BACKGROUND:Thymosin beta 4 × (Tmsb4x) has been highlighted as an important regulator in immune and inflammation responses. Promoted differentiation of mononuclear cells into dendritic cells (DCs) exert a beneficial effect on septicemia. Herein, we investigated the effects of Tmsb4x on the mononuclear cells to affect immune responses during septicemia.METHODS:Initially, we isolated peripheral blood samples from healthy individuals and patients with septicemia for extraction of mononuclear cells, followed by Tmsb4x expression quantification. A cell model was constructed with mononuclear cells through lipopolysaccharide stimulation. The viability and apoptosis were evaluated in response to Tmsb4x silencing or re-expression. Additionally, the proportion of DCs was assessed by determining levels of inflammatory factors as well as by flow cytometric analysis. A mouse septicemia model was developed for in vivo validation.RESULTS:Cell and animal models demonstrated decreased Tmsb4x expression in the setting of septicemia, which led to increased inflammatory response and reduced proportion of DCs, along with inhibited mononuclear cell viability and promoted apoptosis. However, restoration of Tmsb4x facilitated the differentiation of mononuclear cells into DCs.CONCLUSION:To conclude, upregulated Tmsb4x promoted the generation of DCs from mononuclear cells, which contributed to deep understanding of underpinning mechanisms in the development of septicemia.

目的 评估泰它西普加标准疗法治疗中重度活动性系统性红斑狼疮(SLE)的疗效和安全性.方法 通过回顾性分析,观察不同剂量组泰它西普治疗中重度活动性SLE的疗效和安全性.中重度活动性SLE患者被随机分配接受皮下注射泰它西普80mg、160mg、240mg或安慰剂加标准治疗,每周注射一次,共48周.观察不良事件、血常规、尿常规、B淋巴细胞、肝肾功能、免疫功能、抗ds-DNA抗体、SLEDAI评分等,评价泰它西普疗效性和安全性.主要观察终点是用药48周SLE应答指数(SLE Responder Index,SRI).结果 本研究共纳入26例中重度活动性SLE患者.22例(84.6％)患者完成了为期48周的研究,4例(15.4％)患者退出.退出的原因包括疗效缺乏(安慰剂组)、不能坚持每周注射(80mg组)、结核感染(240mg组)和妊娠(240mg组).22例完成试验患者中,安慰剂组5例,80mg组3例,160mg组7例,240mg组7例.在第48周,与安慰剂组相比,泰它西普组获得更高SRI(P<0.05),CD19+B细胞总数、免疫球蛋白IgG、IgM、IgA水平显著降低(P<0.05),补体C3、C4水平升高.而两组间谷丙转氨酶、谷草转氨酶、肌酐和蛋白尿定量变化无明显差异.大多数治疗引起的不良事件(TEAEs)为轻度或中度,组间无显著差异.大多数TEAEs是感染,可通过抗感染控制.结论 泰它西普加标准疗法可以降低系统性红斑狼疮活动度,同时其副作用是可控制的.

目的 探讨SLE患者血清PD-L1与IFN-γ及它们与免疫功能的关系.方法 选取我院2018年1月-2019年12月住院及门诊部诊治的SLE患者50例(SLE组)和健康体检者45例(对照组),根据SLE疾病活动指数(systemic lupus erythe-matosus disease activity index,SLEDAI)将SLE组分为SLE活动组和非活动组(分别为18例,32例).血清PD-L1和IFN-γ水平检测采用ELISA法,细胞表面PD-L1表达检测采用流式细胞术,收集疾病活动性指标和相关实验室数据.结果 ⑴与健康对照组相比,SLE患者外周血CD4+T细胞表面PD-L1分子表达上调,且活动组显著高于非活动组(P<0.01);CD8+T细胞和CD19+B细胞表面PD-L1分子表达下调,且活动组显著低于非活动组(P<0.01);⑵活动组SLE患者PD-L1,补体C3和C4血清水平显著低于非活动组和健康对照组(均P<0.01),而IFN-γ,CRP、SLEDAI及抗dsDNA抗体滴度显著高于非活动组和健康对照组(均P<0.01);⑶SLE患者PD-L1血清水平与IFN-γ、SLEDAI、抗dsDNA抗体滴度和CRP呈显著负相关(r=-0.428,-0.434,-0.453,-0.362,均P<0.05),与补体C3和C4呈显著正相关(r=0.438,0.345,均P<0.05).结论 在SLE患者体内,PD-L1和IFN-γ异常表达于T、B淋巴细胞表面和血清,一起参与免疫功能的调节.

