BXSB小鼠肝脏可诱导共刺激因子的表达

目的观察可诱导共刺激因子（inducible co—Stimulator factor,ICOS）在BXSB狼疮小鼠肝脏的表达,探索这种共刺激分子在狼疮肝损害中的可能作用机制。方法以8周龄正常C57BL／6雄性小鼠作对照,用免疫组化及实时PCR方法,检测ICOS在8、16周周龄雄性BXSB小鼠肝脏的表达。结果①正常组鼠肝组织未见明显ICOS染色,8、16周龄BXSB4,鼠肝组织ICOS阳性细胞位于肝小叶的肝血窦或／和窦周隙内,较平均分布;8周BXSB组、16周BXSB组ICOS mRNA表达水平（4．39±0．89,5．24±0．74）均较正常对照组（1．07±0．08）明显升高（P〈0．01）,16NBXSB组的ICOS mRNA表达水平与8周BXSB组无显著性差异（P〉0．05）;结论BXSB小鼠肝损害的发病、疾病的活动可能与ICOS的分布及在肝脏的表达增加有关。     

系统性红斑狼疮合并消化道损害32例临床分析

目的：探讨系统性红斑狼疮（SLE）合并消化道损害者的临床特点。方法：回顾性分析32例SLE合并消化道损害的患者,收集整理其临床资料,分析其临床特点。结果：食道受累者7例（21．9％）,胃肠道受累者25例（78．1％）其中假性肠梗阻10例（31．2％）,且以肠梗阻为首发症状的2例均误诊为急腹症收住外科,肾脏受累14例（43．8％）。治疗后,24例好转。4例死亡。结论：以消化道症状为首发表现的SLE极易误诊,特别是以吞咽障碍,肠梗阻为首发症状者最易误诊。对有消化道受损表现同时伴有其它脏器受损者应排除有无SLE可能。SLE消化道损害发生率高,对此应提高认识和警惕。     

类风湿性关节炎与系统性红斑狼疮重叠综合征一例报告及文献复习

目的:探讨类风湿关节炎(RA)与系统性红斑狼疮(SLE)重叠综合征(Rhupus综合征)的临床表现及治疗方法,以期提高对本病的认识。方法:对1例类风湿关节炎(RA)与系统性红斑狼疮(SLE)重叠的Rhupus综合征患者的病例资料进行分析。结果:本例患者为中年女性,以RA为首发表现,8年后出现SLE特征性表现。就诊时关节症状较严重,出现多关节变形。本例患者肾脏损害重,糖皮质激素联合甲氨喋呤治疗有效。结论:Rhupus综合征在临床上罕见,加强特异性抗体检查,可减少误诊漏诊,早期正确诊断,积极治疗,对于改善患者预后具有重要意义。     

系统性红斑狼疮患者血清MBL水平变化及其临床意义

目的：研究系统性红斑狼疮（SLE）患者外周血中甘露糖结合凝集素（MBL）水平与SLE的临床表现、经典的血清学指标及疾病活动性指数的相关性。方法：应用固相酶联免疫吸附（ELISA）法检测54例（其中活动期39例、缓解期15例）SLE患者和45名健康志愿者外周血MBL水平,同时检测SLE患者外周血抗dsDNA抗体、C3补体、白细胞计数及循环免疫复合物（CICs）水平,并记录SLE患者主要临床症状（肾脏系统受累、神经系统受累、严重感染等）,疾病活动度用SLEDAI记分。结果：系统性红斑狼疮患者外周血MBL水平显著低于健康志愿者（P〈0．01）;特别是活动期SLE患者血清MBL水平明显降低,与缓解组比较差别具有统计学意义（P〈0．01）;SLE患者血清MBL水平与SLEDAI、抗dsDNA抗体、CICs水平呈负相关,与白细胞计数及C3补体水平呈正相关;并发严重感染的SLE患者组血清MBL水平显著低于无受累组（P〈0．01）。结论：SLE患者血清MBL水平明显降低,血清MBL水平与SLEDAI、抗dsDNA抗体、C3水平、CIC水平、白细胞水平之间明显相关,血清MBL水平较低的患者更易发生比较严重的感染,血清MBL水平可能是SLE潜在生物学标记。     

IL-17 与狼疮性肾炎关系的研究新进展

系统性红斑狼疮是一种涉及多系统损害的自身免疫性疾病,其主要并发症及死亡原因之一是狼疮性肾炎。研究表明,IL-17和产IL-17细胞可以浸润肾脏,与其他细胞因子协同作用,引起肾脏局部炎症反应。拮抗IL-17的生物制剂已应用于银屑病、强制性脊柱炎等免疫介导炎症性疾病,但在系统性红斑狼疮及狼疮性肾炎的研究尚少。本文对IL-17与狼疮性肾炎的关系进行综述,探讨IL-17及其抑制剂在狼疮性肾炎治疗的作用及发展前景。     

The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus

To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control's serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas-FasL pathway.     

