Von Willebrand factor promotes radiation-induced intestinal injury (RIII) development and its cleavage enzyme rhADAMTS13 protects against RIII by reducing inflammation and oxidative stress.

Patients with abdominopelvic cancer undergoing radiotherapy commonly develop radiation-induced intestinal injury (RIII); however, its underlying pathogenesis remains elusive. The von Willebrand factor (vWF)/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) axis has been implicated in thrombosis, inflammation, and oxidative stress. However, its role in RIII remains unclear. In this study, the effect of radiation on vWF and ADAMTS13 expression was firstly evaluated in patients with cervical cancer undergoing radiotherapy and C57BL/6J mice exposed to different doses of total abdominal irradiation. Then, mice with the specific deletion of vWF in the platelets and endothelium were established to demonstrate the contribution of vWF to RIII. Additionally, the radioprotective effect of recombinant human (rh) ADAMTS13 against RIII was assessed. Results showed that both the patients with cervical cancer undergoing radiotherapy and RIII mouse model exhibited increased vWF levels and decreased ADAMTS13 levels. The knockout of platelet- and endothelium-derived vWF rectified the vWF/ADAMTS13 axis imbalance; improved intestinal structural damage; increased crypt epithelial cell proliferation; and reduced radiation-induced apoptosis, inflammation, and oxidative stress, thereby alleviating RIII. Administration of rhADAMTS13 could equally alleviate RIII. Our results demonstrated that abdominal irradiation affected the balance of the vWF/ADAMTS13 axis. vWF exerted a deleterious role and ADAMTS13 exhibited a protective role in RIII progression. rhADAMTS13 has the potential to be developed into a radioprotective agent.

Uranyl Polyoxotungstate Cluster for Visible-Light-Driven Heterogeneous C-H Selective Fluorination.

The selective fluorination of C-H bonds at room temperature using heterogeneous visible-light catalysts is both interesting and challenging. Herein, we present the heterogeneous sandwich-type structure uranyl-polyoxotungstate cluster Na17{Na@[(SbW9O33)2(UO2)6(PO3OH)6]}·46H2O (denoted as U6P6) to regulate the selective fluorination of the C-H bond under visible light and room temperature. This is the first report in which uranyl participates in the fluorination reaction in the form of an insoluble substance. U6P6 is capable of the effective selective fluorination of cycloalkanes and the recyclability of the photocatalyst due to the synergistic effect of multiple uranyl (UO2)2+ and the insolubility of organic reagents of polyoxotungstate. In situ electron paramagnetic resonance spectroscopy captured the generation of cycloalkane radicals during the photoreaction, confirming the mechanism of direct hydrogen atom transfer.

Three-dimensional linkage between meteorological drought and vegetation drought across China.

Advance knowledge of the linkage between meteorological drought and vegetation drought is relevant for the risk of droughts and the impacts on vegetation health. This study employs a 3-dimensional clustering identification method to capture drought events and their characteristics (i.e., drought severity, intensity, area, center, and trajectory) in vegetated regions of China during 1982-2018. The probability of vegetation droughts, triggered by different types of drought events, is investigated by using a K-means trajectory clustering method and copula with the vegetation health index (VHI). Moreover, the impacts of moisture deficit and high temperature caused by drought on vegetation are examined with the vegetation condition index (VCI) and temperature condition index (TCI). The analysis has identified a total of 93 drought events in 1982-2018. The drought occurrences have become more concentrated in space along the time and droughts frequently occur in spring and summer. Drought events are categorized into three types, and droughts in type 1 lead to vegetation droughts with larger area, droughts in type 2 lead to vegetation droughts with stronger intensity, droughts in type 3 pose the least threat to vegetation. Additionally, the impacts of moisture deficit and high temperature have significant seasonal difference and contradictory trends over time. For example, grassland is most sensitive to moisture deficit in summer, while forest is the most sensitive to moisture deficit in spring and winter. The complex response of vegetation to drought is resulted from the combined effects of moisture and heat stress and different regional climate and vegetation types.

Megakaryocyte- and Platelet-Derived Microparticles as Novel Diagnostic and Prognostic Biomarkers for Immune Thrombocytopenia.

