Integration of single-cell RNA-seq and bulk RNA-seq to construct liver hepatocellular carcinoma stem cell signatures to explore their impact on patient prognosis and treatment.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a prevalent form of primary liver cancer. Research has demonstrated the contribution of tumor stem cells in facilitating tumor recurrence, metastasis, and treatment resistance. Despite this, there remains a lack of established cancer stem cells (CSCs)-associated genes signatures for effectively predicting the prognosis and guiding the treatment strategies for patients diagnosed with LIHC. METHODS: The single-cell RNA sequencing (scRNA-seq) and bulk RNA transcriptome data were obtained based on public datasets and computerized firstly using CytoTRACE package and One Class Linear Regression (OCLR) algorithm to evaluate stemness level, respectively. Then, we explored the association of stemness indicators (CytoTRACE score and stemness index, mRNAsi) with survival outcomes and clinical characteristics by combining clinical information and survival analyses. Subsequently, weighted co-expression network analysis (WGCNA) and Cox were applied to assess mRNAsi-related genes in bulk LIHC data and construct a prognostic model for LIHC patients. Single-sample gene-set enrichment analysis (ssGSEA), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) analysis were employed for immune infiltration assessment. Finally, the potential immunotherapeutic response was predicted by the Tumor Immune Dysfunction and Exclusion (TIDE), and the tumor mutation burden (TMB). Additionally, pRRophetic package was applied to evaluate the sensitivity of high and low-risk groups to common chemotherapeutic drugs. RESULTS: A total of four genes (including STIP1, H2AFZ, BRIX1, and TUBB) associated with stemness score (CytoTRACE score and mRNAsi) were identified and constructed a risk model that could predict prognosis in LIHC patients. It was observed that high stemness cells occurred predominantly in the late stages of LIHC and that poor overall survival in LIHC patients was also associated with high mRNAsi scores. In addition, pathway analysis confirmed the biological uniqueness of the two risk groups. Personalized treatment predictions suggest that patients with a low risk benefited more from immunotherapy, while those with a high risk group may be conducive to chemotherapeutic drugs. CONCLUSION: The current study developed a novel prognostic risk signature with genes related to CSCs, which provides novel ideas for the diagnosis, prognosis and treatment of LIHC.

Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics.

Despite the challenges posed by drug resistance and side effects, chemotherapy remains a pivotal strategy in cancer treatment. A key issue in this context is macroautophagy (commonly known as autophagy), a dysregulated cell death mechanism often observed during chemotherapy. Autophagy plays a cytoprotective role by maintaining cellular homeostasis and recycling organelles, and emerging evidence points to its significant role in promoting cancer progression. Cisplatin, a DNA-intercalating agent known for inducing cell death and cell cycle arrest, often encounters resistance in chemotherapy treatments. Recent studies have shown that autophagy can contribute to cisplatin resistance or insensitivity in tumor cells through various mechanisms. This resistance can be mediated by protective autophagy, which suppresses apoptosis. Additionally, autophagy-related changes in tumor cell metastasis, particularly the induction of Epithelial-Mesenchymal Transition (EMT), can also lead to cisplatin resistance. Nevertheless, pharmacological strategies targeting the regulation of autophagy and apoptosis offer promising avenues to enhance cisplatin sensitivity in cancer therapy. Notably, numerous non-coding RNAs have been identified as regulators of autophagy in the context of cisplatin chemotherapy. Thus, therapeutic targeting of autophagy or its associated pathways holds potential for restoring cisplatin sensitivity, highlighting an important direction for future clinical research.

Study protocol for a single-centre randomised controlled trial to investigate the effect of lung recruitment in paediatric patients after cardiac surgery.

INTRODUCTION: A number of published studies have revealed that lung recruitment can improve oxygenation, shorten the duration of mechanical ventilation (MV) and decrease mortality in adults with acute hypoxaemic respiratory failure, especially patients with acute respiratory distress syndrome. However, few articles have assessed lung recruitment in paediatric patients, especially after cardiac surgery. This clinical trial aimed to determine whether lung recruitment can reduce the duration of MV in paediatric patients with hypoxaemic respiratory failure after cardiac surgery. METHOD AND ANALYSIS: In this trial, we will randomly assign 234 paediatric patients (aged 28 days to 14 years) within 72 hours after cardiac surgery with an arterial oxygen tension (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2/FiO2) of <300 to either a lung recruitment group or a conventional group. The primary endpoint will be the duration of MV. The secondary endpoints will be ventilator-free days, PaO2/FiO2, respiratory system compliance, duration of non-invasive ventilation, reintubation rate, length of intensive care unit stay, length of hospital stay, occurrence of serious adverse events (barotrauma, persistent hypotension and arrhythmia), postoperative pulmonary complications. ETHICS AND DISSEMINATION: The ethics committee of West China Hospital of Sichuan University granted ethics approval for this study (20 August 2019). The results will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900025990.

The use of clozapine is protective for low bone mineral density induced by prolactin-raising antipsychotics in inpatients with schizophrenia.

