Carrying both the heterozygous Myh6-R453C and Tnnt2-R92W mutations aggravate the hypertrophic cardiomyopathy phenotype in mice.

Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle that is dominated by variations in eight genes encoding sarcomere proteins. Although there are clinical or basic research reports that carrying double mutations can lead to more severe HCM phenotypes, there are also research reports that after reanalyzing the reported mutations, the severity of clinical symptoms in patients with double mutations did not significantly increase compared to patients with only one mutation. To determine whether double pathogenic mutations can aggravate the phenotype of hypertrophic cardiomyopathy in mice, we constructed mice carrying single pathogenic heterozygous mutation Myh6-R453C or Tnnt2-R92W and mice carrying both pathogenic heterozygous mutations. Our results showed that mice with double heterozygous mutations exhibited significant hypertrophic cardiomyopathy phenotypes at 4 weeks of age, and the degree of hypertrophy was significantly higher than that of single heterozygous mutant mice of the same age. Our study suggests that carrying the two pathogenic heterozygous mutations simultaneously can aggravate the phenotype of HCM in mice, which provides experimental evidence for the genotype-phenotype relationship of double pathogenic mutations and provides reference significance for clinical risk stratification of HCM patients.

Analysis of long noncoding RNAs expression profiles in the human cardiac fibroblasts with cardiac fibrosis.

Cardiac fibrosis is a common pathological feature of cardiac remodelling process with disordered expression of multiple genes and eventually lead to heart failure. Emerging evidence suggests that long noncoding RNAs (lncRNAs) have emerged as critical regulators of various biological processes. However, the exact mechanisms of lncRNAs as mediators in cardiac fibrosis have not been fully elucidated. This study aimed to profile the lncRNA expression pattern in human cardiac fibroblasts (HCFs) with cardiac fibrosis. We treated HCFs with transforming growth factor-ß (TGF-ß) to induce their activation. Then, strand-specific RNA-seq was performed to profile and classify lncRNAs; and perform functional analysis in HCFs. We study the transformation of HCFs with molecular and cell biology methods. Among all identified lncRNA candidates, 176 and 526 lncRNAs were upregulated and downregulated respectively in TGF-ß-stimulated HCFs compared with controls. Functional analyses revealed that the target genes of differentially expressed lncRNAs were mainly related to focal adhesion, metabolic pathways, Hippo signaling pathway, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy. As a representative, novel lncRNAs NONHSAG005537 and NONHSAG017620 inhibited the proliferation, migration, invasion, and transformation of HCFs induced by TGF-ß. Collectively, our study established the expression signature of lncRNAs in cardiac fibrosis and demonstrated the cardioprotective role of NONHSAG005537 and NONHSAG017620 in cardiac fibrosis, providing a promising target for anti-fibrotic therapy.

Temporal Dynamics of Public Emotions During the COVID-19 Pandemic at the Epicenter of the Outbreak: Sentiment Analysis of Weibo Posts From Wuhan.

BACKGROUND: The ongoing COVID-19 pandemic has led to an increase in anxiety, depression, posttraumatic stress disorder, and psychological stress experienced by the general public in various degrees worldwide. However, effective, tailored mental health services and interventions cannot be achieved until we understand the patterns of mental health issues emerging after a public health crisis, especially in the context of the rapid transmission of COVID-19. Understanding the public's emotions and needs and their distribution attributes are therefore critical for creating appropriate public policies and eventually responding to the health crisis effectively, efficiently, and equitably. OBJECTIVE: This study aims to detect the temporal patterns in emotional fluctuation, significant events during the COVID-19 pandemic that affected emotional changes and variations, and hourly variations of emotions within a single day by analyzing data from the Chinese social media platform Weibo. METHODS: Based on a longitudinal dataset of 816,556 posts published by 27,912 Weibo users in Wuhan, China, from December 31, 2019, to April 31, 2020, we processed general sentiment inclination rating and the type of sentiments of Weibo posts by using pandas and SnowNLP Python libraries. We also grouped the publication times into 5 time groups to measure changes in netizens' sentiments during different periods in a single day. RESULTS: Overall, negative emotions such as surprise, fear, and anger were the most salient emotions detected on Weibo. These emotions were triggered by certain milestone events such as the confirmation of human-to-human transmission of COVID-19. Emotions varied within a day. Although all emotions were more prevalent in the afternoon and night, fear and anger were more dominant in the morning and afternoon, whereas depression was more salient during the night. CONCLUSIONS: Various milestone events during the COVID-19 pandemic were the primary events that ignited netizens' emotions. In addition, Weibo users' emotions varied within a day. Our findings provide insights into providing better-tailored mental health services and interventions.

