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BackgroundNon-small cell lung cancer (NSCLC) ranks among the most prevalent and lethal malignancies globally. Fatty acids (FAs) play a significant role in diverse physiological and pathological mechanisms, yet their precise involvement in NSCLC remains poorly understood.MethodsThis study utilized a large-scale prospective cohort of 249,132 participants, observed over an average of 12 years, to investigate the relationship between different FAs and NSCLC risk. Analytical approaches included Cox proportional hazards regression, Kaplan–Meier survival analysis, accelerated failure time (AFT) modeling, and restricted cubic spline (RCS) analysis.ResultsDuring the follow-up period, 1,460 participants were diagnosed with NSCLC. Cox regression analysis demonstrated that elevated levels of docosahexaenoic acid (DHA), linoleic acid (LA), and omega-3 were inversely associated with NSCLC risk. Kaplan–Meier curves, along with AFT models, corroborated that elevated concentrations of DHA and LA significantly delayed NSCLC onset. Additionally, RCS analysis uncovered nuanced dose–response relationships between these FAs and NSCLC. Stratified analyses highlighted variability based on smoking status, gender, and body mass index subgroups.ConclusionThe concentration of specific FAs exhibits a significant association with NSCLC risk. These results offer a foundation for devising dietary FA composition adjustments aimed at reducing NSCLC risk.

BackgroundAumolertinib demonstrated superior progression-free survival (PFS) and a well-tolerated toxicity profile compared to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, patient-reported outcomes (PROs) of aumolertinib have not been published.MethodsIn this real-world study, the efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. PROs were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC Quality of Life lung cancer-specific module (QLQ-LC13) in advanced NSCLC patients receiving aumolertinib as initial therapy. Pre-specified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling in hands or feet, chest pain, arm or shoulder pain, and pain at other sites.ResultsA total of 33 patients were included, 23 of whom had efficacy information up to January 2024. The median follow-up time was 264 days (interval: 36–491 days). The objective response rate and disease control rate were 65.2% and 91.3%, respectively. The EORTC QLQ-LC30 general health status scale showed that functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by the EORTC QLQ-LC13 showed that improvements in cough, sore mouth or tongue, tingling in hands or feet, chest pain, arm or shoulder pain, and other pain sites were both clinically and statistically significant after 6 months of aumolertinib treatment (p < 0.05).ConclusionIn this real-world study, aumolertinib showed comparable disease control and objective response rates as reported in the AENEAS trial for advanced NSCLC patients with EGFR-sensitizing mutations. Aumolertinib treatment improved PROs, further supporting it in first-line clinical practice.

BackgroundIn China, people’s perceptions towards electronic cigarettes during Corona Virus Disease 2019 (COVID-19) pandemic compared with pre-pandemic conditions have not been explored. Exploring the perceptions of medical workers regarding e-cigarettes is crucial, as they serve as a trusted source of information and providers of smoking cessation counselling for smokers. This cross-sectional study was designed to explore the awareness and perceptions of e-cigarettes among Chinese medical and other groups in the context of the COVID-19 pandemic.MethodsA cross-sectional survey was performed using an online, anonymous, and self-administered questionnaire. The questionnaire contained sections for collecting participants’ general information and Likert scale questions regarding smoking status, perceptions of e-smoking, attitude, and willingness to use e-cigarettes. The respondents included medical students, clinical doctors, and other occupations. Data analysis was performed using tools such as descriptive analysis, binary logistic regression, and multivariate regression.ResultsA total of 952 people completed the questionnaire, and 96.54% of them reported to have heard about e-cigarettes. The most common source of information about e-cigarettes was advertising. Notably, 28 of the 116 smokers reported that they had used e-cigarettes. Independent-samples T-tests results showed that medical groups believed e-cigarettes contained tar (p = 0.03). Most of the medical and non-medical participants maintained neutral attitudes towards e-cigarette policies (38.3%) and prices (49.2%) but their views were significantly different (p 40, OR = 9.794, 95CI% = 1.683–56.989, p = 0.011) and the older adult used fewer than the young (18–40, OR = 4.797, 95CI% = 0.930–24.744, p = 0.061; > 40, OR = 9.794, 95CI% = 1.683–56.989, p = 0.011).ConclusionThis study found that individuals tend to hold negative attitudes towards the awareness, perceptions, and willingness to use e-cigarettes. Medical groups are less likely to use e-cigarettes, but misperceptions are still prevalent among them. This calls for additional training for such medical personnel to improve their capacity to provide necessary counselling to smokers. E-cigarettes advertisements were the main source of information for young individuals to learn about e-cigarettes, and hence measures should be taken to restrict exposure of young individuals to e-cigarettes.

