雷公藤多甙片与甲氨喋呤联合治疗类风湿关节炎的临床疗效及对炎症因子的影响

目的:研究雷公藤多苷片联合甲氨蝶呤治疗类风湿关节炎(RA)的临床疗效及对血清炎症因子的影响。方法:选取2014年1月-2015年8月我院收治的RA患者60例,按治疗方法的不同分为观察组和对照组各30例,观察组应用雷公藤多苷片联合甲氨蝶呤治疗,对照组单纯应用甲氨蝶呤治疗,对比两组的临床疗效及治疗前后临床症状、红细胞沉降率(ESR)、C反应蛋白(CRP)及类风湿因子(RF)水平。结果:观察组的总有效率为93.33%,明显高于对照组的73.33%(P0.05);治疗后观察组的临床症状(晨僵时间、关节压痛及肿胀数、关节疼痛度及肿胀指数)均较对照组明显改善(P0.05);治疗后两组血清ESR、CRP、RF水平均降低,且观察组明显低于对照组(P0.05);观察组不良反应率为13.33%,低于对照组的10.00%,差异无统计学意义(P0.05)。结论:雷公藤多苷片联合甲氨蝶呤治疗RA能够有效控制炎症反应,改善临床症状,临床疗效显著,且不增加副反应,是一种安全可靠的联合治疗方案,值得推广应用。     

戈利木单抗联合雷公藤多甙对甲氨蝶呤治疗反应不佳活动性类风湿关节炎的效果及安全性分析

目的:分析戈利木单抗联合雷公藤多苷对甲氨蝶呤(MTX)治疗反应不佳活动性类风湿关节炎(RA)的临床效果及安全性。方法:选择MTX治疗反应不佳(MTX治疗超3个月,但应答不足)的活动性RA患者66例,按照随机数字表法分为对照组与试验组各33例,对照组单用雷公藤多苷治疗,试验组加用戈利木单抗治疗,测定两组治疗前后血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)水平的变化,记录晨僵时间、关节肿胀数目、关节压痛数目,评定治疗效果,采用视觉模拟评分法(VAS)评定患者关节疼痛程度、患者对疾病总体症状的耐受情况,监测两组不良事件的发生情况。结果:(1)治疗后,两组ESR、CRP、RF均降低,与同组治疗前对比差异有统计学意义(P0.05),试验组ESR、CRP降低幅度高于对照组(P0.05);(2)治疗后,两组晨僵时间减少、关节肿胀及压痛数目均减少,与治疗前对比差异有统计学意义(P0.05),试验组各指标改善幅度均高于对照组(P0.05);(3)治疗后,两组VAS评分均降低,与治疗前对比差异有统计学意义(P0.05),试验组降低幅度高于对照组(P0.05);(4)试验组ACR50、ACR70所占比例均高于对照组(P0.05);(5)试验组、对照组不良反应发生率对比差异无统计学意义(P0.05)。结论:戈利木单抗联合雷公藤多苷治疗MTX反应不佳活动性RA疗效肯定,可下调患者ESR、CRP水平,缩短晨僵时间,显著改善患者症状,减轻关节疼痛程度,且安全性高。     

