An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging.

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

Feasibility and Acceptability Evaluation of a Digital Therapeutic Program for Improving Cancer Prevention: A Quasi-experimental Pre-post Interventional Pilot Study.

Previous studies have proved that healthy behaviors hinder the onset and progression of tumors. Digital therapeutics (DTx), playing a pivotal role in facilitating behavioral adjustments through educational interventions, lifestyle support, and symptom monitoring, contribute to the goal of tumor prevention. We aim to optimize the evaluation of the feasibility and acceptability of DTx for cancer prevention. This involves assessing AITI's daily activity rates and user feedback, and comparing changes in behavioral habits and differences in SF-36 before and after the intervention. In a 4-week trial with 57 participants engaging actively, we found both the average daily activity rate and 4-week retention rate at 35 (61.4%). The USE Questionnaire scores (validity, ease of use, acquisition, and satisfaction) ranged from 68.06 to 83.10, indicating AITI's user-friendliness and acceptability. Furthermore, positive habit changes were noted among participants in exercise and diet (p < 0.0001), suggesting the effectiveness of the DTx approach in modifying behavioral habits related to physical activity and nutrition. This pilot study underscores the potential of DTx in advancing cancer prevention. However, larger and longer studies are needed to comprehensively assess its impact.

Functionalizing tetrahedral framework nucleic acids-based nanostructures for tumor in situ imaging and treatment.

Timely in situ imaging and effective treatment are efficient strategies in improving the therapeutic effect and survival rate of tumor patients. In recent years, there has been rapid progress in the development of DNA nanomaterials for tumor in situ imaging and treatment, due to their unsurpassed structural stability, excellent material editability, excellent biocompatibility and individual endocytic pathway. Tetrahedral framework nucleic acids (tFNAs), are a typical example of DNA nanostructures demonstrating superior stability, biocompatibility, cell-entry performance, and flexible drug-loading ability. tFNAs have been shown to be effective in achieving timely tumor in situ imaging and precise treatment. Therefore, the progress in the fabrication, characterization, modification and cellular internalization pathway of tFNAs-based functional systems and their potential in tumor in situ imaging and treatment applications were systematically reviewed in this article. In addition, challenges and future prospects of tFNAs in tumor in situ imaging and treatment as well as potential clinical applications were discussed.

Advances in liposomes loaded with photoresponse materials for cancer therapy.

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study.

BACKGROUND: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. METHODS: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. RESULTS: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. CONCLUSIONS: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. TRIAL REGISTRATION: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03645655 .

Efficacy and safety of patient-controlled intravenous analgesia after APS team standardized postoperative pain management: A 6-year experience of an acute pain service in 107802 Chinese patients.

There are few studies on the impact of postoperative pain management (such as Acute Pain Service, APS) on the prognosis of patients, especially the research on large samples, even less data on Chinese patients. It is reported that only 25.12 % of hospitals in China have established APS or similar teams, and less than 10 % of them are responsible for the whole process of postoperative analgesia services. Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology has established a professional APS team led by anesthesiologists (TJ-APS), and has a standardized workflow and management system. Based on the TJ-APS standardized postoperative pain management, the incidence and adverse effects of postoperative pain in different types of surgical patients were analyzed. In total, 107,802 patients receiving intravenous PCA from the Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology were selected between January 2016 and December 2021, which were under TJ-APS standardized postoperative analgesia process, postoperative analgesia strategy based on the principle of "low opioid, multimodal, specialization and individualization", as well as regular ward rounds and 24-h on call on-duty system. We assessed the incidence and adverse effects of postoperative pain in different types of surgical patients. Based on the TJ-APS standardized postoperative pain management, the incidence of poor postoperative analgesia in patients with intravenous PCA is significantly lower than that reported in the current literature (20 %), and mainly occurs in biliary-pancreatic surgery, extrahepatic surgery and gastrointestinal surgery. The overall incidence of adverse effects was 5.52 %, of which nausea and vomiting was the highest, especially among gynecological tumors and gynecological patients, which were 10.75 % and 8.68 % respectively, but both were lower than the level reported in the current literature (20 %). This APS multimodal management and analgesia process can provide reference and guidance for PCA management of postoperative acute pain.

Foliar application of iron impacts flavonoid glycosylation and promotes flavonoid metabolism in coloured rice.

Coloured rice is known as a healthcare food owing its rich flavonoid content. To better understand the effects of iron on the flavonoid metabolism of coloured rice grains, different concentrations of FeSO4 were foliar sprayed on to red rice Yuhongdao 5815 (RR) and black rice Nanheinuo (BR). The results revealed the association of iron with the increased accumulation of anthocyanins in BR and proanthocyanins in RR along with enhancements in their antioxidant capacities and total flavonoid contents. Metabolomic analysis revealed that the differential metabolites between the iron treated coloured rice and the control primarily occurred because of the O-linked glycosylation of aglycones, which are involved in the flavonoid pathway. RR exhibited a significantly higher number of differential metabolites compared with BR. Thus, foliar FeSO4 application affects the O-linked glycosylation and positively regulates flavonoid metabolism.