BackgroundAurora kinase A (AURKA) plays a pivotal role in regulating cell mitosis and tumor progression. However, its prognostic significance across diverse cancer types remains relatively unexplored.MethodsWe conducted a comprehensive analysis of AURKA expression in various cancers using data from The Cancer Genome Atlas, Genotype-Tissue Expression, and The Human Protein Atlas databases. Our investigation encompassed an exploration of the associations between AURKA expression and clinical characteristics, shedding light on potential functional roles of AURKA. Additionally, we delved into the relationship between AURKA and the tumor microenvironment. To substantiate the role of AURKA, we carried out in vitro experiments in esophageal adenocarcinoma (EAC), prostate cancer (PRAD), and pancreatic cancer (PAAD) cells.ResultsOur analysis revealed that AURKA is prominently overexpressed in a majority of the cancer types under investigation. Elevated AURKA expression correlated closely with poorer prognosis and advanced tumor stages. AURKA was found to be associated with key pathways involved in the cell cycle and arachidonic acid metabolism. Moreover, AURKA expression exhibited significant correlations with immunoregulatory genes and immune cell profiles. Notably, in vitro experiments demonstrated that silencing AURKA expression resulted in reduced cell viability in EAC, PRAD, and PAAD cells, as well as a decrease in clone formation, cell cycle elongation, diminished cell invasion and reduced spheroid size in EAC cells (OE33 and OE19).ConclusionOur study elucidates the oncogenic role of AURKA and underscores its prognostic value across a spectrum of cancers, including EAC. These findings suggest that AURKA holds promise as a predictive biomarker for EAC and various other tumor types.

Background: Cuproptosis, as a recently discovered type of programmed cell death, occupies a very important role in hepatocellular carcinoma (HCC) and provides new methods for immunotherapy; however, the functions of cuproptosis in HCC are still unclear.Methods: We first analyzed the transcriptome data and clinical information of 526 HCC patients using multiple algorithms in R language and extensively described the copy number variation, prognostic and immune infiltration characteristics of cuproptosis related genes (CRGs). Then, the hub CRG related genes associated with prognosis through LASSO and Cox regression analyses and constructed a prognostic prediction model including multiple molecular markers and clinicopathological parameters through training cohorts, then this model was verified by test cohorts. On the basis of the model, the clinicopathological indicators, immune infiltration and tumor microenvironment characteristics of HCC patients were further explored via bioinformation analysis. Then, We further explored the key gene biological function by single-cell analysis, cell viability and transwell experiments. Meantime, we also explored the molecular docking of the hub genes.Results: We have screened 5 hub genes associated with HCC prognosis and constructed a prognosis prediction scoring model. And the model results showed that patients in the high-risk group had poor prognosis and the expression levels of multiple immune markers, including PD-L1, CD276 and CTLA4, were higher than those patients in the low-risk group. We found a significant correlation between risk score and M0 macrophages and memory CD4+ T cells. And the single-cell analysis and molecular experiments showed that BEX1 were higher expressed in HCC tissues and deletion inhibited the proliferation, invasion and migration and EMT pathway of HCC cells. Finally, it was observed that BEX1 could bind to sorafenib to form a stable conformation.Conclusion: The study not only revealed the multiomics characteristics of CRGs in HCC but also constructed a new high-accuracy prognostic prediction model. Meanwhile, BEX1 were also identified as hub genes that can mediate the cuproptosis of hepatocytes as potential therapeutic targets for HCC.

