Altered small-world and disrupted topological properties of functional connectivity networks in patients with nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is a disease of the optic nerve, but its effect on brain network topology is still unclear.This study aimed to investigate brain network alterations in NAION patients and to explore their relationship with functional impairment. METHODS: Resting-state functional MRI data were collected from 23 NAION patients and 23 matched healthy control subjects.We used graph theory analysis to investigate the global and nodal network topological properties,and network-based statistical (NBS) methods were used to explore intergroup differences in functional connectivity (FC) strength. RESULTS: Compared to the control group, NAION patients had lower global efficiency, normalized clustering coefficient and small-world values and higher characteristic path length (P < 0.05). In the hub distributions of functional networks, the NAION group had one hub region disappearing and four hub regions appearing in nodal degree centrality (Dc), and two hubs disappearing and one hub region appearing in nodal betweenness centrality (Bc). The NAION group also had enhanced brain FC primarily associated with the frontal, prefrontal, parietal lobes and cerebellum. Furthermore, the right temporal pole, superior temporal gyrus (r = -0.424), the right inferior temporal gyrus (r = -0.414), the right cerebellar lobule Ⅵ (r = 0.450), and the left cerebellar lobule crus Ⅰ (r = 0.584) were significantly correlated with clinical severity. CONCLUSION: NAION patients show disruption and redistribution of FC in specific regions of the brain network, which may be associated with visual impairment.

Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.

Background and Objectives: Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Methods: This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). Results: The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. Conclusions: This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.

The relationship between women's body mass index and breast cancer outcomes was U-shaped.

Background: Several studies have analyzed the relationship between body mass index (BMI) and the prognosis of breast cancer (BC). However, whether their relationship is linear or curvilinear remains unclear. This cohort study examined the specific relationship between BMI and BC outcomes. Methods: This retrospective cohort study included 1049 BC patients from March 7, 2013 through December 31, 2019 in a hospital. Kaplan-Meier curves, multivariate Cox proportional models, and restricted cubic spline (RCS) was used to analysis the relationship between BMI and overall survival (OS) and breast cancer-specific survival (BCSS) was analyzed. Results: During a median of 4.87 (IQR:3.26-6.84) years of follow-up period, 71 patients (6.77%) died, of which 50 (70.42%) were attributed to BC. RCS analysis revealed a U- shaped relationship between BMI levels and OS and BCSS after adjusting for other variables. The turning points of the U-shaped curves were 23 kg/m2. On the left side of the turning point, the risk of OS (HR, 0.83; 95% CI, 0.70, 0.98) and BCSS (HR, 0.80; 95% CI, 0.65, 0.98) were adversely correlated with BMI. In contrast, to the right of the turning point, the risk of OS (HR, 1.22; 95% CI, 1.10, 1.37) and BCSS (HR, 1.28; 95% CI, 1.13, 1.46) was positively related to BMI. Kaplan-Meier curves and multivariate Cox regression analyses shown consistent results with RCS analyses. Conclusion: BMI was an independent prognostic factor for BC, and had a U-shaped relationship with OS and BCSS. Interventions should be designed to improve patient outcomes based on BMI.

Sex Differences in the Impact of Metabolic Dysfunction-associated Fatty Liver Disease on the of Patients with Hepatocellular Carcinoma After Radical Resection.

Background: International experts have put forward a new definition for metabolic dysfunction-associated fatty liver disease (MAFLD). Nonetheless, sex differences in MAFLD function in hepatocellular carcinoma (HCC) survival is still unknown. Therefore, the current work focused on exploring the gender-specific association of MAFLD effect on prognosis after radical resection of liver cancer. Methods: The long-term prognostic outcomes of 642 HCC patients undergoing hepatectomy were analyzed retrospectively. To calculate overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier (KM) curve was plotted. Further, using Cox proportional model to explore the prognostic factors. Sensitivity analysis was performed using propensity score matching (PSM) to balance the confounding bias. Results: For MAFLD patients, median OS and RFS times were 6.8 years and 6.1 years, respectively, compared to 8.5 years and 2.9 years in non-MAFLD patients. KM curve shown that compare with non-MAFLD patients, MAFLD patients had a higher survival rate in men, but had a lower survival rate in women (P<0.05). Multivariate analysis showed that MAFLD was significantly risk factor with mortality in the female (HR = 5.177, 95%CI: 1.475-18.193). However, MAFLD was not related to RFS This correlation was consistent after PSM analysis. Conclusions: MAFLD can improve the mortality of women undergoing radical resection for liver cancer, which independently estimate disease prognosis but is not related to recurrence-free survival.