西洛他唑在急性脑梗死患者rt-PA溶栓治疗后的作用及对血清CD62p、CD63、PAF的作用分析

摘要 目的：探讨西洛他唑在急性脑梗死患者重组人组织型纤溶酶原激活物（rt-PA）溶栓治疗后的作用及对血清血小板溶酶体膜蛋白（CD63）、α颗粒膜糖蛋白（CD62p）、血小板活化因子（PAF）的作用分析。方法：选择2020年2月至2022年2月我院接诊的90例急性脑梗死患者,按照随机数表法分为观察组及对照组,各45例。两组均接受rt-PA溶栓治疗,对照组溶栓后使用阿司匹林治疗,观察组在对照组基础上,联合西洛他唑治疗,均连续治疗14 d。比较两组临床疗效、血清CD62p、CD63、PAF、全血粘度、血浆粘度和红细胞比容（HCT）及美国国立卫生院卒中量表（NIHSS）评分、巴氏量表（Barthel指数）评分的变化及出血事件发生率。结果：观察组患者的临床疗效总有效率为91.11%,高于对照组的73.33%,有统计学意义（P＜0.05）;观察组血清CD62p、CD63、PAF均比对照组低,有统计学意义（P＜0.05）;观察组全血粘度、血浆粘度、HCT均比对照组低,有统计学意义（P＜0.05）;观察组的NIHSS评分均低于对照组,Barthel指数高于对照组,有统计学意义（P＜0.05）;两组出血事件总发生率比较,无统计学意义（P＞0.05）。结论：西洛他唑在急性脑梗死患者rt-PA溶栓治疗后的作用明显,可有效降低血清CD62p、CD63、PAF的表达,改善血小板功能,安全性较好,值得临床推广。     

阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受型类风湿关节炎的临床疗效

目的:探讨阿达木单抗注射液联合白芍总苷治疗甲氨蝶呤不耐受风湿关节炎患者的临床疗效。方法:收集我院治疗的86例甲氨蝶呤不耐受的类风湿关节炎患者,随机分为实验组和对照组,每组43例。对照组患者给予阿达木单抗注射液治疗,实验组患者在对照组基础上给予白芍总苷胶囊治疗。观察并比较两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)以及临床疗效进行检测并比较。结果:与治疗前相比,治疗后两组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平均下降(P0.05);与对照组相比,实验组患者的晨僵时间、血沉(ESR)、类风湿因子(FR)水平较低(P0.05),临床治疗有效率较高(P0.05)。结论:阿达木单抗注射液联合白芍总苷能够降低甲氨蝶呤不耐受的类风湿关节炎患者的ESR、FR水平,改善患者的临床症状,临床疗效较好。     

雷公藤多苷联合激素对成人NS糖皮质激素抵抗及HSP90的影响

为探讨雷公藤多苷联合激素治疗成人肾病综合征(NS)的临床效果及对患者糖皮质激素抵抗、热休克蛋白90(HSP90)表达的影响,本研究将82例肾病综合征患者按随机数字表法分为对照组与观察组两组,每组41例,两组均予以基础对症处理,对照组采用糖皮质激素泼尼松治疗,1 mg/kg,8周或尿蛋白阴转2周后逐渐减量,维持20 mg/d,观察组加用雷公藤多苷片治疗,20 mg/次,3次/d,共治疗24周。并将观察组与对照组比较,结果发现,观察组治疗总有效率高于对照组(p0.05),且治疗后,两组尿蛋白定量降低,总蛋白(TP)、血清白蛋白(ALB)均上升,与同组治疗前对比差异有统计学意义(p0.05),观察组尿蛋白定量降低幅度、TP及ALB上升幅度高于对照组(p0.05);且观察组血肌酐(Cr)、尿素氮(BUN)、糖皮质激素受体β(GRβ)、HSP90均降低,与同组治疗前及对照组治疗后对比差异有统计学意义(p0.05);同时观察组不良反应发生率略低于对照组,但未见统计学差异。对成人NS患者采用雷公藤多苷联合糖皮质激素治疗较单纯激素治疗总有效率高,且可明显改善患者肾功能及糖皮质激素抵抗,下调HSP90表达。     