This study aims to assess the effects of the partial replacement of whole corn silage (WCS) with fermented pineapple peel residue (FPPR) on growth, serological parameters, muscle quality, rumen microorganisms, and fecal microorganisms. A total of 24 Chuanzhong black goats weighing 10.23 ± 1.42 kg were evaluated in a randomized complete trial design in accordance with the following treatments: (1) 0% FPPR in the diet, (2) 25% FPPR in the diet, and (3) 50% FPPR in the diet. In goats, the partial substitution of FPPR for WCS increased the abundance of probiotics, such as Blautia, Butyrivibrio fibrisolvens, and Ruminococcus albus, and did not exert significant effects on overall serological parameters and muscle quality. In conclusion, the partial substitution of FPPR for WCS in the diet did not impair or affect the productive performance of goats.

ObjectiveTo analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes.Methods193 children with ADHD were included in our study from February 2017 to February 2020 in the Children’s ADHD Clinic of the author’s medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the “corplot” package was used for correlation analysis.ResultsAmong the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD.ConclusionThere were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

BackgroundMedical students play an indispensable role in providing smoking cessation counseling. Despite the rapid increase in tobacco use, there is little data on what Chinese medical students know or are taught about it. This study aims to investigate the relationship between medical students' tobacco education level, clinical experience, and tobacco cessation counseling (TCC) provided by medical students.MethodsThis cross-sectional study was carried out among clinical medical students of Chongqing medical university. An anonymous, self-administered questionnaire included items on demographic information, perceptions, and perceived preparedness, clinical medical students' self-reported level of education about alternative tobacco products, and traditional cigarettes. We assessed their perspectives toward TCC using a 5-point Likert scale. Descriptive and binary logistic regression analyses were carried out.ResultsA total of 1,263 medical students completed the questionnaire. The majority of students (85%) expressed a willingness to provide TCC to patients in need. However, only half of the students stated unequivocally that they knew some ways and methods of tobacco cessation, while 18% stated that they did not know methods of tobacco cessation. Tobacco education and clinical experience were significantly associated with the ability to provide TCC. Our findings revealed that students with more clinical experience (undergraduates: B = 0.326, P < 0.001; postgraduates: B = 0.518, P < 0.001) were significantly more likely to have a greater self-reported comprehensive ability to provide TCC.ConclusionTobacco education and clinical experience can enhance the ability of medical students to provide smoking cessation counseling. There is a need to focus on alternative tobacco products with changing times, and curriculum planners should collaborate to incorporate comprehensive tobacco prevention and cessation training into the medical school curriculum.

BackgroundTo determine the association of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with cognitive impairment using optical coherence tomography angiography (OCTA).MethodsA cross-sectional, community-based study utilizing data from the participants enrolled between August 2019 and January 2020 in the Jidong Eye Cohort Study. We assessed the vessel density in RCP and GCC thickness using OCTA, and cognitive testing using the Montreal Cognitive Assessment (MoCA). Cognitive impairment in this study was defined as MoCA score < 24. We used multivariable analysis to evaluate the association of RCP and GCC with cognitive impairment after adjusting for confounders.ResultsThis study analyzed 1555 participants. The mean age of participants was 52.3 (8.4) years, and 861 (55.4%) were women. Cognitive impairment was observed in 268 (17.2%) participants. The adjusted odds ratio (OR) with 95% confidence interval (95% CI) for parafovea vessel density in the deep RCP with cognitive impairment was 1.20 (1.03–1.39). For vessel area and length density surrounding foveal avascular zone with cognitive impairment, the ORs with 95% CIs were 1.23 (1.07–1.41) and 1.30 (1.13–1.49), respectively. For thickness in the superior GCC with cognitive impairment, the OR with 95% CI was 1.16 (1.01–1.32).ConclusionLower vessel density in the RCP and thinner GCC were associated with cognitive impairment. Our results suggest that alterations in the RCP and GCC could provide further evidence when assessing the cognitive function and may even be potentially useful biomarkers in the detection of cognitive impairment.