脐血间充质干细胞治疗严重性系统性红斑狼疮的临床疗效初探

目的探讨脐血间充质干细胞对严重性系统性红斑狼疮（SLE）的治疗效果。方法从健康产妇足月分娩的脐带血（UCB）中分离单个核细胞、培养制备间充质干细胞（MSCs）。MSCs培养到第三代时,取样UCB-MSCs,用流式细胞术进行性质鉴定显示：UCB-MSCs高表达CD29,CD90;不表达CD34和CD45。收集生长良好的第三代UCBMSCs。（5.0-6.0）×10^7个细胞加入100ml含1﹪人血白蛋白的生理盐水中,静脉滴注;每天1次,6-10d,一疗程;3-6个月后再用第2疗程。结果通过UCB-MSCs输注,使现有方法治疗无效的2例严重性系统性红斑狼疮患者的症状完全恢复。第1例SLE伴严重狼疮肾,狼疮脑10年,双下肢水肿,皮肤坏疽,溃疡深达骨面,剧痛难眠1年。经治医生动员她截肢保命。UCB-MSCs治疗后10d,病情明显好转,双下肢水肿几乎全部消退。治疗6个月后,11处坏疽、溃疡的疮面10个疮面基本愈合。10个月后患者的坏疽,溃疡的疮面全部愈合,能自由活动,进入正常生活。第2例SLE伴狼疮肾,狼疮脑4年,一年来贫血严重,靠每周输血维持生命。UCB-MSCs治疗二个疗程后,咳嗽,呕吐症状明显好转,浮肿和双侧胸腔积液消失,各项检查指标基本正常,不需要输血治疗。恢复休学多年的学习生活。二者均随访8年,病情稳定,没发现复发症状。结论 UCB-MSCs治疗2例严重性红斑狼疮,取得一定的疗效;这种新的技术可望成为治疗严重性系统性红斑狼疮的辅助疗法。     

Proteomic profiling of urine: implications for lupus nephritis

Introduction: Lupus nephritis (LN) is a common and significant manifestation, affecting 60% of adults and 80% of children with systemic lupus erythematosus, with up to 30% of patients progressing to end stage renal disease. There remains an unmet need for non-invasive markers of disease activity, damage, and response to therapy. In addition, non-invasive biomarkers that predict therapeutic efficacy are needed to enable cost-effective clinical trials of novel agents.

Areas covered: This review examines the methodological aspects of urinary proteomics, the role of proteome profiling in identifying promising urinary biomarkers in LN, and the translation of research findings into clinically useful tools in the management of LN.

Expert opinion: Targeted and unbiased proteomics have identified several promising urinary biomarkers that predict LN activity, damage (chronicity), and response to therapy. In particular, a combination of biologically plausible urinary biomarkers termed as RAIL (Renal Activity Index for Lupus) has emerged as an excellent predictor of LN activity as well as response to therapy, being able to predict efficacy within 3 months of therapy. If validated in additional large prospective studies, the RAIL biomarkers will transform the care of patients with LN, allowing for a personalized and predictive approach and improved outcomes.     

系统性红斑狼疮患者外周血单个核细胞中C-myc和ras癌蛋白的表达及NK亚群的状况

作者检测了系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)中 C-myc.Ki-ras 和Ha-ras 三种癌蛋白的表达和自然杀伤细胞(NK)亚群状况。结果显示,SLE 患者血液淋巴细胞和单核细胞中上述三种癌蛋白的阳性率均显著高亍健康对照组(P<0.001);而 SLE 组 NK 总数和CD16~+.CD16~+.57~+亚群细胞数则显著低于对照组(P<0.001)。作者结合文献讨论了 SLE 患者PBMC 中癌基因激活的可能机制和重要意义,以及与 NK 细胞和其亚群改变之间的相互关系。     

活血解毒、益气养阴法治疗狼疮性血管炎临床及免疫研究

目的:观察活血解毒、益气养阴法对狼疮性血管炎临床疗效及免疫功能的影响。方法:选择系统性红斑狼疮患者60例,其中活动期伴血管炎40例,非活动期20例,同时选择20例健康人作为对照组,检测可溶性血栓调节素(sTM)、血管内皮生长因子(VEGF)的水平、抗中性粒细胞胞浆抗体(ANCA)的阳性率;并将40例活动期伴血管炎患者随机分为中西医结合治疗组(狼疮饮+常规西药)和对照组(常规西药),治疗6个月后观察临床疗效,并检测治疗前和治疗后第1,6个月sTM、VEGF、ANCA水平和阳性率变化。结果:中西医结合治疗组疗效优于对照组,治疗组治疗后sTM、VEGF、ANCA水平和阳性率下降优于对照组(P<0.05)。结论:中西医结合治疗可提高狼疮性血管炎的疗效,改善免疫功能。     

