A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

超市连锁店熟食卤味销售的HACCP研究

应用HACCP的原理和方法,对超市连锁店熟食卤味销售进行了危害因素分析,找出了关键控制点(CCP),提出了控制措施,并建议超市连锁店销售非包装熟食卤味时使用密封低温冷藏展示柜。     

Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland

Background  Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV).
Objectives  We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients.
Methods  One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction–reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes.
Results  In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples ( P  =   0·046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2–8). Tumours from IS patients were from a younger age group (mean age 57·4 years) than IC patients (mean age 73·8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) ( P  <   0·001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin.
Conclusions  A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.     

Bayesian estimation of a random effects heteroscedastic probit model

Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison.     

聚合酶链反应检测铜绿假单胞菌感染性角膜溃疡的实验研究及临床应用

目的：探索聚合酶链反应（PCR）技术对铜绿假单胞菌感染性角膜溃疡快速诊断的可行性。优越性及其在临床应用中的价值。方法：建立PCR检测标准铜绿假单胞菌方法，对兔铜绿假单胞菌感染性角膜溃疡模型研究并应用于临床，并与细菌培养做比较。结果：铜绿假单胞菌扩增出一条长504bp的阳性条带，其他常见细菌，人和兔正常角膜组织均为阴性，动物模型PCR敏感性为93.8%。特异性为100.0%；细菌培养敏感性为68.7%。特异性为93.7%。临床标本PCR阳性率为66.7%；细菌培养阳性率为38.1%。结论：PCR技术对快速检测实验室和临床标本中的铜绿假单胞菌具有重要的应用价值。     

Aspergillus Iris Granuloma: A Case Report with Review of Literature

We report the case of a 25-year-old male patient who presented with complaints of redness, photophobia, and decreased vision in the right eye of a week's duration. Slit-lamp biomicroscopic examination revealed a cream-colored, irregular elevated inferior iris mass, extending on to the anterior lens surface. Differential diagnoses of a fungal granuloma, a medulloepithelioma, and an amelanotic melanoma were considered. An excisional biopsy of the mass was performed through a superior clear corneal incision. Polymerase chain reaction analysis of the aqueous humor showed a positive pan fungal genome. Histopathology of the biopsied mass showed a giant cell granuloma with surrounding numerous branching, septate hyphae. Culture growth revealed Aspergillus fumigatus We report this case because of the rarity of Aspergillus iris granuloma as a primary presentation of endogenous Aspergillosis and review the relevant literature. Absence of a significant systemic history compounded the diagnostic dilemma in our patient. Definitive differentiation of this rare entity from a foreign body, amelanotic melanoma, and other inflammatory conditions such as sarcoidosis and tuberculosis, may be possible only on microbiological and histo-pathological evaluation.     

Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.