BackgroundChronic insomnia disorder has become a significant public health issue， and it may be associated with dyslipidemia. Previous studies on dyslipidemia in patients with chronic insomnia disorder have mainly focused on exploring the relationship between subjective short sleep duration and dyslipidemia， while there have been limited studies on the relationship between objective short sleep duration and dyslipidemia. ObjectiveTo explore the relationship between objective short sleep duration and dyslipidemia in patients with chronic insomnia disorder， in order to provide references for the prevention and intervention of dyslipidemia in this population. MethodsA total of 103 patients who were hospitalized at The Third Hospital of Mianyang from August 2022 to November 2023 and met the diagnostic criteria for chronic insomnia disorder as defined in the International Classification of Sleep Disorder， third edition （ICSD-3） were retrospectively collected. The objective sleep duration of the patients was obtained through polysomnography. The patients were divided into two groups based on their objective sleep duration： the group with objective sleep duration ≥ 7 hours （n=71） and the group with objective sleep duration < 7 hours （n=32）. Binary Logistic regression analysis was used to explore the impact of objective sleep duration < 7 hours on dyslipidemia. ResultsAmong 103 patients with chronic insomnia disorder， 59 cases （57.28%） were identified with dyslipidemia. The comparison of dyslipidemia conditions between the group with objective sleep duration ≥ 7 hours and the group with objective sleep duration < 7 hours showed a statistically significant difference （χ²=5.956， P<0.05）. Compared with the group with objective sleep duration ≥7 hours， the group with objective sleep duration < 7 hours exhibited significantly lower high-density lipoprotein cholesterol levels， and reduced sleep efficiency （t=-2.003， -5.482， P<0.05 or 0.01）. Binary Logistic regression analysis results showed that the risk of abnormal blood lipids in patients with chronic insomnia disorder with objective sleep duration < 7 hours was 3.128 times higher than that of patients with objective sleep duration ≥ 7 hours （OR=3.128， 95% CI： 1.139–8.588）. ConclusionObjective short sleep duration may be a risk factor for dyslipidemia in patients with chronic insomnia disorder.

Objective:To investigate the mechanism of Fusobacterium nucleatum ( Fn) in regulating the formation of neutrophil extracellular trap (NET) to aggravate colitis. Methods:With a completely randomized design, 15 C57BL/6 mice were randomly divided into negative control group, dextran sulfate sodium (DSS) A group (DSS-induced colitis), and DSS+ Fn A group (DSS-induced colitis with Fn infection); another 15 C57BL/6 mice were randomly divided into DSS B group, DSS+ Fn B group, and GSK484 group (DSS-induced colitis with Fn infection and followed by intraperitoneal injection of peptidylarginine deiminase 4 (PAD4)inhibitor GSK484), with 5 mice in each group. The Fn-infected neutrophils (HL-60 cell) model and PAD4-inhibited cell model were established and divided into neutrophil-like control cell (induced with 1.25% dimethylsulfoxide), Fn+ neutrophil-like cell (neutrophil-like cells co-cultured with Fn), and GSK484 cell ( Fn+ neutrophil-like cell co-cultured with GSK484) with a completely randomized design. The neutrophil-like control and Fn+ neutrophil-like cells were divided into 2 batches to conduct experiments before and after PAD4 inhibition separately.The expression of zonula occludens-1 (ZO-1), neutrophil elastase (NE), reactive oxygen species, PAD4, and citrullinated histone H3(cit-H3) were analyzed by immunohistochemistry staining, Western blotting, and flow cytometry assay. Two-tailed t test was used for statistical analysis. Results:The results of immunohistochemical staining showed that compared with those of the DSS A group, the expression levels of NE, PAD4 and cit-H3 of the DSS+ Fn A group were upregulated, and the expression level of ZO-1 was downregulated; compared with those of the DSS+ Fn B group, the expression level of ZO-1 of the GSK484 group was upregulated, and the expression levels of cit-H3 and PAD4 were downregulated. The results of Western blotting demonstrated that, before the PAD4 inhibition, the expression levels of NE, PAD4 and cit-H3 of the Fn+ neutrophil-like cell were all higher than those of the neutrophil-like control cell (1.52±0.11 vs. 1.00±0.19, 1.21±0.06 vs. 1.00±0.07, 1.59±0.16 vs. 1.00±0.16), and the differences were statistically significant ( t=-4.13, -3.86, and -4.47; P=0.014, 0.014, and 0.018); after the PAD4 inhibition, the expression levels of PAD4, cit-H3, and NE of the GSK484 cell were all lower than those of the Fn+ neutrophil-like cell (0.95±0.09 vs. 1.27±0.04, 1.15±0.34 vs. 2.29±0.50, 1.22±0.14 vs. 1.68±0.12), and the differences were statistically significant ( t=5.61, 3.24, and 4.49; P=0.005, 0.032, and 0.011). The results of flow cytometry assay indicated that the positive rate of reactive oxygen species of the DSS+ Fn A group was higher than that of the DSS A group ((21.15±2.93)% vs. (11.14±1.42)%), and the positive rate of reactive oxygen species of the Fn+ neutrophil-like cell was also higher than that of the neutrophil-like control cell before the PAD4 inhibition ((51.69±6.94)% vs.(31.95±3.31)%), and the differences were statistically significant( t=5.33 and 4.45, P=0.006 and 0.011). Conclusion:Fn can promote neutrophil to release NET by upregulating reactive oxygen/PAD4/cit-H3 signaling pathway, which disrupt the intestinal barrier and aggravate colitis.