目的:探讨PD-L1和IFN-α与系统性红斑狼疮(SLE)患者免疫功能异常的关系.方法:选取2018年1月～2019年12月于我院就诊的SLE患者52例(SLE组)和健康志愿者48例(对照组).根据抗dsDNA抗体检测结果,将SLE组分为抗dsDNA抗体阳性组(18例)和阴性组(34例).ELISA检测血清PD-L1和IFN-α,分别采用ELISA法和间接免疫荧光法检测抗dsDNA抗体,流式细胞术检测细胞表面PD-1和PD-L1,速率散射比浊法检测补体C3和C4,免疫比浊法检测CRP.结果:与对照组相比,SLE患者外周血CD4+T细胞表面PD-1和PD-L1表达上调,阳性组高于阴性组(P＜0.01);CD8+T和CD19+B细胞表面PD-1表达上调,PD-L1表达下调,阳性组与阴性组比较差异均有统计学意义(P＜0.01);与阴性组和对照组相比,阳性组血清PD-L1、补体C3和C4显著降低,而IFN-α、CRP、SLEDAI及抗dsDNA抗体滴度显著增高(P＜0.01);SLE患者血清PD-L1与IFN-α、SLEDAI、抗dsDNA抗体滴度和CRP呈显著负相关(r=-0.468,-0.494,-0.493,-0.352,P＜0.05),与补体C3和C4呈显著正相关(r=0.498,0.326,P＜0.05).结论:PD-L1和IFN-α异常表达于SLE患者T、B淋巴细胞表面和血清,共同参与细胞及体液免疫功能调节.

目的 了解狼疮肾炎(LN)患者血清趋化因子CXCL13表达变化,并观察其与肾脏受损、B细胞浸润的关系.方法 采用ELISA方法检测不同受试者血清CXCL13水平.采用免疫组化法观察LN患者穿刺肾组织CD3、CD20、CD21表达并分析其与CXCL13关系.随访10例初诊LN患者并观察治疗6个月后血清CXCL13变化.结果 血清CXCL13在LN组中表达明显高于无肾脏受累SLE组、健康对照组(χ2=30.169,P<0.001). SLE患者血清CXCL13水平与SLEDAI呈正相关(r=0.55,P<0. 001),与补体C3呈负相关(r=-0.39,P<0.001).Ⅲ型和Ⅳ型LN患者血清CXCL13水平均较V型LN患者升高(P均<0.05).通过对肾组织研究发现,CD20+LN患者血清CXCL13水平高于CD20-LN患者(Z=2.844,P=0.004);2类LN患者(CD20+细胞及CD3+细胞均有表达且两者呈区域分布)血清CXCL13水平较0类LN患者(CD20+细胞无表达,和/或CD3+细胞表达)和1类LN患者(CD20+细胞表达,和/或CD3+细胞表达,两者呈散在分布)均明显升高(P均<0.05).初诊LN患者接受激素、免疫抑制剂治疗6个月后血清CXCL13水平、SLEDAI评分均降低.结论 CXCL13在SLE发病过程中发挥重要作用,可能参与肾脏受累过程,引起B细胞在肾组织中异常聚集、形成异位淋巴样组织.

