Comprehensive analysis of consensus molecular subtypes for ovarian cancer from bulk to single-cell perspectives.

Molecular subtypes play a pivotal role in guiding preclinical and clinical risk assessment and treatment strategies in cancer. In this study, we extracted whole-tissue transcriptomic data from 1987 ovarian cancer patients spanning 26 independent Gene Expression Omnibus cohorts. A total of four consensus subtypes (C1-C4) were identified, notably, subtype C1 samples exhibited a poor prognosis and higher M2 macrophages infiltration, whereas subtype C2 samples demonstrated the best prognosis and higher CD4 resting T cells infiltration. Additionally, we characterized cancer- and stromal-specific gene expression profiles, and conducted an analysis of ligand-receptor interactions within these compartments. Based on cancer compartment, subtype-specific interactions as well as gene signatures for each molecular subtype were identified. Leveraging single-cell transcriptomic data, we delineated malignant epithelial cells with four molecular subtypes and observed an increase in C1 cell proportions from primary to relapse to metastasis stages, with a corresponding decrease in C2 cell proportions. Furthermore, we investigated subtype-specific interaction with T cells through integrated analysis of bulk and single-cell datasets. Finally, we developed a robust ten-gene risk model based on subtype gene signatures for prognostic evaluation in ovarian cancer, demonstrating its efficacy across independent datasets. In summary, this study systematically explored ovarian cancer molecular subtypes and provided a framework for other cancer types.

The effectiveness of positive psychological interventions for patients with cancer: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effectiveness of positive psychological interventions on quality of life, positive psychological outcomes and negative psychological outcomes in patients with cancer. BACKGROUND: Patients with cancer often suffer from various psychological problems and have a poor quality of life. Positive psychological interventions have been increasingly applied to patients with cancer, but the results of these studies have not been synthesized. DESIGN: A systematic review and meta-analysis of randomized controlled trials according to PRISMA. METHODS: Six English databases and four Chinese databases were searched from the inception to December 2022. Two reviewers independently assessed the risk of bias using the Cochrane Risk of Bias tool. RevMan was used for meta-analysis. RESULTS: Twenty-nine randomized controlled trials examined the effects of positive psychological interventions including meaning therapy, dignity therapy, positive psychotherapy, mindfulness- based intervention, life review, expressive writing intervention, acceptance and commitment psychotherapy, attention and interpretation therapy, compassion training and spiritual therapy on patients with cancer. Positive psychological interventions significantly improved the quality of life, enhanced positive psychological outcomes including well-being, meaning of life, self-esteem, optimism, resilience and self-efficacy and alleviated negative psychological outcomes including depression, anxiety and hopelessness. However, the heterogeneity of some outcomes was rather high, due to the wide diversity of the interventions included. CONCLUSION: Positive psychological interventions have potentially positive effects on improving quality of life, enhancing positive psychological outcomes and alleviating negative psychological outcomes in patients with cancer. However, due to the heterogeneity and the lack of follow-up studies, more high-quality studies are needed to confirm the results of our review and to clarify the long-term effects of positive psychological interventions. RELEVANCE TO CLINICAL PRACTICE: As feasible psychological interventions, healthcare professionals can consider applying appropriate positive psychological interventions according to the condition of cancer patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Sex differences orchestrated by androgens at single-cell resolution.

Sex differences in mammalian complex traits are prevalent and are intimately associated with androgens1-7. However, a molecular and cellular profile of sex differences and their modulation by androgens is still lacking. Here we constructed a high-dimensional single-cell transcriptomic atlas comprising over 2.3 million cells from 17 tissues in Mus musculus and explored the effects of sex and androgens on the molecular programs and cellular populations. In particular, we found that sex-biased immune gene expression and immune cell populations, such as group 2 innate lymphoid cells, were modulated by androgens. Integration with the UK Biobank dataset revealed potential cellular targets and risk gene enrichment in antigen presentation for sex-biased diseases. This study lays the groundwork for understanding the sex differences orchestrated by androgens and provides important evidence for targeting the androgen pathway as a broad therapeutic strategy for sex-biased diseases.