An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ.

In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HPAP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HPAP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ. The specificity, sensitivity and serum stability of DTF-HPAP were verified in vitro, and DTF-HPAP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HPAP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.

Multi-target meridians classification based on the topological structure of anti-cancer phytochemicals using deep learning.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) meridian is the key theoretical guidance of prescription against tumor in clinical practice. However, there is no scientific and systematic verification of therapeutic action of herbs under meridians context. Several studies have determined the Chinese herbal medicine (CHM) phytochemicals for intrinsic attribute or meridians classification based on artificial intelligence (AI) tools. However, it is challenging to represent the complex molecular structures with large heterogeneity through the current technologies. In addition, the multiple correspondence between herbs and meridians has not been paid much attention. AIM OF THE STUDY: We aim to develop an AI framework to classify multi-target meridians through the topological structure of phytochemicals. MATERIALS AND METHODS: A total of 354 anti-cancer herbs, their corresponding TCM meridians and 5471 ingredient compounds were collected from public databases of CancerHSP, ETCM, and Hit 2.0. The statistical analysis of herbal and compound datasets, clustering analysis of the associated cancers, and correlational analysis of meridian tropism were preliminary conducted. Then a deep learning (DL) hybrid model named GRMC consisting of graph convolutional network (GCN) and recurrent neural network (RNN) was employed to generate the meridian multi-label sequences based on molecular graph. RESULTS: The curing herbs against tumors have tight relationships to lung, liver, stomach, and spleen meridians. These herbs behave different properties in curing certain cancer. Certain cancer types have co-occurrence such as ovarian, bladder and cervical cancer. Compounds have multitarget meridians with characteristics of higher-order correlations. Compared with the other state-of-the-art algorithms on the datasets and previous methods dealing with conventional fixed fingerprints of herbal compounds, the proposed GRMC has superior overall performance on testing dataset with the one error of 0.183, hamming loss of 0.112, mean averaged accuracy (MAA) of 0.855, mean averaged precision (MAP) of 0.891, mean averaged recall (MAR) of 0.812, and mean averaged F1 score (MAF) of 0.849. CONCLUSIONS: The proposed method can predict multi-targeted meridians through neural graph features in herbal compounds and outperforms several comparison methods. It could provide a basis for understanding the molecular scientific evidence of TCM meridians.

NTRK1-mediated protection against manganese-induced neurotoxicity and cell apoptosis via IGF2 in SH-SY5Y cells.

BACKGROUND: Excessive manganese (Mn) exposure has been linked to neurotoxicity, cognitive impairments. Neurotrophic Receptor Kinase 1 (NTRK1) encodes Tropomyosin kinase A (TrkA), a neurotrophic receptor, as a mediator of neuron differentiation and survival. Insulin-like growth factor 2 (IGF2), a pivotal member of the insulin gene family, plays a crucial role in brain development and neuroprotection. Despite this knowledge, the precise mechanisms through which NTRK1 and IGF2 influence cell responses to Mn-induced neuronal damage remain elusive. METHODS: Cell apoptosis was assessed using CCK8, TUNEL staining, and Western blot analysis of cleaved Caspase-3. Lentiviral vectors facilitated NTRK1 overexpression, while small interfering RNAs (siRNAs) facilitated IGF2 knockdown. Real-time Quantitative PCR (qPCR) determined gene expression levels, while Western blotting measured protein expression. RESULTS: The study reveals that NTRK1 inhibits MnCl2-induced apoptosis in SH-SY5Y cells. NTRK1 overexpression significantly upregulated IGF2 expression, and subsequent siRNA-IGF2 experiments confirmed IGF2's pivotal role in NTRK1-mediated neuroprotection. Notably, the study identifies that NTRK1 regulates the expression of IGF2 in the neuroprotective mechanism with the involvement of ER stress pathways. DISCUSSION: The study reveals NTRK1's neuroprotective role via IGF2 against Mn-induced neurotoxicity and ER stress modulation in SH-SY5Y cells. These findings offer insights into potential therapies for neurodegenerative disorders related to Mn exposure and NTRK1 dysfunction, driving future research in this domain.

Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.