Comprehensive landscape of the IPAF inflammasomes in pan-cancer: A bulk omics research and single-cell sequencing validation.

BACKGROUND: IPAF (ICE-protease Activating Factor) is a nucleotide-binding/leucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. METHODS: We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (http://xena.ucsc.edu/) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis: Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. RESULTS: First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8+ T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. CONCLUSION: A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.

Comprehensive pan-cancer analysis identifies cellular senescence as a new therapeutic target for cancer: multi-omics analysis and single-cell sequencing validation.

Although cellular senescence has long been recognized as an anti-tumor mechanism, mounting evidence suggests that in some circumstances, senescent cells promote tumor growth and malignancy spread. Therefore, research into the exact relationship between cellular senescence and tumor immunity is ongoing. We analyzed changes in the expression, copy number variation, single-nucleotide variation, methylation, and drug sensitivity of cellular senescence-related genes in 33 tumor types. The cellular senescence score was calculated using the single-sample gene-set enrichment analysis. The correlations between cellular senescence score and prognosis, tumor immune microenvironment (TIME), and expression of tumor immune-related genes were comprehensively analyzed. Single-cell transcriptome sequencing data were used to assess the activation state of cellular senescence in the tumor microenvironment (TME). The expression of cellular senescence-associated hub genes varied significantly across cancer types. In these genes, missense mutation was the major type of single nucleotide polymorphism, and heterozygous deletion and heterozygous amplification were the major types of copy number variation. Moreover, the cellular senescence pathway in tumors was sensitive to drugs such as XMD13-2, TPCA-1, methotrexate, and KIN001-102. Furthermore, the cellular senescence score was significantly higher in most cancer types, related to poor prognosis. The expression of immune checkpoint molecules such as NRP1, CD276, and CD44 was significantly correlated with the cellular senescence score. Monocyte cellular senescence was significantly higher in the TME of kidney renal clear cell carcinoma cells than in normal tissues. The findings of this study provide insights into the important role of cellular senescence in the TIME of human cancers and the effect of immunotherapy.

MicroRNA-24 regulates the growth and chemosensitivity of the human colorectal cancer cells by targeting RNA-binding protein DND1.

PURPOSE: This study was designed to investigate the role and therapeutic potential of miR-24 in colorectal cancer (CRC). METHODS: The CRC cell lines HCT116, RKO, SW480, SW48, and the non-cancer cell line CCD-18Co were used in the present study. The miR-24 expression was determined by qRT-PCR analysis. Cell viability was determined by MTT assay. Apoptosis was examined by acridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining. Transfection was performed by Lipofectamine 2000. Protein levels were examined by western blot analysis. RESULTS: miR-24 was significantly downregulated in CRC cell lines. Ectopic expression of miR-24 caused significant decrease in the cell viability by initiating apoptotic cell death of colorectal SW48 cancer cells, indicative of its tumor suppressive role. Moreover, miR-24 overexpression also enhanced the chemosensitivity of SW48 cells to 5-fluorouracil (5-FU). In silico analysis together with dual luciferase reporter assay indicated the RNA binding protein DND1 was the potential target of miR-24 in SW48 cells. Investigation of DND1 expression in CRC cell lines showed up to 5.3-fold upregulation of DND1. Nonetheless, ectopic expression of miR-24 in SW48 cells resulted in the downregulation of DND1 expression. Additionally, silencing of DND1 in the SW48 cells also caused inhibition of SW48 cell proliferation. Moreover, overexpression of DND1 could rescue the tumor suppressive effects of miR-24, indicating direct involvement of DND1 in the miR-24 mediated inhibitory effects on SW48 cell proliferation. CONCLUSION: The miR-24 acts as a tumor suppressor and may prove essential in the treatment of CRC.

Spatial Patterns of Decreased Cerebral Blood Flow and Functional Connectivity in Multiple System Atrophy (Cerebellar-Type): A Combined Arterial Spin Labeling Perfusion and Resting State Functional Magnetic Resonance Imaging Study.

