Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

重症肺炎患儿血清sIL-2R、PGRN、Copeptin表达及与其预后的相关性分析

目的:探讨血清可溶性白细胞介素-2受体(sIL-2R)、血清颗粒蛋白前体(PGRN)、肽素(Copeptin)在重症肺炎患儿中的表达水平,并分析其与重症肺炎预后的相关性。方法:选取某院2021年1月—2022年12月收治的肺炎患儿183例为研究对象,根据病情严重程度分为重症肺炎组(n=80)和普通肺炎组(n=103),另选取同期100例健康体检儿童为健康组。比较3组受试者入组时血清sIL-2R、PGRN、Copeptin水平,绘制ROC曲线分析各指标对重症肺炎的诊断价值,比较不同预后患儿入组时血清各指标水平及小儿危重病例评分(PCIS)、急性生理慢性健康(APACHEII)评分水平,并分析入组时血清指标预测预后的危险度。结果:重症肺炎组患儿入院时血清sIL-2R、PGRN、Copeptin水平分别为(648.47±100.27)U/mL、(36.17±10.47)μg/L、(62.77±14.21)pmol/L),高于普通肺炎组患儿入院时的(461.51±79.64)U/mL、(30.66±7.21)μg/L、(47.66±11.47)pmol/L和健康组的(214.79±39.47)U/mL、(26.31±4.14)μg/L、(11.27±6.94)pmol/L,差异均有统计学意义(P<0.05)。入组时血清sIL-2R、PGRN、Copeptin水平联合检测诊断重症肺炎的ROC曲线下面积(AUC)为0.789。预后不良组患儿血清sIL-2R、PGRN、Copeptin水平及APACHEII评分分别为(715.98±79.51)U/mL、(43.79±8.97)μg/L、(68.49±6.79)pmol/L、(22.81±3.79)分,高于预后良好组患儿的(627.44±45.69)U/mL、(33.82±8.46)μg/L、(60.99±7.21)pmol/L、(20.16±3.68)分,PCIS评分为(72.14±6.44)分,低于预后良好组患儿的(81.51±7.41)分,差异均有统计学意义(P<0.05)。血清sIL-2R、PGRN、Copeptin水平与PCIS评分均呈负相关,与APACHEII评分均呈正相关(P<0.05)。入组时血清sIL-2R、PGRN、Copeptin高水平患儿发生预后不良的危险度是低水平的2.981、4.637、3.458倍,差异有统计学意义(P<0.05)。结论:重症肺炎患儿血清sIL-2R、PGRN、Copeptin表达水平升高,与重症肺炎预后密切相关,可作为预测预后的辅助指标。

肺癌患者放疗前后外周血DC细胞和血清sIL-2R、HMGB-1变化及其与预后的关系研究

目的 探讨肺癌患者放疗前后外周血DC细胞和血清sIL-2R、HMGB-1水平变化及临床意义。方法 收集肺癌患者124例,采用适形调强放疗(intensity modulated radiation therapy, IMRT)技术治疗,于放疗前、放疗后抽取空腹状态下静脉血4 ml,采用免疫磁珠法检测外周血DC细胞(DC1、DC2)水平,采用双抗体夹心酶联免疫法检测血清sIL-2R、HMGB-1水平。统计不同性别、年龄、是否吸烟、病理类型、是否手术、KPS评分、临床分期的肺癌患者外周血DC细胞和血清sIL-2R、HMGB-1水平,并分析患者预后与血清sIL-2R、HMGB-1水平的关系,单因素和多因素COX回归分析影响肺癌患者预后因素。结果 肺癌患者放疗前后外周血DC细胞水平比较,P>0.05。肺癌患者治疗后血清sIL-2R、HMGB-1水平与治疗前比较,P<0.05。治疗前,血清sIL-2R水平在不同性别、年龄、是否吸烟、病理类型方面比较,P>0.05,在是否手术、不同KPS评分、临床分期、淋巴结转移方面比较,P<0.05;血清HMGB-1水平在不同病理类型方面比较,P>0.05,在不同性别、年龄、是否吸烟、是否手术、不同KPS评分、临床分期、淋巴结转移方面比较,P<0.05;治疗后,血清sIL-2R水平在不同性别、年龄、是否吸烟、病理类型方面比较,P>0.05,在是否手术、不同KPS评分、临床分期、淋巴结转移方面比较,P<0.05;血清HMGB-1水平在不同性别、年龄、是否吸烟、病理类型、是否手术、KPS评分、临床分期、淋巴结转移方面比较,P<0.05。死亡组患者血清sIL-2R、HMGB-1水平均高于生存组(P<0.05)。死亡组DC2低于生存组(P<0.05)。经单因素、多因素COX回归分析显示,临床分期(Ⅲ~Ⅳ期)、淋巴结转移、sIL-2R、HMGB-1水平异常上升、DC2比例下降均是导致肺癌患者预后差的独立危险因素。结论 肺癌患者放疗前后外周血DC细胞无明显变化,但血清sIL-2R、HMGB-1水平治疗后较治疗前均明显降低,其sIL-2R、HMGB-1水平异常上升及DC2比例下降均为患者预后独立危险因素,可预测预后。

多发性骨髓瘤患者血清sIL-2R表达情况与患者预后的关系

目的探究多发性骨髓瘤(MM)患者血清sIL-2R表达情况与患者预后的关系。方法选取开封市人民医院2018年3月~2020年7月收治的72例MM患者作为研究对象,根据预后情况将72例MM患者分为存活组、死亡组,分析MM患者死亡的危险因素,绘制受试者工作特征曲线(ROC)判断发生死亡时血清sIL-2R最佳截断值,根据线下面积评估血清sIL-2R表达水平与患者预后的关系。结果随访3年中,72例MM患者存活45例(62.50%),死亡27例(37.50%)。死亡组MM分期Ⅲ期人数比例高于存活组,β_(2)-微球蛋白水平(β_(2)-MG)、血清钙(Ca)水平、sIL-2R水平及轻链比值(K/λ),高于存活组,差异有统计学意义(P<0.05)。Logistic多因素回归分析结果显示,MM分期、β_(2)-MG、Ca、sIL-2R水平及K/λ值,均为MM患者死亡的危险因素(P<0.05)。ROC曲线显示,MM患者最佳截断值为328.50,曲线下面积为0.903,灵敏度为86.75%,特异度为88.75%,95%CI(1.27~3.01),提示血清sIL-2R水平可用于预测MM患者的预后情况。结论sIL-2R水平对MM患者的预后有着重要的预测价值,MM分期、β_(2)-MG、Ca水平及K/λ值,均为MM的危险因素。

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody

Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.

Fluence of Glucosidorum Tripterygii Totorum on joint and serum soluble interleukin-2 receptor in patients with ankylosing spondylitis

Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.

Effects of Aprotinin on Serum Interleukin-2 and Soluble Interleukin-2 Receptor during Cardiopulmonary Bypass

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

恶性肿瘤患者血清sIL-2R的检测

本文采用ELISA夹心法,对66例恶性肿瘤患者血清中可溶性白细胞介素2受体进行检测,以39例健康学生做对照,结果显示恶性肿瘤患者血清slL-2R 含量明显高于对照组(P<0.01)。并对血清sIL-2R 水平在肿瘤诊断及预后判断中的意义进行了探讨。

腹腔化疗对胃癌腹水患者癌相关抗原及sIL-2R水平影响

目的腹腔化疗胃癌伴腹水者近期疗效的预测。方法２８例晚期胃癌伴腹水者腹腔内注射卡铂，治疗前、后分别测定腹水中消化道癌相关抗原（ＣＣＡ）及ｓＩＬ┐２Ｒ含量。结果凡对腹水治疗近期有效者，腹水中ＣＣＡ含量显著降低，ｓＩＬ┐２Ｒ水平显著下降；无效或近期疗效不显者，则两者水平下降不明显，甚至升高。结论治疗前、后该二指标的测定。

原发性肝癌肝动脉热化疗栓塞后患者T细胞亚群及sIL-2R的改变

目的 研究肝癌患者肝动脉热化疗栓塞前后 T细胞亚群及 s IL - 2 R的变化及其临床意义。方法 采用免疫荧光染色法及双抗体夹心法 ,检测 30例原发性肝癌患者治疗前后的 T细胞亚群及 s IL- 2 R的改变 ,并与健康对照组比较分析。结果 肝癌组治疗前 Th降低 ,Ts和 s IL- 2 R增高 ,与对照组比较有显著差异 ,P<0 .0 1 ,治疗后 Th升高 ,Ts和 s IL- 2 R降低 ,治疗前后比较有显著差异 P<0 .0 1。结论 检测肝癌患者 T细胞亚群 ,s IL- 2 R的情况 ,有助了解病人的免疫状况 ,对判断病人预后 ,指导综合治疗有一定价值。热化疗栓塞的疗效优于文献报道的单纯化疗栓塞。

