Abnormality in Peripheral and Brain Iron Contents and the Relationship with Grey Matter Volumes in Major Depressive Disorder.

Major depressive disorder (MDD) is a prevalent mental illness globally, yet its etiology remains largely elusive. Recent interest in the scientific community has focused on the correlation between the disruption of iron homeostasis and MDD. Prior studies have revealed anomalous levels of iron in both peripheral blood and the brain of MDD patients; however, these findings are not consistent. This study involved 95 MDD patients aged 18-35 and 66 sex- and age-matched healthy controls (HCs) who underwent 3D-T1 and quantitative susceptibility mapping (QSM) sequence scans to assess grey matter volume (GMV) and brain iron concentration, respectively. Plasma ferritin (pF) levels were measured in a subset of 49 MDD individuals and 41 HCs using the Enzyme-linked immunosorbent assay (ELISA), whose blood data were simultaneously collected. We hypothesize that morphological brain changes in MDD patients are related to abnormal regulation of iron levels in the brain and periphery. Multimodal canonical correlation analysis plus joint independent component analysis (MCCA+jICA) algorithm was mainly used to investigate the covariation patterns between the brain iron concentration and GMV. The results of "MCCA+jICA" showed that the QSM values in bilateral globus pallidus and caudate nucleus of MDD patients were lower than HCs. While in the bilateral thalamus and putamen, the QSM values in MDD patients were higher than in HCs. The GMV values of these brain regions showed a significant positive correlation with QSM. The GMV values of bilateral putamen were found to be increased in MDD patients compared with HCs. A small portion of the thalamus showed reduced GMV values in MDD patients compared to HCs. Furthermore, the region of interest (ROI)-based comparison results in the basal ganglia structures align with the outcomes obtained from the "MCCA+jICA" analysis. The ELISA results indicated that the levels of pF in MDD patients were higher than those in HCs. Correlation analysis revealed that the increase in pF was positively correlated with the iron content in the left thalamus. Finally, the covariation patterns obtained from "MCCA+jICA" analysis as classification features effectively differentiated MDD patients from HCs in the support vector machine (SVM) model. Our findings indicate that elevated peripheral ferritin in MDD patients may disrupt the normal metabolism of iron in the brain, leading to abnormal changes in brain iron levels and GMV.

Mechanical, Thermal Properties, and Extreme Phase Stability of High-Entropy Diborides (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2.

High-entropy diborides (HEDBs) have gained significant attention in industrial applications due to their vast composition space and tunable properties. We propose a solid solution reaction at high temperatures and pressures that successfully synthesized and sintered a novel, dense, and phase-pure HEDB (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2. A high asymptotic Vickers hardness of 26.3 ± 0.6 GPa and a bulk modulus of 320.5 ± 10.6 GPa were obtained. Additionally, we investigated the thermal oxidation process using TG-DSC from room temperature to 1500 °C and explored the phase stability of HEDBs under high-pressure conditions through in situ high-pressure synchrotron radiation X-ray diffraction. We analyzed the formation of lattice distortion, chemical bonding, and band structure in (V0.2Nb0.2Ta0.2Cr0.2W0.2)B2 using first-principles calculations. Surprisingly, we found that the predominant distortion in diborides occurs in the boron layer, supported by ELF. This may be due to uneven electron transfer rather than a straightforward correlation with the atomic radius. These results provide a novel synthesis process and additional experimental data on the mechanical and thermal properties and high-pressure phase stability of HEDBs. Our study offers further insights into the microscopic structure of lattice distortion in HEDBs, which could prove crucial for the selection and design of engineering advanced HEDBs.

Morphological changes in the cerebellum during aging: evidence from convolutional neural networks and shape analysis.

The morphology and function of the cerebellum are associated with various developmental disorders and healthy aging. Changes in cerebellar morphology during the aging process have been extensively investigated, with most studies focusing on changes in cerebellar regional volume. The volumetric method has been used to quantitatively demonstrate the decrease in the cerebellar volume with age, but it has certain limitations in visually presenting the morphological changes of cerebellar atrophy from a three-dimensional perspective. Thus, we comprehensively described cerebellar morphological changes during aging through volume measurements of subregions and shape analysis. This study included 553 healthy participants aged 20-80 years. A novel cerebellar localized segmentation algorithm based on convolutional neural networks was utilized to analyze the volume of subregions, followed by shape analysis for localized atrophy assessment based on the cerebellar thickness. The results indicated that out of the 28 subregions in the absolute volume of the cerebellum, 15 exhibited significant aging trends, and 16 exhibited significant sex differences. Regarding the analysis of relative volume, only 11 out of the 28 subregions of the cerebellum exhibited significant aging trends, and 4 exhibited significant sex differences. The results of the shape analysis revealed region-specific atrophy of the cerebellum with increasing age. Regions displaying more significant atrophy were predominantly located in the vermis, the lateral portions of bilateral cerebellar hemispheres, lobules I-III, and the medial portions of the posterior lobe. This atrophy differed between sexes. Men exhibited slightly more severe atrophy than women in most of the cerebellar regions. Our study provides a comprehensive perspective for observing cerebellar atrophy during the aging process.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