How investment in public health has impacted the prevalence of tuberculosis in China: A study of provincial variations between 2005 and 2015.

How do public investments in public health actually impact health outcomes? This question has not been investigated enough, especially regarding infectious diseases. This study investigates the correlations between public health expenditure and the incidence of tuberculosis in China using a provincial panel dataset. The analysis focuses on the correlations between public health expenditure and tuberculosis incidence, using the fixed effects models and Two Stage Least Squares (2SLS) method. Overall, a 10% increase of public health expenditure per capita is associated with a 0.0019% decrease of tuberculosis incidence. A series of robustness tests show that the correlation between public health expenditure and TB incidence is valid. Future research should focus more on the performance of public health, particularly infectious diseases like tuberculosis, and provide references for health policymakers.

Association between disaster experience and quality of life: the mediating role of disaster risk perception.

PURPOSE: Disasters may impair people's quality of life (QoL) indirectly through disaster risk perception. We intended to address this point by analyzing the correlation between disaster experience and QoL with a test of the mediating effects of risk perception at the example of earthquake. METHODS: We employed the 2013 Taiwan Social Change Survey data as the data source (N = 1481). Unadjusted ordinal logistic regression models examined the correlation of disaster experience with QoL and earthquake risk perception at first. Another set of ordinal regressions were conducted to explore the mediating effect of earthquake risk perception between earthquake experience and QoL. RESULTS: Earthquake experience had negative impact on QoL measured by self-reported happiness, general health status, and life satisfaction. People who had earthquake experience perceived higher earthquake risk compared to those who had never experienced an earthquake. Risk perception measured by perceived likelihood of future earthquake as a mediating factor for the impact of earthquake experience on QoL from the dimensions of both self-reported happiness and life satisfaction was confirmed. CONCLUSIONS: Findings are consistent with existing reports about the association between disaster experience and QoL. Research using multi-dimensional measures of disaster risk perception and QoL is needed to inform post-disaster recovery programs.

Long-Term Health Consequences Among Wenchuan Earthquake Adult Survivors: Implications of a Framework for Postearthquake Reconstruction.

The objective of this study was to examine the longitudinal health consequences of the Wenchuan earthquake. Based on descriptive analyses of national-level data and multivariate analyses on a six-wave repeated cross-sectional survey, the findings suggested that after 8 years health risks remained high among earthquake-affected survivors; however, a process of recovery existed. To conceptualize these findings, in this study, we proposed a three-stage recovery model in which the postdisaster health status was divided into three stages: acute, stagnant, and adaptive. At each stage, the health risk varied, and over time, associations between health outcomes and protective factors varied. The three-stage recovery model identified the trends of long-term health consequences among adult earthquake survivors and provided guidance for postdisaster reconstruction in China on the basis of protective factors analyses.

PPARγ is regulated by miR-27b-3p negatively and plays an important role in porcine oocyte maturation.