Objective:To explore the value of combining gut microbiota and clinical features for preoperative microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).Methods:Clinical data and fecal samples were collected from 71 HCC patients who underwent curative resection at Ningbo Second Hospital between Jan 2023 and Aug 2024. Among them, 41 patients were assigned to the training set and 30 to the validation set. Gut microbiota composition was analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was used to evaluate the influence of clinical features on the microbiota. Differences in alpha and beta diversity between the MVI-negative and MVI-positive groups were assessed. Differential genera were identified using the Wilcoxon test and LEfSe analysis. A random forest model and Logistic regression were employed to screen key differential genera, followed by ROC analysis. Genera with high ROC values were further validated in the validation set.Results:RDA indicated that MVI was a key factor influencing gut microbiota composition. The random forest model (AUC=0.925), combined with Logistic regression analysis, identified four genera: Acidovorax ( OR=0.618), Tissierella ( OR=1.293), Chitinophaga ( OR=4.596), and Virgisporangium ( OR=0.960), as well as two clinical features: tumor diameter ( OR=0.668) and liver cirrhosis ( OR=14.011), as independent risk factors. ROC analysis showed that in the training set, the combination of Chitinophaga (AUC=0.71) and tumor diameter (AUC=0.75) had the best diagnostic performance (AUC=0.87). In the validation set, the combination of Virgisporangium (AUC=0.80) and tumor diameter (AUC=0.79) yielded the highest diagnostic performance (AUC=0.87). Conclusions:A genomics-based model combining gut microbiota and clinical features shows promising predictive value for noninvasive preoperative assessment of MVI status in HCC patients.

BackgroundInternet addiction poses serious harm to the physical and mental health of college students. Insecure attachment is one of the key factors of internet addiction， while self-compassion and psychological resilience serve as crucial psychological factors closely related to it. However， the chain mediating role of self-compassion and psychological resilience between insecure attachment and college students' internet addiction remains unclear. ObjectiveTo explore the mediating role of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction in college students， so as to provide references for the prevention and intervention of internet addiction in this population. MethodsFrom November 2023 to February 2024， a total of 1 380 college students were recruited using a cluster sampling method from two universities in Sichuan Province. The assessment was conducted using the Chinese Internet Addiction Scale （CIAS）， the Self-Compassion Scale （SCS）， the Experiences in Close Relationships Scale （ECR）， and the Resilience Scale for Chinese Adolescents （RSCA）. Pearson correlation analysis was conducted to examine the correlations of the scores of each scale. Model 6 in Process 4.2 was used to test the mediating roles of self-compassion and psychological resilience in the relationship between insecure attachment and internet addiction among college students. ResultsA total of 1 232 （89.28%） college students completed the valid questionnaire survey. The ECR score was positively correlated with the CIAS score （r=0.299， P<0.01）， and SCS score was positively correlated with the RSCA score （r=0.299， P<0.01）. The ECR score was negatively correlated with both SCS score and RSCA score （r=-0.122、-0.147，P<0.01）； the SCS score was negatively correlated with both RSCA score and CIAS score （r=-0.238、-0.263， P<0.01）. Self-compassion and psychological resilience were the pathways between insecure attachment and internet addiction， with effect sizes of 0.015 （95% CI： 0.007–0.023） and 0.010 （95% CI： 0.004–0.017）， respectively. Self-compassion and psychological resilience played chain mediating role between insecure attachment and internet addiction， with effect sizes of 0.003 （95% CI： 0.001–0.006）. ConclusionInsecure attachment can directly affect internet addiction in college students， and it can also influence internet addiction through independent pathway of self-compassion and psychological resilience， as well as the chain mediating pathways involving both self-compassion and psychological resilience.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Pediatric uveitis is an inflammatory disease involving iris, ciliary body and choroid. Compared with adult uveitis, pediatric uveitis has insidious onset and is easy to delay treatment. In recent years, biological agents have made remarkable progress in the treatment of non-infectious uveitis (NIU) in children. Anti-tumor necrosis factor-alpha drugs represented by Adalimumab have shown good effects in the control of inflammation, the saving of glucocorticoids, the frequency of uveitis attacks and the improvement of visual prognosis. At the same time, other biologics such as B cell antagonists, T cell antagonists, interleukin-6 antagonists and Janus kinase inhibitors were also gradually tested in children with NIU, bringing good news to children who failed to respond to anti-tumor necrosis factor-alpha drugs. With the in-depth understanding of the diagnosis and treatment of NIU children by clinicians, as well as the characteristics and therapeutic application of various biological agents, it is helpful to develop a more diversified and individualized treatment plan for children, so as to save the vision of children and children's families.

