Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

妊高征患者淋巴细胞β_2－肾上腺素能受体结合量改变及与新生儿体重关系的研究

应用放射配体结合分析，测定４０例正常晚期妊娠妇女及４０例妊高征妇女外周血淋巴细胞β_２－肾上腺素能受体（β_２－ＡＲ）结合量，并测定两组妇女分娩的新生儿体重。结果为：１．正常晚期妊娠妇女外周淋巴细胞β_２－ＡＲ结合量明显降低，妊高征妇女β_２－ＡＲ结合量降低更显著；２．妊高征孕妇组的新生儿出生体重明显低于正常妊娠组的新生儿体重；３．孕妇β_２－ＡＲ结合量与新生儿出生体重呈明显正相关，提示好高征与机体β_２－ＡＲ结合量下降有关，β_２－ＡＲ改变影响胎儿生长发育。     

An electrical admittance based index of thoracic intracellular water during head-up tilt in humans

During 50 degrees head-up tilt (HUT), the number of erythrocytes within the thorax has been shown to be reduced by approximately 25% and this level is retained during a maintained tilt, whilst that in the thigh increases by approximately 70%. To evaluate whether the electrical admittance of intracellular water (ICW) may be used to monitor this redistribution of red cells in humans, we determined the regional difference in the reciprocal value of the impedance at 1.5 and 100 kHz for the thorax (thoraxICW) and for the leg (legICW). In ten subjects all variables remained unchanged during head-down tilt but during HUT, presyncopal symptoms were induced in eight subjects after a mean of 27 (SEM 7) min as mean heart rate dropped from 85 (SEM 4) to 66 (SEM 3) beats x min(-1), mean arterial blood pressure from 80 (SEM 3) to 60 (SEM 5) mmHg, and mean oxygen saturation of venous blood from 76 (SEM 2)% to 73 (SEM 3)% (P < 0.05). The mean haematocrit increased from 50 (SEM 5)% to 52.5 (SEM 3.5)% (P < 0.01) and mean central venous pressure decreased during tilting (from a mean of 1 (SEM 1) to a mean of -1 (SEM 1) mmHg; P < 0.05) and returned to value at rest during the maintained tilt. Mean thoracic impedances increased by 7.0 (SEM 1.0) ohms (1.5 kHz) and 5.4 (SEM 1.2) ohms (100 kHz), and mean leg impedances decreased by 9.3 (SEM 1.2) ohms (1.5 kHz) and 3.1 (SEM 1.0) ohms (100 kHz) (P < 0.01). Mean thoraxICW decreased at 40 degrees HUT and remained reduced by 11 (SEM 2) S x 10(-4) (P < 0.05) until the presyncopal symptoms developed, at which time it was lower by 16 (SEM 2) S x 10(-4) (P < 0.01). Mean legICW increased from 97 (SEM 15) to 99 (SEM 15) S x 10(-4) (P = 0.08) during HUT but decreased during maintained tilt (to 94 (SEM 15) S x 10(-4); P < 0.05). The results suggested that during HUT, the difference in electrical admittance at a high and a low frequency current reflects the reduced number of red cells within the thorax.     

Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

损毁单侧黑质-纹状体通路的大鼠SVZ、纹状体和黑质神经前体细胞的变化

研究成年大鼠脑室下区 (SVZ)神经前体细胞 (neural precursors)在黑质 -纹状体通路损伤后的反应 ,本研究用 6-羟多巴胺单侧纹状体注射以损毁黑质 -纹状体通路 ,损毁 10 d后腹腔注射 Brd U ,连续 4d,每日两次 ;在 SVZ、纹状体和黑质部位用免疫组化方法检测 Brd U、nestin以及 GFAP阳性细胞。结果显示 :(1) 6-羟多巴胺损毁黑质 -纹状体通路后 ,伤侧 SVZ的 Brd U阳性细胞数明显增多 ,并成簇分布 ;nestin和 GFAP阳性细胞数也增多 ,但以 GF AP阳性细胞增多明显 ;(2 )伤侧纹状体可见大量 Br-d U、GFAP以及少量 nestin阳性细胞分布 ,而健侧只有少量 GFAP阳性细胞 ;(3 )伤侧可见 Brd U阳性细胞在 SVZ和纹状体之间呈条带样分布 ;(4 )伤侧黑质除酪氨酸羟化酶阳性神经元减少外 ,未见 Brd U、GFAP和 nestin阳性细胞表达。上述结果表明 ,6-羟多巴胺损毁黑质 -纹状体通路后 ,SVZ神经前体细胞活动增强 ,有向纹状体迁移的趋势。     