目的 观察血清和脑脊液铁蛋白水平的变化对人类认知功能的影响,评估其与阿尔茨海默病(AD)疾病进程的关系.方法 随机选取萍乡市人民医院神经内科门诊及住院年龄在18～75岁的AD患者(AD组)、轻度认知功能障碍患者(MCI组)及认知功能正常者(CN组)各30例,随访1年,分别检测3组患者0、6、12月血清和脑脊液铁蛋白水平,评估各组认知功能评分,探讨血清和脑脊液铁蛋白水平与阿尔茨海默病患者认知功能障碍的关系.结果 三组组间比较提示血清和脑脊液铁蛋白及认知功能水平的变化差异均有统计学意义(P＜0.05);与基线期比较,CN组内对照各观察指标差异无统计学意义(P＞0.05),MCI组及AD组组内各观察指标差异有统计学意义(P＜0.05).结论 血清和脑脊液铁蛋白水平两者结合参考,能够早期预测人类认知功能障碍的严重程度,且其水平与认知功能呈负相关,铁蛋白水平越高,认知功能越差,即认知功能损害程度越重.

目的:探讨外周血中性粒细胞胞外诱捕网在痛风中的意义及加味四妙汤的可能作用机制.方法:选取28例健康患者为健康组,选取痛风患者60例并随机分为对照组、 观察组各30例.对照组使用塞来昔布治疗,观察组在对照组基础上采用加味四妙汤治疗.比较痛风组与健康组NETs含量,治疗前后对照组和观察组NETs含量及其与CRP的关系.结果:痛风组与健康组NETs比较差异有统计学意义(P<0.001);痛风患者NETs与CRP呈正相关(P<0.001);对照组与观察组治疗后NETs比较差异有统计学意义(P<0.05).结论:NETs可能参与痛风的炎症过程,其含量可能与炎症程度有关,加味回妙汤可能通过降低NETs缓解痛风炎症.

Objective To discuss the effect of rh TNFR:Fc ankylosing spondylitis secondary to bone destruction and OPG/RANKL system.Methods In our hospital outpatient and inpatient treatment,diagnosis of ankylosing spondylitis (ankylosing spondylitis,AS) 60 patients were randomly divided into two groups of 30 patients (treatment group) group a:rh TNFR:Fc+methotrexate+sulfasalazine;(control group) group II:methotrexate+sulfasalazine,treatment for 24 weeks,enzyme-linked immunosorbent assay (ELISA) determination of the two groups of patients with bone metabolism markers osteocalcin (OC),C-telopeptide (CTX) and receptor activator of nuclear factor-κB promoter ligand (RANKL),osteoprotegerin (OPG),and compare the two groups.AS patients with pelvic score sheet using the Bath AS Radiology score evaluation before selecting treatment and 24 weeks after two time points and safety assessments.Results After treatment,the expression of CTX decreased in both groups (P<0.05).The expression of CTX in treatment group was significantly higher than that in control group (P<0.05).The expression of OPG in the two groups after treatment was higher than that in the control group (P<0.05) and the expression in the treatment group was higher than that in the control group (P<0.05).The expression of RANKL in both groups was lower than that in the control group (P<0.05) and the expression of RANKL in the treatment group was lower than that in the control group (P<0.05).After 24 weeks,the pelvic score of the two groups was lower than that before treatment (P<0.05).There was no significant difference between the two groups (P>0.05).The adverse effects of the two groups were analyzed.The results showed that there was no significant difference between the two groups side effect.Conclusion rh TNFR:Fc treatment of ankylosing spondylitis secondary to bone destruction can effectively reduce bone metabolism and promote bone formation,which with fewer side effects and fewer adverse reactions is most effective.

通过对Graves病(GD)甲亢患者131碘治疗前及治疗后不同阶段细胞因子白介素-2(IL-2)、白介素-6(IL-6)以及促甲状腺受体抗体(TRAb)变化的研究,得出结论:细胞因子参与了GD发生、发展及与131碘治疗后疾病预后有关.

