Immunologic cross-reactivity between different albumin-bound isocyanates

Sera of six workers with conclusive evidence for IgE-mediated sensitization to isocyanates were used for evaluation of immunologic cross-reactivities among eight different isocyanate-protein conjugates. In all cases RAST and/or skin-test investigations revealed the presence of IgE antibodies reacting specifically with HSA conjugated with those isocyanates to which workers were exposed as well as with other isocyanates with which they had not been in contact. By the RAST inhibition technique, moderate to strong mutual cross-reactivities between all tested isocyanate-HSA conjugates--even between aromatic and aliphatic ones--could be demonstrated in tests with five sera. The magnitudes of cross-reactivities differed, however, from one patient to another. One serum contained IgE antibodies that were almost completely specific to TDI-HSA; with this serum only weak cross-reactivities with other isocyanate conjugates could be demonstrated. These results indicate the predominance of closely related antigenic determinants in HSA conjugated with different isocyanates. The common antibody-binding regions are obviously recognized to different extents by antibodies of clinically sensitized workers, indicating individual differences in specificities and avidities of antibody populations. Nearly complete lack of IgE binding of ovalbumin-bound TDI in RAST and RAST inhibition indicates carrier-specific antigenicity of isocyanate-protein conjugates. In addition, since unmodified HSA did not bind IgE, antigenic determinants of the conjugates studied should be predominantly formed by the isocyanate-protein bond regions and concurrently by neighboring amino acid residues of the HSA molecule.     

论黑土地民俗与迟子建小说

迟子建的小说散发着浓郁的黑土地民俗气息．民俗构成她小说叙述的框架,深化了小说的思想意蕴,寄托着她对故乡昔日生活的深切怀恋．由于神话传说的滋养,她的小说弥漫着神秘的气息和氛围．     

Diagnostic and prognostic value of serum Chitinase 3‐like protein 1 in hepatocellular carcinoma

The serum Chitinase 3‐like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α‐fetoprotein (AFP), tumor‐node‐metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient''s OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α‐fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.     

Exploring the role of chitinase-3-like protein 1 in recurrence patterns among patients with differentiated thyroid cancer†

Our understanding of the oncogenic drivers involved in thyroid cancers continues to expand. In a recent issue of this journal, Cheng et al explore the role of chitinase-3-like protein 1 (CHI3L1) in the development of thyroid cancer and its recurrence. They show increased levels of CHI3L1 in papillary and anaplastic thyroid malignancies (PTC and ATC, respectively) but baseline expression of the protein in benign thyroid pathologies. These were most pronounced in PTCs with BRAF mutations. High levels of CHI3L1 were shown to be associated with a higher likelihood of extrathyroidal extension and lymph node metastasis, more advanced TNM stage, a higher frequency of harboring a BRAF^V600E mutation, and a higher risk of disease recurrence. Pathologic features, including clonogenicity, migratory, invasive and angiogenic properties, were reduced in a CHI3L1-knockdown thyroid cancer cell line. The cysteine-rich angiogenic inducer 61 (CYR61) pathway was identified as a potential mediator of CHI3L1 pathogenesis, but a full mechanistic pathway was not delineated. Findings regarding CHI3L1-associated pathogenicity are in line with published data available for a number of other cancers. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Propofol and erythropoietin antioxidant properties in rat brain injured tissue

So far, several treatment modalities have been attempted to brain protection in cases such as brain trauma, stroke or brain hemorrhage. However, a treatment method that the effect begins immediately and definitely helpful has not been discovered yet. In this study, we aimed to compare the effects of propofol and erythropoietin (Epo) on brain injury caused by oxidative stress and antioxidant properties of these agents after closed head injury (CHI) in rats. For this study, female Wistar Albino rats were divided into five groups: non-traumatic control group, trauma performed group CHI, trauma with propofol (100 mg/kg) intraperitoneally (i.p.), trauma with Epo (5000 U/kg) i.p. and trauma with propofol and Epo performed study groups. Twenty-four hours after CHI, rats were sacrificed and the brains were removed. Superoxide dismutase (SOD), catalase (CAT), xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) levels were measured in brain tissue. MDA and NO levels were decreased significantly in Groups Epo, Propofol and Epo+Propofol than Group CHI (p<0.01). XO activity was significantly lower in Group Epo than Group CHI (p<0.05). Epo and propofol decreased oxidative stress by decreasing MDA and NO level in brain tissue after CHI. However, combination of Epo and propofol has no significant beneficial advantage than Epo or propofol alone.     

融会·继承·创新——跟师池晓玲教授临证学习有感

池教授为全国名老中医药专家学术经验继承人,临床多年,学验俱丰,善于集合各家之长,并巧妙结合中国传统文化、中国古哲学思想指导临床,创新性地提出了多维立体系列疗法体系治疗肝病的思想与方法。作者通过跟师过程中对临证所遇的验案进行总结,领会其独特的带教魅力。     

Elevated plasma YKL-40 and risk of infectious disease: a prospective study of 94665 individuals from the general population