Effects of meaning therapy on spirituality, psychological health, and quality of life in patients with cancer: A systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to systematically review studies of meaning therapy on patients with cancer and to evaluate its effectiveness on spiritual outcomes, psychological outcomes, and quality of life (QOL). Methods: A comprehensive literature search were performed in five international databases (PubMed, Embase, Web of Science, The Cochrane Library, and CINAHL) and four Chinese databases (CNKI, Wanfang Data, VIP, and CBM) from the inception to August 2023. The methodological quality of each included studies was evaluated by using the revised Cochrane risk-of-bias tool for randomized trials. The random-effects model or fixed-effects model was utilized for effect size analysis, and the standardized mean difference (SMD) or mean difference (MD) along with its corresponding 95% confidence interval (CI) was computed. Meta-analysis was conducted by using the RevMan software 5.4.1. Results: Eight randomized controlled trials with 1251 participants were included in this review. Meta-analyses revealed that meaning therapy can significantly improve the spiritual outcomes including meaning in life (SMD = -0.48; 95% CI = -0.89 to -0.07; P = 0.02), hopelessness (SMD = -0.30; 95% CI = -0.51 to -0.09; P = 0.005), self-esteem (MD = -2.74; 95% CI = -4.17 to -1.32; P = 0.0002) and spiritual well-being (MD = -3.32; 95% CI = -5.63 to -1.01; P = 0.005), psychological outcomes including anxiety (MD = -0.66; 95% CI = -1.30 to -0.01; P = 0.05), depression (SMD = -0.37; 95% CI = -0.55 to -0.20; P < 0.0001), psychological distress (SMD = -0.35; 95% CI = -0.70 to -0.01; P = 0.04) and desire for hastened death (MD = -0.76; 95% CI = -1.47 to -0.05; P = 0.04), and QOL (SMD = -0.29; 95% CI = -0.50 to -0.09; P = 0.006) in patients with cancer. Conclusions: Meaning therapy has positive effects on improving spirituality, psychological health, and QOL of patients with cancer. More high-quality randomized controlled trials with larger sample sizes are warranted to confirm the results of our review and to clarify the long-term effects of meaning therapy in the future. Systematic review registration: PROSPERO (No. CRD42021278286).

The effects of hospice care education on first-year undergraduate nursing students in mainland China: A mixed-methods study.

BACKGROUND: With the rising number of people with end-stage chronic diseases, the demand for hospice care has increased dramatically. As the future health professionals for the implementation of hospice care, undergraduate nursing students in mainland China still lack knowledge and skills of hospice care, thus hospice care education plays a vital role in its development. OBJECTIVES: To understand the effects of hospice care education on nursing students' death attitudes, end-of-life attitudes, humanistic care qualities, and their learning experiences. DESIGN: This study used a mixed-methods design. SETTING: A University of Chinese Medicine in mainland China. PARTICIPANTS: The first-year undergraduate nursing students (n = 65). METHODS: A mixed-methods study was conducted to evaluate the impact of a hospice care course from March to June 2021. The quantitative part included a quasi-experimental study designed with pre- and post-intervention measurements and the qualitative part included a descriptive qualitative study with semi-structured individual interviews. RESULTS: The quantitative data revealed that after the course, nursing students experienced improvements in their death attitudes, end-of-life attitudes, and humanistic care qualities. Two categories were identified from the qualitative data. The category of "Gain from learning" included 4 themes (Confronting death and thinking about life; Understanding and agreeing with the idea of hospice care; Perceiving the humanistic spirit of medicine; Enhancing of the nursing discipline cognition and professional identity) and the category of "Course feedback" included 2 themes (Expressing recognition for the course arrangement; Making suggestions on the course optimization). CONCLUSIONS: Hospice care education had a positive influence on nursing students. Students expressed satisfaction with the course arrangement. However, future hospice care courses should further optimize the curriculum designs by increasing the discussion of death-related topics, sharing more real clinical cases, recruiting students from different majors, and providing clinical practice, to provide high-quality nursing education for the development of hospice care.

Comprehensive analyses of brain cell communications based on multiple scRNA-seq and snRNA-seq datasets for revealing novel mechanism in neurodegenerative diseases.