活血解毒、益气养阴法治疗狼疮性血管炎临床及免疫研究

目的：观察活血解毒、益气养阴法对狼疮性血管炎临床疗效及免疫功能的影响。方法：选择系统性红斑狼疮患者60例,其中活动期伴血管炎40例,非活动期20例,同时选择20例健康人作为对照组,检测可溶性血栓调节素（sTM）、血管内皮生长因子（VEGF）的水平、抗中性粒细胞胞浆抗体（ANCA）的阳性率;并将40例活动期伴血管炎患者随机分为中西医结合治疗组（狼疮饮＋常规西药）和对照组（常规西药）,治疗6个月后观察临床疗效,并检测治疗前和治疗后第1,6个月sTM、VEGF、ANCA水平和阳性率变化。结果：中西医结合治疗组疗效优于对照组,治疗组治疗后sTM、VEGF、ANCA水平和阳性率下降优于对照组（P〈0.05）。结论：中西医结合治疗可提高狼疮性血管炎的疗效,改善免疫功能。     

血清胱抑素C作为新型肾功指标在狼疮肾炎中的临床意义

目的:探讨血清胱抑素C在狼疮肾炎的诊断及治疗监测中的临床意义.方法:检测106名狼疮肾炎患者的血清胱抑素C(sCysC)、血清肌酐(sCr)、尿素氮(BUN)、肾小球滤过率(GFR),24小时尿蛋白(uTP)、血清白蛋白(sAlb)、C-反应蛋白(CRP)水平,分析sCysC与上述指标的相关性及其在治疗过程中的动态变化...     

Th 细胞因子IL-17、IFN-γ、IL-4 在狼疮性肾炎中的表达及意义

目的:探讨T辅助细胞(Th)相关细胞因子在狼疮性肾炎发病中的免疫机制作用。方法:64例系统性红斑狼疮患者和28例健康体检者作为对照,采用酶联免疫吸附测定法(ELISA法)检测所有受试者血清IL-17、IFN-γ、IL-4水平,并对其与SLEDAI、SDI、24小时尿蛋白量相关性进行研究。结果:狼疮性肾炎组血清IL-17水平显著高于狼疮无肾炎组和健康对照组(P<0.001),狼疮性肾炎组血清IFN-γ水平显著高于狼疮无肾炎组(P<0.05)和健康对照组(P<0.01),血清IL-4水平在狼疮性肾炎组、狼疮无肾炎组均显著高于健康对照组(P<0.01)。狼疮性肾炎组IFN-γ/IL-4比值显著高于狼疮无肾炎组(P<0.01)和健康对照组(P<0.05);狼疮无肾炎组IFN-γ/IL-4比值显著低于健康对照组(P<0.01)。SLE患者血清IFN-γ表达水平与SLEDAI积分呈正相关(r=0.402,P<0.05),血清IL-17、IL-4表达水平与SLEDAI、SDI、抗ds-DNA抗体、C3、24小时尿蛋白量均无相关性。结论:狼疮性肾炎患者外周血中IL-17、IFN-γ、IL-4等促炎细胞因子均有不同程度升高促起炎症发生及组织损伤,参与了狼疮性肾炎的免疫发病过程。     

武汉单极虫感染对异育银鲫皮肤微生物的影响

研究以异育银鲫为研究对象,通过16S rDNA高通量测序分析,探究武汉单极虫感染对其皮肤微生物物种组成、丰富度和多样性的影响。结果显示,健康组和感染组异育银鲫皮肤微生物共有30门、80纲、188目、295科、475属、692种、939个OTUs,其中健康组特有OTU数为308个,感染组特有OTU数为342个。根据α多样性分析发现,感染组微生物多样性较健康组显著升高、丰富度显著降低; β多样性分析发现,健康组和感染组皮肤微生物群落结构存在显著差异。比较分析发现,在门水平上,健康组和感染组优势菌门均为厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、蓝藻门(Cyanobacteria)、放线菌门(Actinobacteria)和拟杆菌门(Bacteroidetes),但在丰富度上存在差异;在属水平上,丰富度在1%以上的有20个属级单元,健康组以乳球菌属(Lactococcus)为主,感染组以无色杆菌属(Achromobacter)为主,分别占各组总微生物数量的58.99%和48.67%。线性判别分析和功能预测发现,感染组中致病菌的丰富度和微生物潜在致病性较健康组显著增加。综上所述,武汉单极虫感染能够引起异育银鲫皮肤微生物失调和致病菌丰富度增加,进而可能导致细菌的继发感染。     