大动脉炎(Takayasu Arteritis，TA)属于大血管炎的一种，主要累及大动脉及其主要分支的慢性炎性肉芽肿性血管炎，也可累及中小血管[1]。属于自身免疫病，临床病理是以血管壁炎症和纤维素样坏死为主要特征，临床表现多样。 TA好发于40岁以下人群，年轻女性患者超过80％，男女患病比率为1：4.5左右，西方的患病率为0.5-0.8/10，而日本的患病率最高，为4/10万[2，3]，我国目前尚未见相关的流行病学报道。临床治疗方面，虽然近些年来，生物制剂和血管内介入治疗为一些传统免疫抑制剂治疗效果不佳的难治性血管炎提供了较好的治疗选择[4-7]，但仍以糖皮质激素联合使用免疫抑制剂为主要的治疗手段。

特发性炎性肌病（idiopathic inflammatory my-opathies，IIM）是一组以四肢近端肌肉受累为突出表现的异质性疾病[1]，以多发性肌炎（polymyositis， PM）和皮肌炎（dermatomyositis，DM）最常见。DM表现为四肢近端肌群、肩胛肌群、颈部和咽喉部肌群等受累的炎症性肌病及特征性皮损，缺乏皮损者则为PM。自1916年Sterze首次报道PM并发胃癌以来，关于DM/PM伴发恶性肿瘤的报道层出不穷。由于该病的病理过程复杂，临床表现千变万化并缺乏判断活动度的特异性指标，早期诊断困难，加上目前尚无确切有效的治疗方案，造成该病预后差，死亡率高。本文从流行病学、发病机制、实验室检查、临床症状、治疗与预后、筛查的意义等方面综述如下，旨在为提高临床医生对该病的认识。

目的：探讨异甘草酸镁治疗抗风湿药物所致肝损害的临床疗效及经济学指标。方法观察组以异甘草酸镁治疗抗风湿药物所致肝损害30例.对照组以复方甘草酸苷治疗抗风湿药物所致肝损害30例，观察两组治疗前后症状、体征以及肝功能各项指标的变化情况，以及两组患者经济学指标。结果与对照组相比，异甘草酸镁可明显改善抗风湿药物所致肝损害患者肝功能指标(均<0.05)，成本效益比显著缩短(<0.05)。结论异甘草酸镁治疗抗风湿药物所致药物性肝损害的效果较好，值得临床推广使用。

目的观察治疗前后骨代谢标志物、影像学及血清OPG/RANKL的变化,评价补肾中药联合重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白（rh TNFR:Fc）治疗强直性脊柱炎（AS）继发骨质疏松（OP）的临床疗效。方法将60例AS患者随机分为两组,治疗1组（30例）以补肾中药加rh TNFR:Fc治疗,治疗2组（30例）采用rh TNFR:Fc治疗,两组疗程均为24周。观察指标包括治疗前后骨钙素（OC）、C-端肽（CTX）、NF-κB受体活化因子配体（RANKL）及骨保护素（OPG）的水平;并对治疗前后的骶髂关节、髋关节X线影像进行Bath AS放射学评分（BASRI）。结果 （1）骨代谢标志物:在治疗24周后两组与各自治疗前比较,血清OC均显著增加,CTX均显著下降（P＜0.05）;治疗后两组间比较,治疗1组比治疗2组血清OC显著增加,CTX显著下降（P＜0.05）。（2）影像BASRI评分:两组患者的骶髂关节评分（BASRI-SIJ）和髋关节评分（BASRI-h）在两组间及自身治疗前后比较均无显著差异（P＞0.05）。（3）血清OPG、RANKL水平:两组在治疗24周后与各自治疗前比较血清OPG均显著升高（P＜0.05）,RANKL均显著下降（P＜0.05）,OPG/RANKL比值均显著升高（P＜0.05）;治疗后两组间比较,治疗1组比治疗2组OPG显著升高（P＜0.05）,RANKL显著下降（P＜0.05）,OPG/RANKL比值显著升高（P＜0.05）。结论 rh TNFR:Fc治疗可通过调节骨代谢及OPG系统,有效阻止骶髂关节及髋关节的骨破坏;补肾中药联合rh TNFR:Fc治疗AS继发OP,影响骨代谢及血清OPG/RANKL水平更显著（P＜0.05）,阻止AS患者出现的骨质破坏,是治疗AS的较佳方案。

