An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

The utilization of biotinylated RNA baits on captured sequencing of cancer marker genes functional regions / Монголын Анагаах Ухаан

Background@#Nucleic acid sequencing is a multi-step process taken place in medical research or diagnostic laboratories. Since the emerge of second generation sequencing technology generally referred as next generation sequencing (NGS), the mass parallel reads covering human genome or transcriptome is achieved by cost cut down over thousand folds. Though the technology made tremendous push forward to various applications, its data analysis time and effort still takes worrisome time and human effort, bringing the emerge of next-step demand: targeted mass sequencing of only desired part from human genome or transcriptome with lower material cost and labor. By targeted sequencing, both run cost and data analysis process can be further cut down, and the read results are more reliable on changes such as determining varied number of repeats, heterozygote alleles, deletions, chromosomal scale abnormality and more. @*Objective@#In this study, we explored the utilization of biotinylated RNA baits on captured sequencing of cancer marker genes functional regions.@*Method@#Targeted NGS was achieved by capturing desired genomic regions using preparatory nucleic acid probes. RNA bait capturing of desired genomic regions has shown to have high specificity and quality. </br> The study was carried out with informed consent obtained from patients, with the approval №53 in 2018.03.15 by Medical Ethics committee, Ministry of Health, Mongolia.@*Result@#By preparing library of biotinylated RNA baits with 75000 unique sequences, we achieved mass parallel sequencing of human 410 cancer-marker-genes’ exons and UTRs with average read depth ~760, and covered thousands of SNPs on 5 genomic DNA samples. Tissue samples derived from breast cancer and ovary cancer had SNP and deletion on 7 marker genes (BRCA1, BRCA2, ATM, BRIP1, PTEN, TP53, RAD51C) not registered in database.@*Conclusion@#Experiments showed RNA baits with up to 117 nucleotide length, produced from ssDNA oligonucleotide stock, can be utilized to capture desired regions of human genome, and bring the cost of captured mass sequencing to 1500 USD, with 93.14-93.33% of Q30 read quality.

A nanocleaner specifically penetrates the blood‒brain barrier at lesions to clean toxic proteins and regulate inflammation in Alzheimer's disease

Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A

Postoperative Refractive Changes after Optic Capturing

PURPOSE: To present postoperative refractive changes in patients with optic capturing. METHODS: This retrospective review was comprised of 81 eyes of 69 presenile and senile cataract patients who had undergone cataract surgeries, and 20 eyes of 11 pediatric cataract patients who had undergone irrigation and aspiration of the cataract, posterior continuous curvilinear capsulorhexis (PCCC) and optic capturing. Presenile and senile cataract patients were divided into three groups: Group I: Phacoemulsification with posterior chamber lens implantation (Phaco with PCL), 37 eyes; Group II: Phaco with PCL and PCCC, 22 eyes; Group III: Phaco with PCL, PCCC and optic capturing, 22 eyes. Preoperative target refractive error and postoperative refractive errors were compared postoperatively. RESULTS: Hyperopic shiftings were noticed in Groups I and II, but were not statistically significanct. However, statistically significant hyperopic shifting was found in Group III. In pediatric populations, we found no statistically significant refractive changes. CONCLUSIONS: PCCC alone does not cause refractive change postoperatively. When performing optic capturing, postoperative hyperopic shifting must be considered.

Compar Bon of sensitivity and specificity of specific IgM detected by indirect-ELISA and capturing-ELISA / 西安交通大学学报(医学版)

Objective To assess the differences in the specificity and the sensitivity in detecting specific IgM by indirect ELISA and capturing-ELISA methods,and to analyze the possible causes of those differences.Methods The HBc-IgM and EHF-IgM level in serum samples from activity Hepatitis B patients and hemorrhagic fever patients with renal syndrome were determined by both indirect-ELISA and capturing-ELISA methods,and the differences in the positive rate,positive threshold value and the specificity between those two methods were compared. Results Specific murine IgM diluted in PBS were detected by indirect-ELISA and capturing-ELISA,and the specificity and sensitivity of those two methods were similar.Results showed that sensitivity of indirect-ELISA was lower than capturing-ELISA in detecting specific IgM in serum from patients with activity Hepatitis B and hemorrhagic fever patients with renal syndrome.The IgM level in hepatitis B and hemorrhagic group treated with thioglycol became negative detected by those two methods,suggesting that both of them have the anti-IgM epitope-specificity.Cross reaction results demonstrated that the reagent detecting IgM from the two methods had the specificity to the specific antigen. Conclusion It is recommended to detect IgM level by capturing-ELISA method for the early diagnosis of acute infectious disease,pathological changes,immune reaction and prognoses of chronic continuous infectious disease.Applying the indirect-ELISA method to detect IgM level to diagnose acute infectious disease is to discuss in the future.

Monitoring of Human Cytomegalovirus(HCMV) Infection in Patients with Diabetes and Its Clinical Significance / 中华医院感染学杂志

OBJECTIVE To monitor human cytomegalovirus(HCMV) infection in patients with diabetes and its clinical significance.METHODS HCMV pp65-mRNA and anti-HCMV pp65-IgM were simultaneously tested by RT-PCR using the primer sequences from HCMV pp65 genome and ELISA method was used in 727 patients with diabetes and control group.RESULTS The positive rates of HCMV pp65-IgM and HCMV pp65-mRNA in 727 patients with diabetes were 11.14% and 16.64%,respectively.There was a significant difference compared with control groups(HCMV pp65-IgM,0.87% and HCMV pp65-mRNA,2.17%)(P