Eltrombopag can promote platelet implantation after allogeneic hematopoietic stem cell transplantation as safely and similarly to thrombopoietin.

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50 mg/d from +1 day until PLT >50 × 109/L or 1 month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, the median time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT \counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT.

High Tribocatalytic Performance of FeOOH Nanorods for Degrading Organic Dyes and Antibiotics.

Tribocatalysis is vitally important for electrochemistry, energy conservation, and water treatment. Exploring eco-friendly and low-cost tribocatalysts with high performance is crucial for practical applications. Here, the highly efficient tribocatalytic performance of FeOOH nanorods is reported. The factors related to the tribocatalytic activity such as nanorod diameter, surface area, and surface roughness are investigated, and the diameter of the FeOOH nanorods is found to have a significant effect on their tribocatalytic performance. As a result, under ultrasonic excitation, the optimized FeOOH nanorods exhibit superior tribocatalytic degradation toward rhodamine B (RhB), acid orange 7, methylene blue, methyl orange dyes, and their mixture. The RhB and mixed dyes are effectively degraded within 20 min (k = 0.179 min-1 ) and 35 min (k = 0.089 min-1 ), respectively, with the FeOOH nanorods showing excellent reusability. Moreover, antibiotics, such as tetracycline hydrochloride, phenol, and bisphenol A are efficiently degraded. Investigation of the catalytic mechanism reveals that the friction-generated h+ as well as these yielded •OH and •O2 - active radicals participate in the catalytic reaction. This work not only shed light on the design of high-performance tribocatalyst but also demonstrates that by harvesting mechanical energy, the FeOOH nanorods are promising materials for removing organic contaminants in wastewater.

Characteristics of Molecular Genetic Mutations and Their Correlation with Prognosis in Adolescent and Adult Patients with Acute Lymphoblastic Leukemia.

INTRODUCTION: The prognosis of acute lymphoblastic leukemia (ALL) in adolescents and adults is poor, and recurrence is an important cause of their death. Changes of genetic information play a vital role in the pathogenesis and recurrence of ALL; however, the impact of molecular genetic mutations on disease diagnosis and prognosis remains unexplored. This study aimed to explore the frequency spectrum of gene mutations and their prognostic significance, along with the minimal residual disease (MRD) level and hematopoietic stem cell transplantation (HSCT), in adolescent and adult patients aged ≥15 years with ALL. METHODS: The basic characteristics, cytogenetics, molecular genetics, MRD level, treatment regimen, and survival outcome of patients with untreated ALL (≥15 years) were collected, and the correlation and survival analysis were performed using the SPSS 25.0 and R software. RESULTS: This study included 404 patients, of which 147 were selected for next-generation sequencing (NGS). NGS results revealed that 91.2% of the patients had at least one mutation, and 67.35% had multiple (≥2) mutations. NOTCH1, PHF6, RUNX1, PTEN, JAK3, TET2, and JAK1 were the most common mutations in T-ALL, whereas FAT1, TET2, NARS, KMT2D, FLT3, and RELN were the most common mutations in B-ALL. Correlation analysis revealed the mutation patterns, which were significantly different between T-ALL and B-ALL. In the prognostic analysis of 107 patients with B-ALL, multivariate analysis showed that the number of mutations ≥5 was an independent risk factor for overall survival and the RELN mutation was an independent poor prognostic factor for event-free survival. DISCUSSION: The distribution of gene mutations and the co-occurrence and repulsion of mutant genes in patients with ALL were closely related to the immunophenotype of the patients. The number of mutations ≥5 and the RELN mutation were significantly associated with poor prognosis in adolescent and adult patients with ALL.

Appraising the role of circulating concentrations of micronutrients in attention deficit hyperactivity disorder: a Mendelian randomization study.