雷公藤多甙联合福辛普利治疗小儿HSPN的疗效观察

本研究的为探讨雷公藤多甙联合福辛普利治疗小儿过敏性紫癜性肾炎(Henoch-Schonlein purpura nephritis,HSPN)的临床疗效及相关机制。选取2013年1月~2015年1月收入我院的94例过敏性紫癜性肾炎患儿,根据随机数字表法分为对照组和观察组,各47例。两组患者均给予常规内科治疗,对照组患儿在此基础上给予福辛普利钠,观察组患儿在对照组的基础上给予雷公藤多甙片。比较两组患儿的临床资料。治疗后,比较两组患儿免疫球蛋白水平、PT、APPT、PLT、FIB水平的变化情况。观察组的总有效率显著高于对照组,且复发率显著低于对照组(p0.05)。观察组的收缩压、舒张压、24 h尿蛋白量及腹痛、关节疼痛和水肿消失时间等临床症状的改善均显著优于对照组(p0.05)。治疗后,两组患者Ig A水平均显著降低(p0.05),且观察组较对照组降低更明显(p0.05);对照组PT较治疗前无明显改变(p0.05),而观察组PT则显著升高(p0.05),组间比较差异显著(p0.05);两组患者PLT较治疗前均显著降低(p0.05),且观察组较对照组降低更明显,组间比较差异显著(p0.05)。雷公藤多甙联合福辛普利对小儿HSPN临床疗效较好,可显著改善患者症状,其机制可能与降低Ig A水平、抑制细胞免疫、升高PT、降低PLT计数,以及改善凝血功能相关。     

白芍总苷联合甲氨蝶呤治疗类风湿关节炎的药物作用研究

本研究通过大鼠试验探究白芍总苷联合甲氨蝶呤治疗类风湿关节炎(rheumatoid arthritis,RA)的药物作用。将60只类风湿关节炎的大鼠模型随机均分为3组,每组20只,分为对照组、治疗组以及联合组。对照组大鼠不进行任何治疗,治疗组大鼠采用甲氨蝶呤治疗,联合组采用白芍总苷联合甲氨蝶呤治疗。分别比较3组大鼠治疗前、治疗1周、2周、4周后的关节肿胀程度以及疼痛程度。采用酶联免疫吸附法(ELISA)检测各组治疗4周后TNF-α、IL-1β、IL-2、IL-6、IL-10等细胞因子的水平,并进行比较。下丘脑β-END、L-ENK以及血清Ig G、血浆SP采用放射免疫法测定。治疗1周、2周、4周后治疗组、联合组疼痛症状显著均低于对照组,治疗2周、4周后联合组与治疗组差异显著,有统计学意义(p0.05);治疗1周、2周、4周后治疗组、联合组足肿胀指数与对照组差异显著,治疗4周后联合组与治疗组差异显著,有统计学意义(p0.05);治疗组、联合组治疗4周后TNF-α、IL-1β、IL-2、IL-6、IL-10水平与对照组差异显著,治疗组与联合组差异显著,有统计学意义(p0.05);治疗组、联合组治疗4周后β-END、L-ENK、SP、IgG水平与对照组差异显著,治疗组与联合组差异显著,有统计学意义(p0.05)。通过大鼠试验证明在RA的治疗中,运用白芍总苷联合甲氨蝶呤治疗相较于单独使用甲氨蝶呤治疗具有更好的疗效。     

艾拉莫德片联合双醋瑞因治疗类风湿关节炎的临床疗效及对患者血清IL-17、IL-23水平的影响

目的:探讨艾拉莫德片联合双醋瑞因治疗类风湿关节炎的临床疗效及对患者血清白介素(IL)-17、IL-23水平的影响。方法:选择2015年9月至2017年9月我院接诊的96例类风湿关节炎患者,通过随机数表法将其分为观察组(n=48)和对照组(n=48),两组均给予甲氨蝶呤片及常规对症治疗,对照组在此基础上给予艾拉莫德片治疗,观察组在对照组的基础上联合双醋瑞因胶囊治疗,两组均以4周为1个疗程,连续治疗6个疗程。比较两组的临床疗效、治疗前后临床症状评分、实验室指标[红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)]、免疫学指标[免疫球蛋白(Ig)G、IgA、IgM]及血清IL-17、IL-23水平的变化及治疗期间不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率为89.58%(43/48),明显高于对照组的70.83%(34/48)(P0.05);两组关节疼痛、关节压痛、关节肿胀、晨僵时间评分、ESR、CRP、RF、IgG、IgA、IgM较治疗前均显著降低(P0.05),观察组以上指标均明显低于对照组(P0.05);两组血清IL-17、IL-23水平均较治疗前显著降低(P0.05),观察组血清IL-17、IL-23水平均明显低于对照组[(11.23±1.30)pg/ml vs(16.49±1.79)pg/mL,(83.41±10.25)pg/mL vs(103.52±12.47)pg/mL](P0.05)。两组治疗期间药物不良反应总发生率比较无显著差异(P0.05)。结论;艾拉莫德片联合双醋瑞因治疗类风湿关节炎患者的效果显著,可明显改善患者的临床症状,促进关节功能恢复,其内在机制可能和降低血清IL-17、IL-23的表达相关。     