Low bone mineral density (BMD) is common among patients with schizophrenia; however, the pathogenesis is still unclear. Different types of antipsychotics may have different effects on BMD in inpatients with schizophrenia. INTRODUCTION: This retrospective study aimed to evaluate the effects of prolactin-raising (PR) antipsychotics vs. clozapine combined with PR antipsychotics on BMD of patients with schizophrenia and analyzed clinically related factors that may affect BMD. METHODS: A total of 125 participants (males/females = 62/63) were included. Patients were treated with PR antipsychotics vs. clozapine combined with PR antipsychotics. They were similar in demographic and clinical characteristics. BMD was examined in their lumbar spine and proximal femur by a dual-energy X-ray (DEXA) absorption measurement device. Laboratory variables (including blood levels of prolactin, estradiol, testosterone, and cortisol) were collected. RESULTS: Among 125 inpatients with schizophrenia, the prevalence of osteoporosis and low BMD (including osteoporosis and osteopenia) was 26.4% and 64%. The average BMD T value in patients receiving clozapine combined with PR antipsychotics was significantly higher than in patients receiving PR antipsychotics (p < 0.05). Patients in the clozapine combined with PR antipsychotic group had higher testosterone levels than the PR antipsychotic group (Z = - 2.77, p = 0.006). Linear logistic regression analysis indicated that clozapine combined with PR antipsychotic treatment (p < 0.05) and higher estradiol level (p < 0.05) may be significantly associated with higher BMD. CONCLUSIONS: Our results suggest that the use of clozapine may be a protective factor for low BMD induced by PR antipsychotics in inpatients with schizophrenia. The possible mechanism is that clozapine may protect BMD by regulating estrogen and testosterone levels, but the mechanism by which clozapine regulates these two sex hormones needs further investigation.

Synthesis of gelatin-stabilized gold nanoparticles and assembly of carboxylic single-walled carbon nanotubes/Au composites for cytosensing and drug uptake.

Gelatin-stabilized gold nanoparticles (AuNPs-gelatin) with hydrophilic and biocompatible were prepared with a simple and "green" route by reducing in situ tetrachloroauric acid in gelatin. The nanoparticles showed the excellent colloidal stability. UV-vis spectra, transmission electron microscopy (TEM), and atomic force microscopy revealed the formation of well-dispersed AuNPs with different sizes. By combination of the biocompatibility of AuNPs and excellent conductivity of carboxylic single-walled carbon nanotubes (c-SWNTs), a novel nanocomposite was designed for the immobilization and cytosensing of HL-60 cells at electrodes. The immobilized cells showed sensitive voltammetric response, good activity, and increased electron-transfer resistance. It can be used as a highly sensitive impedance sensor for HL-60 cells ranging from 1 x 10(4) to 1 x 10(7) cell mL(-1) with a limit of detection of 5 x 10(3) cell mL(-1). Moreover, the nanocomposite could effectively facilitate the interaction of adriamycin (ADR) with HL-60 cells and remarkably enhance the permeation and drug uptake of anticancer agents in the cancer cells, which could readily lead to the induction of the cell death of leukemia cells.

Analysis of nonadherent apoptotic cells by a quantum dots probe in a microfluidic device for drug screening.

This technical note describes a facile technique to screen some anticancer drugs and evaluate their effects on nonadhesive leukemic cells in an easily fabricated microfluidic device by utilizing the Annexin V conjugated quantum dots as apoptosis detection probes. The cell immobilizing structures and gradient-generating channels were integrated within the device which was fabricated in one-single step. The nonadhesive leukemic HL-60 cells can be felicitously immobilized and cultured on the dam structures at a proper lateral pressure. We then delivered Annexin V functionalized quantum dots which can readily bind to the outer membrane of apoptotic cells and distinguish the apoptosis from unaffected cells with single cell level resolution. The diffusion time of quantum dots reduced to 5 min before imaging. The capabilities of evaluating drug effect on HL-60 cell line have been shown in both population way and individual cell level. The technique presented herein can bridge the gap between the quantum dots based in vitro cell imaging and the analysis of individual apoptotic cell in a microfluidic system, allows an easy operating protocol to screen some clinically available anticancer drugs.

Preparation and bioapplication of high-quality, water-soluble, biocompatible, and near-infrared-emitting CdSeTe alloyed quantum dots.

A facile method is developed for the preparation of high-quality, water-soluble, and near-infrared (NIR)-emitting CdSeTe alloyed quantum dots (AQdots) with L-cysteine as the capping agent. By changing the size and the composition of AQdots the photoluminescent quantum yield (QY) can reach as high as 53% and the emission color can be tuned between visible and NIR regions (580-814 nm). Furthermore, the prepared NIR-emitting AQdots have been successfully applied for HL-60 cell imaging and glucose and cholesterol assay, which demonstrates the great potential of the AQdots for biological applications.

Fabrication of a novel impedance cell sensor based on the polystyrene/polyaniline/Au nanocomposite.

Gold nanoparticles (AuNPs) were assembled on the surface of polystyrene (PS) and polyaniline (PANI) core-shell nanocomposite (PS@PANI) for the immobilization of HL-60 leukemia cells to fabricate a cell electrochemical sensor. The immobilized cells exhibited irreversible voltammetric response and increased the electron transfer resistance with a good correlation to the logarithmic value of concentration ranging from 1.6 x 10(3) to 1.6 x 10(8) cells mL(-1) with a limit of detection of 7.3 x 10(2) cells mL(-1) at 10 sigma. This biosensor was simple, low cost and disposable, which implied that the PS@PANI/Au composites can regard as the potential applications for clinical applications.