哮喘儿童外周血T细胞亚群水平表达

目的探讨哮喘儿童外周血T细胞亚群表达极其在发病机制中的作用。方法10例健康儿童为对照组,15例确诊支气管哮喘的儿童为实验组。采用流式细胞术检测CD3^＋、CD4^＋、CD8^＋T细胞百分数。结果实验组与对照组比较,经检验各组（P〉0．05）,差异无显著性。结论哮喘发作1～3d内的患儿外周血中T细胞亚群水平表达与正常儿童无差异。     

HPLC法测定四制香附丸中橙皮苷的含量

目的建立高效液相色谱测定四制香附丸中橙皮苷含量的方法.方法以十八烷基硅烷键合硅胶为填充剂;乙腈-0.2%磷酸水溶液(21:79)为流动相;检测波长为284 nm.结果线性关系为Y=1.9848 X 2.1951,相关系数r=0.9995,线性范围在70.24～561.92 ng,平均回收率101.34%(n=6),RSD=1.08%.结论本法操作简便准确,可作为四制香附丸中橙皮苷含量的质量控制方法.     

Prognostic significance of resident CD103+CD8+T cells in human colorectal cancer tissues

The prognostic significance and clinical implications of resident CD103⁺CD8⁺T cells in human colorectal cancer tissues still remains largely unexplored. In our present study, we aimed to characterize the resident CD8⁺T cells in human colorectal cancer tissues by using double staining of CD103 and CD8, and further evaluated the prognostic significance of resident CD8⁺T cells in colorectal cancer. We found that the OS rate of the colorectal cancer patients with higher infiltration of CD8⁺T cells, or with higher numbers of resident CD103⁺CD8⁺T cells, or with higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in cancer tissues was significantly better than that of the patients with lower infiltration of CD8⁺T cells, or with lower numbers of resident CD103⁺CD8⁺T cells, or with higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in cancer tissues, respectively. Moreover, higher infiltration of CD8⁺T cells in colorectal cancer tissues was significantly and inversely correlated with advanced TNM stage. Higher numbers of resident CD103⁺CD8⁺T cells in colorectal cancer tissues were significantly and inversely correlated with distant metastasis status. Higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in colorectal cancer tissues was significantly and inversely correlated with age status. The COX model analysis demonstrated that higher infiltration of CD8⁺T cells, higher numbers of resident CD103⁺CD8⁺T cells, or higher ratio of CD103⁺CD8⁺T cells over total CD8⁺T cells in colorectal cancer tissues, could serve as independent prognostic predictors for colorectal cancer patients. Taken together, our present study demonstrated the density of tumor infiltrating CD8⁺T cells or the numbers of resident CD103⁺CD8⁺T cells in colorectal tissues could be used as an important prognostic predictor for this malignancy.     

ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Memory T‐cell exhaustion and tolerance in transplantation

One of the biggest barriers to achieving allograft tolerance is the presence of immunological memory within the recipient, which confers a faster, more robust immune response that is in most cases more resistant to pharmacologic immunosuppression. This review will identify the mechanisms by which alloreactive T cells arise within hosts prior to transplantation, and explore the properties of immunological memory that contribute to allograft rejection. In doing so we will also illuminate how targeting pathways that induce memory T cell exhaustion can promote allograft tolerance. Recent studies demonstrating the impact of the allograft microenvironment on memory cell survival and activation, as well as new therapeutic strategies that are being explored to mitigate memory driven allograft rejection, will also be reviewed.     

The nationwide distribution and trends of hepatitis C virus genotypes in mainland China

Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical for treatment regimen selection, vaccine design, and drug development. This study aimed to understand the dynamic distribution of HCV genotypes in Mainland China. Three hundred sixty-two studies published from January 1993 to December 2017 involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors, 1509 former paid plasma donors, 160 sexually encounters, and 1992 human immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95% confidence intervals [CIs]) was estimated through the Freeman-Tukey double arcsine transformation by period, region, and risk group. A sharp decline of the subtype 1b was observed in all regions except in northwestern and central regions. The genotypes 3 and 6 showed an obvious increase in southern and southwestern regions and have already spread nationwide. After 2010, subtype 1b was the most dominant variant in all regions and risk groups, accounting for 54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second most prevalent strain in all regions except in the south and southwest, with 15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region and 3b and 3a in southwestern region had a higher proportion of infections than that in other regions. In addition, the genotypes 3 and 6 are already prevalent in almost all risk groups. The distribution of HCV genotypes were sharply shifting in China in the past three decades. The HCV subtype 1b posed a sharp decline, whereas genotypes 3 and 6 played an increasing role in the regional and populational HCV pandemic.     

The evolution and molecular characteristics of H9N2 avian influenza viruses in Jiangxi of China

To understand the evolution and molecular characteristics of Jiangxi H9N2 viruses, we isolated 17 viruses in 2011 and analyzed their characteristics. Phylogenetic analyses revealed that their hemagglutinin genes originate from JS/1/00-like sublineage, neuraminidase genes originate from BJ/94-like sublineage, PB1, PA, NP, and NS genes all come from SH/F/98-like sublineage, PB2 genes originate from ST/163/04-like sublineage, while M genes come from G1-like sublineage. Genotype analysis showed that our isolates were classified as genotype 57. Molecular analyses indicated that our strains contained specific sites characteristic of low-pathogenic viruses. The current study once again highlights the necessity for continued surveillance of novel H9N2 viruses.     

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing,China

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.     

The clinical significance of plasma CFHR 1–5 in lupus nephropathy

A deficiency of complement factor H may lead to excessive consumption of C3 and an increase in C3b deposition, which are important pathological characteristics of lupus nephritis. Complement factor H-related proteins (CFHRs), comprising CFHR1 to CFHR5 (CFHR1–5), are members of the wider factor H/CFHR family. Their role in lupus nephritis remains unclear. In this study, we compared circulating levels of CFHR1–5 in 152 patients diagnosed with lupus nephritis and 20 unrelated healthy individuals to explore the relationship between the expression of CFHR1–5 and development of the disease. We found that plasma levels of CFHR3 and CFHR5 were higher in patients with lupus nephritis than in healthy individuals; also, CFHR3 and CFHR5 concentrations increased with increasing systemic lupus erythematosus disease activity index (SLEDAI) values (P < 0.05). Pearson's and Spearman's correlation test results confirmed that plasma CFHR3 and CFHR5 levels in lupus nephritis patients were positively correlated with proteinuria and levels of creatinine (Cr) and anti-dsDNA (correlation coefficients = 0.491–0.717, P < 0.05), while they were negatively correlated with plasma C3 levels and eGFR [correlation coefficients = –(0.706–0.788), P < 0.05]. Receiver operating characteristic (ROC) curve analysis results confirmed that plasma CFHR3 and CFHR5 levels were predictive of SLEDAI values and disease end points (area under the curve = 0.664–0.884, P < 0.05), with patients with both high CFHR3 and high CFHR5 exhibiting the shortest progression-free survival. Thus, both CFHR3 and CFHR5 are of prognostic value in lupus nephritis status.