Development and validation of an ECM-related prognostic signature to predict the immune landscape of human hepatocellular carcinoma.

BACKGROUND: The global burden of hepatocellular carcinoma (HCC) is increasing, negatively impacting social health and economies. The discovery of novel and valuable biomarkers for the early diagnosis and therapeutic guidance of HCC is urgently needed. METHODS: Extracellular matrix (ECM)-related gene sets, transcriptome data and mutation profiles were downloaded from the Matrisome Project and The Cancer Genome Atlas (TCGA)-LIHC datasets. Coexpression analysis was initially performed with the aim of identifying ECM-related lncRNAs (r > 0.4, p < 0.001). The screened lncRNAs were subjected to univariate analysis to obtain a series of prognosis-related lncRNA sets, which were incorporated into least absolute selection and shrinkage operator (LASSO) regression for signature establishment. Following the grouping of LIHC samples according to risk score, the correlations between the signature and clinicopathological, tumour immune infiltration, and mutational characteristics as well as therapeutic response were also analysed. lncRNA expression levels used for modelling were finally examined at the cellular and tissue levels by real-time PCR. All analyses were based on R software. RESULTS: AL031985.3 and MKLN1-AS were ultimately identified as signature-related lncRNAs, and both were significantly upregulated in HCC tissue samples and cell lines. The prognostic value of the signature reflected by the AUC value was superior to that of age, sex, grade and stage. Correlation analysis results demonstrated that high-risk groups exhibited significant enrichment of immune cells (DCs, macrophages and Tregs) and increased expression levels of all immune checkpoint genes. Prominent differences in clinicopathological profiles, immune functions, tumour mutation burden (TMB) and drug sensitivity were noted between the two risk groups. CONCLUSIONS: Our signature represents a valuable predictive tool in the prognostic management of HCC patients. Further validation of the mechanisms involved is needed.

Self-assembly of Hyaluronic Acid-Cu-Quercetin flavonoid nanoparticles: synergistic chemotherapy to target tumors.

Background: In this study, a natural compound quercetin (Qu) was investigated for its various antitumor effects. However, due to its poor water solubility and low bioavailability, its clinical application is limited. To overcome this constraint, a modification was to Qu, which resulted in the creation of novel flavonoid self-assembling nanoparticles (HCQ NPs). Methods: HCQ NPs were synthesized by a self-assembly method and characterized using transmission electron microscopy, the Malvern Zetasizer instrument, X-ray photoelectron spectroscopy (XPS), the ultraviolet-visible spectrophotometric method (UV-vis), Fourier transform infrared (FITR) and inductively coupled plasma mass spectrometry. Extracellular, methylene blue spectrophotometric analysis was used to determine the ability of HCQ NPs to react with different concentrations of H2O2 to form hydroxyl radicals (•OH). Intracellular, DCFH-DA staining was used to detect the ability of HCQ NPs to react with H2O2 to generate reactive oxygen species. Flow cytometry was used to detect the uptake of HCQ NPs by MDA-MB-231 cells at different time points. The biocompatibility of HCQ NPs was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Calcein AM/PI double staining and the CCK-8 assay were used to evaluate the synergistic antitumor effect of HCQ NPs and H2O2. Results: HCQ NPs showed uniformly sized analogous spherical shapes with a hydrodynamic diameter of 55.36 ± 0.27 nm. XPS revealed that Cu was mainly present as Cu2+ in the HCQ NPs. UV-vis absorption spectrum of the characteristic peak of HCQ NPs was located at 296 nm. Similarly, FTIR spectroscopy revealed a complex formation of Qu and Cu2+ that substantially changed the wavenumber of the 4-position C = O characteristic absorption peak. Based on the proportion of Qu and Cu2+ (1:2), the total drug loading of Qu and Cu2+ in the HCQ NPs for therapeutic purposes was calculated to be 9%. Methylene blue spectrophotometric analysis of •OH indicated that Cu can lead to the generation of •OH by triggering Fenton-like reactions. HCQ NPs rapidly accumulated in MDA-MB-231 cells with the extension of time, and the maximum accumulation concentration was reached at about 0.5 h. Calcein AM/PI double staining and CCK-8 revealed synergistic antitumor effects of HCQ NPs including the chemotherapeutic effect of Qu and chemodynamic therapy by Cu2+ in a simulated tumor microenvironment. HCQ NPs demonstrated very low toxicity in LO2 cells in the biocompatibility experiment. Conclusion: This study show cases a new method of creating self-assembled flavonoid HCQ NPs that show great for fighting cancer.

ALDH1A1 in Cancers: Bidirectional Function, Drug Resistance, and Regulatory Mechanism.