Altered cell-derived microparticles (MPs) have been reported in multiple autoimmune diseases. However, the roles of megakaryocyte- and platelet-derived MPs (MKMPs and PMPs) in immune thrombocytopenia (ITP) have not been investigated. In this study, we examined plasma MKMP and PMP levels in patients with ITP and evaluated their potential diagnostic values. Plasma MKMP and PMP levels were analyzed by flow cytometry in a discovery set of ITP patients (n = 78), non-immune thrombocytopenia (TP) patients (n = 69), and age- and gender-matched healthy controls (n = 88). Samples from a therapy set of ITP patients (n = 21) were used to assess the response to thrombopoietin receptor agonist (TPO-RA) treatment. Spearman correlation analysis was performed between MP levels and disease parameters. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic values of the MPs. We found that plasma MKMP and PMP levels were significantly lower in ITP patients than those in healthy controls (p values < 0.0001) but higher than in those in TP patients (p < 0.002 and p < 0.0002, respectively). After normalization to platelet counts, PMP/Platelet ratios in ITP patients were higher than those in TP patients and healthy controls (p values < 0.001). PMP/Platelet ratios had a diagnostic value for ITP (area under the curve = 0.808, p < 0.0001) with 73.1% sensitivity and 77.3% specificity. MKMP levels can be used to discriminate ITP from TP with a cut-off value of 112.5 MPs/µL and a sensitivity of 74.4%. Moreover, both MKMP and PMP levels were elevated in ITP patients who responded to TPO-RA treatment. Plasma PMP levels positively correlated with platelet counts in the responders (r = 0.558, p < 0.01). Our results indicate that plasma MKMP and PMP levels are decreased in ITP patients and that plasma MKMP and PMP levels may serve as biomarkers for ITP diagnosis and prediction of TPO-RA treatment response.

The prognostic role of fatty acid metabolism-related genes in patients with gastric cancer.

Background: With the deepening research on fatty acid metabolism, people have achieved a preliminary understanding of it in the development and prognosis of tumors. However, few studies are still on the expression pattern and prognostic value of fatty acid metabolism-related genes in gastric cancer (GC). Methods: We chose 93 genes relevant to fatty acid metabolism from the Gene Set Enrichment Analysis (GSEA) database. We analyzed differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA) patients. Univariate Cox analysis and LASSO regression were used to select the genes most related to prognosis and therefore developed a prognosis model. In addition, a dataset of 76 samples from Gene Expression Omnibus (GEO) selected as a test set to aid in the development of a prognostic model. The prognostic relevance of this model was confirmed using Kaplan-Meier survival analysis, univariate/multivariate Cox analysis, and receiver operating characteristic (ROC) curve. Finally, enrichment analysis and protein-protein interaction (PPI) were used to analyze the functional differences of patients with different risk. Immune infiltration analysis based on CIBERSORT could check the infiltration degree and immune function changes of immune cell subtypes in patients with different risk groups. Results: Overexpression of ELOVL4, ADH4, CPT1C, and ADH1B was linked to poor overall survival (OS) in GC patients, according to our findings. Furthermore, according to prognostic factors, patients with lower risk score tend to have better prognosis than patients with higher risk score. In addition, we also found that the infiltration levels of B cells, dendritic cells, auxiliary T cells, mast cells, neutrophils and tumor-infiltrating lymphocytes in patients with high-risk group were significantly increased, and the type II IFN response of immune cells, CCR and MHC class I receptor functions were significantly enhanced, suggesting that the tumor microenvironment immune activity in patients with high-risk group was active. Conclusions: Four fatty acid metabolism-related genes were discovered to be closely connected to the prognosis of individuals with GC. Through analysis and verification, we believed that this prognostic model was reliable and instructive in the prediction of the prognosis of GC.

The relationship between Helicobacter pylori and pancreatic cancer: a meta-analysis.