Nd-YAG激光汽化结合光动力学治疗对鼻咽癌患者SIL-2R、IL-2水平及NK活性的影响

应用双抗体夹心ＥＬＩＳＡ法、３Ｈ－ＴｄＲ掺入法和１２５Ｉ－ＵｄＲ释放法对２４例鼻咽癌（ＮＰＣ）患者ＹＡＧ激光汽化结合光动力学治疗前后外周血可溶性ＩＬ－２受体（ＳＩＬ－２Ｒ）、白细胞介素２（ＩＬ－２）水平和自然杀伤细胞（ＮＫ）活性分别进行测定。结果表明鼻咽癌患者在接受激光光动力学治疗后ＳＩＬ－２Ｒ水平呈明显下降（Ｐ＜０．０００５），而ＩＬ－２水平和ＮＫ活性显著上升（Ｐ＜０．０００５）。结果提示激光光动力学治疗对恢复鼻咽癌患者免疫功能起促进作用。

冠心病患者血清sFas和sFasL及sIL-2R的水平

目的 :探讨血清 s Fas、s Fas L和 s IL- 2 R水平与冠心病 (CHD)之间的关系。方法 :应用酶联免疫吸附双抗体夹心法测定 30例 CHD患者 (CHD组 )和 2 6例非冠心病患者 (对照组 )的血清 s Fas、s Fas L和 s IL - 2 R水平。结果 :CHD组患者 s Fas水平 (ng/ L)为 15 83.4 1± 174 .4 6 ,明显高于对照组 (1374 .5 5± 142 .4 2 ) ,P<0 .0 1。与对照组比较 ,CHD组患者血清 s IL- 2 R水平 (ng/ L)显著增高 (94 4 .5 0± 395 .5 9vs6 5 2 .4 5± 16 3.36 ,P<0 .0 1) ,且 CHD患者血清 s Fas水平与 s IL- 2 R水平呈正相关 (r=0 .4 18,P<0 .0 5 )。两组血清 s Fas L水平差别无显著性 (P>0 .0 5 )。结论 :高水平的血清 s Fas、s IL- 2 R与 CHD有关。高水平的血清 s Fas有可能通过抑制激活的 T细胞凋亡而导致冠状动脉事件的发生发展。

狼疮静对活动性SLE患者血清sIL-2R、TNF-α的影响

细胞因子在系统性红斑狼疮发病机理中起着重要的作用,并和病情的活动有密切关系。不少研究结果认为sIL-2R与病情活动呈正相关,TNF-α在活动期明显异常。为了探讨狼疮静的疗效及对病情活动的影响,我们检测了42例中药组和20例西药组SLE患者血清中sIL-2R和TNF-α水平的变化。结果显示:两组患者这二种细胞因子水平都有明显降低,而中药治疗能更好地降低血清sIL-2R的水平,较之单用西药治疗更为有效地控制病情。

生殖器疱疹患者干扰素治疗前后血清IL-2及sIL-2R水平变化

目的 探讨生殖器疱疹（ ＧＨ） 患者细胞免疫功能。方法 采用单克隆与多克隆双抗体夹心法测定血清白介素２（ＩＬ２） 及可溶性白介素２ 受体（ｓＩＬ２ Ｒ） 水平。结果 ２７ 例ＧＨ 患者治疗前ＩＬ２ 水平明显低于正常人，ｓＩＬ２ Ｒ水平明显高于正常人。经干扰素α２ａ 治疗后ＩＬ２ 水平明显高于治疗前，ｓＩＬ２ Ｒ 明显低于治疗前。结论 ＧＨ 患者存在细胞免疫功能低下，且与病程相关。干扰素治疗有助于患者免疫功能恢复，减少ＧＨ 复发及消除单纯疱疹病毒潜伏感染。