中药联合化疗对ALL患者CD4、CD25细胞调节及sE-cad的影响

目的:研究中药联合化疗方案对急性淋巴细胞白血病(Acute lymphocytic leukemia,ALL)患者CD4+、CD25+细胞调节的影响、血清s E-cad的影响以及临床意义。方法:选取我院血液科收治的急性淋巴细胞白血病患者60例,随机分为两组,其中对照组30例给予常规化疗方案治疗,中药组30例在常规化疗方案的基础上加用中药辅助治疗。对比治疗前后患者血常规、CD4+、CD25+细胞及血清s E-cad的改变。结果:1治疗后两组患者CD4+、CD25+T细胞较治疗前均显著下降,差异有统计学意义(P0.05),与对照组相比,中药组CD4+、CD25+T细胞下降明显,差异有统计学意义(P0.05);2治疗后两组患者血清s E-cad均改善,且中药组(55.58±10.47)较对照组(67.27±11.32)明显下降,差异有统计学意义(P0.05);3两组有效率比较重,中药组总有效率(86.67%)明显优于对照组(66.67%),差异有统计学意义(P0.05)。结论:中药联合化疗治疗急性淋巴细胞白血病CD4+、CD25+T细胞调节及血清s E-cad的改变明显,对临床具有指导意义。     

甲氨蝶呤联合来氟米特治疗类风湿性关节炎的疗效及对血清 CRP、IL-8及 TNF-α水平的影响

目的:探讨甲氨蝶呤联合来氟米特治疗类风湿性关节炎(RA)的疗效及对患者血清C反应蛋白(CRP)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平的影响。方法:选择2015年1月至2017年3月我院收治的RA患者106例,采用随机数字表法分为观察组(53例)和对照组(53例),两组均给予常规治疗,对照组加用甲氨蝶呤治疗,观察组在对照组的基础上加用来氟米特治疗,治疗4个月后,评价两组患者的临床疗效、临床症状,并对比两组患者血清CRP、IL-8及TNF-α水平变化。结果:治疗4个月后,观察组临床总有效率为96.23(51/53),高于对照组的79.25(42/53),差异有统计学意义(P0.05)。治疗前两组晨僵时间、压痛关节数、肿胀关节数等主要临床症状比较差异无统计学意义(P0.05);治疗4个月后,两组晨僵时间较治疗前缩短,压痛及肿胀关节数减少,且观察组晨僵时间短于对照组,压痛及肿胀关节数少于对照组(P0.05)。治疗前两组患者血清CRP、IL-8及TNF-α水平比较差异无统计学意义(P0.05);治疗4个月后,两组血清CRP、IL-8及TNF-α水平均较治疗前降低,且观察组低于对照组(P0.05)。治疗期间,观察组药物相关不良反应发生率为13.21(7/53),与对照组的11.32(6/53)比较,差异无统计学意义(P0.05)。结论:甲氨蝶呤联合来氟米特治疗RA的疗效理想,可显著改善患者的临床症状及降低血清CRP、IL-8及TNF-α水平。     

Synthesis and CD structural studies of CD52 peptides and glycopeptides

The syntheses of five natural and N-terminal acetylated peptides and glycopeptides of the CD52 antigen are described. Solid phase peptide synthesis was employed in the construction of the target compounds from Fmoc-protected commercial amino acids and synthetic glycan-asparagine conjugates. Circular dichroism studies of the synthetic targets showed that they exist as random coils in solution, and no significant change in secondary structure was observed when the CD52 peptide was either acetylated at the N-terminus or glycosylated at the Asn³ residue with a disaccharide or a fucose-containing branched trisaccharide.     