LTBP2 regulates cisplatin resistance in GC cells via activation of the NF-κB2/BCL3 pathway.

Gastric cancer (GC) often develops resistance to cisplatin treatment, but while latent transforming growth factor ß-binding protein (LTBP2) is recognized as a potential regulator in GC, its specific role in cisplatin resistance is not fully understood. This study investigated LTBP2's impact on cisplatin resistance in GC. LTBP2 expression was assessed in various GC cell lines, and its correlation with cisplatin sensitivity was determined through cell viability assays. Lentivirus-mediated LTBP2 silencing in HGC-27 cells demonstrated enhanced cisplatin sensitivity, reduced cell proliferation, and inhibition of the NF-κB2/Bcl-3/cyclin D1 pathway. Additionally, transient transfection overexpressed the NFκB2 gene in LTBP2-silenced HGC-27/DDPR cells, restoring cisplatin sensitivity and upregulating p52/Bcl-3/cyclin D1. In conclusion, silencing LTBP2 could effectively inhibit cell proliferation and mitigate cisplatin resistance via the NFKB noncanonical pathway NFKB2 p52/Bcl-3/cyclin D1. These findings propose LTBP2 as a potential therapeutic target for overcoming cisplatin resistance in GC patients.

Preterm Birth Alters the Regional Development and Structural Covariance of Cerebellum at Term-Equivalent Age.

Preterm birth is associated with increased risk for a spectrum of neurodevelopmental disabilities. The cerebellum is implicated in a wide range of cognitive functions extending beyond sensorimotor control and plays an increasingly recognized role in brain development. Morphometric studies based on volume analyses have revealed impaired cerebellar development in preterm infants. However, the structural covariance between the cerebellum and cerebral cortex has not been studied during the neonatal period, and the extent to which structural covariance is affected by preterm birth remains unknown. In this study, using the structural MR images of 52 preterm infants scanned at term-equivalent age and 312 full-term controls from the Developing Human Connectome Project, we compared volumetric growth, local cerebellum shape development and cerebello-cerebral structural covariance between the two groups. We found that although there was no significant difference in the overall volume measurements between preterm and full-term infants, the shape measurements were different. Compared with the control infants, preterm infants had significantly larger thickness in the vermis and lower thickness in the lateral portions of the bilateral cerebral hemispheres. The structural covariance between the cerebellum and frontal and parietal lobes was significantly greater in preterm infants than in full-term controls. The findings in this study suggested that cerebellar development and cerebello-cerebral structural covariance may be affected by premature birth.

Predictive value of free triiodothyronine to free thyroxine ratio on contrast-associated acute kidney injury and poor prognosis in euthyroid patients after percutaneous coronary intervention.

PURPOSE: The purpose of the study was to explore the predictive value of free triiodothyronine to free thyroxine ratio (FT3/FT4) on contrast-associated acute kidney injury (CA-AKI) and poor prognosis in euthyroid patients after percutaneous coronary intervention (PCI). METHODS: The present study included 3,116 euthyroid patients who underwent elective PCI. The main outcome was CA-AKI, and the secondary outcome was long-term mortality. All patients were divided into three groups according to the tertiles of FT3/FT4 levels. RESULTS: During hospitalization, a total of 160 cases (5.1%) of CA-AKI occurred. Restricted cubic spline (RCS) analysis indicated a linear and negative relationship between FT3/FT4 and CA-AKI risk (P for nonlinearity = 0.2621). Besides, the fully-adjusted logistic regression model revealed that patients in tertile 3 (low FT3/FT4 group) had 1.82 times [odds ratio (OR): 1.82, 95% confidence interval (CI): 1.13-3.02, P = 0.016] as high as the risk of CA-AKI than those in tertile 1 (high FT3/FT4 group). Similarly, patients in tertile 3 were observed to have a higher incidence of long-term mortality [fully-adjusted hazard ratio (HR): 1.58, 95% CI: 1.07-2.32, P = 0.021]. Similarly, the Kaplan-Meier curves displayed significant differences in long-term mortality among the three groups (log-rank test, P < 0.001). CONCLUSION: In euthyroid patients undergoing elective PCI, low levels of FT3/FT4 were independently associated with an increased risk of CA-AKI and long-term mortality. Routine evaluation of FT3/FT4 may aid in risk stratification and guide treatment decisions within this particular patient group.