茯苓对家兔模型SIL-2R、IL-2、TNF-α的影响

观察茯苓对家兔 型变态反应模型制模前、后或制模过程中对可溶性白细胞介素 - 2受体 (SIL - 2 R)、白介素 - 2 (IL- 2 )、肿瘤坏死因子 (TNF- α)的影响。采用 sc正常马血清的方法、建立 型变态反应模型 ,分别于制模过程中或制模后连续 ig,并间断取血测定 SIL - 2 R、IL - 2、TNF-α。结果制模后给药组 SIL - 2 R下降 (P<0 .0 1) ,IL - 2上升(P<0 .0 5 ) ,TNF- α下降 (P<0 .0 1) ;边制模边给药组 SIL- 2 R下降 (P<0 .0 1) ,IL- 2上升 (P>0 .0 5 ) ,TNF- α下降(P>0 .0 1)。提示茯苓对 型变态反应中 SIL - 2 R、TNF-α有抑制作用 ,对 SIL - 2 R、IL - 2有调节作用。

肝癌、肝硬化患者血清TNF-α,IL-2,sIL-2R检测的临床意义

目的 了解原发性肝癌、代偿期肝硬化、失代偿期肝硬化患者血清肿瘤坏死因子 α(TNF α)、白细胞介素 2 (IL 2 )、可溶性白细胞介素 2受体 (sIL 2R)水平的变化 ,探讨其临床意义。方法 原发性肝癌 33例 ,肝炎后肝硬化 6 0例。分为肝癌组 33例 ,肝硬化代偿期组 30例 ,肝硬化失代偿期组 30例。采用双抗体夹心酶联免疫法检测血清TNF α、IL 2、sIL 2R水平。肝癌组患者追踪 2月至 2年 ,观察其变化情况。结果 1 原发性肝癌组血清TNF α、sIL 2R水平明显高于各期肝炎后肝硬化组 ,而血清IL 2水平较各期肝炎后肝硬化组显著降低。 2 肝硬化失代偿期组血清TNF α、sIL 2R水平明显高于肝硬化代偿期组 ,而肝硬化失代偿期组IL 2水平低于肝硬化代偿期组。 3 原发性肝癌组经有效手术治疗及导管化疗者血清TNF α及sIL 2R水平较治疗前明显降低 ,IL 2则较前升高 ,而未经有效治疗或治疗时已是晚期者TNF α及sIL 2R水平逐渐升高 ,IL 2则逐渐降低。结论 本文提示原发性肝癌及肝炎后肝硬化与TNF α、IL 2及sIL 2R有密切相关性。TNF α、IL 2及sIL 2R水平的变化有助于了解肝硬化的进展情况 ,早期发现恶性肿瘤并决定治疗的预后。

恶性肿瘤、创伤及炎症患者血清TNF-α、IL-6和sIL-2R含量的比较

目的 :通过比较恶性肿瘤、创伤及感染性炎症患者血清中 TNF-α、IL-6和 s IL-2 R的含量 ,对这 3类疾病在发病机理上的内在联系进行探讨。方法 :选择 1未经治疗的恶性肿瘤患者 3 7例 ,其中肺癌 1 5例、宫颈癌 1 2例、胃癌 5例、肝癌和食管癌各 2例、恶性间皮瘤1例。2未经治疗无并发症的机械性创伤患者 41例 ,创伤严重度评分 ( ISS)为 1 6.81± 1 .74。3急性感染性炎症患者 2 5例 ,其中肺炎及呼吸道感染 1 3例、淋巴结炎和急性胃肠炎各 3例、急性化脓性胆囊炎和盆腔脓肿各 2例、输卵管及肝脏脓肿各 1例。 4正常对照组 3 0例。采用 EL ISA法测定血清中 TNF-α、IL -6和 s IL -2 R的含量。结果 :各组患者血清细胞因子含量均明显高于正常对照组 ( P<0 .0 0 2～ 0 .0 0 1 ) ,但 3类疾患之间增高的程度不同 ( P<0 .0 5～ 0 .0 1 )。TNF-α和 IL-6增高的顺序皆为炎症 >创伤 >恶性肿瘤 ( P<0 .0 5～ 0 .0 1 ) ;s IL-2 R以炎症增高最显著 ,次为恶性肿瘤 ,创伤最低。结论 :恶性肿瘤、创伤及感染性炎症时 ,血清细胞因子水平在质上的相同使得这 3类疾病之间可相互影响、相互加重 ,在量上的区别造成各自程度不同的炎症反应与免疫反应的病理过程 。