Previous observational researches have discovered a connection between circulating concentrations of micronutrients and attention deficit hyperactivity disorder (ADHD). However, the results may be influenced by confounding factors and reverse causation. This study aims to explore the causal relationship between circulating concentrations of micronutrients and ADHD using Mendelian randomization (MR). In a two-sample MR context, we used summary data from the major European genome-wide association studies (GWAS) for these illnesses to assess the genetically anticipated effects of circulating concentrations of micronutrients on ADHD risk. In order to achieve this, we took single nucleotide polymorphisms (SNPs) from the GWAS that were highly related with concentrations of nine micronutrients. The corresponding data for ADHD were extracted from the Psychiatric Genomics Consortium. Inverse-variance weighted (IVW) method was used as the main MR analysis, and the reliability of the study's conclusions was assessed using sensitivity analyses. Our MR analyses showed that the copper level may be associated with a reduced risk of ADHD. However, the significance of the research results is weak. There were no clear relationships between other micronutrients and ADHD. Our sensitivity studies confirmed the findings of the primary IVW MR analyses. According to this study, there may be some association between copper level and ADHD, but the significance of the research results is weak, and it is recommended that copper level should be used as a long-term monitoring indicator for further research. The results provide a new idea for the further study of ADHD, and provide guidance for the prevention and treatment of ADHD.

Psychiatric disorders and cardiovascular diseases: A mendelian randomization study.

Background: Previous researches have demonstrated a connection between psychiatric disorders and cardiovascular diseases (CVDs), but the cause-and-effect relationship is still unclear. To that goal, the mendelian randomization (MR) method was used to study the causal link between psychiatric disorders and CVDs. Methods: Genome-wide association studies (GWAS) data were collected for four CVDs, including coronary artery disease (n = 547,261), atrial fibrillation (n = 537,409), heart failure (n = 977,323) and ischemic stroke (n = 440,328). Summary data for four psychiatric disorders, including bipolar disorder (n = 51,710), major depressive disorder (n = 480,359), schizophrenia (n = 127,906) and attention deficit hyperactivity disorder (n = 55,374), came from the Psychiatric Genomics Consortium (PGC). All participants were European. The IVW method was mainly used, and the reliability of the results was increased using sensitivity analyses such as MR-Egger, Cochrane's Q test, MR-PRESSO and leave-one-out. Results: MR revealed that the attention deficit hyperactivity disorder was linked to an increased risk of atrial fibrillation (OR, 1.085; 95% CI, 1.021-1.153; P = 0.008), heart failure (OR, 1.117; 95% CI, 1.044-1.195; P = 0.001), and ischemic stroke (OR, 1.146; 95% CI, 1.052-1.248; P = 0.002). The schizophrenia was linked to an increased risk of heart failure (OR, 1.035; 95% CI, 1.006-1.066; P = 0.017), but was found to be suggestively inverse associated with coronary artery disease (OR, 0.969; 95% CI, 0.941-0.997; P = 0.03). The major depressive disorder was associated with higher odds of coronary artery disease (OR, 1.109; 95% CI, 1.018-1.208; P = 0.018), while the bipolar disorder was linked to a reduced incidence of coronary artery disease (OR, 0.894; 95% CI, 0.831-0.961; P = 0.002) and heart failure (OR, 0.889; 95% CI, 0.829-0.955; P = 0.001). There were no clear relationships between other psychiatric disorders and CVDs. Conclusion: The results provide genetic proof of a possible causal relationship between psychiatric disorders and CVDs. These results imply that psychiatric disorders may be the cause of some CVDs, and that some abnormal mental states may increase or reduce the likelihood of CVDs, providing guidance for the CVDs prevention.

Establishment of a prognostic model for melanoma based on necroptosis-related genes.

In this study, the clinical implications and potential functions of necroptosis-related genes (NRGs) in melanoma were systematically characterized. A novel NRG signature was then constructed to analyze the immune status and prognosis of patients with melanoma. The NRG signatures for melanoma prognosis were searched using the Cancer Genome Atlas (TCGA) dataset and followed by stepwise Cox regression analysis. Patients with melanoma were divided into two groups, and survival analysis, receiver operating characteristic (ROC), and univariate and multivariate analyses were subsequently performed. The correlation of risk score (RS) with tumor immunity and RT-polymerase chain reaction (PCR) was analyzed to further verify the gene signatures. Data on tumor mutational burden (TMB) and chromosomal copy number variation (CNV) were analyzed. Three NRGs were identified as prognostic risk signatures and were significantly related to overall survival (OS) in melanoma. The signatures had better diagnostic accuracy. Furthermore, analysis of mutations in the NRGs and the incidence of chromosomal CNV helped to reveal the relationship between mutations and melanoma occurrence. A nomogram was established based on RSs. The risk characteristics were significantly associated with immunity and high risk is closely correlated with melanoma development. In vitro experiments revealed that necrostatin-1 (Nec-1) promoted cell viability and repressed the expression levels of interleukin (IL)12A and proprotein convertase subtilisin/kexin type (PCSK)1. Additionally, the expression levels of IL12A, CXCL10, and PCSK1 decreased in tumor tissues of melanoma patients. NRGs exert vital roles in immunity and might be applied as a prognostic factor of melanoma.

Identification of ORM1, vWF, SPARC, and PPBP as immune-related proteins involved in immune thrombocytopenia by quantitative LC-MS/MS.

BACKGROUND: Immune thrombocytopenia (ITP) is a common autoimmune disease characterized by loss of immune tolerance to platelet autoantigens leading to excessive destruction and insufficient production of platelets. METHOD: Quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed to detect the differentially expressed proteins in bone marrow samples from active ITP patients and normal controls. RESULT: Our bioinformatic analysis identified two upregulated proteins (ORM1 and vWF) and two downregulated proteins (PPBP and SPARC) related to immune function. The four proteins were all found to be related to the tumor necrosis factor (TNF) -α signalling pathway and involved in the pathogenesis of ITP in KEGG pathway analysis. CONCLUSION: Bioinformatics analysis identified differentially expressed proteins in bone marrow that are involved in the TNF-α signalling pathway and are related to the activation of immune function in ITP patients. These findings could provide new ideas for research on the loss of immune tolerance in ITP patients.

PAX5 aberrant expression incorporated in MIPI-SP risk scoring system exhibits additive value in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma with highly heterogeneous clinical courses. Paired-box 5 (PAX5), the regulator of B cell differentiation and growth, is abnormally expressed in several types of cancers. Herein, we explored the prognostic value of PAX5 in MCL by comprehensively analyzing the clinical features and laboratory data of 82 MCL cases. PAX5 positivity was associated with shorter overall survival (OS; p = 0.011) and was identified as an independent prognostic factor in MCL patients. The elevated ß2-MG (p = 0.027) and advanced Mantle Cell Lymphoma International Prognostic Index (MIPI) score (p = 0.014) were related to positive PAX5 expression. The MIPI-SP risk scoring system was established and exhibited a superior prognostic value for OS depending on an area under the curve (AUC) of 0.770 (95% CI, 0.658-0.881) than MIPI score. Bioinformatic analysis of PAX5-related genes supported the mechanistic roles of PAX5 in MCL. This study provides insight into the potential role of PAX5 in MCL, and the novel risk scoring system MIPI-SP optimizes the risk stratification and facilitates prognosis evaluation in MCL patients. KEY MESSAGES: • Paired-box 5 positivity indicated adverse prognosis in mantle cell lymphoma patients. • Positive PAX5 expression was related to MIPI score and ß2-MG in MCL patients. • MIPI-SP risk scoring system has superior prognostic value than MIPI score in MCL.

Construction of a prognostic model of luteolin for endometrial carcinoma.

OBJECTIVE: Endometrial cancer is one of the most common tumors of the female reproductive system, and the existing treatment options for advanced and metastatic endometrial cancer have certain limitations. The antitumor activity of luteolin has been gradually discovered. The purpose of this study was to predict the potential of luteolin in the treatment of endometrial cancer and to provide reference for future clinical drug use. METHODS: The target gene database of luteolin and differential gene dataset of uterine corpus endometrial carcinoma (UCEC) have been constructed to obtain the differential genes (DR-DEGs) for luteolin and UCEC. The Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis are performed at the same time. Genes associated with prognosis in DR-DEGs were screened and validated using univariate and multivariate COX risk regression analysis so as to construct a prognostic model. Genes are divided into high-risk and low-risk groups according to risk scores for survival analysis and the predictive effect of the model is evaluated. The role of immune function in UCEC is investigated by immune infiltration and immune checkpoint analysis Finally, Transwell experiment was conducted to investigate the effect of luteolin on the migration ability of endometrial cancer cells, and the expression changes of MMP1, IL-17 and VEGF were detected by q-PCR. RESULTS: Through the GO, KEGG and GSEA enrichment analysis, we have found a significant enrichment in "IL 17 signaling (IL-17) pathway", "oxidative stress response" and "HOMOLOGOUS_RECOMBINATION". Through multivariate COX risk regression analysis, four genes associated with the prognosis are harvested, including "PRSS1, MMP1, ERBB2 and NUF2" which belong to high-risk genes. Kaplan-Meier analysis shows that the survival rate in the high risk group is lower than that in the low risk group, and the receiver operating characteristic (ROC) curve reveals that the predictive effect of the model is good and stable (area under 1-year curve (AUC) 0.569, two-year AUC 0.628 and three-year AUC 0.653). Immune infiltration and immune checkpoint analysis suggest that "CD40", "T cells regulatory (Tregs)", "dendritic cells resting" and "dendritic cells activated" are correlated with survival and prognosis in UCEC patients. In in vitro experiments, we found that the migration ability of endometrial cancer cells was significantly reduced after luteolin treatment, and the expressions of MMP1, IL-17 and VEGF were all decreased. CONCLUSION: Through bioinformatic analysis, we found that luteolin could slow down the progression of UCEC by inhibiting the production of inflammatory mediators such as IL-17 and oxidative stress, and constructed genetic prognostic models associated with them: PRSS1, MMP1, ERBB2 and NUF2, respectively. In addition, we found that luteolin has an inhibitory effect on the migration of endometrial cancer cells and can reduce the expressions of MMP1, IL-17 and VEGF, thus easing the progression of endometrial cancer.

Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis.

BACKGROUND: Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. Twenty newly diagnosed active primary ITP patients who had not been treated with glucocorticosteroids, immune globulin or immunosuppressants prior to sampling were enrolled in this study. Bone marrow blood mononuclear cells were used for whole exome sequencing to further elucidation the variant genes of ITP. METHODS: High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing, and the results were confirmed by Sanger sequencing. The signaling pathways and cellular processes associated with the mutated genes were identified with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. RESULTS: The results showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including phosphatase and tensin homolog, insulin receptor, and coagulation factor C homology were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B signaling pathways (signal transduction) and platelet activation (immune system). CONCLUSION: Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.

Effects of selenium supplementation on Polycystic Ovarian Syndrome: a systematic review and meta-analysis on randomized clinical trials.

BACKGROUND: This study provides a systematic review and meta-analysis of randomized controlled trials, which examined the effect of the selenium supplementation on polycystic ovary syndrome (PCOS). METHODS: Confirmed studies related to selenium supplementation and PCOS were searched from the databases of EMBASE, PubMed and Web of Science. Data were reported as weighted mean difference (WMD) or standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis was performed with Stata version 12.0. RESULTS: A total of 389 cases (selenium group n = 195, control group n = 194) were included in this studies. This meta-analysis showed that selenium supplementation has a positive effect on TAC, and supplementation of selenium does not significantly improve the level of BMI, Weight, LDL, HDL, Triglycerides, Total Testosterone, HOMA-IR, NO, GSH, MDA and FPG. CONCLUSION: Although selenium can improve TAC in PCOS patients, it has no significant effect on BMI, Total Testosterone, et al. In terms of the results of this meta-analysis, it is not recommended for patients with PCOS to use selenium as a regular trace element supplement. Based on the improving effect of selenium on TAC, supplementation of selenium may have a positive effect on improving follicle quality for some PCOS patients who have poor follicle quality caused by oxidative stress or who want to undergo IVF.

The Absence of IL-12Rß2 Expression on Recipient Nonhematopoietic Cells Diminishes Acute Graft-versus-Host Disease in the Gastrointestinal Tract.

The gastrointestinal (GI) tract is a frequent target organ in acute graft-versus-host disease (aGVHD), which can determine the morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells recognize allogeneic Ags presented by host APCs, proliferate, and differentiate into Th1 and Th17 cells that drive GVHD pathogenesis. IL-12 has been shown to play an important role in amplifying the allogeneic response in preclinical and clinical studies. This study demonstrates that IL-12Rß2 expression on recipient nonhematopoietic cells is required for optimal development of aGVHD in murine models of allo-HCT. aGVHD attenuation by genetic depletion of IL-12R signaling is associated with reduced MHC class II expression by intestinal epithelial cells and maintenance of intestinal integrity. We verified IL-12Rß2 expression on activated T cells and in the GI tract. This study, to our knowledge, reveals a novel function of IL-12Rß2 in GVHD pathogenesis and suggests that selectively targeting IL-12Rß2 on host nonhematopoietic cells may preserve the GI tract after allo-HCT.

Necroptosis-Related LncRNA Signatures for Prognostic Prediction in Uterine Corpora Endometrial Cancer.

Necroptosis is one of the common modes of apoptosis, and it has an intrinsic association with cancer prognosis. However, the role of the necroptosis-related long non-coding RNA LncRNA (NRLncRNAs) in uterine corpora endometrial cancer (UCEC) has not yet been fully elucidated at present. Therefore, the present study is designed to investigate the potential prognostic value of necroptosis-related LncRNAs in UCEC. In the present study, the expression profiles and clinical data of UCEC patients were downloaded from TCGA database to identify the differentially expressed NRLncRNAs associated with overall survival. A LncRNA risk model was constructed via Cox regression analysis, and its prognostic value was evaluated. We have also further evaluated the relationships between the LncRNA features and the related cellular function, related pathways, immune status, and immune checkpoints m6A-related genes. Seven signatures, including PCAT19, CDKN2B-AS1, LINC01936, LINC02178, BMPR1B-DT, LINC00237, and TRPM2-AS, were established to assess the overall survival (OS) of the UCEC in the present study. Survival analysis and ROC curves indicated that the correlated signature has good predictable performance. The normogram could accurately predict the overall survival of the patients with an excellent clinical practical value. Enrichment analysis of gene sets indicated that risk signals were enriched in several immune-related pathways. In addition, the risk characteristics were significantly correlated with immune cells, immune function, immune cell infiltration, immune checkpoints, and some m6A-related genes. This study has identified seven necroptosis-related LncRNA signatures for the first time, providing a valuable basis for a more accurate prognostic prediction of UCEC.

Mechanism investigation and experiment validation of capsaicin on uterine corpus endometrial carcinoma.

Background: Using bioinformatics analysis and experimental operations, we intend to analyze the potential mechanism of action of capsaicin target gene GATA1 in the treatment of uterine corpus endometrial carcinoma (UCEC) and develop a prognostic model for the disease to validate this model. Methods: By obtaining capsaicin and UCEC-related DR-DEGs, the prognosis-related gene GATA1 was screened. The survival analysis was conducted via establishing high and low expression groups of GATA1. Whether the GATA1 could be an independent prognostic factor for UCEC, it was also validated. The therapeutic mechanism of capsaicin-related genes in UCEC was further investigated using enrichment analysis and immune methods as well as in combination with single-cell sequencing data. Finally, it was validated by cell experiments. Results: GATA1, a high-risk gene associated with prognosis, was obtained by screening. Kaplan-Meier analysis showed that the survival of the high expression group was lower than that of low expression group. ROC curves showed that the prediction effect of the model was good and stable (1-year area under curve (AUC): 0.601; 2-years AUC: 0.575; 3-years AUC: 0.610). Independent prognosis analysis showed that the GATA1 can serve as an independent prognostic factor for UCEC. Enrichment analysis showed that "neuroactive Ligand - receptor interaction and TYPE I DIABETES MELLITUS" had a significant enrichment effect. Single-cell sequencing showed that the GATA1 was significantly expressed in mast cells. Cell experiments showed that the capsaicin significantly reduced the UCEC cell activity and migration ability, as well as inhibited the expression of GATA1. Conclusion: This study suggests that the capsaicin has potential value and application prospect in the treatment of UCEC. It provides new genetic markers for the prognosis of UCEC patients.

S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission.

Graft-versus-host disease (GVHD) significantly contributes to patient morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT). Sphingosine-1-phosphate (S1P) signaling is involved in the biogenetic processes of different immune cells. In the current study, we demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P. Using genetic and pharmacologic approaches, we demonstrated that inhibition of Sphk1 or S1PR1 substantially attenuated acute GVHD (aGVHD) while retaining the graft-versus-leukemia (GVL) effect. At the cellular level, the Sphk1/S1P/S1PR1 pathway differentially modulated the alloreactivity of CD4+ and CD8+ T cells; it facilitated T-cell differentiation into Th1/Th17 cells but not Tregs and promoted CD4+ T-cell infiltration into GVHD target organs but was dispensable for the CTL activity of allogeneic CD8+ T cells. At the molecular level, the Sphk1/S1P/S1PR1 pathway augmented mitochondrial fission and increased mitochondrial mass in allogeneic CD4+ but not CD8+ T cells by activating the AMPK/AKT/mTOR/Drp1 pathway, providing a mechanistic basis for GVL maintenance when S1P signaling was inhibited. For translational purposes, we detected the regulatory efficacy of pharmacologic inhibitors of Sphk1 and S1PR1 in GVHD induced by human T cells in a xenograft model. Our study provides novel mechanistic insight into how the Sphk1/S1P/S1PR1 pathway modulates T-cell alloreactivity and validates Sphk1 or S1PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse. This novel strategy may be readily translated into the clinic to benefit patients with hematologic malignancies and disorders.

Necroptosis-related lncRNA signature predicts prognosis and immune response for cervical squamous cell carcinoma and endocervical adenocarcinomas.

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent.

Effects of antioxidant intervention in patients with polycystic ovarian syndrome: A systematic review and meta-analysis.

BACKGROUND: The role of antioxidant intervention in polycystic ovary syndrome (PCOS) patients has been increasingly investigated in recent years. In order to further clarify whether antioxidant therapy is beneficial for PCOS patients and the emphasis of its effects, this study provides a systematic review and meta-analysis of randomized controlled trials examining the effect of antioxidant intervention on PCOS. METHODS: Enrolled study designs related to antioxidant interventions and PCOS, published from 1999 to 2020, were searched from EMBASE, PubMed, and Web of Science databases to sort out proven studies on antioxidant interventions and PCOS. Data were reported as weighted mean difference (WMD) or standard mean difference with associated confidence intervals of 95%. The analysis was conducted using Stata version 16.0. RESULTS: Twenty-three studies were included in total. Antioxidant intervention had a positive impact on homeostasis model assessment of insulin resistance (WMD = -0.37, P = .011) and Triglycerides (WMD = -25.51, P < .001). And antioxidant intervention did not improve testosterone levels significantly (WMD = -0.20, P = .2611). Subgroup analysis showed that except for the D-chiro-inosito subgroup, no difference in body mass index was observed between the intervention group and the control group. CONCLUSIONS: This meta-analysis demonstrates the efficacy of antioxidant intervention in patients with PCOS, demonstrating that antioxidant intervention has a significant effect on insulin resistance and lipid metabolism improvement. However, antioxidant intervention therapy has no discernible impact on testosterone levels or body mass index. Omega-3 may be a more effective antioxidant intervention for PCOS. In addition, this meta-analysis provides important reference opinions and treatment recommendations for PCOS.

High-throughput DNA methylation analysis in ITP confirms NOTCH1 hypermethylation through the Th1 and Th2 cell differentiation pathways.

BACKGROUND: Immune thrombocytopenia (ITP) is a prevalent autoimmune disease with a complex aetiology where DNA methylation changes are becoming triggers. METHOD: To investigate novel abnormally methylated genes in the pathogenesis of ITP, we performed a high-throughput methylation analysis on 21 ITP patients and 9 normal control samples. We analysed the extent of key methylated genes and their downstream cytokines through Luminex assay or qRT-PCR. Then, bone marrow mononuclear cells were extracted from ITP patients, and decitabine (demethylation drug) was added to the culture medium of cultured cells. qRT-PCR and ELISA were used to detect whether decitabine could effectively affect target genes and related cytokines. RESULTS: Through the STRING and Metascape databases, hypermethylated NOTCH1 can be identified and can influence ITP by regulating many downstream cytokines through Th1 and Th2 cell differentiation pathways. Compared with those in the normal control group, the expression levels of NOTCH1 and its downstream Th2 cytokines (IL-4, IL-10, and GATA3) were significantly decreased and those of Th1 cytokines (IFN-γ, IL-12, and TNF-α) were significantly increased in the ITP group. Decitabine exerts its demethylation effect, so the expression of NOTCH1 and its related cytokines in the ITP group treated with 100 nM decitabine were significantly reversed. CONCLUSIONS: Our results suggest that the pathogenesis of ITP may exert its influence on epigenetics through alteration of DNA methylation at regulatory regions of the target NOTCH1 gene in the Th1 and Th2 cell differentiation pathways. At the same time, decitabine may achieve a therapeutic effect on ITP by demethylation.

The effect of metformin on low birth weight girls with precocious puberty: A protocol for systematic review and meta-analysis.

BACKGROUND: In recent years, the role of metformin in girls with precocious puberty (PP) has been increasingly frequently studied. The objective of this present study is to assess the effect of metformin on low birth weight girls with precocious puberty (LBW-PP girls). METHODS: We search the confirmed studies about circulating metformin and PP from the databases of EMBASE, PubMed, and Web of Science. Data were reported as weighted mean difference (WMD) and associated 95% confidence intervals (CIs). Analysis was performed by Review Manager 5.3 and Stata version 12.0. RESULTS: A total of 205 cases (metformin group n = 102, untreated group n = 103) were included in this study. The meta-analysis of randomized controlled trials (RCTs) suggested that metformin had statistically significant effects on testosterone (P = .001), androstenedione (P = .022), bone mineral density (BMD; P = .151), triglycerides (P ≤ .001), body mass index Z score (BMI Z score; P ≤ .001), dehydroepiandrosterone-sulfate (DHEAS; P = .053), sex hormone-binding globulin (SHBG; P = .049), high-density lipoprotein (HDL) cholesterol (P ≤ .001), low-density lipoprotein (LDL) cholesterol (P = .021), fat mass (P ≤ .001), lean mass (P = .025), and fasting insulin (P = .002). CONCLUSION: This meta-analysis provided evidence of the efficacy of metformin in girls with LBW-PP girls, which proved that metformin could improve metabolism and reduce weight. Metformin had a positive effect on preventing LBW-PP girls from developing into obesity and polycystic ovarian syndrome. In addition, this meta-analysis provided important reference opinions and directions for the treatment of LBW-PP girls.

Exploring the mechanism and experimental verification of puerarin in the treatment of endometrial carcinoma based on network pharmacology and bioinformatics analysis.

Endometrial carcinoma is one of the two cancers with rising mortality and morbidity in recent years. In the light of many controversies about its treatment, it is urgent to construct a new prognostic model and to find out new therapeutic directions. As a small drug molecule widely used in clinical treatment and experimental research in China, puerarin has recently been proven to have obvious anti-cancer effects in multiple cancer cells. In this study, bioinformatics analysis and experimental validation were used to explore the potential mechanism of puerarin for endometrial carcinoma and construct a prognostic model. A total of 22 drug-related differential genes were found by constructing a database of drug targets and disease genes. The protein-protein interaction network was constructed for GO and KEGG enrichment analysis to initially explore the potential mechanism of its therapeutic effects. To construct the prognostic model, validation was performed by risk regression analysis and LASSO analysis. Finally, two prognostic genes-PIM1 and BIRC5 were determined to establish high and low risk groups. Kaplan-Meier analysis displayed a higher survival rate in the low-risk group than in the high-risk group. ROC curves indicated the stable and good effect in prediction (one-year AUC is 0.626; two-year AUC is 0.620; three-year AUC is 0.623). The interrelationship between immunity and its disease was explored by immune infiltration analysis. Finally, the potential effect of puerarin on endometrial carcinoma cells was further verified by experiments.