To elucidate the key miRNAs and the signalling pathways that are involved in porcine oocyte maturation, we performed a deep sequencing analysis of the miRNAs of pig germinal vesicle (GV) oocytes and metaphase II (MII) oocytes. Seven differentially expressed (DE) miRNAs were identified and the expression levels of miR-21 and miR-27b-3p were further confirmed by QPCR analysis. The target genes of 7 DE miRNAs were predicted and subjected to pathway analysis. Interestingly, fatty acid metabolism and fatty acid biosynthesis were the top two significantly enriched molecular functions during oocyte maturation. Heat map, which was built with 7 DE miRNAs and the enriched the molecular functions, revealed that miR-21, miR-27b-3p, miR-10a-5p and miR-10b-5p were involved in fatty acid metabolism. In particular, the regulatory role of miR-27b-3p on peroxisome proliferator-activated receptor-γ (PPARγ) was confirmed by their inversed expression patterns in GV and MII oocytes and luciferase report assays. In addition, we observed that PPARγ agonist (rosiglitazone) treatment significantly enhanced porcine oocyte maturation rate and early embryo developmental competent. Taken together, our results demonstrated that miR-27b and its target, PPARγ, play the vital roles in pig oocyte maturation through regulating the fatty acid metabolism. These data increased our understanding of the regulatory gene networks in porcine oocyte maturation and development.

Florfenicol induces more severe hemotoxicity and immunotoxicity than equal doses of chloramphenicol and thiamphenicol in Kunming mice.

Amphenicols are effective, broad-spectrum antibiotics that function by inhibiting the peptidyl transferase activity of bacteria, while the drugs can also inhibit mitochondrial protein synthesis in eukaryotes through the same mechanism, which leads to multi-organ toxicity. Some side effects of each drug have been studied, while differences in the severity of the hemotoxicities and immunotoxicities of amphenicols have not been reported. Thus, it is important to identify, evaluate, and compare the potential hemotoxicities and immunotoxicities to guide their proper use in humans and animals, which will guarantee food safety and animal welfare. Ovalbumin-immunized Kunming mice were gavaged daily with amphenicols for seven days. Blood samples were collected for hematology analysis, and measuring anti-ovalbumin antibody levels and serum intereukin-2 concentrations. The bone marrow, spleen and thymus were collected for histopathology and apoptosis analyzes. Bone marrow nucleated cells (BMNCs) and splenocytes were harvested to determine their cell cycle stages and to analyze lymphocyte proliferation. The results demonstrated that amphenicols, especially florfenicol (FLO), induced cell cycle arrest and apoptosis of hematopoietic cells, and it changed the bone marrow hematopoietic microenvironment by decreasing the number of peripheral blood cells. Moreover, amphenicols, especially FLO, induced hypoplasia and atrophy of the spleen and thymus, induced cell cycle arrest, as well as splenocyte apoptosis, and decreased the proliferation and viability of lymphocytes and the humoral and cellular immunity of the treated mice. These results suggest that amphenicols induce hemotoxicity and immunotoxicity to some extent, and that FLO induces more severe toxicity than equal doses of chloramphenicol (CAP) and thiamphenicol (TAP).

Injectable Living Probiotic Dressing Built by Droplet-Based Microfluidics and Photo-Cross-Linking to Prevent Pathogenic Infection and Promote Wound Repair.

The treatment of infected wounds faces great challenges due to the emergence of antibiotic resistance and the lack of persistence in drug release. Here, a living probiotic dressing is constructed by integrating droplet-shearing and photo-cross-linking. Saccharomyces boulardii (S. boulardii), the only probiotic used clinically, is encapsulated and attached to a wound under light irradiation. A double-layer hydrogel provides a protective barrier for cell growth and proliferation while preventing the escape of S. boulardii. The living probiotic dressing shows superior biosafety with fibroblast cells. Strikingly, in vitro and in vivo experiments indicate that the living probiotic dressing not only inhibits bacterial survival and colonization, but also alleviates inflammation and accelerates wound closure. More significantly, the living probiotic dressing promotes collagen deposition and neovascularization, which accelerates wound healing. This work can provide new ideas for clinical wound treatment and widen the application of probiotics in tissue engineering.

Traditional bullying, cyberbullying, and quality of life among adolescents in 35 countries: Do cultural values matter?

RATIONALE: Substantial evidence indicates that involvement in school bullying has been linked to lower quality of life (QoL). Yet there is little information elucidating the link between bullying involvement and QoL in different cultures. OBJECTIVE: This study investigated the associations between different types of bullying involvement and QoL among adolescents. The moderating roles of cultural values in the relationship between bullying involvement and QoL were examined. METHODS: This study included representative samples from 35 countries (N = 184,017) using data from the 2017/2018 Health Behavior in School-Aged Children (HBSC) survey and the new 2023 World Cultural Map Scores from the World Values Survey Wave 7 (2017/2021). Multilevel mixed-effects analysis was employed to examine individual-level and country-level effects simultaneously. RESULTS: All types of bullying involvement were associated with lower QoL, with being a victim having the lowest QoL. Adolescents in societies that prioritize higher self-expression values exhibited a reduced propensity to engage in school bullying. In countries with higher self-expression values, there was a more pronounced negative association between bullying involvement and QoL. Traditional/Secular-rational values had no significant and consistent moderating effect on the association between bullying involvement and QoL. Those results were quite similar for both traditional bullying and cyberbullying. CONCLUSION: These findings imply that cultural values are closely intertwined with adolescent bullying and quality of life. Therefore, prevention and intervention programs should pay more attention to addressing bullying and promoting the QoL of adolescents according to various cultural values.

Trust in Government, Perceived Integrity and Food Safety Protective Behavior: The Mediating Role of Risk Perception.

Objective: This study examined the correlations between trust in government and the public's protective behaviors regarding food safety, focusing on the mediating role of risk perception. Methods: The 2013 (1,432 samples) and 2019 (1,276 samples) Taiwan Social Change Survey data were analyzed using ordinary least squares regression models. The bootstrap method was used to examine the mediating effect of risk perception. Results: Perceived integrity of government regarding food safety issues influences all four types of food protective behaviors directly and indirectly via risk perceptions. The four protective behaviors were "not eating that food," "preparing food kit," "preferring organic food," and "overall behaviors." Trust in government directly influences part of the protective food behaviors, while no mediating effects of risk perception were found. Conclusion: The results of this study will deepen our understanding of food consumption behavior, identify key factors that influence public food protective behaviors, and inform food safety management to implement strategies necessary to improve food consumption.

COVID-19 impacts and adolescent suicide: The mediating roles of child abuse and mental health conditions.

BACKGROUND: Considerable research has established the harmful impacts of the COVID-19 pandemic on children's and adolescents' health and well-being. However, the literature has been constrained by studies using less representative samples, hindering the generalization of the findings. OBJECTIVE: This study aimed to investigate the associations of employment disruption and school closures during the pandemic with suicidal ideation and behavior in children and adolescents-and to consider the potential mediating effects of child psychological and physical abuse and subsequent mental health conditions. PARTICIPANTS AND SETTING: This study used the Adolescent Behaviors and Experiences data (n = 4692) - a nationally representative survey administered by the CDC of the United States from January to June 2021. METHODS: Logistic regression models were conducted to investigate the associations. A series of multiple mediation models were performed. RESULTS: School closures directly reduced child psychological and physical abuse and suicidal ideation and behavior. Employment disruption did not directly predict suicidal ideation and behavior but primarily through child abuse. Mental health's mediation role was significant in the associations between child psychological abuse and suicidal ideation and behavior, but no evidence suggested the same mediating pattern for the physical abuse-suicidal ideation and behavior relationship. Within the covariates, sexual orientation was the most consistent and highest risk factor. CONCLUSIONS: This study contributes to current knowledge on disaster impact, child abuse, and suicidal ideation and behavior, and it can also provide policy and intervention awareness for social workers.

Sequential hydrogenation of nitroaromatics to alicyclic amines via highly-dispersed Ru-Pd nanoparticles anchored on air-exfoliated C3N4 nanosheets.

Developing efficient and green catalytic systems is highly desired in the syntheses of alicyclic amines via hydrogenation of nitroaromatics. Herein, we developed Ru-Pd dual active site catalysts in which Ru and Pd species were anchored and highly dispersed on air-exfoliated carbon nitride (Ru-Pd/C3N4-air). As-prepared catalysts were employed in the hydrogenation of nitrobenzene (NB) to cyclohexylamine (CHA). Compared with single Ru or Pd based catalysts, Ru-Pd dual active site catalysts obtained a higher CHA production rate of 26.7 mol CHA mol-1 Ru·Pd h-1 at 80 °C and 3 MPa H2. The activation energy for the hydrogenation of the nitro group and benzene ring was calculated as 26.26 kJ mol-1 and 66.30 kJ mol-1, respectively. Intrinsic kinetic studies demonstrated that Pd was the dominant metal for hydrogenation of nitro group, while Ru was dominant for benzene ring. Thereinto, the corresponding non-dominant metals enhanced activation and dissociation of H2, thereby improving catalytic activity significantly. This excellent performance of Ru-Pd catalysts could be attributed to highly dispersed Ru-N x and Pd-N x at a nanoscale distance, which was conducive to metal-assisted hydrogenation. Stability investigation showed that the performance of Ru-Pd catalysts could be essentially maintained at a high level. Additionally, the substrate scope could be successfully extended to hydrogenation of other nitroaromatics with different substituents.

Antifungal bio-coating of endotracheal tube built by overexpressing the MCP1 gene of Saccharomyces boulardii and employing hydrogel as a "house" to antagonize Candida albicans.

BACKGROUND: For some ICU patients, an artificial airway must be established with an endotracheal tube, but Candida albicans can easily adhere to the tube surface and form a biofilm, leading to potentially life threatening fungal infections. Therefore, it is urgent to prevent and reduce C. albicans infections introduced by the endotracheal tube. However, there are few antifungal drugs effective against C. albicans, and each of these drugs may have adverse effects on human cells. Saccharomyces boulardii is regarded as an alternative strategy to inhibit the adhesion of C. albicans, but it is affected by environmental stress. We hypothesized that it is feasible to strengthen the antagonistic ability of S. boulardii via encapsulating and genetically modification. METHODS: In this study, a bioactive material carrying the overexpressed MCP1 gene of Saccharomyces boulardii was constructed based on one-step photo-crosslinking. This material achieved spatial growth control of S. boulardii by encapsulating each S. boulardii cell within a hydrogel pore. The bioactive material was coated on an endotracheal tube and tested for its ability to inhibit the adhesion of C. albicans. Additionally, the material's antagonistic activity towards C. albicans was evaluated by detecting intracellular Adenosine-triphosphate content, reactive oxygen species level and the activity of antioxidative enzymes. Tissue invasion experiment was executed to further evaluate the anti-adhesion ability of S. boulardii bio-coating. RESULTS: Encapsulating the overexpression of MCP1 by S. boulardii in hydrogel pores enhanced the viability of probiotics in the presence of high salt and oxidation stress. When used as the coating of an endotracheal tube, the S. boulardii bioactive material efficiently inhibited the adhesion of C. albicans by impairing the activities of superoxide dismutase and catalase and disturbing mitochondrial functions. In vivo, the S. boulardii bioactive material coating displayed good biocompatibility and reduced the host tissue invasion and virulence of C. albicans. CONCLUSIONS: The integration of genetic modification and immobilization model breaks the bottleneck of previous application of microorganisms, and provides a new way to prevent fungal infections introduced by endotracheal tubes.

How is COVID-19 Being Contained in China? An Observational Study on the Local Level.

OBJECTIVE: This article investigates how a Chinese local government responded to the ongoing coronavirus disease 2019 (COVID-19) outbreak, and the lessons can be valuable for the ongoing response efforts worldwide. METHODS: This case study used primarily participant observations and interviews with stakeholders. RESULTS: We find that nonpharmaceutical interventions, especially the physical distancing measures, are the primary tools used to contain the spread of the virus, and these actions keep changing to adapt to the situation of the local cases and the directions from the central government. Medical countermeasures, maintenance of essential public services, and effective public communications tactics are important allies of the strict physical distancing measures, which can enforce the public's compliance. CONCLUSIONS: Local governments are the frontlines of emergency response. Both regulated policies (eg, physical distancing) and supportive services (eg, medical and essential living support) are necessary to the success of public health emergency response.

Topical and emotional expressions regarding extreme weather disasters on social media: a comparison of posts from official media and the public.

Understanding media frames and the public resonance during disasters is essential for making inclusive climate change and adaptation policies in the context of increasingly extreme weather events. In this study, we use the extreme weather and flood event that occurred in July 2021 in Zhengzhou, China, as a case study to investigate how official media in China reported this event and how the public responded. Moreover, since one accountability investigation report regarding this disaster was released in January 2022, we also compared these posts between the emergency response period and the post-crisis learning period after the report's release. Topic modeling using the LDA (Latent Dirichlet Allocation) method and emotion analysis were conducted to analyze the posts from Weibo, China's primary social media platform. The results demonstrated that the posts from official media and the public comments differed in both topics and emotions, with relatively little coherence. During the emergency response period, the media's posts focused more on the facts, such as the extreme weather event, the places where it occurred, the impacts, and the search and rescue efforts, while the public comments were more about help appeals from the neglected ones in the rural areas, and emotional expressions such as moral support, condolence or encouragement to the victims and their families. After the accountability investigation in January, the media's posts primarily covered the investigation process, the punishment, the attribution of disaster consequences, and the lessons learned, while the public's comments were relatively emotional, praised the good, condoled the victims, and condemned the villains. The dominant emotion from the media's posts was "like" in July 2021, but it became depression in January 2022. Anger was the prevalent emotion from the public during all the stages. This study provided valuable knowledge to the current understanding of the different patterns and dynamics of official media reports and the public's resonance in disaster management.

What Do You Mean by Community Resilience? More Assets or Better Prepared?

OBJECTIVES: Understanding people's perception of community resilience to disaster is important. This study explores the correlations of household livelihood assets, the adopted household disaster preparedness activities, and individuals' assessment of community resilience. METHODS: The data was collected in 2018 by surveying a group of survivors affected by the 2008 Wenchuan earthquake in China. The CART (Community Advancing Resilience Toolkit) was used to measure individuals' perception of community resilience, while the livelihood assets included financial, physical, natural, human, and social capitals owned by the family, and the preparedness contained 13 activities. Ordinary least squares (OLS) regression models were used to test our hypotheses. RESULTS: Social capital is consistently and positively associated with the overall individuals' perceived community resilience, while the natural, human, and financial capitals' effects are not significant. The awareness and participation preparedness activities are positively correlated with the perceived community resilience, but the material preparedness activities are not. CONCLUSIONS: Social capital and disaster preparedness activities are critical in building community resilience. Community resilience can be achieved by making the community more connected and by providing disaster preparedness interventions.

Associations between school bullying and anxiety in children and adolescents from an ethnic autonomous county in China.

School bullying is a widespread public health issue that negatively impacts the mental health of children and adolescents. This study aimed to investigate associations between school bullying involvement and anxiety of children and adolescents. A survey covering all types of pre-college schools (primary, middle, high, and vocational school) was conducted in an ethnic autonomous county in China. 1,943 students participated in this study. Being a victim of verbal (OR=3.08, 95%CI = [2.43,3.91]), physical (OR=3.24, 95%CI = [2.46,4.27]), relational (OR=3.72, 95%CI = [2.90,4.76]), or cyberbullying (OR=3.47, 95%CI = [2.61,4.61]) were associated with increased symptoms of generalized anxiety. Similarly, being a perpetrator of verbal (OR=2.12, 95%CI = [1.45,3.10]), physical (OR=1.85, 95%CI = [1.22,2.79]), relational (OR=1.78, 95%CI = [1.15,2.74]), or cyber-bullying (OR=1.59, 95%CI = [1.08,2.33]) were related to a higher degree of anxiety. Moreover, in both victims and perpetrators higher levels of anxiety were associated with a greater number of types of bullying they were involved in, suggesting a dose-response relation between school bullying involvement and anxiety. Therefore, both bullying victims and perpetrators need mental health support and anti-bullying strategies should address different forms of bullying evenhandedly.

Examining the Prevalence and Risk Factors of School Bullying Perpetration Among Chinese Children and Adolescents.

Background and Objectives: School bullying threatens the health of children and adolescents, such as mental health disorders, social deviant behaviors, suicidal behaviors, and coping difficulties. The present study aims to address (1) prevalence rates of both traditional and cyber school bullying perpetration, and (2) the associations between self-control, parental involvement, experiencing conflicts with parents, experiencing interparental conflict, and risk behaviors, and school bullying perpetration among Chinese children and adolescents. Method: This study used data from a national representative school bullying survey (n = 3,675) among children and adolescents from all grades (primary school 4th grade to high school 12th grade) in seven cities in China. Negative binomial regression was used to estimate the effects of these predictive factors on traditional and cyber school bullying perpetration, respectively. Seven control variables were included, such as gender, boarding school, family socioeconomic status, and parents' education levels. Results: The sample comprised 52% female, 18% at boarding school, 70% of the participants' academic performance was average or above. Approximately 17.3% of the participants reported participating in traditional school bullying against their peers, and 7.8% perpetrated cyberbullying behaviors. Also, after controlling sociodemographic characteristics and high self-control, parental involvement reduced the likelihood of traditional and cyberbullying perpetrating. Experiencing interparental conflict and risk behavior was significantly associated with increased perpetration of traditional and cyber school bullying. We found that having a conflict with parents was significantly associated with cyberbullying perpetration. Implications: Findings have implications for practice. Anti-bullying intervention programs targeting this population should consider these factors. For example, school administrators may develop school programs involving parents in the efforts and interventions workshops improving children and adolescents' levels of self-control. Limitations are also discussed.

Prognostic efficacy and prognostic factors of TACE plus TKI with ICIs for the treatment of unresectable hepatocellular carcinoma: A retrospective study.

Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. Local combined systemic therapy is widely used in the treatment of unresectable hepatocellular cancer (uHCC). This retrospective study was to investigate the prognostic effect and prognostic factors of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICIs) in the treatment of uHCC. A retrospective analysis of 171 patients with uHCC was performed in our hospital from April 27, 2015 to October 18, 2021. According to different treatment options, patients were divided into TACE group (n=45), TACE+TKI group (n=76) and TACE+TKI+ICIs group (n=50). In this study, we found that, the median overall survival (mOS) of TACE+TKI+ICIs group was significantly better than TACE+TKI group and TACE group [24.1 (95% CI 15.1-33.1) months vs 14.9 (95% CI 10.7-19.1) months vs 11.4 (95% CI 8.4-14.5) months, hazard ratio (HR) 0.62; 95% CI 0.47-0.81; P=0.002]. A visible difference in the median progression-free survival (mPFS) interval between the groups was discovered [10.6 (95% CI6.5-14.7) months in TACE+TKI+ICIs group vs. 6.7 (95% CI 5.5-7.9) months in the TACE+TKI group vs. 6 (95% CI 2.3-9.7) months in the TACE group (HR 0.66; 95% CI 0.53-0.83; P<0.001)]. The objective response rates (ORR) in the TACE group, TACE+TKI group, and TACE+TKI+ICIs group were 31.1%, 35.5%, and 42%, and the disease control rate (DCR) were 51.1%, 65.8%, and 80%. There were no adverse events (AEs) of arthralgia, diarrhea, rash, and pruritus in the TACE group. The incidence of grade 3 AEs (Hypertension) in the TACE+TKI+ICIs group was significantly higher than that in TACE+TKI and TACE groups (28% vs 17.1% vs 6.7%, P=0.024), and secondly, the morbidity of rash and pruritus in the TACE+TKI+ICIs group was apparently higher than that in the TACE+TKI group (P<0.05). Multivariate analysis showed that ECOG-PS 2 (HR=2.064, 95%CI 1.335-3.191, P=0.001), Hepatitis B virus (HR=2.539, 95%CI 1.291-4.993, P=0.007), AFP≥400 ng/ml (HR= 1.72, 95%CI 1.12-2.643, P=0.013), neutrophil-lymphocyte ratio (NLR) ≥2.195 (HR=1.669, 95%CI 1.073-2.597, P=0.023) were independent risk factors for OS in uHCC patients. So, TACE+TKI+ICIs therapy can prolong the OS and improve the prognosis of patients effectively, with a well-characterized safety profile.