High-risk neuroblastoma (HR-NB) has a significantly lower survival rate compared to low- and intermediate-risk NB (LIR-NB) due to the lack of risk classification diagnostic models and effective therapeutic targets. The present study aims to characterize the differences between neuroblastomas with different risks through transcriptomic and metabolomic, and establish an early diagnostic model for risk classification of neuroblastoma.Plasma samples from 58 HR-NB and 38 LIR-NB patients were used for metabolomics analysis. Meanwhile, NB tissue samples from 32 HR-NB and 23 LIR-NB patients were used for transcriptomics analysis. In particular, integrative metabolomics and transcriptomic analysis was performed between HR-NB and LIR-NB. A total of 44 metabolites (P < 0.05 and fold change > 1.5) were altered, including 12 that increased and 32 that decreased in HR-NB. A total of 1,408 mRNAs (P < 0.05 and |log2(fold change)|> 1) showed significantly altered in HR-NB, of which 1,116 were upregulated and 292 were downregulated. Joint analysis of both omic data identified 4 aberrant pathways (P < 0.05 and impact ≥ 0.5) consisting of glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism. Importantly, a HR-NB risk classification diagnostic model was developed using plasma circulating-free S100A9, CDK2, and UNC5D, with an area under receiver operating characteristic curve of 0.837 where the sensitivity and specificity in the validation set were both 80.0%. This study presents a novel pioneering study demonstrating the metabolomics and transcriptomics profiles of HR-NB. The glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism were altered in HR-NB. The risk classification diagnostic model based on S100A9, CDK2, and UNC5D can be clinically used for HR-NB risk classification.

Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.

Introduction: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. Methods: We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. Results: The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Discussion: Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy.

OBJECTIVE: To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients. METHODS: The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy. RESULTS: Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing's syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49-413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0-100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0-97.7%). CONCLUSION: In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Continuous Analgesia with Intercostal Catheterization after Thoracoscopy.

BACKGROUND: There are few studies on continuous intercostal nerve block after single operation hole thoracoscopic surgery, that is, two-port thoracoscopic surgery. OBJECTIVE: To evaluate the analgesic effect of continuous intercostal nerve block after thoracoscopic surgery. METHODS: A total of 80 patients who underwent single operation hole thoracoscopic surgery in our hospital between September 2020 and June 2021 were enrolled and divided into two groups. Based on basic analgesia, an intercostal catheter was placed during the operation for continuous intercostal block analgesia after the operation in the experimental group (group A, n = 40). The control group (group B, n = 40) was treated with sufentanil intravenous analgesia after surgery, which is namely "basic analgesia." The postoperative pain scores, restlessness during the recovery period, effect on reducing opioid use, postoperative chest complications, patient satisfaction, etc., were compared between the two groups. RESULTS: The pain scores of patients in group A were significantly lower compared with those in group B at 12, 24, 36, and 48 hours after surgery (3.325 ± 1.163 vs. 4.550 ± 1.176, 2.650 ± 1.001 vs. 4.000 ± 1.038, 2.325 ± 0.917 vs. 3.700 ± 0.966, and 1.775 ± 1.050 vs. 3.150 ± 1.075, p < 0.001, respectively). Sufentanil consumption in group A was significantly lower than in group B at 48 hours after surgery (98.625 ± 4.158 vs. 106.000 ± 7.228, p < 0.001). CONCLUSION: Multimodal analgesia is ideal for early pain control after thoracotomy. A continuous intercostal nerve block can effectively reduce postoperative pain in patients.

Integration of clinical characteristics and molecular signatures of the tumor microenvironment to predict the prognosis of neuroblastoma.

This study aimed to analyze the clinical characteristics, cell types, and molecular characteristics of the tumor microenvironment to better predict the prognosis of neuroblastoma (NB). The gene expression data and corresponding clinical information of 498 NB patients were obtained from the Gene Expression Omnibus (GEO: GSE62564) and ArrayExpress (accession: E-MTAB-8248). The relative cell abundances were estimated using single-sample gene set enrichment analysis (ssGSEA) with the R gene set variation analysis (GSVA) package. We performed Cox regression analyses to identify marker genes indicating cell subsets and combined these with prognostically relevant clinical factors to develop a new prognostic model. Data from the E-MTAB-8248 cohort verified the predictive accuracy of the prognostic model. Single-cell RNA-seq data were analyzed by using the R Seurat package. Multivariate survival analysis for each gene, using clinical characteristics as cofactors, identified 34 prognostic genes that showed a significant correlation with both event-free survival (EFS) and overall survival (OS) (log-rank test, P value < 0.05). The pathway enrichment analysis revealed that these prognostic genes were highly enriched in the marker genes of NB cells with mesenchymal features and protein translation. Ultimately, USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP) (log-rank test, P value < 0.0001, median EFS: 640.5 vs. 2247 days, median OS: 1279.5 vs. 2519 days). The risk model was also regarded as a prognostic indicator independent of MYCN status, age, and stage. Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB. Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. KEY MESSAGES: Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP). Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB.

High Expression of Triggering Receptor Expressed on Myeloid Cells 1 Predicts Poor Prognosis in Glioblastoma.

