Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Since the beginning of the new century, advances in understanding the intricate interactions between oncology and the immune system have accelerated the rapid development of immune checkpoint inhibitors for the treatment of non-small cell lung cancer. However, resistance to immunotherapy is inevitable. Therefore, uncovering the mechanisms of immunotherapy resistance, proposing strategies to overcome resistance, and identifying future research directions are imperative. Given the limitations of space in each article, this review will explore the complex mechanisms underlying immunotherapy resistance. These mechanisms involve almost all cell types within the body, excluding foreign cancer cells. Notably, these cells serve as recipients (either inhibitory or stimulatory, or both) and producers of signals, playing different roles in various contexts. At the molecular level, these mechanisms include genetic and epigenetic abnormalities in all cells within the microenvironment, as well as the influence of a variety of protein kinase, growth factors, and cytokines with temporal and spatial heterogeneity. At the macroscopic level, host factors such as nutritional metabolism, comorbidities, and microbiota within the organs, as well as neuro-psychological regulation, influence the efficacy of immunotherapy.

Background Exposure to volatile organic compounds (VOCs) has been observed in both living and working environments. Volatile organic compounds metabolites (VOCMs) in urine can be used to assess the exposure to VOCs and potentially cause adverse effects on human body. Objective To quantitatively evaluate urinary VOCMs and their associations with renal function damage, and further trace the characteristics of potential environmental exposure to provide scientific evidence for effective prevention measures. Methods The study included a total of 6028 samples from four cross-sectional studies in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, with exposure and health outcomes matched. Generalized linear models were employed to assess the associations of urinary VOCMs (urinary creatinine adjusted) with urinary protein levels and estimated glomerular filtration rate (eGFR), with coviriables including gender, age, body mass index, education, smoking, alcohol consumption, exercise frequency, diabetes, and hypertension. Weighted quantile sum (WQS) approach was utilized to analyze the effects of mixed exposure and to rank the contribution of individual VOCMs. The associations between VOCMs and associated living environments and occupational exposure characteristics were further investigated. Results Among the enrolled study participants (n=6028), a total of 11 urinary VOCMs were measured, with 10 metabolites having a positive rate of over 80% (84.59%-99.99%). There were 604 individuals (10.0%) having urinary protein abnormalities and 2831 individuals (47.0%) with eGFR reduced. Through a single and a multiple generalized linear model, 5 VOCMs exhibited statistically significant associations with urinary protein abnormalities and/or reduced eGFR levels (P<0.05): N-acetyl-S-(N-methylaminocarbonyl)-L-cysteine (AMC), N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEM), N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHB), 2-hydroxy-2-phenylacetic acid (MAD), and N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MB3). The WQS index indicated a significantly positive association between VOCMs and urinary protein abnormalities, and DHB contributed the most. The analysis on the potential sources of VOCs exposure showed that those who worked as a private entrepreneur or an employee (vs. government employees), rent houses (vs. owned real estate), had less number of rooms in the residence, fueled cars at self-service gas stations, and inhaled paint fumes in the past 48 h associated with higher VOCMs (P < 0.05) and DHB contributed the most. Conclusion Multiple VOCMs in urine are associated with significantly kidney function injuries. The mixture exposure to VOCMs is significantly associated with higher risks of urinary protein abnormalities. Occupational category, housing ownership, ways to fuel a car, and inhalation of paint odors are closely related with VOCMs levels.

Objective To explore the application value of deep learning image reconstruction(DLIR)algorithm in low-dose deep inferior epigastric artery(DIEA)computed tomography angiography(CTA).Methods A total of 59 patients undergoing DIEA CTA were prospectively selected and randomly divided into two groups:group A(29 cases)and group B(30 cases).Group A was the conventional radiation dose group(tube voltage 120 kVp),the tube current was dose modulation 3,and the iterative reconstruction algo-rithm was Karl 5.Group B was the low radiation dose group(tube voltage 120 kVp),the tube current was dose modulation 2,with DLIR reconstruction algorithm,and four levels of DLIR(1-4)were reconstructed and labeled as groups B1 to B4.The mean tube current,vol-ume CT dose index(CTDIvol),and dose length product(DLP)of group A and group B were recorded,and the effective dose(ED)was calculated.The CT and standard deviation(SD)values of the external iliac artery and psoas major muscle were measured on axial images of each group,and signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.Two observers using double-blind method independently evaluated the DIEA on volume rendering(VR)and maximum intensity projection(MIP)images of each group using a 3-point scale,and a 5-point scale was used to evaluate the overall image quality on axial images.Results Compared with group A,the mean tube current and ED in group B were decreased by 39.33％and 44.09％,respectively(P＜0.05).With the increasing of DLIR level from groups B1 to B4,the SD value of the image gradually decreased,while SNR and CNR gradually increased(P＜0.05).The CNR in groups B3 and B4 was higher than that in group A(P＜0.05).The subjective scores of the two observers were consistent(Kappa value 0.779-0.889,P＜0.05),and there was no statistical significance between group A and group B in the perforating vessels from the DIEA,intramuscular course,and the point of emergence(P＞0.05).With the increase in DLIR level,the subjective score of the overall image quality from group B1 to group B4 showed a trend of first increasing and then decreasing,and the score of group B3 was the highest(4.50±0.51)points,which had no statistical significance compared with group A(4.45±0.51)points(P＞0.05).Conclusion DLIR can effectively reduce the radiation dose of the DIEA CT A scan and ensure the image quality,among which DLIR 3 is the recommended best reconstruction grade.

Objective To explore the application value of 1 024×1 024 reconstruction matrix combined with iterative reconstruc-tion algorithm(Karl)in deep inferior epigastric artery(DIEA)computed tomography angiography(CTA).Methods A total of 40 patients who underwent DIEA CTA were prospectively selected and the original data were reconstructed by grouping.Group A was reconstructed using a conventional 512×512 matrix combined with Karl 5 grade.Group B was reconstructed using 1 024×1 024 recon-struction matrix combined with Karl 5,7,and 9 grades,respectively,and 3 subgroups B1-B3 were obtained.The CT and standard devia-tion(SD)values of the external iliac artery and psoas major muscle were measured on axial images,and signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.A 3-point scale was used to evaluate the perforating vessels from the DIEA,intramuscular course,point of emergence,superficial inferior epigastric artery(SIEA)and superficial inferior epigastric vein(SIEV)on volume ren-dering(VR)and maximum intensity projection(MIP)images by two observers,and a 5-point scale was used to evaluate the overall image quality on axial images.Results With the increase of Karl grade in groups B1 to B3,the SD value of the external iliac artery decreased gradually(P＜0.05),while SNR and CNR increased gradually(P＜0.05).The SD values of the external iliac artery in group B2 and group B3 were lower than those in group A(P＜0.05),and SNR and CNR were higher than those in group A(P＜0.05).There was a good consistency in the subjective evaluation between the two observers(Kappa values=0.773-0.872,P＜0.05).The perforating vessels from the DIEA,intramuscular course,point of emergence,SIEA and SIEV display and overall image quality subjective scores of group B2 and group B3 were better than those of group A(P＜0.05),and the scores of group B2 showed the greatest improvement.Conclusion The 1 024 × 1 024 reconstruction matrix combined with the Karl 7 reconstruction algorithm can optimize the image quality and improve the display of the DIEA and perforator microvessels.