CD30/CD30 ligand and CD40/CD40 ligand in malignant lymphoid disorders

CD30 and CD40 are members of the tumor necrosis factor (TNF) receptor family. These two receptors have pleiotropic biologic functions including induction of apoptosis and enhancing cell survival. This review will discuss the pattern of expression of these receptors in malignant lymphoid disorders and their prospective ligands. Understanding issues related to these two ligands and their receptors in lymphoid malignancies may help to improve the classification of these diseases and could open the doors for new treatment strategies.     

CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and prevention of thyroiditis

CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient mice had decreased CD4+CD25+ T cells in spleen compared with wild-type mice, and CD7/CD28-double-deficient mice had decreased numbers of CD4+CD25+ T cells in both thymus and spleen compared with both wild-type and CD28-deficient mice. Functional studies demonstrated that CD4+CD25+ T cells from CD28-deficient and CD7/CD28-double-deficient mice could mediate suppression of CD3 mAb activation of CD4+CD25- wild-type T cells, but were less potent than wild-type CD4+CD25+ T regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice (>1 year) that was not seen in age-matched control mice or single CD7- or CD28-deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for the development of spontaneous thyroiditis. Taken together, these data demonstrated collaborative roles for both CD7 and CD28 in determination of number and function of CD4+CD25+ T regulatory cells in the thymus and peripheral immune sites and in the development of spontaneous thyroiditis.     

Follicular lymphoma intratumoral CD4+CD25+GITR+ regulatory T cells potently suppress CD3/CD28-costimulated autologous and allogeneic CD8+CD25- and CD4+CD25- T cells

Regulatory T cells (T(R)) play a critical role in the inhibition of self-reactive immune responses and as such have been implicated in the suppression of tumor-reactive effector T cells. In this study, we demonstrate that follicular lymphoma (FL)-infiltrating CD8+ and CD4+ T cells are hyporesponsive to CD3/CD28 costimulation. We further identify a population of FL-infiltrating CD4+CD25+GITR+ T(R) that are significantly overrepresented within FL nodes (FLN) compared with that seen in normal (nonmalignant, nonlymphoid hyperplastic) or reactive (nonmalignant, lymphoid hyperplastic) nodes. These T(R) actively suppress both the proliferation of autologous nodal CD8+CD25- and CD4+CD25- T cells, as well as cytokine production (IFN-gamma, TNF-alpha and IL-2), after CD3/CD28 costimulation. Removal of these cells in vitro by CD25+ magnetic bead depletion restores both the proliferation and cytokine production of the remaining T cells, demonstrating that FLN T cell hyporesponsiveness is reversible. In addition to suppressing autologous nodal T cells, these T(R) are also capable of suppressing the proliferation of allogeneic CD8+CD25- and CD4+CD25- T cells from normal lymph nodes as well as normal donor PBL, regardless of very robust stimulation of the target cells with plate-bound anti-CD3 and anti-CD28 Abs. The allogeneic suppression is not reciprocal, as equivalent numbers of CD25+FOXP3+ cells derived from either normal lymph nodes or PBL are not capable of suppressing allogeneic CD8+CD25- and CD4+CD25- T cells, suggesting that FLN T(R) are more suppressive than those derived from nonmalignant sources. Lastly, we demonstrate that inhibition of TGF-beta signaling partially restores FLN T cell proliferation suggesting a mechanistic role for TGF-beta in FLN T(R)-mediated suppression.     