Background: The relationship between Helicobacter pylori (H. pylori, HP) infection and pancreatic cancer would be investigated in this article. Methods: All cohort studies and case-control studies about H. pylori infection and pancreatic cancer up to October 2021 were searched in the databases of PubMed, Embase and Cochrane. The combined odds ratio (OR) and 95% confidence interval (CI) were calculated by R 4.1.0 software. Funnel plot and Egger test were used to evaluate publication bias. Results: A total of 17 studies which included 8 case-control studies, 5 nested case-control studies, and 4 cohort studies were included in this study, and the results of this article have confirmed that the H. pylori infection was significantly correlated with the occurrence of pancreatic cancer (OR =1.30, 95% CI: 1.02-1.64), especially in economically underdeveloped areas (OR =2.10, 95% CI: 1.44-3.05). However, negative results were obtained in the relationship between CagA + H. pylori and pancreatic cancer. Similarly, we also did not find an association between vacuolating cytotoxin gene A-positive strains (VacA-positive H. pylori) and pancreatic cancer. The heterogeneity of this study was significant. Through a sensitivity analysis by the leave-one-out method, we found the results remained unchanged on the whole but the correlation between H. pylori infection and the occurrence of pancreatic cancer in the Asian population was significant. The tests for funnel plot asymmetry indicated that there might be obvious publication bias in this study. After carrying out the Egger test, we proved the existence of the publication bias in this study, which could have a certain impact on the results. Discussion: Based on the currently available data, we confirm that H. pylori infection can increase the incidence of pancreatic cancer in general. CagA/VacA-positive H. pylori infection is not associated with the incidence of pancreatic cancer. H. pylori infection is significantly associated with the incidence of pancreatic cancer in economically underdeveloped areas, while the relationship between H. pylori infection and the incidence of pancreatic cancer in the Asian population is uncertain. In addition, more high-quality studies are needed to be included to confirm this conclusion.

3.0T cardiac magnetic resonance quantification of native T1 and myocardial extracellular volume for the diagnosis of late gadolinium enhancement-negative cardiac amyloidosis.

Background: Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) is useful for the detection of cardiac amyloidosis (CA), but characteristic LGE patterns do not always occur or they appear late in the disease. Native T1 and extracellular volume (ECV) by T1 mapping may improve disease detection and quantify myocardial amyloid load. Methods: Thirty patients with definite CA, 10 patients with possible CA, 20 patients with hypertrophic cardiomyopathy (HCM) and 40 healthy volunteers were performed 3.0-T CMR including cine, pre- and postcontrast T1 mapping and LGE. Receiver-operating characteristic (ROC) curves were constructed to assess the diagnostic ability of native T1 and ECV for CA. Correlation analysis between native T1 or ECV and cardiac biomarkers, structure, and function indexes were assessed using Pearson or Spearman correlation, as appropriate. Results: Native T1 values were 1,429±93, 1,290±49, 1,304±42, and 1,225±21 ms, in definite CA, possible CA, HCM, and healthy controls, respectively. ECV values were 44%±9%, 34%±5%, 33%±4%, and 24%±3%, in definite CA, possible CA, HCM, and healthy controls, respectively. Native T1 [area under curve (AUC) =0.89, 95% confidence interval (CI): 0.75-1.00, P<0.001] and ECV (AUC =0.99, 95% CI: 0.98-1.00, P<0.001) showed good ability to differentiate LGE-negative patients with possible CA from healthy controls, especially ECV. Positive correlations were found between native T1 or ECV and New York Heart Association (NYHA) functional class (r=0.673 and r=0.594, respectively; P<0.001), NT-proBNP (r=0.668 and r=0.603, respectively; P<0.001), troponin T (r=0.724 and r=0.591, respectively; P<0.001), left ventricular (LV) mass index (r=0.668 and r=0.579, respectively; P<0.001), and global LV wall thickness (r=0.765 and r=0.629, respectively; P<0.001). Negative correlations were found between native T1 or ECV and left ventricular ejection fraction (LVEF) (r=-0.761 and r=-0.668, respectively; P<0.001) and left ventricular stroke volume (LVSV) (r=-0.777 and r=-0.729, respectively; P<0.001). Conclusions: Native T1 and ECV, which are able to reflect cardiac biochemistry, structure, and function, have high diagnostic accuracy for detecting CA, especially in LGE-negative patients, and thus could be used for early diagnosis of CA.

The prognostic value and clinical significance of mitophagy-related genes in hepatocellular carcinoma.

