Re-evaluate the Prognostic Value of Absolute Lymphocyte Count in Pediatric Immune Thrombocytopenia.

To re-evaluate the prognostic value of absolute lymphocyte count (ALC) in pediatric immune thrombocytopenia (ITP) from the perspective of age. A total of 242 ITP pediatric patients, including 141 newly diagnosed ITP (nITP), 89 chronic ITP (cITP), and 12 persistent ITP, were retrospectively reviewed for this study. These patients were divided into 3 groups according to age (group 1, ≤24 m; group 2, 24-72 m; and group 3, >72 m). The ALC detected at admission was significantly different between nITP and cITP patients without considering their age difference (5.22 vs. 3.55×10 9 /L, P <0.001). However, no significant difference was discovered after age stratification (≤24 m: 6.52 vs. 5.34×10 9 /L, P =0.161; 24-72 m: 3.78 vs. 3.63×10 9 /L, P =0.748; > 72 m: 2.53 vs. 2.40×10 9 /L, P =0.748). ROC analysis showed that the prognostic value of ALC in ITP children was limited (area under curve (AUC): ≤24 m, 24-72 m, and >72 m were 0.591, 0.570, and 0.542, respectively). Analysis of covariance showed there was no significant difference in ALC between nITP and cITP when considering age as a covariate ( P =0.131). Instead, the ROC showing that platelet to lymphocyte ratio (PLR) has prognostic value in pediatric ITP independent of age stratification (≤24 m: AUC, 0.688; 24-72 m: AUC, 0.741; >72 m: AUC, 0.680). In conclusion, there was no significant difference of ALC between nITP and cITP patients when stratified by different age groups, and PLR may be an optional prognostic indicator for ITP.

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway.

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Positron emission tomographic studies of the association between atherogenesis and aortitis among psoriatic patients.

Introduction: There is increased interest in the use of positron emission tomography (PET) in psoriatic patients. We used PET induced with tracer fluorine-18 (18F) fluorodeoxyglucose (FDG) to study the association between the process of early-atherogenesis (eAg) and aortitis by quantifying enhanced aortic vascular inflammation along with calculation of total coronary plaque load (TCPL) and non-calcified atherosclerotic plaque load (NcAPL). In order to study the utility of aortitis in capturing eAg, we also assessed luminal stenosis atherosclerosis (LSA) and high-risk coronary plaques (HrCP). Material and methods: The study was conducted at our hospital between 1 April 2014 and 31 December 2017, and the analysis was done in July 2018. We recruited 180 consecutive psoriatic patients and subjected them to 18F-FDG PET. However, in order to characterise eAg, 160 out of 180 patients were also subjected to coronary angiographic computed tomographic studies (CACTS). Results: Among 180 psoriatic patients (76 women, 42%) (mean [SD] age, 51.1 [13.2] years), greater prevalence values of LSA (odd ratio [OR], 3.71; 95% confidence interval [CI], 1.84-7.89; p = 0.001) and HrCP (OR, 3.11; 95% CI: 1.54-6.51; p = 0.003) along with enhanced TCPL (standardised ß = 0.44; p < 0.001) were observed in patients with enhanced aortitis. However, the association between aortitis and HrCP was controlled by low-attenuation plaque (LAP), while the same between aortitis and TCPL was controlled by NcAPL (ß = 0.45; p < 0.001). Conclusions: Association between aortitis and broad coronary angiographic indices was achieved and hence predicted the possibility of a surrogate role of aortitis in eAg.

Integrative analysis and identification of key elements and pathways regulated by Traditional Chinese Medicine (Yiqi Sanjie formula) in colorectal cancer.

Introduction: The clinical efficacy of Yiqi Sanjie (YQSJ) formula in the treatment of stage III colorectal cancer (CRC) has been demonstrated. However, the underlying antitumor mechanisms remain poorly understood. Materials and methods: The aim of the present study was to comprehensively characterize the molecular and microbiota changes in colon tissues and fecal samples from CRC mice and in CRC cell lines treated with YQSJ or its main active component, peiminine. Integrative tandem mass tag-based proteomics and ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry metabolomics were used to analyze azoxymethane/dextran sulfate sodium-induced CRC mouse colon tissues. Results: The results showed that 0.8% (57/7568) of all detected tissue proteins and 3.2% (37/1141) of all detected tissue metabolites were significantly changed by YQSJ treatment, with enrichment in ten and six pathways associated with colon proteins and metabolites, respectively. The enriched pathways were related to inflammation, sphingolipid metabolism, and cholesterol metabolism. Metabolomics analysis of fecal samples from YQSJ-treated mice identified 121 altered fecal metabolites and seven enriched pathways including protein digestion and absorption pathway. 16S rRNA sequencing analysis of fecal samples indicated that YQSJ restored the CRC mouse microbiota structure by increasing the levels of beneficial bacteria such as Ruminococcus_1 and Prevotellaceae_UCG_001. In HCT-116 cells treated with peiminine, data-independent acquisition-based proteomics analysis showed that 1073 of the 7152 identified proteins were significantly altered and involved in 33 pathways including DNA damage repair, ferroptosis, and TGF-ß signaling. Conclusion: The present study identified key regulatory elements (proteins/metabolites/bacteria) and pathways involved in the antitumor mechanisms of YQSJ, suggesting new potential therapeutic targets in CRC.

