半枝莲汤,研究对比两组患者临床疗效以及血清T细胞亚群等指标的差异。结果:治疗后研究组和对照组治疗有效率分别为96.7%(29/30)和76.7%(23/30)研究组,临床疗效显著优于对照组(P<0.05);治疗前两组患者乙肝病毒的脱氧核糖核酸(Hepatitis B virus Deoxyribonucleic Acid,HBV-DNA)及肝功能指标无显著变化(P>0.05),研究组治疗后各指标下降程度显著优于对照组(P<0.05);治疗前两组患者CD8^+、CD4^+、CD4^+/CD8^+指标无明显差异(P>0.05),治疗后CD4^+提升,CD8^+下降,CD4^+/CD8^+指标上升,CD8^+、CD4^+、CD4^+/CD8^+指标较对照组更加显著(P<0.05);治疗后研究组和对照组不良反应的发生率分别为6.7%(2/30)和33.3%(10/30),研究组不良反应发生率显著低于对照组(P<0.05)。结论:常规治疗同时联合复方半枝莲汤治疗失代偿期乙型肝炎肝硬化效果显著,可有效改善患者肝功能,抑制HBVDNA的复制,提高免疫功能,且具有良好的治疗安全性。     

Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P₁) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (21–24) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized via a convergent route using the key and optically pure building block 9, which was first synthesized via asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound 21 showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound 23 showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds 21 and 23 both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.     

初发急性白血病患者外周血T淋巴细胞亚群的表达探讨

目的探讨初发急性白血病患者外周血中相关T淋巴细胞亚群表达情况。方法选取2017年2月~2019年3月于我院诊治的34例初发急性白血病患者作为研究对象(试验组),选择同期于我院体检的34例健康体检者作为对照组。检测两组外周血中相关T淋巴细胞亚群指标,对两组CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)、IL-2、IFN-γ、IL-4、IL-10进行比较。结果试验组初发急性白血病患者CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)水平分别为(61.20±4.64)%、(30.53±3.70)%和(1.02±0.23),均明显低于对照组,差异具有统计学意义(P0.05);而试验组初发急性白血病患者CD8+水平为(44.14±3.50)%,明显高于对照组,差异具有统计学意义(P0.05);试验组初发急性白血病患者IL-2为(11.60±1.13)pg/m L、IFN-γ为(23.25±2.50)pg/m L,均明显低于对照组,差异具有统计学意义(P0.05)。试验组初发急性白血病患者IL-4、IL-10分别为(41.36±3.50)pg/m L和(34.50±2.75)pg/m L,均明显高于照组,差异具有统计学意义(P0.05)。结论初发急性白血病患者外周血中CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)、IL-2、IFN-γ表达下降,CD~(8+)、IL-4、IL-10表达提升。     

Booster vaccination with a fractional dose of an oral cholera vaccine induces comparable vaccine-specific antibody avidity as a full dose: A randomised clinical trial

Antibody avidity is an important measure of the quality of vaccine-induced immune responses. Murine and human studies suggest that antibody avidity may be augmented by limiting access to antigen. The primary objective of this study was to evaluate in primed Swedish adults if booster vaccination with fractional doses (1/5th and 1/25th) of a model oral vaccine, the cholera vaccine Dukoral®, results in higher avidity antibody responses compared to boosting with a full vaccine dose. We also evaluated if fractional booster vaccination elicited similar magnitudes of antibody response compared to a full dose, and if the previously observed increase in antibody avidity after booster vaccination 1–2 years later occurred when boosting after a shorter interval.To this end, a randomised, open-label, exploratory Phase-II trial was performed. Swedish adults (n = 44), primed with two full doses of Dukoral®, were randomised into three groups and given a booster dose at either full (n = 14), 1/5th (n = 17) or 1/25th (n = 13) dose four months later. Antibody responses to cholera toxin B-subunit (CTB) were measured in serum and mucosal antibody in lymphocyte secretions (ALS).We found that the 1/5th and 1/25th booster doses had similar abilities as the full dose to induce significantly higher avidity anti-CTB antibody responses in both ALS and serum samples, as compared to after priming vaccination. There was a non-significant trend to lower magnitudes of ALS and serum IgA responses after the 1/5th compared to the full booster dose, and responses after the 1/25th dose were significantly lower.Our findings suggest fractional booster doses of Dukoral® four months after priming result in anti-toxoid mucosal antibody responses with increased antibody avidity compared to after priming vaccinations.ISRCTN registry identifier 11806026.     