Background: Mitophagy has been found to play a significant part in the cancer process in a growing number of studies in recent years. However, there is still a lack of study on mitophagy-related genes' (MRGs) prognostic potential and clinical significance in hepatocellular carcinoma (HCC). Methods: We employed bioinformatics and statistical knowledge to examine the transcriptome data of HCC patients in the TCGA and GEO databases, with the goal of constructing a multigene predictive model. Then, we separated the patients into high- and low-risk groups based on the score. The model's dependability was determined using principal components analysis (PCA), survival analysis, independent prognostic analysis, and receiver operating characteristic (ROC) analysis. Following that, we examined the clinical correlations, pharmacological treatment sensitivity, immune checkpoint expression, and immunological correlations between patients in high and low risk groups. Finally, we evaluated the variations in gene expression between high- and low-risk groups and further analyzed the network core genes using protein-protein interaction network analysis. Results: Prognostic models were built using eight genes (OPTN, ATG12, CSNK2A2, MFN1, PGAM5, SQSTM1, TOMM22, TOMM5). During validation, the prognostic model demonstrated high reliability, indicating that it could accurately predict the prognosis of HCC patients. Additionally, we discovered that typical HCC treatment medicines had varying impacts on patients classified as high or low risk, and that individuals classified as high risk are more likely to fail immunotherapy. Additionally, the high-risk group expressed more immunological checkpoints. The immunological status of patients in different risk categories varies as well, and patients with a high-risk score have a diminished ability to fight cancer. Finally, PPI analysis identified ten related genes with potential for research. Conclusion: Our prognostic model had good and reliable predictive ability, as well as clinical diagnosis and treatment guiding significance. Eight prognostic MRGs and ten network core genes merited further investigation.

Association of mucin family members with prognostic significance in pancreatic cancer patients: A meta-analysis.

OBJECTIVE: The role of biomarkers in the early diagnosis and prognosis prediction of tumors has been paid more and more attention by researchers. Mucins are markers that have been found to have an abnormal expression in many tumors in recent years, which have been proved to have a predictive effect on the prognosis of tumors such as cholangiocarcinoma and colon cancer. However, whether it can predict the prognosis of pancreatic cancer remains unknown. The purpose of our study is to investigate whether the mucins and their subtypes are related to the prognosis of patients with pancreatic cancer. METHODS: We systematically searched the Pubmed, Embase, and Cochrane Library for all eligible studies on the relationship between mucin and the prognosis of patients with pancreatic cancer up to November 2021. We used R 4.12 to calculate the combined risk ratio (HR) and 95% confidence interval (CI). For studies that did not provide HR values, we used scientific methods to calculate their values as accurately as possible. We used fixed effect model due to low heterogeneity. Subgroup analysis and sensitivity analysis were used to study heterogeneity. The funnel plot and Egger test were used to test whether the publication bias existed. The trim and filling method were used to evaluate the impact of publication bias on the results of the study. RESULTS: A total of 18 studies were included in this meta-analysis, including 4 subtypes of mucin family members and 1643 patients. There was a slight heterogeneity between studies (I2 = 24.4%, P = 0.14). Meta-analysis showed that MUC4 (HR = 2.04, 95%CI 1.21;3.45), MUC16 (HR = 2.10, 95%CI 1.31;3.37), and whole mucin (HR = 1.32, 95%CI 1.07;1.63). The expression level was negatively correlated with the prognosis of pancreatic cancer patients, MUC1 (HR = 1.09, 95%CI 0.77;1.54), MUC5 (HR = 1.03, 95%CI 0.47;2.25) The expression level was not related to the prognosis of pancreatic cancer patients. CONCLUSION: The meta-analysis demonstrated that the overall expression level of mucin and the expression levels of MUC4 and MUC16 were important prognostic predictors for pancreatic cancer patients. MUC1 and MUC5 had no predictive value for the prognosis of pancreatic cancer patients. Future studies should validate these and other promising biomarkers. TRIAL REGISTRATION: PROSPERO registration number is CRD42021291962. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291962.

Establishment of a Mouse Severe Acute Pancreatitis Model using Retrograde Injection of Sodium Taurocholate into the Biliopancreatic Duct.

The prevalence of acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is increasing in younger age groups annually. However, there is a lack of effective treatments in the current clinical practice. With the easy accessibility of transgenic and knockout strains and their small size, which allows minimal doses of drugs required for in vivo evaluation, a well-established experimental model in mice is preferred for AP research. Moreover, SAP induced through sodium taurocholate (TC) is currently one of the most widely used and best characterized models. This model has been investigated for novel therapies and possible molecular events during the process of AP. Here, we present the generation of an AP mouse model using sodium taurocholate and a simple homemade microsyringe. Moreover, we also provide the methodology for the subsequent histology and serological testing.

Identification of blood-based key biomarker and immune infiltration in Immunoglobulin A nephropathy by comprehensive bioinformatics analysis and a cohort validation.