Expression of CD16, CD18 and CD56 in tributyltin-exposed human natural killer cells

Tributyltin (TBT) was produced in large quantities for use in wood preservation, marine antifouling paints, disinfection of circulating industrial cooling waters and slime control in paper mills. TBT is found in dairy products, meat and fish. We and others have shown that there are measurable levels of TBT in human blood. BTs appear to increase the risk of cancer and viral infections in exposed individuals. In previous studies, we demonstrated that the NK-cytotoxic function of lymphocytes was greatly diminished after a 1-h exposure to 300 nM TBT or a 24-h exposure to 200 nM TBT. Inhibition induced by a 1-h exposure to 300 nM TBT continues even after removal of the compound. There is also decreased ability of NK cells to bind to tumor target cells when they have been exposed to 200 nM TBT for 24 h. This loss of binding function is not seen when NK cells are exposed to 300 nM TBT for 1 h. However, NK cells exposed to 300 nM TBT for 1 h and then incubated in TBT-free media for 24, 48 or 96 h, show a significant loss of tumor-binding function by 96 h. The effects of TBT on cell surface molecules that are crucial to NK cell function is investigated. The data indicate there is a loss of expression of CD16 and CD56 on NK cells exposed to 200 nM TBT for 24 h. There is no decrease in expression of any of the markers studied when NK cells are exposed to 300 nM TBT for 1 h, consistent with the fact that a 1-h exposure has no effect on the ability of NK cells to bind to tumor targets. However, when NK cells are exposed to 300 nM TBT followed by 24, 48 or 96 h incubations in TBT-free media, there is a significant loss of CD16 and CD18 expression after 24 h and of CD16 and CD56 expression after 48 and 96 h.     

Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells

CD4+ murine T cell clones, TH1 and TH2, can be distinguished by both functional responses and by their patterns of lymphokine secretion. Recently, a mAb, 23G2, which reacts with a subset of CD45 molecules (CD45R), has been reported to bind differentially to clones of TH1 and TH2 cells. In the present study, normal splenic T cells were analyzed for differences in 23G2-reactivity and were separated into two populations based on their density of CD45R (CD45Rhi and CD45Rlo). The CD45Rhi cells secrete more IL-2 than IL-4 after stimulation in vitro; the reverse is true for the CD45Rlo cells. Because neither population secretes only IL-2 or IL-4, we were unable to classify cells as TH1 or TH2. In vivo and in vitro analyses of the CD45Rhi and CD45Rlo cells suggest a lineage relationship between the two subsets that correlates with the degree of Ag exposure and the state of maturation of the mice. In newborn mice and mice raised under sterile conditions, splenic CD4+ T cells are predominantly CD45Rhi. Under conditions of increased antigenic exposure and maturation of the mice, CD45Rlo cells develop; after long term priming in vivo, the majority of specific Ag-reactive cells are CD45Rlo. Adoptive transfer studies using BALB/c nu/nu recipients demonstrate that CD45Rhi cells become CD45Rlo cells and that the recall response (IgG) to specific Ag is mediated by CD45Rlo cells. Taken together, these data indicate that the level of expression of CD45R on CD4+ T cells distinguishes virgin (CD45Rhi) from primed/memory (CD45Rlo) T cells in normal mice.     

Differential Requirement for CD70 and CD80/CD86 in Dendritic Cell-Mediated Activation of Tumor-Tolerized CD8 T Cells

Activated human blood γδ T cells have also been previously demonstrated to behave as professional APCs, although the processes that control APC function have not been characterized. n this study, we show that the acquisition of potent APC function by human blood γδ T cells is achieved after physical interaction with an Ab-coated target cell, a process that we refer to as licensing. In cancer models, licensing of γδ T cells by tumor-reactive mAbs promotes the uptake of tumor Ags and professional presentation to tumor-reactive αβ T cells. We propose that licensing by Ab is a mechanism whereby the adaptive properties of γδ T cells are induced by their innate functions in a spatially and temporally controlled manner.