Leukocytosis,muscle damage and increased lymphocyte proliferative response after an adventure sprint race

The effect of an adventure sprint race (ASR) on T-cell proliferation, leukocyte count and muscle damage was evaluated. Seven young male runners completed an ASR in the region of Serra do Espinhaço, Brazil. The race induced a strong leukocytosis (6.22±2.04×10³ cells/mm³ before vs 14.81±3.53×10³ cells/mm³ after the race), marked by a significant increase of neutrophils and monocytes (P<0.05), but not total lymphocytes, CD3⁺CD4⁺ or CD3⁺CD8⁺ cells. However, the T-cell proliferative response to mitogenic stimulation was increased (P=0.025) after the race, which contradicted our hypothesis that ASR, as a high-demand competition, would inhibit T-cell proliferation. A positive correlation (P=0.03, r=0.79) was observed between the proliferative response of lymphocytes after the race and the time to complete the race, suggesting that the proliferative response was dependent on exercise intensity. Muscle damage was evident after the race by increased serum levels of aspartate amino transferase (24.99±8.30 vs 50.61±15.76 U/L, P=0.003). The results suggest that humoral factors and substances released by damaged muscle may be responsible for lymphocyte activation, which may be involved in muscle recovery and repair.     

中药影响实验性自身免疫性脑脊髓炎CD4+T细胞亚群分化的研究进展

实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)是由CD4⁺T细胞介导的中枢神经系统脱髓鞘性疾病,是国际公认研究多发性硬化(multiple sclerosis,MS)的动物模型。CD4⁺T细胞作为EAE模型的主要免疫应答细胞,存在多个亚群,可分泌多种细胞因子,参与病情进展。CD4⁺T细胞增殖分化及功能紊乱与EAE发病机制密切相关。目前临床尚无治疗MS的有效药物,多以对症应用皮质类固醇激素为主,但不良反应严重,且易产生药物依赖。近年来中药因作用温和、药物安全性较高、成本低、耐受性好等优点逐渐走进大众视野,针对中药对EAE中CD4⁺T细胞亚群分化的影响展开论述,为临床用药提供更多理论基础。     

Effects of Long-time Exposure to Lipopolysaccharide on Intestinal Lymph Node Immune Cells and Antibodies Level in Mice

Background: Endotoxin, widely present in the living environment of humans and animals, leads to endotoxemia during a short period. However, the long-term effects of endotoxin on immune function are unclear. Objective: To determine the importance of long-term endotoxin treatment on function of immune system. Methods: The mice were treated with different doses of lipopolysaccharide (LPS) for a month; the collected samples were then analyzed in terms of value changes in hematological parameters, lymphocyte subtypes, and immunoglobulins level. Results: The number of monocytes (MONO) and neutrophils (NEU) in the three treatment groups was significantly lower than the control after 30 days. However, the proportion of CD8+ T lymphocytes showed a rising trend in the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) while the CD4+ T cell was reduced. At the same time, a decrease was observed in the percentage of CD19+CD38+ B lymphocytes. Interestingly, the change of lymphocytes in PPs was more significant than that in MLNs, suggesting that immune response in the PPs occurred before the MLNs. Consistent with the changes in B cells, the content of IgA and IgG showed a downward trend. Conclusion: Long-term exposure to low-dose endotoxin had little or no effect on the immune function of the body, suggesting that the endotoxin can be rapidly eliminated by the immune system. Nonetheless, the number of immune cells was reduced in the high-dose group. T- and B-lymphocytes were significantly reduced, resulting in a decrease in immunoglobulin level, and showing a significant immune suppression state.     

不同麻醉方法对肝癌切除术后患者肿瘤转移因子、C反应蛋白以及T淋巴细胞的影响

目的研究不同麻醉方法对肝癌患者手术后肿瘤转移因子、C反应蛋白以及T淋巴细胞的影响。方法 64例原发性肝癌患者分为2组。静脉组采用静脉麻醉,联合组采用静脉麻醉复合硬膜外麻醉。比较2组麻醉后不同时间点的血流动力学变化、CK20mRNA阳性率、C反应蛋白水平以及T淋巴细胞亚群的情况。结果 2组T1时ALT和AST水平均高于T0时(P0.05)。2组ALB在T_1时均有下降,且静脉组ALB显著低于联合组(P0.05)。2组TBIL在T_1时升高,且静脉组显著高于联合组(P0.05)。静脉组T_2、T_3时CK20mRNA阳性率和CRP水平显著高于联合组,且2组T_2、T_3时CK20mRNA阳性率和CRP均显著优于T_0、T_1时(P0.05)。2组T_1、T_2、T_3各T细胞亚群均有所下降,且联合组T_1、T_2、T_3时T细胞亚群显著高于静脉组(P0.05)。结论静脉复合麻醉联合胸部硬膜外麻醉能够减轻肝癌切除手术患者围术期的应激反应,降低肿瘤转移因子的阳性率,促进免疫系统功能恢复。