BACKGROUND: To identify the critical genes in the onset and progression of Immunoglobulin A nephropathy (IgAN) and to explore its immune cell infiltration feature. METHODS: Differentially expressed genes (DEGs) were firstly screened from 1 blood-derived dataset GSE73953 and a glomerulus derived dataset GSE93798 through limma analysis, overlap genes omitting and weighted gene correlation network analysis (WGCNA) and further reduced according to expression pattern and correlation with the clinical features: eGFR and proteinuria, followed by external validation using the GSE37460 dataset and an IgAN cohort. In addition, the CIBERSORT tool for immune cell infiltration analysis, ceRNA network construction and Connectivity Map (CMAP) were also performed. RESULTS: A total of 195 DEGs were found, and among them, 3 upregulated (ORMDL2, NRP1, and COL4A1) and 3 downregulated genes (ST13, HSPA8 and PKP4) are verified to correlate clinically, and finally ORMDL2, NRP1 and COL4A1 were validated in patient cohort and with the ability of IgAN discrimination (highest AUC was COL4A1: 97.14%). The immune cell infiltration results revealed that significant differences could be found on resting memory CD4 T cells, activated NK cells, and M2 macrophages between control and IgAN. CONCLUSIONS: Our results demonstrated here that significantly upregulated DEGs: ORMDL2, NRP1 and COL4A1, could be served as the diagnostic marker for IgAN, and dysregulated immune cell infiltration hinted possible the immune system intervention point in the setting of IgAN.

Asymmetric Cyanosilylation of Aldehydes by a Lewis Acid/Base Synergistic Catalyst of Chiral Metal Clusters.

Metal clusters with well-defined crystal structures are extremely useful for studying the synergistic catalytic effects and associated catalytic mechanisms. In this study, two pairs of chiral lanthanide-transition metal clusters (R)/(S)-Co3Ln2 (Ln = Tb or Dy) were synthesized using Schiff-base ligands [(R)- or (S)-H3L] with multiple Lewis base sites (O sites). The as-prepared (R)/(S)-Co3Ln2 chiral metal clusters exhibited good catalytic functionality in the asymmetric synthesis of chiral cyanohydrins, with high conversions of up to 99% and medium-to-high enantiomeric excess values of up to 78%. The catalysis process followed a mechanism in which the bifunctional metal clusters of (R)/(S)-Co3Ln2, containing Lewis acid sites and Lewis base sites, simultaneously activated the aldehydes and trimethylsilyl cyanide, respectively. Consequently, synergistic catalysis was realized. The enantioselectivity of the different aldehydes and stereochemical configuration of the resulting products are attributed to the formation of a steric chiral pocket via the external chiral ligands on the clusters. In addition, heterogeneous asymmetric cyanosilylation using (R)/(S)-Co3Ln2 chiral metal clusters achieved high chemoselectivity and regioselectivity under mild conditions.

(cRGD)2 peptides modified nanoparticles increase tumor-targeting therapeutic effects by co-delivery of albendazole and iodine-131.

Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.

Impacts of the SARS-CoV-2 Pandemic on Young Adult Colorectal Cancer Survivors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has disrupted health care globally with dramatic impacts on cancer care delivery in addition to adverse economic and psychological effects. This study examined impacts of the SARS-CoV-2 pandemic on young adult colorectal cancer (CRC) survivors diagnosed age 18-39 years. Nearly 40% reported delays in cancer-related care, loss of income, and poorer mental health during the pandemic. Impacts were greater for survivors aged 20-29 years, with nearly 60% reporting cancer care delays and 53% experiencing income loss. Such impacts may result in detrimental downstream outcomes for young CRC survivors, requiring specific support, resources, and continued monitoring.

Enantioselective Recognition and Separation of C2 Symmetric Substances via Chiral Metal-Organic Frameworks.

A promising route toward the enantioselective recognition and separation of racemic molecules is the design of chiral metal-organic frameworks (CMOFs) with high enantioselectivity and stability. Herein, we report porous CMOFs Δ- and Λ-RuEu-MOFs constructed from the D3-symmetry helical chiral Ru(phen)3-derived tricarboxylate ligand and Eu2 units, which can be utilized as adsorbents for the enantioselective recognition and separation of 1,1'-bi-2-naphthol (BINOL) derivatives. Investigation of the circular dichroism enantiodifferentiation between the host and guest suggested that Δ- and Λ-RuEu-MOFs can be employed as chiral sensors to discriminate axial enantiomers due to their diastereomeric host-guest relationship. Density functional theory calculations reveal that chiral recognition is attributed to the distinguishing binding affinities stemming from N···H-O hydrogen bonds and π-π stacking between the host and guest. Moreover, the reticulate structure of Δ- and Λ-RuEu-MOFs can be readily recycled and reused for the successive enantioselective separation of BINOL up to 80% ee.

