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.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

营养和激素对家蝇卵黄发生的影响

本实验通过对家蝇取食量的测定，对家蝇进行不同饲料饲喂后，对其不同发育期的血淋巴、脂肪体及和卵巢的发育及卵黄蛋白含量进行观察测定，结果表明，取食蛋白组家蝇血淋巴、脂肪体和卵巢卵黄蛋白含量均高于奶粉组和对照组；羽化４８ｈ后的血淋巴和脂肪体中卵黄蛋白含量为７．３μｇ／μｌ、３１．９μｇ／头；卵巢卵黄蛋白含量为５５．０μｇ／头；在羽化后７２ｈ血淋巴和脂肪体中卵黄蛋白含量分别为２．９μｇ／μｌ、３２．０μｇ／头；卵巢卵黄蛋白含量为８０．０μｇ／头；脉冲式饲喂家蝇后，体内卵黄蛋白含量明显高于对照组，说明蛋白质饲料在家蝇卵黄发生中起重要作用。激素处理结果证明，ＪＨＡ单独处理及ＪＨＡ和蜕皮素协同处理均能促进卵黄蛋白的合成和摄取，而蜕皮素单独处理没有促进作用。最后对营养和激素对生殖的调控作用进行了讨论。     

广西三江县侗族青少年头发中9种元素的含量

目的　确定广西三江县侗族青少年头发中 9种人体必需元素含量的正常值。方法　用偏振塞曼原子吸收仪 ,检测了来自三江县的 993名 7～ 16岁中小学生头发中镍、硒、钴、铬、铁、锌、钙、铜和镁 9种人体必需元素的含量 ,并用SPSS统计软件进行统计分析。结果　广西三江县侗族中小学生头发中 ,镍、硒、钴、铬、铁、锌、钙、铜和镁 9种人体必需元素的含量没有性别差异 ;硒、铬、铁、锌、钙和铜与年龄呈负相关 ;制订了镍、硒、钴、铬、铁、锌、钙、铜、镁 9种元素的头发含量的正常值范围。结论　广西三江县中学生头发中硒、铬、铁、锌、钙和铜含量有明显年龄差异 ,而镍、钴和镁却没有年龄差异。     

Genetic typing and HIV-1 diagnosis by using 96 capillary array electrophoresis and ultraviolet absorption detection

Current high-throughput approaches to the analysis of PCR products are based primarily on electrophoretic separation and laser-excited fluorescence detection. We show that capillary array electrophoresis can be applied to HIV-1 diagnosis and D1S80 VNTR genetic typing based simply on UV absorption detection. The additive contribution of each base pair to the total absorption signal provides adequate detection sensitivity for analyzing most PCR products. Not only is the use of specialized and potentially toxic fluorescent labels eliminated, but also the complexity and cost of the instrumentation are greatly reduced.     

Interleukin 1 as a tumor cytostatic mediator released from tumor ascites-treated macrophages

Peritoneal macrophages from DBA/2 mice, elicited by injection of Corynebacterium parvum (C.p.), were in vitro activated to Eb tumor cytostasis by incubation with tumor-induced ascites that was harvested 7 days after intraperitoneal Eb injection. The active cytostasis-mediating compound was found to be interleukin 1 (IL 1). When tumor ascites was fractionated according to molecular weight size, the most active IL 1-inducing fraction was found to comprise molecules of greater than 100,000 daltons. The data show that tumor-bearing hosts are capable of producing compounds that induce a high IL 1 secretion which may enable macrophages to mount an antiproliferative effect against tumor cells.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios.

The glutamate pathways are involved in diverse processes such as learning and memory, epilepsy, and they play important roles in neural plasticity, neural development, and neurodegeneration. It has been proposed that autism could be a hypoglutamatergic disorder. Recently, Jamain et al. reported that the glutamate receptor 6 (GluR6 or GRIK2) is in linkage disequilibrium with autism. In the present study, the transmission disequilibrium test (TDT) and the haplotype transmission were performed to analyze the four SNPs (SNP1: rs995640; SNP2: rs2227281; SNP3: rs2227283; SNP4: rs2235076) of GluR6 in 174 Chinese Han parent-offspring trios. The TDT demonstrated that the two SNPs (SNP2 and SNP3) showed preferential transmission (TDT P = 0.032). The global chi(2) test for haplotype transmission also revealed an association between GluR6 and autism (chi(2) = 10.78, df = 3, P = 0.013). Our results suggested that GluR6 is in linkage disequilibrium with autism.     

糖皮质激素受体对大鼠中性粒细胞粘附的影响

本文通过Percoll梯度离心法分离获得大鼠中性粒细胞(PMNS)后,采用PMNS与玻璃珠粘附的模型,通过给予Dex及糖皮质激素受体(GR)阻断剂Mifepristone(RU_(38486))研究大鼠PMNS粘附过程中GR的作用。结果显示,Dex可以明显抑制PMNS的粘附,其作用随着Dex浓度的增大而增强;单纯给予不同浓度的RU_(38486)未发现明显的PMNS粘附增强,说明RU_(38486)本身对离体的PMNS粘附没有明显的作用;若同时给予Dex和RU_(38486),则Dex抑制PMNS粘附的作用逐渐减小,直至完全逆转。该结果强烈提示:糖皮质激素(GC)具有抑制PMNS粘附的作用,其作用是通过GR介导的,当GR被阻断时,这一抑制作用减弱,甚至消失。