Multiple system atrophy (MSA) is a progressive neurodegenerative disease. However, little is known about the regional cerebral blood flow (rCBF) and functional connectivity changes in the disease. In this study, the magnetic resonance imaging (MRI) data including 24MSA-c-type patients and 20 healthy controls were collected by using voxel wise arterial spin labeling (ASL) perfusion analysis, several regions of the altered rCBF were identified in the MSA c-type patients. And then, the changes of the functional connectivities of identified rCBF regions were analyzed by using functional MRI (fMRI). Finally, rCBF value of cerebellum was extracted to differentiate the MSA c-type patients and controls. Compared with the controls, the MSA c-type patients showed distinct disruption of rCBF in the cerebellum. The disconnection of the identified cerebellar regions was revealed in several regions in the MSAc-type patients, including right middle frontal gyrus (MFG), right precuneus, left superior temporal gyrus (STG), right lingual gyrus, left postcentral gyrus (PoCG), right cerebellum 7b, right cerebellum 8, and left cerebellum 4,5. These regions were involved in the default mode network (DMN), sensorimotor network, visual associated cortices, and cerebellum. Using the rCBF value of vermis as biomarker, the two groups can be differentiated and reached a sensitivity of 95.8% and specificity of 100%. This is the first study to demonstrate the MSA-specific rCBF abnormalities using the ASL method, which are closely associated with several functional networks on resting state fMRI. The rCBF of vermis might be used as the potential imaging biomarker for the early diagnosis of MSA c-type.

Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection.

OBJECTIVE: This retrospective study aimed to investigate the associations between the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and disease severity in patients with chronic HBV infection-related liver disease (CHB). METHODS: Patients with CHB were retrospectively identified. Clinical data for 172 HBV-infected patients and 40 healthy controls were collected from the electronic patient medical record system database of our hospital. RESULTS: HBV-related-compensated-cirrhosis patients (HBV-CC patients) had a significantly lower mean PLR than did other patients (P<0.001). HBV-related-decompensated-cirrhosis patients (HBV-DC patients) had a significantly higher mean NLR than did any other patients (P<0.001). In the entire cohort of CHB patients, significant correlations were observed between the PLR and both serum HBV DNA (r=0.264, P<0.001) and serum HBeAg (r=0.240, P=0.002). The PLR was significantly correlated with serum HBV DNA in both HBV-CC patients (r=-0.116, P=0.044) and HBV-DC patients (r=0.456, P=0.008). In HBV-Active-Carriers patients (HBV-AC patients), the PLR was positively correlated with serum HBeAg level (r=0.321, P=0.023). In HBV-DC patients, the NLR was positively correlated with serum HBeAg level (r=0.372, P=0.033). In the logistic regression prediction model, a predictive probability cutoff of 0.392 had the highest sensitivity and specificity (sensitivity, 91.2%; specificity, 84.0%) in distinguishing between HBV-CC and HBV-AC patients. A NLR cutoff value of 2.94 had the highest sensitivity and specificity (sensitivity, 81.8%; specificity, 88.2%) in distinguishing between HBV-DC and HBV-CC patients. CONCLUSION: The PLR and NLR partially reflect the amounts of serum HBV DNA and serum HBeAg levels circulating in CHB patients. The logistic regression model including the PLR and age most accurately distinguished between HBV-CC and HBV-AC patients. The NLR may be useful for follow-up in HBV-CC patients to predict disease progression. In summary, the PLR and NLR provided a supplementary means for effectively managing chronic HBV infection and disease.

Impaired function of the intestinal barrier in a novel sub-health rat model.

Sub-health is a state featuring a deterioration in physiological function between health and illness, and the sub-health condition has surfaced as life-threatening in humans. The aim of the present study was to establish a sub-health model in rats, and investigate the function of the intestinal barrier in the sub-health rats and rats following intervention. To establish a sub­health model, the rats were subjected to a high­fat and sugar diet, motion restriction and chronic stress. Their serum glucose and triglyceride levels, immune function and adaptability were then measured. The levels of diamine oxidase and D­lactic acid in the plasma were analyzed as markers of the intestinal permeability. The protein and mRNA expression levels of anti­apoptotic YWHAZ in the colonic tissue was detected using immunohistochemical and reverse transcription­quantitative polymerase chain reaction analyses In the present study, the sub­health rat model was successfully established, and sub­health factors increased the intestinal permeability and reduced the expression of YWHAZ. Providing sub­health rats with normal living conditions did not improve the function of the intestinal barrier. In conclusion, the results of the present study demonstrated that intestinal disorders in the sub­health rat model may result from the damage caused by reduce intestinal barrier function as well as the decreased expression levels of YWHAZ. Additionally, rats in the sub­health condition did not recover following subsequent exposure to normal living conditions, suggesting that certain exercises or medical intervention may be necessary to improve sub-health symptoms.