Lactate dehydrogenase-to-albumin ratio: A superior inflammatory marker for predicting contrast-associated acute kidney injury after percutaneous coronary intervention.

PURPOSE: Inflammation is commonly considered a mechanism underlying contrast-associated acute kidney injury (CA-AKI). This study aimed to explore the predictive capability of the novel inflammatory marker lactate dehydrogenase-to-albumin ratio (LAR) for CA-AKI following percutaneous coronary intervention (PCI), and further compare it with other common inflammatory biomarkers. METHODS: This study enrolled 5,435 patients undergoing elective PCI. The primary outcome was CA-AKI, and the secondary outcome was all-cause mortality. All patients were grouped into three groups based on the LAR tertiles. RESULTS: Three hundred fifteen patients (5.8%) experienced CA-AKI during hospitalization. The fully adjusted logistic regression suggested a significant increase in the risk of CA-AKI in LAR Tertile 3 (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.68-3.83, p < .001) and Tertile 2 (OR: 2.11, 95% CI: 1.42-3.20, p < .001) compared to Tertile 1. Additionally, receiver operating characteristic (ROC) analysis demonstrated that LAR exhibited significantly superior predictive capability for CA-AKI compared to other inflammatory biomarkers. Regarding the secondary outcome, multivariate COX regression analysis showed a positive correlation between elevated LAR levels and all-cause mortality. CONCLUSION: In patients undergoing elective PCI, LAR was significantly independently associated with CA-AKI, and it stood out as the optimal inflammatory biomarker for predicting CA-AKI.

A V-shaped association between high-density lipoprotein cholesterol levels and poor outcomes in patients after percutaneous coronary intervention.

BACKGROUND: High density lipoprotein cholesterol (HDL-C) is considered as "good cholesterol". Recent evidence suggests that a high HDL-C level may increase the risk of poor outcomes in some populations. PURPOSE: To investigate the association between HDL-C levels and poor outcomes in patients after percutaneous coronary intervention (PCI). METHODS: Patients undergoing PCI during January 2012 and December 2018 were consecutively recruited and divided into three groups with different HDL-C levels: HDL-C ≤ 25 mg/dL, 25 < HDL-C ≤ 60 mg/dL, HDL-C > 60 mg/dL by the restricted cubic spline (RCS) analysis and assessed for all-cause mortality (ACM). The association between HDL-C levels and poor outcomes was assessed by multivariable cox regression analysis. RESULTS: The patients were followed with a median duration of 4 years. Of the 7284 participants, 727 all-cause deaths and 334 cardiovascular deaths occurred. A V-shaped association of HDL-C with the prognosis was observed, patients with either excessively low or high HDL-C levels reporting a higher risk than those with midrange values. After adjustment for confounding factors, the former exhibited a higher cumulative rate of ACM and cardiovascular mortality (CM) than the latter [low HDL-C: for ACM, hazard ratio (HR), 1.96; 95%CI, 1.41, 2.73, P < 0.001; for CM, HR, 1.66; 95%CI, 1.03, 2.67; P = 0.037; high HDL-C: for ACM, HR, 1.73; 95%CI, 1.29, 2.32, P < 0.001; for CM, HR, 1.73; 95%CI, 1.16, 2.58; P = 0.007]. CONCLUSION: HDL-C levels display a V-shaped association with poor outcomes in patients after PCI, with excessively high or low HDL-C suggesting a higher mortality risk. An optimal HDL-C level may fall in the range of 25-60 mg/dL.

WD repeat domain 76 predicts poor prognosis in lower grade glioma and provides an original target for immunotherapy.

BACKGROUND: The WD40 repeat (WDR) domain provides scaffolds for numerous protein-protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported. METHODS: Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results. RESULTS: The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1). CONCLUSIONS: This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.

A Pilot Study About the Role of PANoptosis-Based Genes in Atherosclerosis Development.

