Development of the Life Gatekeeper suicide prevention training programme in China: a Delphi study.

Background: Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents. Aims: The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide. Methods: The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel. Results: Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme. Conclusions: This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.

Emerging roles of tRNA in cancer.

Transfer RNAs (tRNAs) play pivotal roles in the transmission of genetic information, and abnormality of tRNAs directly leads to translation disorders and causes diseases, including cancer. The complex modifications enable tRNA to execute its delicate biological function. Alteration of appropriate modifications may affect the stability of tRNA, impair its ability to carry amino acids, and disrupt the pairing between anticodons and codons. Studies confirmed that dysregulation of tRNA modifications plays an important role in carcinogenesis. Furthermore, when the stability of tRNA is impaired, tRNAs are cleaved into small tRNA fragments (tRFs) by specific RNases. Though tRFs have been found to play vital regulatory roles in tumorigenesis, its formation process is far from clear. Understanding improper tRNA modifications and abnormal formation of tRFs in cancer is conducive to uncovering the role of metabolic process of tRNA under pathological conditions, which may open up new avenues for cancer prevention and treatment.

A multicomponent digital intervention to promote help-seeking for mental health problems and suicide in sexual and gender diverse young adults: A randomized controlled trial.

BACKGROUND: LGBTQ+ community's higher susceptibility to worse mental health outcomes and more help-seeking barriers compared to the cis-heterosexual population. Despite the LGBTQ+ population facing higher mental health risks, there has been a dearth of research focusing on developing tailored interventions targeting them. This study aimed to assess the effectiveness of a digital multicomponent intervention in promoting help-seeking for mental health issues in LGBTQ+ young adults. METHODS AND FINDINGS: We recruited LGBTQ+ young adults aged between 18 and 29 who scored moderate or above on at least 1 dimension of the Depression Anxiety Stress Scale 21 and did not have help-seeking experiences in the past 12 months. Participants (n = 144) were stratified by gender assigned at birth (male/female) and randomly allocated (1:1 ratio) to the intervention or active control parallel condition by generating a random number table, so they were blinded to the intervention condition. All participants received online psychoeducational videos, online facilitator-led group discussions, and electronic brochures in December 2021 and January 2022, with the final follow-up in April 2022. The contents of the video, discussion, and brochure are help-seeking for the intervention group and general mental health knowledge for the control group. The primary outcomes were help-seeking intentions for emotional problems and suicidal ideation and attitudes toward seeking help from mental health professionals at the 1-month follow-up. The analysis was performed by including all participants based on their randomized group regardless of adherence to the protocol. A linear mixed model (LMM) was used for analysis. All models were adjusted for baseline scores. Chinese Clinical Trial Registry: ChiCTR2100053248. A total of 137 (95.1%) participants completed a 3-month follow-up, and 4 participants from the intervention condition and 3 from the control condition did not complete the final survey. Compared with the control group (n = 72), a significant improvement was found in help-seeking intentions for suicidal ideation in the intervention group (n = 70) at post-discussion (mean difference = 0.22, 95% CI [0.09, 0.36], p = 0.005), 1-month (mean difference = 0.19, 95% CI [0.06, 0.33], p = 0.018), and 3-month follow-ups (mean difference = 0.25, 95% CI [0.11, 0.38], p = 0.001). There was also a significant improvement in the intervention condition on the help-seeking intention for emotional problems at 1-month (mean difference = 0.17, 95% CI [0.05, 0.28], p = 0.013) and 3-month follow-ups (mean difference = 0.16, 95% CI [0.04, 0.27], p = 0.022) compared with the control group. Participants' depression and anxiety literacy and help-seeking encouragement related knowledge in intervention conditions showed significant improvements. There were no significant improvements in actual help-seeking behaviors, self-stigma toward seeking professional assistance, depression, and anxiety symptoms. No adverse events or side effects were observed. However, the follow-up time point was limited to 3 months which might not be long enough for drastic mindset and behavioral changes in help-seeking to occur. CONCLUSIONS: The current intervention was an effective approach in promoting help-seeking intentions, mental health literacy, and help-seeking encouragement-related knowledge. Its brief yet integrated intervention format could also be utilized in treating other imminent concerns confronted by LGBTQ+ young adults. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100053248.

Transfer RNA-derived small RNAs in tumor microenvironment.

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge.

Internet-based interventions to promote help-seeking for mental health in LGBTQ+ young adults: Protocol for a randomized controlled trial.

Background: Compared to its cis-heterosexual counterpart, the sexual and gender minority (SGM) population is disproportionately susceptible to mental health problems, including depression, anxiety, and minority stress. They are also facing unique help-seeking barriers when in need of support. Past research has shown promising results in using interventions to promote help-seeking intentions and attitudes of the cis-heterosexual population. However, there were no known help-seeking interventions targeting the SGM population. This protocol illustrates a study design to test the efficacy of a newly-developed internet-based program aimed to promote help-seeking for mental health in LGBTQ+ young adults. Methods: This study is a randomized controlled trial that aims to promote and improve the SGM young adults' help-seeking by integrating animated psychoeducational videos, group discussion, and the SGM youth help-seeking brochure. Primary outcomes, including help-seeking intentions and attitudes, will be measured at baseline, post-intervention, one-month post-intervention, and three-month post-intervention. The secondary outcomes, including help-seeking stigma, help-seeking literacy, mental health literacy, and help-seeking behaviors, will be measured at the same time points. Discussion: This is an internet-based, multi-dimensional, and integrative intervention tailored to the needs of the SGM population. It addresses an important gap in the current landscape of mental health promotion for the SGM population. The findings from this trial will provide new knowledge on promoting help-seeking among the SGM population, paving the road for future research that focuses on addressing mental health issues faced by the SGM population. Trial registration: Chictr.org.cn: ChiCTR2100053248.

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

Correction to: Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy.

After publication of the article [1], authors found out that Fig. 1 was inadvertently replaced.

Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy.

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.

Circular RNAs function as ceRNAs to regulate and control human cancer progression.

Circular RNAs (circRNAs) are connected at the 3' and 5' ends by exon or intron cyclization, forming a complete ring structure. circRNA is more stable and conservative than linear RNA and abounds in various organisms. In recent years, increasing numbers of reports have found that circRNA plays a major role in the biological functions of a network of competing endogenous RNA (ceRNA). circRNAs can compete together with microRNAs (miRNAs) to influence the stability of target RNAs or their translation, thus, regulating gene expression at the transcriptional level. circRNAs are involved in biological processes such as tumor cell proliferation, apoptosis, invasion, and migration as ceRNAs. circRNAs, therefore, represent promising candidates for clinical diagnosis and treatment. Here, we review the progress in studying the role of circRNAs as ceRNAs in tumors and highlight the participation of circRNAs in signal transduction pathways to regulate cellular functions.