基于联邦半监督学习的皮肤病变智能识别

近年来,深度学习技术已广泛应用于皮肤病变识别。然而在实际应用场景中,单一医疗机构存在训练数据有限、有标签样本不足,以及集中式学习易泄露隐私等问题。针对上述问题,本文提出了一种基于联邦半监督学习的皮肤病变智能识别机制。具体地,设计了一个基于联邦学习的云边协同皮肤病变智能识别模型,该模型在保护用户隐私的前提下,协同训练各个医疗机构数据,可为用户提供准确便捷的诊断服务。接着,设计了一种面向数据异构的半监督损失函数,以有效控制局部模型与全局模型之间的差异。此外,通过融合多重随机采样与准确率加权方法,明确各个本地模型的贡献,并将各个不均匀的本地模型聚合成一个全局共识模型,以进一步降低数据异构的影响。最后,实验结果表明,相较于近期提出的几种机制,所提机制在性能和可扩展性方面表现更优。     

Common silent mutations in all types of hereditary complement C1q deficiencies

Hereditary complete deficiency of complement component C1q is a rare genetic disorder that is associated with severe recurrent infections and a high prevalence of lupus-erythematosus-like symptoms. In the past, several single nucleotide polymorphisms have been identified in all three genes coding for the C1q A, B, and C chains. These point mutations which either lead to termination codons, frameshift, or amino acid exchanges were thought to be responsible for these defects as no other nonsense or missense mutations were found. As a result of the aberrations, either a nonfunctional C1q antigen is present or no C1q protein is detectable in the patients' sera. Screening 46 individuals from seven families with different forms of C1q deficiencies identified a homologous silent mutation at position Gly70 (GGG>GGA) of the C1q A gene of all 11 C1q-deficient patients. A high number of family members that were heterozygous for the coding mutations carried the silent mutation in the homozygous (18%) or heterozygous (36%) state. In addition to the Gly70 mutation in the A gene, another homozygous silent mutation (C gene at position Pro14, CCT>CCC) was detected in all C1q-deficient patients.     

基于联邦深度学习的皮肤病智能诊断研究

近年来,基于人工智能的皮肤病智能诊断已经成为智慧医疗领域的热门课题。然而由于单一机构的数据有限,局部训练的神经网络难以满足医疗诊断服务的性能需求,从分散机构中收集数据的集中式学习又存在隐私泄漏的风险。基于上述挑战,本文提出一种基于联邦深度学习的皮肤病智能诊断算法。具体地,对比主流的集中式学习,为了在整合多方数据时防止隐私泄漏,本文引入了联邦学习。各客户端将本地模型发送到中心服务器进行聚合,中心服务器再将聚合得到的全局模型同步到各客户端,实现神经网络模型的训练。进一步,为了解决联邦学习中数据异构性的问题,本文在交叉熵损失的基础上增加了修正项,通过修正项限制本地模型和全局模型间的差异,增加模型对异构数据的关注度,从而减小数据异构对诊断结果的影响。实验结果表明,本文所提的皮肤病智能诊断算法与现有相关方案相比,诊断准确度提高了3%~4%,达到75.9%。     

Entire male pigs in farrow-to-finish pens—Effects on animal welfare

Aggressive and sexual behaviour can hamper animal welfare in entire male pig production. The aim of the present study was to investigate if rearing entire male pigs in sibling groups (in farrow-to-finish pens) could reduce aggressive and sexual behaviour and thereby improve animal welfare in entire male pig production. Frequencies of aggressive and sexual behaviour among finishing pigs were recorded in three different groups in one herd; FTF-group (entires + gilts, siblings), mix-group (entires + gilts, mixed) and castrate-group (castrates + gilts, siblings). Frequencies of skin wounds were recorded in this herd and in an additional herd (only FTF-group and mix-group) shortly before the animals were sent to slaughter. Higher skin lesion scores in the entire male pig groups were in accordance with the behaviour data. Rearing entire male pigs in sibling groups reduces aggressive behaviour, though the frequency of the aggressive behaviour bouts was still higher than it was in the castrate-group. The frequency of skin wounds in the FTF-group was reduced to similar levels as in the castrate-group. The findings suggest that rearing entire males in sibling groups may be an appropriate management strategy for improving animal welfare in entire male pig production.