Pediatric uveitis is an inflammatory disease involving iris, ciliary body and choroid. Compared with adult uveitis, pediatric uveitis has insidious onset and is easy to delay treatment. In recent years, biological agents have made remarkable progress in the treatment of non-infectious uveitis (NIU) in children. Anti-tumor necrosis factor-alpha drugs represented by Adalimumab have shown good effects in the control of inflammation, the saving of glucocorticoids, the frequency of uveitis attacks and the improvement of visual prognosis. At the same time, other biologics such as B cell antagonists, T cell antagonists, interleukin-6 antagonists and Janus kinase inhibitors were also gradually tested in children with NIU, bringing good news to children who failed to respond to anti-tumor necrosis factor-alpha drugs. With the in-depth understanding of the diagnosis and treatment of NIU children by clinicians, as well as the characteristics and therapeutic application of various biological agents, it is helpful to develop a more diversified and individualized treatment plan for children, so as to save the vision of children and children's families.

Objective:To explore the value of combining gut microbiota and clinical features for preoperative microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).Methods:Clinical data and fecal samples were collected from 71 HCC patients who underwent curative resection at Ningbo Second Hospital between Jan 2023 and Aug 2024. Among them, 41 patients were assigned to the training set and 30 to the validation set. Gut microbiota composition was analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was used to evaluate the influence of clinical features on the microbiota. Differences in alpha and beta diversity between the MVI-negative and MVI-positive groups were assessed. Differential genera were identified using the Wilcoxon test and LEfSe analysis. A random forest model and Logistic regression were employed to screen key differential genera, followed by ROC analysis. Genera with high ROC values were further validated in the validation set.Results:RDA indicated that MVI was a key factor influencing gut microbiota composition. The random forest model (AUC=0.925), combined with Logistic regression analysis, identified four genera: Acidovorax ( OR=0.618), Tissierella ( OR=1.293), Chitinophaga ( OR=4.596), and Virgisporangium ( OR=0.960), as well as two clinical features: tumor diameter ( OR=0.668) and liver cirrhosis ( OR=14.011), as independent risk factors. ROC analysis showed that in the training set, the combination of Chitinophaga (AUC=0.71) and tumor diameter (AUC=0.75) had the best diagnostic performance (AUC=0.87). In the validation set, the combination of Virgisporangium (AUC=0.80) and tumor diameter (AUC=0.79) yielded the highest diagnostic performance (AUC=0.87). Conclusions:A genomics-based model combining gut microbiota and clinical features shows promising predictive value for noninvasive preoperative assessment of MVI status in HCC patients.