AIMS: Complex cellular communications between glial cells and neurons are critical for brain normal function and disorders, and single-cell level RNA-sequencing datasets display more advantages for analyzing cell communications. Therefore, it is necessary to systematically explore brain cell communications when considering factors such as sex and brain region. METHODS: We extracted a total of 1,039,459 cells derived from 28 brain single-cell RNA-sequencing (scRNA-seq) or single-nucleus RNA-sequencing (snRNA-seq) datasets from the GEO database, including 12 human and 16 mouse datasets. These datasets were further divided into 71 new sub-datasets when considering disease, sex, and region conditions. In the meanwhile, we integrated four methods to evaluate ligand-receptor interaction score among six major brain cell types (microglia, neuron, astrocyte, oligodendrocyte, OPC, and endothelial cell). RESULTS: For Alzheimer's disease (AD), disease-specific ligand-receptor pairs when compared with normal sub-datasets, such as SEMA4A-NRP1, were identified. Furthermore, we explored the sex- and region-specific cell communications and identified that WNT5A-ROR1 among microglia cells displayed close communications in male, and SPP1-ITGAV displayed close communications in the meninges region from microglia to neurons. Furthermore, based on the AD-specific cell communications, we constructed a model for AD early prediction and confirmed the predictive performance using multiple independent datasets. Finally, we developed an online platform for researchers to explore brain condition-specific cell communications. CONCLUSION: This research provided a comprehensive study to explore brain cell communications, which could reveal novel biological mechanisms involved in normal brain function and neurodegenerative diseases such as AD.

Bilateral Interactions in the Mouse Dorsal Inferior Colliculus Enhance the Ipsilateral Neuronal Responses and Binaural Hearing.

The inferior colliculus (IC) is a critical centre for the binaural processing of auditory information. However, previous studies have mainly focused on the central nucleus of the inferior colliculus (ICC), and less is known about the dorsal nucleus of the inferior colliculus (ICD). Here, we first examined the characteristics of the neuronal responses in the mouse ICD and compared them with those in the inferior colliculus under binaural and monaural conditions using in vivo loose-patch recordings. ICD neurons exhibited stronger responses to ipsilateral sound stimulation and better binaural summation than those of ICC neurons, which indicated a role for the ICD in binaural hearing integration. According to the abundant interactions between bilateral ICDs detected using retrograde virus tracing, we further studied the effect of unilateral ICD silencing on the contralateral ICD. After lidocaine was applied, the responses of some ICD neurons (13/26), especially those to ipsilateral auditory stimuli, decreased. Using whole-cell recording and optogenetic methods, we investigated the underlying neuronal circuits and synaptic mechanisms of binaural auditory information processing in the ICD. The unilateral ICD provides both excitatory and inhibitory projections to the opposite ICD, and the advantaged excitatory inputs may be responsible for the enhanced ipsilateral responses and binaural summation of ICD neurons. Based on these results, the contralateral ICD might modulate the ipsilateral responses of the neurons and binaural hearing.

Synaptic excitation underlies processing of paired stimulation in the mouse inferior colliculus.

The inferior colliculus (IC) receives inputs from the ascending auditory pathway and helps localize the sound source by shaping neurons' responses. However, the contributions of excitatory or inhibitory synaptic inputs evoked by paired binaural stimuli with different inter-stimulus intervals to auditory responses of IC neurons remain unclear. Here, we firstly investigated the IC neuronal response to the paired binaural stimuli with different inter-stimulus intervals using in vivo loose-patch recordings in anesthetized C57BL/6 mice. It was found that the total acoustic evoked spikes remained unchanged under microsecond interval conditions, but persistent suppression would be observed when the time intervals were extended. We further studied the paired binaural stimuli evoked excitatory/inhibitory inputs using in vivo whole-cell voltage-clamp techniques and blockage of the auditory nerve. The amplitudes of the contralateral excitatory inputs could be suppressed, unaffected or facilitated as the interaural delay varied. In contrast, contralateral inhibitory inputs and ipsilateral synaptic inputs remained almost unchanged. Most IC neurons exhibited the suppression of contralateral excitatory inputs over the interval range of dozens of milliseconds. The facilitative effect was generated by the summation of contralateral and ipsilateral excitation. Suppression and facilitation were completely abolished when ipsilateral auditory nerve was blocked pharmacologically, indicating that these effects were exerted by ipsilateral stimulation. These results suggested that the IC would inherit the binaural inputs integrated at the brainstem as well as within the IC and synaptic excitations, modulated by ipsilateral stimulation, underlie the binaural acoustic response.