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease.

BACKGROUND: A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. METHODS: Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. RESULTS: Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. CONCLUSIONS: Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

Time from Diagnosis and Correlates of Health-Related Quality of Life among Young Adult Colorectal Cancer Survivors.

The incidence of colorectal cancer (CRC) is rising among young adults. Health-related quality of life (HRQoL) in survivorship is not well-described in this population. We assessed HRQoL among young adult CRC survivors diagnosed from age 18-39 (AYAs) to examine differences by time from diagnosis, and to identify key correlates. A cross-sectional online survey was administered in collaboration with a national patient advocacy organization. The Functional Assessment of Cancer Therapy (FACT-C) was used to measure HRQoL, which assesses HRQoL globally and across 4 domains: emotional, physical, social, and functional. T-tests were conducted to compare HRQoL between survivors who were 6-18 months versus 19-36 months from diagnosis or relapse and multiple linear regression was conducted to identify correlates. The sample (n = 196) had a mean age of 32.2(SD ± 4.5); 116 (59.9%) were male; and the self-reported tumor location was colon (39.3%) or rectal (60.7%). The majority (56.4%) were diagnosed with stage 2 disease; 96.9% were non-metastatic. The mean global HRQoL score was 67.7 out of a possible score of 136. Across domains, mean scores were low. Emotional and physical well-being were significantly higher among survivors who were 19-36 months from diagnosis/relapse compared to those 6-18 months from diagnosis/relapse. Longer time from diagnosis and older current age were associated with higher HRQoL, while more intensive treatment and higher clinical disease stage were negatively associated, particularly in the emotional and physical domains. Overall, HRQoL was low in this population, and further research is needed to inform age-appropriate interventions to improve HRQoL for AYA CRC survivors.

A 14-gene gemcitabine resistance gene signature is significantly associated with the prognosis of pancreatic cancer patients.

To identify a gemcitabine resistance-associated gene signature for risk stratification and prognosis prediction in pancreatic cancer. Pearson correlation analysis was performed with gemcitabine half maximal inhibitory concentration (IC50) data of 17 primary pancreatic cancer lines from Genomics of Drug Sensitivity in Cancer (GDSC) and the transcriptomic data from GDSC and Broad Institute Cancer Cell Line Encyclopedia, followed by risk stratification, expression evaluation, overall survival (OS) prediction, clinical data validation and nomogram establishment. Our biomarker discovery effort identified a 14-gene signature, most of which featured differential expression. The 14-gene signature was associated with poor OS in E-MTAB-6134 (HR 2.37; 95% CI 1.75-3.2; p < 0.0001), pancreatic cancer-Canada (PACA-CA) (HR 1.76; 95% CI 1.31-2.37; p = 0.00015), and 4 other independent validation cohorts: pancreatic cancer-Australia (PACA-AU) (HR 1.9; 95% CI 1.38-2.61; p < 0.0001), The Cancer Genome Atlas (TCGA) (HR 1.73; 95% CI 1.11-2.69; p = 0.014), GSE85916 (HR 1.97; 95% CI 1.14-3.42; p = 0.014) and GSE62452 (HR 1.82; 95% CI 1.02-3.24; p = 0.039). Multivariate analysis revealed that the 14-gene risk score was an independent pancreatic cancer outcome predictor in E-MTAB-6134 (p < 0.001) and TCGA (p = 0.006). A nomogram including the 14-gene was established for eventual clinical translation. We identified a novel gemcitabine resistance gene signature for risk stratification and robust categorization of pancreatic cancer patients with poor prognosis.

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis.

PURPOSE: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. METHODS: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. RESULTS: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. CONCLUSIONS: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.

Association between cytokine profiles and lung injury in COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. METHODS: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. RESULTS: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (ß = 0.397, p < 0.001) and PaO2/FiO2 (ß = - 0.434, p = 0.003). CONCLUSIONS: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.