Objective:To investigate the mechanism of Fusobacterium nucleatum ( Fn) in regulating the formation of neutrophil extracellular trap (NET) to aggravate colitis. Methods:With a completely randomized design, 15 C57BL/6 mice were randomly divided into negative control group, dextran sulfate sodium (DSS) A group (DSS-induced colitis), and DSS+ Fn A group (DSS-induced colitis with Fn infection); another 15 C57BL/6 mice were randomly divided into DSS B group, DSS+ Fn B group, and GSK484 group (DSS-induced colitis with Fn infection and followed by intraperitoneal injection of peptidylarginine deiminase 4 (PAD4)inhibitor GSK484), with 5 mice in each group. The Fn-infected neutrophils (HL-60 cell) model and PAD4-inhibited cell model were established and divided into neutrophil-like control cell (induced with 1.25% dimethylsulfoxide), Fn+ neutrophil-like cell (neutrophil-like cells co-cultured with Fn), and GSK484 cell ( Fn+ neutrophil-like cell co-cultured with GSK484) with a completely randomized design. The neutrophil-like control and Fn+ neutrophil-like cells were divided into 2 batches to conduct experiments before and after PAD4 inhibition separately.The expression of zonula occludens-1 (ZO-1), neutrophil elastase (NE), reactive oxygen species, PAD4, and citrullinated histone H3(cit-H3) were analyzed by immunohistochemistry staining, Western blotting, and flow cytometry assay. Two-tailed t test was used for statistical analysis. Results:The results of immunohistochemical staining showed that compared with those of the DSS A group, the expression levels of NE, PAD4 and cit-H3 of the DSS+ Fn A group were upregulated, and the expression level of ZO-1 was downregulated; compared with those of the DSS+ Fn B group, the expression level of ZO-1 of the GSK484 group was upregulated, and the expression levels of cit-H3 and PAD4 were downregulated. The results of Western blotting demonstrated that, before the PAD4 inhibition, the expression levels of NE, PAD4 and cit-H3 of the Fn+ neutrophil-like cell were all higher than those of the neutrophil-like control cell (1.52±0.11 vs. 1.00±0.19, 1.21±0.06 vs. 1.00±0.07, 1.59±0.16 vs. 1.00±0.16), and the differences were statistically significant ( t=-4.13, -3.86, and -4.47; P=0.014, 0.014, and 0.018); after the PAD4 inhibition, the expression levels of PAD4, cit-H3, and NE of the GSK484 cell were all lower than those of the Fn+ neutrophil-like cell (0.95±0.09 vs. 1.27±0.04, 1.15±0.34 vs. 2.29±0.50, 1.22±0.14 vs. 1.68±0.12), and the differences were statistically significant ( t=5.61, 3.24, and 4.49; P=0.005, 0.032, and 0.011). The results of flow cytometry assay indicated that the positive rate of reactive oxygen species of the DSS+ Fn A group was higher than that of the DSS A group ((21.15±2.93)% vs. (11.14±1.42)%), and the positive rate of reactive oxygen species of the Fn+ neutrophil-like cell was also higher than that of the neutrophil-like control cell before the PAD4 inhibition ((51.69±6.94)% vs.(31.95±3.31)%), and the differences were statistically significant( t=5.33 and 4.45, P=0.006 and 0.011). Conclusion:Fn can promote neutrophil to release NET by upregulating reactive oxygen/PAD4/cit-H3 signaling pathway, which disrupt the intestinal barrier and aggravate colitis.

Objective:To construct a risk prediction model for the inter-hospital transfer of critically ill children using machine learning methods, identify key medical features affecting transfer outcomes, and improve the success rate of transfers.Methods:A prospective study was conducted on critically ill children admitted to the pediatric transfer center of Hunan Children's Hospital from January 2020 to January 2021. Medical data on critical care features and relevant data from the Pediatric Risk of Mortality (PRISMⅢ) scoring system were collected and processed. Three machine learning models, including logistic regression, decision tree, and Relief algorithm, were used to construct the risk prediction model. A back propagation neural network was employed to build a referral outcome prediction model to verify and analyze the selected medical features from the risk prediction model, exploring the key medical features influencing inter-hospital transfer risk.Results:Among the 549 transferred children included in the study, 222 were neonates (40.44%) and 327 were non-neonates (59.56%). There were 50 children in-hospital deaths, resulting in a mortality rate of 9.11%. After processing 151 critical care medical feature data points, each model selected the top 15 important features influencing transfer outcomes, with a total of 34 selected features. The decision tree model had an overlap of 72.7% with PRISMⅢ indicators, higher than logistic regression (36.4%) and Relief algorithm (27.3%). The training prediction accuracy of the decision tree model was 0.94, higher than the accuracy of 0.90 when including all features, indicating its clinical utility. Among the top 15 important features selected by the decision tree model, the impact on transfer outcomes was ranked as follows based on quantitative feature violin plots: base excess, total bilirubin, ionized calcium, total time, arterial oxygen pressure, blood parameters (including white blood cells, platelets, prothrombin time/activated partial thromboplastin time), carbon dioxide pressure, blood glucose, systolic blood pressure, heart rate, organ failure, lactate, capillary refill time, temperature, and cyanosis. Eight of these important features overlapped with PRISMⅢ indicators, including systolic blood pressure, heart rate, temperature, pupillary reflex, consciousness, acidosis, arterial oxygen pressure, carbon dioxide pressure, blood parameters, and blood glucose. The decision tree was used to select the top 15 medical features with high impact on the neonatal and non-neonatal datasets, respectively. A total of 19 features were selected, among which there were 8 differences and 11 overlap terms between the important features of the neonatal and non-neonatal.Conclusions:Machine learning models could serve as reliable tools for predicting the risk of inter-hospital transfer of critically ill children. The decision tree model exhibits superior performance and helps identify key medical features affecting inter-hospital transfer risk, thereby improving the success rate of inter-hospital transfers for critically ill children.