Does Adjuvant Treatment With Ginkgo Biloba to Statins Have Additional Benefits in Patients With Dyslipidemia?

Objective: Ginkgo biloba are widely used alone or in combination with other lipid-lowering agents in the treatment of dyslipidemia in China. We conducted this meta-analysis to investigate whether adjuvant treatment with ginkgo biloba leaves to statins has incremental benefits in patients with dyslipidemia.Methods: Potential studies were searched from PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang database up to October 2017. Only randomized controlled trials (RCTs) comparing the efficacy and safety of ginkgo biloba leaves plus statins versus statins alone in patients with dyslipidemia were included.Results: Eight RCTs involving 664 patients were included. Compared with statins therapy alone, combination of statins and ginkgo biloba leaves therapy achieved greater reductions in triglycerides [mean difference (MD) -0.32 mmol/L; 95% confidence interval (CI) -0.43 to -0.20], total cholesterol (MD -0.61 mmol/L; 95% CI -0.90 to -0.33), or low-density lipoprotein cholesterol (LDL-C) (MD -0.32 mmol/L; 95% CI -0.48 to -0.16), and a greater increment in high-density lipoprotein cholesterol (MD 0.26 mmol/L; 95% CI 0.15 to 0.37). Subgroup analyses showed that ginkgo biloba leaves plus simvastatin appeared to achieve a greater reduction in serum levels of triglycerides, total cholesterol, and LDL-C than in combination with atorvastatin therapy.Conclusion: This meta-analysis suggests that adjuvant treatment with ginkgo biloba leaves appears to improve blood lipid parameters than statins therapy alone. More well-designed RCTs are needed to investigate the benefits of the combination of statins and ginkgo biloba leaves

Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell

BackgroundCuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified.Methods14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy.ResultsBased on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect.ConclusionCIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy

Factors impacting the benefits and pathogenicity of Th17 cells in the tumor microenvironment

Tumor development is closely associated with a complex tumor microenvironment, which is composed of tumor cells, blood vessels, tumor stromal cells, infiltrating immune cells, and associated effector molecules. T helper type 17 (Th17) cells, which are a subset of CD4+ T cells and are renowned for their ability to combat bacterial and fungal infections and mediate inflammatory responses, exhibit context-dependent effector functions. Within the tumor microenvironment, different molecular signals regulate the proliferation, differentiation, metabolic reprogramming, and phenotypic conversion of Th17 cells. Consequently, Th17 cells exert dual effects on tumor progression and can promote or inhibit tumor growth. This review aimed to investigate the impact of various alterations in the tumor microenvironment on the antitumor and protumor effects of Th17 cells to provide valuable clues for the exploration of additional tumor immunotherapy strategies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Prognosis Role of AST/ALT (De Ritis) Ratio in Patients with Adult Secondary Hemophagocytic Lymphohistiocytosis

Purpose. Secondary hemophagocytic lymphohistiocytosis (sHLH) accompanied by liver involvement, characterized by hepatomegaly and increased liver enzymes, is usually associated with elevated mortality. However, the magnitude of these associations remains unknown. Our objective was to assess the associations of the aspartate transaminase/alanine transaminase (AST/ALT, De Ritis) ratio with overall survival among adult patients with sHLH. Methods. A retrospective analysis was performed on 289 patients aged 18–86 years with complete serum transaminase data at diagnosis of sHLH. Multivariate Cox regression analyses and restricted cubic splines were conducted to address the association between the De Ritis ratio and the risk of mortality. Results. The median De Ritis ratio for the entire study population was 1.34 (IQR: 0.84-2.29). After a median follow-up time of 60 (range 17-227.5) days, 205 deaths occurred. After fully adjusting for hepatomegaly, albumin, fibrinogen, EBV, ferritin, etiologies, and treatment strategies, the adjusted hazard ratios (HRs) with corresponding confidence intervals (CIs) of mortality for the 2 st tertile and 3 st tertile were 1.2 (0.8-1.7) and 1.6 (1.1-2.2), respectively (P<0.01 for trends). Restricted cubic spline confirmed a linear association between the log2-transformed De Ritis ratio and the risk of mortality. Moreover, this trend persisted in subgroups with MHLH, hyperferrinaemia, sCD25≤20,000 ng/L, patients without EBV infection, and those received treatment. Conclusions. The De Ritis ratio is a strong and independent predictor for overall survival in patients with sHLH. As a readily available biomarker in routine clinical practice, it is used to identify patients with sHLH with inferior overall survival

DataSheet_1_Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell.zip

BackgroundCuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified.Methods14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy.ResultsBased on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect.ConclusionCIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy.</p

DataSheet_1_Construction and validation of a RARRES3-based prognostic signature related to the specific immune microenvironment of pancreatic cancer.zip