Objective: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in children, which is characterized by inattention, hyperactivity and impulsivity. Using resting-state functional magnetic resonance imaging (R-fMRI), the alterations of static and dynamic characteristics of intrinsic brain activity have been identified in patients with ADHD. Yet, it remains unclear whether the concordance among indices of dynamic R-fMRI is altered in ADHD.Methods: R-fMRI scans obtained from 50 patients with ADHD and 28 healthy controls (HC) were used for the current study. We calculated the regional dynamic changes in brain activity indices using the sliding-window method and compared the differences in variability of these indices between ADHD patients and HCs. Further, the concordance among these dynamic indices was calculated and compared. Finally, the relationship between variability/concordance of these indices and ADHD-relevant clinical test scores was investigated.Results: Patients with ADHD showed decreased variability of dynamic amplitude of low-frequency fluctuation (dALFF) in the left middle frontal gyrus and increased one in right middle occipital gyrus, as compared with the HCs. Besides, ADHD patients showed decreased voxel-wise concordance in the left middle frontal gyrus. Further, lower voxel-wise concordance in ADHD’s left middle frontal gyrus was associated with more non-perseverative errors in Wisconsin Card Sorting Test, which reflects worse cognitive control.Conclusion: Our findings suggest that variability and concordance in dynamic brain activity may serve as biomarkers for the diagnosis of ADHD. Further, the decreased voxel-wise concordance is associated with deficit in cognitive control in ADHD patients.

Objective: Genetic variation, especially polymorphism of the dopamine D4 receptor gene (DRD4), has been linked to deficits in self-regulation and executive functions and to attention deficit hyperactivity disorder (ADHD), and is related to the structural and functional integrity of the default mode network (DMN), the executive control network (ECN) and the sensorimotor network (SMN). The aim of this study was to explore the effects of the 2-repeat allele of the DRD4 gene on brain network connectivity and behaviors in children with ADHD.Methods: Using independent component analysis (ICA) and dimension analyses, we examined resting-state functional magnetic resonance imaging (fMRI) data obtained from 52 Asian medicine-naive children with ADHD (33 2-repeat absent and 19 2-repeat present).Results: We found that individuals with 2-repeat absent demonstrated increased within-network connectivity in the right precuneus of the DMN, the right middle frontal gyrus (MFG) of the SMN compared with individuals with 2-repeat present. Within the ECN, 2-repeat absent showed decreased within-network connectivity in the left inferior frontal gyrus (IFG) and the left anterior cingulate cortex. A deeper study found that connectivity strength of the left IFG was directly proportional to the Stroop reaction time in 2-repeat absent group, and as well as the right MFG in 2-repeat present group.Conclusion: Polymorphisms of the DRD4 gene, specifically 2-repeat allele, had effects on the ECN, the SMN and the DMN, especially in the prefrontal cortex (PFC) circles. ADHD children with DRD4 2-repeat allele have aberrant resting-state within-network connectivity patterns in the left IFG and the right MFG related to dysfunction in inattention symptom. This study provided novel insights into the neural mechanisms underlying the effects of DRD4 2-repeat allele on ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells. However, whether Sophocarpine protects the liver by regulating NK cell activity remains unclear. In this study, the modulating effect of Sophocarpine on NK cells in the liver was investigated. The results showed that Sophocarpine dramatically decreased the production of pro-inflammatory cytokines and attenuated the liver injury induced by Poly I: C/D-GalN in C57BL/6- mice. More importantly, Sophocarpine pre-treatment significantly suppressed NK cell activation and downregulated the expression of NKG2D, a receptor responsible for NK cell activation. Moreover, the protein levels of DAP12, ZAP76 and Syk decreased, as did their corresponding mRNA levels. Overall, our study demonstrates that Sophocarpine inhibits NK cell activity, thus making it a promising therapy for ILI. [ABSTRACT FROM AUTHOR]