Aldehyde dehydrogenases 1 family member A1(ALDH1A1) gene codes a cytoplasmic enzyme and shows vital physiological and pathophysiological functions in many areas. ALDH1A1 plays important roles in various diseases, especially in cancers. We reviewed and summarized representative correlative studies and found that ALDH1A1 could induce cancers via the maintenance of cancer stem cell properties, modification of metabolism, promotion of DNA repair. ALDH1A1 expression is regulated by several epigenetic processes. ALDH1A1 also acted as a tumor suppressor in certain cancers. The detoxification of ALDH1A1 often causes chemotherapy failure. Currently, ALDH1A1-targeted therapy is widely used in cancer treatment, but the mechanism by which ALDH1A1 regulates cancer development is not fully understood. This review will provide insight into the status of ALDH1A1 research and new viewpoint for cancer therapy.

Path Optimization of Medical Waste Transport Routes in the Emergent Public Health Event of COVID-19: A Hybrid Optimization Algorithm Based on the Immune-Ant Colony Algorithm.

In response to the emergent public health event of COVID-19, the efficiency of transport of medical waste from hospitals to disposal stations is a worthwhile issue to study. In this paper, based on the actual situation of COVID-19 and environmental impact assessment guidelines, an immune algorithm is used to establish a location model of urban medical waste storage sites. In view of the selection of temporary storage stations and realistic transportation demand, an efficiency-of-transport model of medical waste between hospitals and temporary storage stations is established by using an ant colony-tabu hybrid algorithm. In order to specify such status, Wuhan city in Hubei Province, China-considered the first city to suffer from COVID-19-was chosen as an example of verification; the two-level model and the immune algorithm-ant colony optimization-tabu search (IA-ACO-TS) algorithm were used for simulation and testing, which achieved good verification. To a certain extent, the model and the algorithm are proposed to solve the problem of medical waste disposal, based on transit temporary storage stations, which we are convinced will have far-reaching significance for China and other countries to dispatch medical waste in response to such public health emergencies.

Analysis of the survival time in 302 elderly patients with esophageal cancer / 中国胸心血管外科临床杂志

@#Objective To explore the possible factors which influence the survival time of elderly patients with esophageal cancer. Methods We retrospectively analyzed the data of patients with esophageal cancer treated in the First Hospital of Lanzhou University, Gansu Province Tumor Hospital from January 2012 to October 2016. Kaplan-Meier method was used to estimate and analyze the single factor, survival curve with log-rank test. The Cox regression model was used for multivariate prognostic analysis． Results According to the inclusion and exclusion criteria, 302 patients were eventually collected, including 231 males and 71 females, with an average age of 66.0±6.0 years. The univariate analysis showed that age, tumor stage, tumor site, Karnosfsky performance satus (KPS) score, and treatment were prognostic factors (P<0.05). Multivariate analysis showed that the patient age and treatment were independent factors for overall survival (OS) and progress-free survival (PFS) (P<0.05). The OS and PFS of the patients with age≤70 years were better than those of the patients more than 70 years. Chemotherapy alone and surgery alone was better for survival situation than radiotherapy alone. Conclusion Age and treatment are independent prognostic factors in survival time of the elderly patients with esophageal cancer.

Clinical application of tubeless trans-subxiphoid thoracoscopic surgery in anterior mediastinal tumor resection: A case control study / 中国胸心血管外科临床杂志

@#Objective To discuss the safety, feasibility and advantages of tubeless trans-subxiphoid thoracoscopic surgery in anterior mediastinal tumor resection. Methods A total of 32 patients suffering anterior mediastinal tumor were enrolled, including 17 patients (8 males and 9 females) with average age of 31.8±8.4 years who had been performed tubeless trans-subxipohoid tharcoscopic surgery and 15 patients (8 males and 7 females) with average age of 31.1±9.2 years who had been performed traditional trans-subxipohoid tharcoscopic surgery. The differences of surgical duration, the lowest intraoperative arterial oxygen saturation (SaO2), postoperative awaking time, postoperative pain visual analogue score (VAS), postoperative pulmonary recruitment time, duration of postoperative hospital stay and hospitalization cost were analyzed. Results Postoperative awaking time (18.5±1.8 min vs. 28.9±4.2 min, P=0.000), postoperative VAS (1.6±0.6 vs. 3.5±7.4, P=0.000), duration of postoperative hospital stay (2.5±7.2 d vs. 4.3±1.1 d, P=0.000) and hospitalization cost (3.2±1.1 ten thousand RMB vs. 4.9±1.1 10 ten thousand RMB, P=0.000) in the tubeless group were better than those in the control group. There was no significant difference in surgical duration (51.7±6.5 min vs. 55.1±8.5 min), the lowest intraoperative SaO2 (98.5%±0.9% vs. 98.1%±0.8%), postoperative pulmonary recruitment time (33.9±12.2 d vs. 38.4±15.2 d, P>0.05) between the two groups. Conclusion Tubeless trans-subxiphoid thoracoscopic surgery is safe, feasible and advanced in anterior mediastinal tumor resection.