Correlation Analysis Between Trace Elements and Colorectal Cancer Metabolism by Integrated Serum Proteome and Metabolome.

Colorectal cancer (CRC) is currently the third most common cancer with a high mortality rate. The underlying molecular mechanism of CRC, especially advanced CRC, remains poorly understood, resulting in few available therapeutic plans. To expand our knowledge of the molecular characteristics of advanced CRC and explore possible new therapeutic strategies, we herein conducted integrated proteomics and metabolomics analyses of 40 serum samples collected from 20 advanced CRC patients before and after treatment. The mass spectrometry-based proteomics analysis was performed under data-independent acquisition (DIA), and the metabolomics analysis was performed by ultra-performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). Trace elements including Mg, Zn, and Fe were measured by inductively coupled plasma spectrometry (ICP-MS) analysis. Four of the 20 patients had progressive disease (PD) after treatment, and clinical test results indicated that they all had impaired liver functions. In the proteomics analysis, 64 proteins were discovered to be significantly altered after treatment. These proteins were enriched in cancer-related pathways and pathways participating immune responses, such as MAPK signaling pathway and complement/coagulation cascades. In the metabolomics analysis, 128 metabolites were found to be significantly changed after treatment, and most of them are enriched in pathways associated with lipid metabolism. The cholesterol metabolism pathway was significantly enriched in both the proteomics and metabolomics pathway enrichment analyses. The concentrations of Mg in the serums of CRC patients were significantly lower than those in healthy individuals, which returned to the normal range after treatment. Correlation analysis linked key lipids, proteins, and Mg as immune modulators in the development of advanced CRC. The results of this study not only extended our knowledge on the molecular basis of advanced CRC but also provided potential novel therapeutic targets for CRC treatment.

Molecular Characterization of Advanced Colorectal Cancer Using Serum Proteomics and Metabolomics.

Colorectal cancer (CRC) is a growing public health concern due to its high mortality rate. Currently, there is a lack of valid diagnostic biomarkers and few therapeutic strategies are available for CRC treatment, especially for advanced CRC whose underlying pathogenic mechanisms remain poorly understood. In the present study, we investigated the serum samples from 20 patients with stage III or IV advanced CRC using data-independent acquisition (DIA)-based proteomics and ultra-performance liquid chromatography coupled to time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS) metabolomics techniques. Overall, 551 proteins and 719 metabolites were identified. Hierarchical clustering analysis revealed that the serum proteomes of advanced CRC are more diversified than the metabolomes. Ten biochemical pathways associated with cancer cell metabolism were enriched in the detected proteins and metabolites, including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, etc. A protein-protein interaction network in advanced CRC serum was constructed with 80 proteins and 21 related metabolites. Correlation analysis revealed conserved roles of lipids and lipid-like molecules in a regulatory network of advanced CRC. Three metabolites (hydroquinone, leucenol and sphingomyelin) and two proteins (coagulation factor XIII A chain and plasma kallikrein) were selected to be potential biomarkers for advanced CRC, which are positively and significantly correlated with CEA and/or CA 19-9. Altogether, the results expanded our understanding of the physiopathology of advanced CRC and discovered novel potential biomarkers for further validation and application to improve the diagnosis and monitoring of advanced CRC.

Design of a microfluidic chip consisting of micropillars and its use for the enrichment of nasopharyngeal cancer cells.

The aim of the present study was to discuss the design of a microfluidic chip consisting of columns, and its use for the enrichment of nasopharyngeal cancer (NPC) cells. A microfluidic chip experiment was simulated using FLUENT software. Within the microfluidic chip, aptamers were bound to the reaction chamber (consisting of columns) using a biotin-avidin system. Cell suspension was introduced into the reaction chamber to capture NPC cells. NPC cells were subsequently eluted, and the capture rate of the cells was calculated. The modified aptamer-bound microfluidic chip was able to capture NPC cells with a capture rate of ~90%. The modified aptamer-bound microfluidic chip has a wide range of potential applications for the diagnosis of NPC.