Background: As a chronic inflammatory disease, atherosclerosis (AS) and ischemia events are primarily affected by inflammation in AS. PANoptosis has been implicated in many human systemic disorders, including infection, cancer, neurodegeneration, and inflammation. On the other hand, little is understood about PANoptosis's function in AS. Methods: We used consensus clustering to divide the GSE100927 dataset into two panoptosis-related subgroups. PANoptosis-associated genes were screened by differential analysis and weighted gene co-expression network analysis (WGCNA) and enriched by ClueGO software. Investigating LASSO regression and MCODE to identify AS Diagnostic Markers. Immunoinfiltration analysis and single-cell analysis were used to search for cell types associated with the diagnostic genes. Final validation was performed by polymerase chain reaction (PCR). Results: We classified the GSE100927 dataset into two PANoptosis-related subtypes based on the expression of PANoptosis-related genes (PRGs) using consensus clustering. A total of 36 PANoptosis-associated genes were screened in the differentially expressed genes and WGCNA-related module. 4 hub genes were identified by MCODE and LASSO regression, and 3 AS diagnostic markers (ACP5, CCL3, HMOX1) were screened by external validation set. Immunoinfiltration analysis and single-cell analysis showed that the three diagnostic markers were associated with macrophages, and PCR results demonstrated that ACP5 and HMOX1 could be used as AS diagnostic markers. Conclusion: Our study identified ACP5 and HMOX1 as diagnostic genes for AS that may be associated with PANoptosis. ACP5 and HMOX1 may be involved in the pathogenesis of AS by regulating macrophage PANoptosis.

Effectiveness and associated factors of varicella vaccination on school outbreaks / 中国学校卫生

Objective@#To evaluate the effectiveness of varicella vaccine in varicella outbreaks and to analyze the influencing factors, and to provide a reference for making the targeted prevention and controlling measures.@*Methods@#A total of 3 888 students with no history of varicella were selected from 2 schools with varicella outbreak in Guangdong Province in 2021, a retrospective cohort study was conducted by using questionnaire survey, rate ratio ( RR ) and vaccine effectiveness ( VE ) values were calculated and Logistic regression was uses to analyze the factors influencing the protective effect of varicella.@*Results@#There were 138 confirmed cases of varicella among the participants. There was no significant sex difference in the vaccination rate( χ 2=1.36, P =0.51), but there was significant difference in the vaccinattion rate of different age groups( χ 2=555.82, P <0.01). The overall protective effect of VarV was 66.94%(95% CI =56.17%-77.71%), and the protective effect of 2 doses of vaccine( VE = 90.02% , 95% CI =83.13%-96.90%) was higher than that of 1 dose( VE =49.40%, 95% CI =32.36%-66.44%)( χ 2=24.93, P < 0.01 ). The high fever rates in the vaccinated and unvaccinated groups were 7.69% and 25.81%, with significant difference( χ 2= 6.29 , P <0.05). The rates of moderate and severe skin lesions of vaccinated and unvaccinated groups was 20.00% and 50.00%, respectively, and the difference was statistically significant( χ 2=11.32, P <0.01). The protective effects of varicella vaccine against high fever and moderate to severe rash were 70.19%(95% CI =42.11%-98.27%) and 60.00%(95% CI =38.15%-81.85%). Stratified analysis showed that there were significant differences in different years of vaccination( χ 2=37.87, P <0.05), while there were no significant differences in age of vaccination and vaccine manufacturer ( P >0.05).@*Conclusion@#Varicella vaccination can prevent chickenpox infection and reduce the severity of the disease. However, the efficacy of varicella vaccine was affected by vaccination years. It is recommended to improve the vaccination coverage of varicella vaccine to prevent the outbreak of the epidemic.

Comprehensive Analysis of Differentially Expressed lncRNAs in the Perivascular Adipose Tissue of Patients with Coronary Heart Disease.

Background: Coronary heart disease is a highly prevalent inflammatory disease caused by coronary atherosclerosis. Numerous studies have revealed that perivascular adipose tissue is closely associated with atherosclerosis. Here, we conducted a comprehensive analysis of long non-coding RNAs and mRNAs differentially expressed in perivascular adipose tissue in patients with coronary heart disease. Methods: We conducted Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes. Furthermore, single sample gene set enrichment analysis, immune infiltration analysis, and co-expression analysis of differentially expressed long non-coding RNAs and immune gene sets were performed. Finally, the starBase and miRTarBase databases were used to construct a competing endogenous RNA network. Results: The results show that aortic perivascular adipose tissue has higher inflammation and immune infiltration levels in patients with coronary heart disease. Dysregulated long non-coding RNAs may be related to immunity, inflammation, and hypoxia. Conclusions: The findings of this study provide new insights into atherosclerosis and coronary heart disease.