BackgroundTumor immune microenvironment (TiME) is prognostically instructive in Pancreatic adenocarcinoma (PAAD). However, the potential value of TiME-related genes in the individualized immunotherapy of PAAD has not been clarified.MethodsCorrelation between Immune-Related Genes (IRGs) and immune-related transcription factors (TFs) was performed to prove the immune correlation of selected genes. Immune-related molecular subtypes were identified by consensus clustering. The TiME-score, an immune microenvironment-related prognostic signature for PAAD, was constructed using minimum absolute contraction and selection operator regression (Lasso-Cox). The International Cancer Genome Consortium (ICGC) dataset validated the reliability of TiME-score as external validation. Single-cell samples from GSE197177 confirmed microenvironment differences of TiME-score hub genes between tumor and its paracancer tissues. Then, RARRES3, a hub gene in TiME-score, was further analyzed about its upstream TP53 mutation and the specific immune landscape of itself in transcriptome and Single-cell level. Eventually, TiME-score were validated in different therapeutic cohorts of PAAD mice models.ResultsA 14-genes PAAD immune-related risk signature, TiME-score, was constructed based on IRGs. The differences of TiME-score hub genes in single-cell samples of PAAD cancer tissues and adjacent tissues were consistent with the transcriptome. Single-cell samples of cancer tissues showed more pronounced immune cell infiltration. The upstream mutation factor TP53 of RARRES3 was significantly enriched in immune-related biological processes. High RARRES3 expression was correlated with a worse prognosis and high macrophages M1 infiltration. Additionally, the immunohistochemistry of hub genes AGT, DEFB1, GH1, IL20RB, and TRAF3 in different treatment cohorts of mice PAAD models were consistent with the predicted results. The combination of immunotherapy, chemotherapy and targeted therapy has shown significantly better therapeutic effects than single drug therapy in PAAD.ConclusionTiME-score, as a prognostic signature related to PAAD-specific immune microenvironment constructed based on RARRES3, has predictive value for prognosis and the potential to guide individualized immunotherapy for PAAD patients.</p

Point-of-Care Diagnosis on Selenium Nutrition Based on Time-Resolved Fluorometric Glycoaffinity Chromatography

Given the lack of timely evaluation of the well-received selenium fortification, a neat lateral-flow chromatographic solution was constructed here by using the recently identified urinary selenosugar (Sel) as a strongly indicative marker. As there are no ready-made receptors for this synthetic standard, phenylboronic acid (PBA) esterification and Dolichos biflorus agglutinin (DBA) affinity joined up to pinch and pin down the analyte into a sandwich-type glycol complex. Pilot lectin screening on homemade glycan microarrays verified such a new pairing between dual recognizers as PBA-Sel-DBA with a firm monosaccharide-binding constant. To quell the sample autofluorescence, europium nanoparticles with efficient long-life afterglow were employed as conjugating probes under 1 μs excitation. After systematic process optimizations, the prepared Sel-dipstick achieved swift and sensitive fluorometry over the physiological level of the target from 0.1 to 10 μM with a detection limit down to 0.06 μM. Further efforts were made to eliminate matrix effects from both temperature and pH via an approximate formula. Upon completion, the test strips managed to quantify the presence of Sel in not just imitated but real human urine, with comparable results to those in the references. As far as we know, this would be the first in-house prototype for user-friendly and facile diagnosis of Se nutrition with fair accuracy as well as selectivity. Future endeavors will be invested to model a more traceable Se-supplementary plan based on the rhythmic feedback of Sel excretion

MoS₂ Nanoprobe for MicroRNA Quantification Based on Duplex-Specific Nuclease Signal Amplification

MicroRNAs (miRNAs) play significant regulatory roles in physiologic and pathologic processes and are considered as important biomarkers for disease diagnostics and therapeutics. Simple, fast, sensitive, and selective detection of miRNAs, however, is challenged by their short length, low abundance, susceptibility to degradation, and homogenous sequence. Here, we report a novel design of nanoprobes for highly sensitive and selective detection of miRNAs based on MoS₂-loaded molecular beacons (MBs) and duplex-specific nuclease (DSN)-mediated signal amplification (DSNMSA). We show that MoS₂ nanosheets not only exhibit high affinity toward MBs but also act as an efficient quencher for absorbed MBs. The strong fluorescence-quenching ability of MoS₂ in combination with cyclic DSNMSA contributes to the superior sensitivity of our method, with a limit of detection 4 orders of magnitude lower than that of traditional hybridization methods. Moreover, the nanoprobes also show high selectivity for discriminating homogenous miRNA sequences with one-base differences because of the discrimination ability of MBs and DSN. Furthermore, we demonstrate that the MoS₂-loaded MB nanoprobes can be utilized for multiplexed detection of miRNAs. Given its high sensitivity and specificity, as well as the multiplexed function; this novel method as an effective tool shows a great promise for simultaneous quantitative analysis of multiple miRNAs in biomedical research and clinical diagnosis