Pigeon allergens in indoor environments: a preliminary study

BACKGROUND: Few studies have measured pigeon allergens in non pigeon coop environments. This study was conducted to determine approximate pigeon dropping allergen concentrations in indoor environments. METHODS: Polyclonal antibody serum was prepared by injecting a rabbit three times with crude wild pigeon dropping extract in 50 mM Tris buffer with Freund's adjuvant. One hundred and fifteen dust samples were collected in a pigeon-infested school, pigeon coops, homes and hospitals and analyzed by a direct competitive pigeon enzyme-linked immunosorbent assay (ELISA). RESULTS: The highest level of pigeon allergen inhibitory activity were recorded in four samples from pigeon coop bedding samples with a median activity of 11.2% relative to pigeon droppings. The second highest level of pigeon allergens was in a pigeon-infested high school with a median or 7.4% activity relative to pigeon droppings. At an entrance underneath pigeon roosts, one sample had a relative inhibitory activity of 62.3%. Pigeon allergen inhibitory levels were generally low in the home and hospital samples, but nevertheless 46 out of 89 of these samples were still above detection limit. CONCLUSIONS: This study suggests that large concentrations of pigeon allergens can be found in buildings without domestic pigeons such as the pigeon-infested high school.     

TCRVβ7.1基因修饰T细胞对乳腺癌细胞杀伤作用的研究

目的：观察TCPVβ7．1基因转染前后正常人外周血淋巴细胞对乳腺癌细胞株杀伤活性的影响。方法：脂质体包裹PdWA3.1vβ7.1后转染健康人PBMC，流式细胞仪检测PdWA3.1Vβ7.1基因表达，改良MIT法检测TCRVβ7．1基因转染前后正常人外周血淋巴细胞对乳腺癌细胞株杀伤活性。结果：TCRVβ7．1基因转染可显著增加正常人PBMC该基因表达，转染前后正常人外周血淋巴细胞对乳腺癌细胞株杀伤活性有显著性差异。结论：用TCR基因修饰可明显提高正常人PBMC对乳腺癌细胞杀伤作用。     

RPGRIP1s with distinct neuronal localization and biochemical properties associate selectively with RanBP2 in amacrine neurons

RPGR and RPGRIP1 are molecular partners with vital roles in retinal function. Mutations in RPGR are implicated in heterogeneous retinal phenotypes, while those in RPGRIP1 lead to Leber congenital amaurosis. RPGR and RPGRIP1s differentially localize in photoreceptors among species. This may contribute to phenotype disparities among species bearing mutations in RPGR. However, it cannot account for the phenotype heterogeneity associated with RPGR- and RPGRIP1-linked mutations in the human. The existence of RPGRIP1 isoforms with distinct cellular, subcellular localizations and biochemical properties in the retina is shown. High mass RPGRIP1 isoforms, p175/p150, enriched in the outer segment (OS) compartment of photoreceptors are identified. The remaining isoforms are present across subcellular fractions, including nuclei and are soluble. The p175/p150 are predominantly sequestered in the cytoskeleton-insoluble fraction of OS and nuclei. In selective amacrine cells, and in the transformed photoreceptor line, 661W, RPGRIP1s localize at restricted foci to nuclear pore complexes and/or the vicinity of these. Among the nucleoporins, RPGRIP1 isoforms selectively associate in vivo with RanBP2 (Nup358). RPGRIP1s also decorate microtubules in 661W cells and occasionally form coiled-like inclusion bodies in the perikarya. These results support distinct but complementary functions of RPGRIP1 isoforms in cytoskeletal-mediated processes in photoreceptors and amacrine neurons, and may explain the Leber phenotype linked to RPGRIP1 mutations in humans. Moreover, the data implicate a role of RanBP2 in the pathogenesis of neuro(retino)pathies and as a docking station to mediate the nucleocytoplasmic shuttling of RPGRIP1s and their interaction with other partners in amacrine and 661W neurons.     

颈部囊肿与瘘管的诊断和治疗

目的：总结颈部囊肿与瘘管的诊治经验。方法：93例行手术治疗,其中鳃裂囊肿15例,鳃裂瘘管10例,皮样囊肿1例,囊状淋巴管瘤4例,甲状舌骨囊肿37例,甲状舌管瘘管25例,癌性淋巴液囊肿1例,随访1－10年。结果：93例中,囊性淋巴管瘤1例复发后失访,另1例行2次手术,癌性淋巴液囊肿1例半年后死于肺转移,鳃裂瘘管2例3次手术,甲状舌管瘘管1例复发,鳃裂瘘管术后1例迟发性面瘫,一次手术治愈,无术后并发症。结论：颈部囊肿与瘘管的诊断除依据术前检查外,主要是依据术中的发现和术后病理检查。B超、CT等是有效的辅助检查.手段治疗上应彻底切除囊壁与瘘管,避免复发。术中应避免损伤颈部的大血管和神经。甲状舌管瘘管须切除舌骨中段2cm,这是防止术后复发的关键。     

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol

International Urology and Nephrology - The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy...