The mutual overlapping impact of stress and infection on mental health problems in adolescents and youths during and after COVID-19 pandemic in China.

BACKGROUND: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students. METHODS: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups. RESULTS: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001). LIMITATION: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms. CONCLUSION: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students.

IGSF6 is a novel biomarker to evaluate immune infiltration in mismatch repair-proficient colorectal cancer.

Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell-cell interactions in tumor microenvironment, encompassing processes such as cell-cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

UBR4 deficiency causes male sterility and testis abnormal in Drosophila.

Introduction: It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model. Methods: Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila. Results: We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility. Discussion: Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.

Comparison of stigmatizing views towards COVID-19 and mental disorders among adolescent and young adult students in China.

Objective: Infectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China. Methods: A total of 9,749 adolescents and young adults aged 15-24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views. Findings: The prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (ß = 0.025, p < 0.05), those without quarantine experience (ß = 0.035, p < 0.001), those with lower educational level (p < 0.001), those with lower family income (p < 0.01), and those with higher PTSD symptoms (ß = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income (p < 0.01), depression symptoms (ß = 0.056, p < 0.001), anxiety symptoms (ß = 0.051, p < 0.001), and mental health problems (ß = 0.027, p < 0.05). Conclusion: The stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions.

Impact of Radiotherapy Combined With Chemotherapy on Long-Term Outcomes of Patients With Recurrent Nasopharyngeal Carcinoma.

Background: It remains controversial whether the application of chemotherapy has an impact on recurrent nasopharyngeal carcinoma (rNPC) patients with salvage radiotherapy. Here, we aimed to evaluate treatment outcomes of rNPC patients and derive a prognostic model to assess the benefit of chemotherapy in patients with re-radiotherapy. Methods: This study was conducted as a retrospective study. In total, 340 rNPC patients treated with salvage intensity-modulated radiotherapy (IMRT) or radiochemotherapy (RCT) from October 2006 to September 2019 were included in this study. Overall survival (OS) was the primary outcome. Kaplan-Meier method was employed to detect the prognostic difference with Log-rank tests. The Cox regression analysis was performed to explore the potential prognostic factors while the multivariate Cox analysis was used to identify candidate variables for the prognostic model of OS. Results: The 5-year actuarial rates of OS, progression-free survival, loco-regional progression-free survival, and distant metastases-free survival did not show significant difference between the IMRT and RCT groups (P > .05). Age at recurrence and rT category were found to be the independent prognostic factors for OS. We found that rNPC patients suffered poor OS in the high-risk group (patients with higher age at recurrence and advanced rT category) (high-risk vs low-risk, HR = 1.87, 95% CI: 1.36-2.57, P < .001). Salvage RT alone may be superior to RCT for patients in the low-risk group (RCT group vs RT group, HR = 1.89, 95% CI: 1.11-3.20, P = .038). Conclusion: Salvage RT combined with chemotherapy cannot improve survival outcomes for rNPC. More novel clinical trials should be explored to develop individualized strategies to improve survival and minimize toxicities.

Synthesis of high drug loading, reactive oxygen species and esterase dual-responsive polymeric micelles for drug delivery.

Stimulus-responsive, controlled-release systems are of great importance in medical science and have drawn significant research attention, leading to the development of many stimulus-responsive materials over the past few decades. However, these materials are mainly designed to respond to external stimuli and ignore the key problem of the amount of drug loading. In this study, exploiting the synergistic effect of boronic esters and N-isopropylacrylamide (NIPAM) pendant, we present a copolymer as an ROS and esterase dual-stimulus responsive drug delivery system that has a drug loading of up to 6.99 wt% and an entrapment efficiency of 76.9%. This copolymer can successfully self-assemble into polymer micelles in water with a narrow distribution. Additionally, the measured CMC hinted at the good stability of the polymeric micelles in water solution, ensuing long circulation time in the body. This strategy for increasing the drug loading on the basis of stimulus response opens up a new avenue for the development of drug delivery systems.

Assessment of Burden Among Family Caregivers of Schizophrenia: Psychometric Testing for Short-Form Zarit Burden Interviews.

Objective: Although various short forms of Zarit Burden Interview (ZBI) have been developed, there is a lack of standard psychometric testing and comparison among them. The study aims to examine the psychometric properties of ten short versions of the most frequently used ZBI among a sample of schizophrenia caregivers and to find the one with the best performance. Methods: Cross-sectional door-to-door survey of ZBI-22 and a series of validated instrument data from 327 family caregivers of schizophrenia patients in a Chinese rural community were conducted from October 2015 to January 2016. Reliability was assessed using McDonald's omega coefficient (ω). Validity including concurrent validity, known group's validity, and criterion validity were assessed by Spearman correlations and Mann-Whitney U tests. Overall discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Reliability was generally good for all short forms (ω = 0.69-0.84), except for the Gort ZBI-4 (ω = 0.58), which is acceptable considering its small item numbers. Concurrent validity was good across all various ZBI forms with significant negative correlations with patient's function (r = -0.34 to -0.48, p < 0.01), as well as significant positive correlations with caregiver's depression (r = 0.49-0.65, p < 0.01), and anxiety symptoms (r = 0.45-0.58, p < 0.01). Known groups' validity (carers with disease vs. without disease; carers being parents vs. spouse vs. others) showed inconsistent results among various short forms. Criterion validity was generally good for all short forms with significant positive correlations with Family Burden Interview Schedule (r = 0.67-0.75, p < 0.01), except for the Higginson ZBI-1(r = 0.57, p < 0.01). Discriminative ability was also good for all short forms (AUC range: 0.85-0.99), with various cutpoints proposed. Among all ten short forms, the Ballesteros ZBI-12 and the Gort ZBI-7 outperformed others with almost equally good performance in comprehensive psychometric testing. Conclusions: This study provides support for the reliability, validity, and discriminative ability of the ten various short forms of ZBI for use among schizophrenia family caregivers, with the Ballesteros ZBI-12 and the Gort ZBI-7 endorsed as the best ones.