Background: Glioblastoma (GBM) is a highly malignant tumor with poor prognosis, and new treatment strategies are urgently needed. Currently, the role of triggering receptor expressed on myeloid cells 1 (TREM-1) in tumors has been studied, but the role of TREM-1 in GBM remains unclear. Methods: Immunohistochemical staining for TREM-1 was performed in 91 patients diagnosed with GBM. Clinicopathological characteristics and survival times were recorded. TREM-1 expression and its effect on prognosis were analyzed using online Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases. The expression profile of TCGA-GBM cohort was used to perform functional enrichment analysis. The CIBERSORT method and Tumor Immune Estimation Resource (TIMER) database were used to estimate the tumor-infiltrating immune cells (TIICs). The ESTIMATE algorithm was used to estimate the immune-stromal scores. Finally, the relationships of TREM-1 with TIICs, immune-stromal score, and immune checkpoint genes (ICGs) were analyzed. Results: The expression of TREM-1 was upregulated in GBM, and high TREM-1 expression predicted a poor prognosis. TREM-1, surgical resection, postoperative radiotherapy, and temozolomide (TMZ) chemotherapy were associated with the survival time of patients with GBM, but only surgical resection and TREM-1 expression were independent prognostic factors. GBM with high TREM-1 expression exhibited increased neutrophil and macrophage infiltration. TREM-1 was positively associated with the immune-stromal score and multiple ICGs, and most of which were involved in immunosuppressive responses. Conclusion: The present study revealed that high expression of TREM-1 in GBM is an independent poor prognosis factor and that TREM-1 is associated with the immunosuppressive microenvironment. Thus, blocking TREM-1 may be a strategy for enhancing the GBM immune response.

Transcriptomics reveals the effects of NTRK1 on endoplasmic reticulum stress response-associated genes in human neuronal cell lines.

Background: NTRK1 gene, encoding TrkA, is essential for the nervous system and drives a variety of biological processes, including pain. Given the unsatisfied analgesic effects of some new drugs targeting NTRK1 in clinic, a deeper understanding for the mechanism of NTRK1 in neurons is crucial. Methods: We assessed the transcriptional responses in SH-SY5Y cells with NTRK1 overexpression using bioinformatics analysis. GO and KEGG analyses were performed, PPI networks were constructed, and the functional modules and top 10 genes were screened. Subsequently, hub genes were validated using RT-qPCR. Results: A total of 419 DEGs were identified, including 193 upregulated and 226 downregulated genes. GO showed that upregulated genes were mainly enriched in response to endoplasmic reticulum (ER) stress, protein folding in ER, etc., and downregulated genes were highly enriched in a series of cellular parts and cellular processes. KEGG showed DEGs were enriched in protein processing in ER and pathways associated with cell proliferation and migration. The finest module was dramatically enriched in the ER stress response-related biological process. The verified seven hub genes consisted of five upregulated genes (COL1A1, P4HB, HSPA5, THBS1, and XBP1) and two downregulated genes (CCND1 and COL3A1), and almost all were correlated with response to ER stress. Conclusion: Our data demonstrated that NTRK1 significantly influenced the gene transcription of ER stress response in SH-SY5Y cells. It indicated that ER stress response could contribute to various functions of NTRK1-dependent neurons, and therefore, ER stress response-associated genes need further study for neurological dysfunction implicated in NTRK1.

Plasma circulating cell-free MYCN gene: A noninvasive and prominent recurrence monitoring indicator of neuroblastoma.

The postoperative recurrence of neuroblastoma (NB) patients is an essential reason for the high mortality of NB due to the lack of early, non-invasive, and dynamic strategies for monitoring NB recurrence. Therefore, whether the plasma circulating cell-free MYCN gene as an indicator for monitoring of NB recurrence was systematically evaluated. The MYCN copy number and NAGK (reference gene) copy number (M/N) ratio in plasma and corresponding tumor tissues of NB patients was detected using an economical, sensitive, and specific single-tube dual RT-PCR approach developed in this study. The plasma M/N ratio of the MYCN gene amplification (MNA) group (N = 25, median M/N ratio = 4.90) was significantly higher than that of the non-MNA group (N = 71, median M/N ratio = 1.22), p < .001. The M/N ratio in NB plasma (N = 60) was positively correlated with the M/N ratio in NB tumor tissue (N = 60), with a correlation coefficient of 0.9496. In particular, the results of dynamic monitoring of postoperative plasma M/N ratio of NB patients showed that an abnormal increase in M/N ratio could be detected 1-2 months before recurrence in NB patients. In summary, the single-tube double RT-PCR approach can be used to quantitatively detect MYCN copy number. The copy number of MYCN in the tissue and plasma of NB patients is consistent with each other. More importantly, the circulating cell-free MYCN gene of NB patients can be used as a monitoring indicator for early, non-invasive, and dynamic monitoring of NB recurrence.