<正>肝脏是人体的重要器官,主要承担机体分泌、解毒、代谢等重要生理功能,同时它又是具有独特免疫学特性的淋巴器官,具有参与天然免疫和适应性免疫的多种细胞,是初始T细胞活化的场所,功能障碍后易产生各种免疫性疾病,诱导移植耐受。而自身免疫性肝病就是机体自身免疫反应超负荷或持续时间过久引起肝组织损伤,肝功能异常及相应临床症状的一组疾病,通常包括自身免

<正>系统性硬化病(svstemic sclerosis,SSc)是一种以小血管功能和结构异常,皮肤、内脏纤维化,免疫系统活化等为特征的全身性疾病,属系统性自身免疫性疾病,是硬皮病的一个亚类,它不仅侵犯皮肤、关节肌肉,还侵犯包括肺、肾、心脏、胃肠道等在内的内脏器官。系统性硬化皮肤早期病理特

目的:对重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(依那西普)治疗幼年脊柱关节病(JSpA)的临床疗效与安全性进行评价。方法:所有患者均符合欧洲脊柱关节病研究组(ESSG)分类标准,年龄≤16岁,病情处于活动期,关节炎数≥2,肌腱端炎数≥3,总体疼痛VAS≥4(0～10),对NSAIDs和传统DMARDs疗效不佳,给予依那西普0.4mg/kg,每周2次(最大用量至50mg/w),疗程12周。评价指标为0、4、8、12周关节炎数、肌腱端炎数、总体疼痛评分VAS、晨僵时间及实验室炎症反应指标红细胞沉降率(ESR)和C反应蛋白浓度(CRP)等。并随访至48周,观察依那西普减量维持和停用依那西普后患者病情状况。随时记录观察期间不良事件。结果:26例患者完成了12周的观察。4周后,关节炎数和肌腱端炎数均减少,与各自基线水平比较差异有统计学意义(P<0.05),8、12周时这种情况继续改善;其他各项疗效指标也反映出相似的改善程度和趋势;实验室炎症反应指标12周后也明显下降(P<0.05)。随访过程中,16例患者降低依那西普剂量密度继续使用,病情维持稳定。停用依那西普的患者中,多数病情加重。不良反应均为轻度,未发现结核、严重感染等情况。结论:依那西普可以迅速改善JSpA的症状和体征,降低用药频率可维持疗效,安全性较好。

Objective To evaluated bone metabolism,radiology and OPG / RANKL serum levels in patients with ankylosing spondylitis (AS) treated with Gu Ling tang and rh TNFR:Fc. Methods Fifty two AS patients were randomly divided into 2 groups:the therapy group (26 cases) treated with Gu Ling tang and rh TNFR:Fc,the control group (26 cases) treated with rh TNFR:Fc only. Serum samples from the patients were obtained at baseline and 24 weeks after treatment. Disease activity indexes and serum levels of Osteocalcin(OC),C-terminal telopeptides (CTX),receptor activator of nuclear factor-κB ligand (RANKL),and osteoprotegerin (OPG) were measured before and after treatment respectively. And the X-ray images of patient's pelvis were graded based on BASRI before and after treatment. Results After 24 weeks of treatment,the clinical efficacy indexes were significantly improved in patients of both groups(P0.05),and no significant difference was found in the indexes between the two groups. Bone metabolism:Serum levels of OC were significantly increased(P0.05),while serum levels of CTX were significantly decreased(P0.05) in the two groups after 24 weeks. Between two groups,serum levels of OC and CTX were significantly(P0.05)after 24 weeks of treatment. BASRI:Improvement of BASRI-SIJ and BASRI-h were not significant(P 0.05) after 24 weeks and improvement in two groups. Between two groups,changes of BASRI-SIJ and BASRI-h were not significant(P 0.05). Serum levels of OPG and RANKL:Serum levels of OPG were significantly elevated (P 0.05) and serum levels of RANKL were significantly decreased after treatment at week 24 (P0.05),in two groups. Between two groups,serum levels of RANKL/OPG were significantly(P0.05)after 24 weeks of treatment. Conclusion Gu Ling tang with rh TNFR:Fc may be effective for reducing disease activity and improving bone metabolism. It is indicated that Gu Ling tang may interrupt the osteoclasia and radiological improvement through adjusting OPG system in patients with AS.