ObjectivesYKL-40 is an acute phase protein elevated in patients with infectious and inflammatory diseases. We tested the hypothesis that baseline elevated YKL-40 is associated with increased risk of future infectious disease in healthy individuals in the general population.MethodsWe prospectively followed 94 665 individuals from the Danish general population for up to 23 years and analysed for plasma YKL-40 levels (n = 21 584) and CHI3L1 rs4950928 genotype (n = 94 184). Endpoints were any infection, bacterial pneumonia, urinary tract infection, skin infection, sepsis, diarrhoeal disease, and other infections.ResultsFor YKL-40 percentile category 91–100% versus 0–33%, the multifactorially and C-reactive protein (CRP) adjusted hazard ratios were 1.71 (95% confidence interval 1.50–1.96; p 4 × 10⁻¹⁴) for any infection, 1.97 (1.64–2.37; p 4 × 10⁻¹³) for bacterial pneumonia, 1.62 (1.24–2.11; p 0.002) for urinary tract infection, 1.74 (1.31–2.32; p 2 × 10⁻⁴) for skin infection, 1.76 (1.25–2.46; p 0.004) for sepsis, 1.90 (1.29–2.78; p 0.002) for diarrhoeal disease and 2.71 (1.38–5.35; p 0.01) for other infections. In multifactorially and CRP-adjusted models, a twofold increase in YKL-40 was associated with increased risk of all infectious disease endpoints. Mendelian randomization did not support causality, as CHI3L1 rs4950928 was associated with 94% and 190% higher YKL-40 levels (for CG and CC versus GG genotype), but not with increased risk of any infectious disease endpoint.DiscussionBaseline elevated plasma YKL-40 was not a cause but a strong marker of increased risk of future infectious diseases in individuals in the general population.     

SPINK5 is associated with early‐onset and CHI3L1 with late‐onset atopic dermatitis

We have recently showed that filaggrin (FLG) mutations are associated only with early‐onset of AD, but not with late‐onset of AD. Consequently, other susceptibility genes should receive attention, especially in patients with late‐onset of AD. Our aim was to assess the associations between development of AD and the polymorphisms rs2303067 in SPINK5 and rs490928 in CHI3L1. A study population of 241 AD patients and 164 healthy controls was genotyped for two polymorphisms (rs2303067 in SPINK5 and rs490928 in CHI3L1). Rs2303067 in SPINK5 was significantly associated with early‐onset AD (≤8 years: p = .003; OR = 2.57) and was characterized by the need for hospitalization (p = .006; OR = 2.76), prolonged duration (≥10 years; p = .008; OR = 2.32) and more body parts affected (p = .015; OR = 2.01). In contrast, rs490928 in CHI3L1 was associated with late‐onset AD (>8 years: p = .048; OR = 1.65) and was characterized by no need for hospitalization (p = .049; OR = 1.59), shorter duration (<10 years; p = .017; OR = 1.94) and fewer body parts affected (p = .049; OR = 1.75). Our results confirmed that different AD phenotypes, specifically early‐ and late‐onset AD, have different genetic backgrounds. Early‐onset AD was associated with rs2303067 in SPINK5, which is involved in skin barrier functioning, and late‐onset was associated with rs4950928 in CHI3L1, which is involved in the immune response. Future studies should examine the early‐ versus late‐onset subgrouping more closely.     

多房棘球蚴病患者肝病灶组织差异表达基因的研究

目的探讨多房棘球蚴感染小鼠肝差异基因在多房棘球蚴病患者肝病灶组织中的表达情况及意义。方法选取高通量基因表达数据库中编号为GSE24376的小鼠感染多房棘球蚴基因芯片数据集,分析感染小鼠和未感染小鼠之间的差异表达基因,对差异表达基因进行基因本体(GO)分析。取6例多房棘球蚴病患者肝病灶组织和距离病灶组织2 cm的周围肝组织,采用荧光定量PCR检测2个高表达差异基因mRNA相对转录水平。取45份多房棘球蚴病患者石蜡包埋肝组织样品(炎性反应和肝纤维化改变严重的病灶29份,较少炎性细胞浸润和肝纤维化病变的肝组织16份),采用免疫组化法分析2个高表达差异基因的表达情况。用SPSS 21.0统计学软件对数据进行统计分析。结果生物信息学分析结果显示,共筛选出21个差异表达基因,其中9个基因表达上调,12个基因表达下调。GO分析结果显示,差异基因主要位于细胞内囊泡及细胞外基质等细胞成分中,参与了中性粒细胞的脱颗粒及活化等生物过程,并且具有CC趋化因子受体结合活性及趋化因子活性。高表达差异基因CHI3L3 (在人体中为CHI3L1)和CCL8荧光定量PCR结果显示,6例多房棘球蚴病患者肝病灶组织中CHI3L1和CCL8 mRNA相对转录水平均高于病灶周围肝组织(P <0.01),最高倍数分别达7倍和9倍。免疫组化分析结果显示:29份多房棘球蚴病患者肝组织炎性反应和肝纤维化改变严重的病灶样品中,有20份(占69%)呈CHI3L1蛋白高表达,其主要着色部位位于细胞浆;有22份(占76%)呈CCL8蛋白高表达。16份多房棘球蚴病患者肝组织轻微炎症样品中,2份(占13%)呈CHI3L1蛋白阳性;4份(占33%)呈CCL8蛋白阳性。炎性反应和肝纤维化改变严重的病灶组织中,CHI3L1和CCL8蛋白的阳性表达率分别达96%和97%,均高于轻微炎症肝组织的3%和8%(P <0.01)。结论 CHI3L1和CCL8蛋白在多房棘球蚴病患者肝组织中表达增高,提示二者在机体对虫体的免疫应答过程中发挥了一定作用。