Objective To evaluate the efficacy of using rhIL-1Ra for the treatment of active RA.Methods The study was based on the use of multi-center,randomized,double-blind,parallel-controlled clinical trial research.40 cases of active RA were obtained from Test Center of Nan-fang hospital.Based on the program 3:1 ratio,the patients were randomly divided into rhIL-1Ra group(treatment group) and the MTX group(control group).30 cases of treatment group were treated with rhIL-1Ra combined with MTX;10 cases of the control group were treated with MTX for 24 weeks.The main evaluation index was the comparison of the proportion of patients reached ACR20 after 12 weeks and 24 weeks to the baseline.The secondary evaluation was the comparison of the proportion of patients reached ACR50,ACR70 after 12 weeks and 24 weeks to the baseline.The index are duration of morning stiffness,joint swelling and joint tenderness count,VAS score,health assessment questionnaire(HAQ),the level of acute phase reactants(ESR,CRP),and the sharp score of dual wrist imaging at week 24.Results 30 cases of treatment group treated with rhIL-1Ra plus MTX,10 cases of the control group to MTX treatment,and follow-up observation,treatment of After the first 12 weeks of treatment the treatment group ACR20 reached 73%,ACR50 37%,and ACR70 13%,while the control group ACR20 reached 10%,ACR50 10%,and ACR70 0%(P = 0.000);after 24 weeks the treatment group ACR20 reached 87%,ACR50 50%,ACR70 37%,while for the control group ACR20 reached 50%,ACR50 10% and ACR70 0%(P = 0.000).The other indicators also reflects the effect of similar extent and trend of improvement(P = 0.000).The sharp score of dual wrist joint for(1) the treatment group:the average joint erosion score at week 0 was 2.33 and at week 24 was 2.23(P = 0.795);the average joint narrow score at week 0 was 1.70 and at 24 weeks was 1.43(P = 0.343),(2) the control group:the average joint erosion score at week 0 was 2.60 and at 24 weeks was 3.60(P = 0.024);the average joints narrow score at week 0 was 1.70 and at 24 weeks was 2.50(P = 0.019).Conclusion The efficacy of rhIL-1Ra combined with MTX was better than MTX alone.The treatment can significantly control the course of RA and prevent the progress of RA.

OBJECTIVE:To evaluate the efficacy of recombinant human tumor necrosis factor receptor-Fc fusion protein (rh TNFR:Fc) in the treatment of active ankylosing spondylitis (AS). METHODS:68 patients with active AS underwent subcutaneous injection of rh TNFR: Fc 25 mg twice a week for 24 weeks. The following indexes were observed: improvement of at least 20% of reported symptoms, based on the multicomponent Assessments in AS (ASAS) response criteria (ASAS 20) at weeks 2, 6, 12 and 24, ASAS 50 and ASAS 70 responses, and improved scores on individual components of ASAS, including Bath AS disease activity index (BASDAI), acute phase reactants, and Bath AS metrology index (BASMI). And the X-ray images of patient's pelvis at weeks 0, 12, and 24 were graded based on BASRI. RESULTS:After treatment of rh TNFR:Fc the primary and secondary efficacy end points of the 68 patients were all improved compared with the baseline values. During the process of treatment, the number of patients with the efficacy achieving ASAS20 was gradually rising: 44 cases (64.7%) at week 12 and 58 (85.0%) at week 24. The efficacy of 41 cases (60.3% ) reached ASAS50 and that of 34 cases reached ASAS70 at week 24. Other efficacy end points also reflected the similar effect and were improved significantly compared with the baseline values at different time points ( all P < 0.01). BASRI showed that the radiological improvement of sacroiliac joint was not significant (P > 0.05) and that the radiological improvement of hip was not obvious at week 12 (P > 0.05) but significant at week 24 (P < 0.05). CONCLUSION:rh TNFR:Fc rapidly improves the signs and symptoms of active AS.