Search

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R 2 ) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with R CV 2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (R P 2 ) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier B.V.)

This article investigates a laser-directed energy deposition additive manufacturing (AM) method, based on coaxial powder feeding, for preparing quartz glass. Through synergistic optimization of line deposition and plane deposition experiments, key parameters of laser coaxial powder feeding AM were identified. The corresponding mechanical properties, thermal properties, and microstructure of the bulk parts were analyzed. The maximum mechanical strength of the obtained quartz glass element reached 72.36 ± 5.98 MPa, which is ca. 95% that of quartz glass prepared by traditional methods. The thermal properties of the obtained quartz glass element were also close to those prepared by traditional methods. The present research indicates that one can use laser AM technology that is based on coaxial powder feeding to form quartz glass with high density and good thermodynamic properties. Such quartz glass has substantial potential in, for example, optics and biomedicine., Competing Interests: No competing financial interests exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal., (© 2024. The Author(s).)

Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes., Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models., Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/μg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/μg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression., Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Pan, Ruan, Lei, Lin, Wang and Zhao.)

Background: Essential tremor (ET) is an autosomal dominant inheritance disorder. Mutations in fusion sarcoma (FUS), mitochondrial serine peptidase 2 (HTRA2), teneurin transmembrane protein 4 (TENM4), sortilin1 (SORT1), SCN11A, and notch2N-terminal-like (NOTCH2NLC) genes are associated with familial ET., Methods: A proband with ET was tested using whole-exome sequencing and repeat-primed polymerase chain reaction. Subsequently, the family members were screened for the suspected mutation, and the results were verified using Sanger sequencing. The relationship between pedigree and phenotype was also analyzed, and structural and functional changes in the variants were predicted using bioinformatics analysis., Results: In a family with ET, the proband (III4) and the proband's father (II1), grandfather (I1), uncle (II2), and cousin (III5) all presented with involuntary tremors of both upper limbs. The responsible mutation was identified as TENM4 c.1262C > T (p.P421L), which showed genetic co-segregation in the family survey. AlphaFold predicted a change in the spatial position of TENM4 after the P421L mutation, which may have affected its stability. AlphaFold also predicted P421L to be a deleterious variation, which would lead to lower degrees of freedom of the TENM4 protein, thereby affecting the protein's structure and stability. According to the bioinformatics analysis, TENM4 (p.P421L) may reduce the signal reaching the nucleus by affecting the expression of TENM4 messenger RNA (mRNA), thereby impairing the normal oligodendrocyte differentiation process and leading to impaired myelination., Conclusion: This study revealed that the TENM4 (p.P421L) pathogenic missense variation was responsible for ET in the proband., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions., Methods: We developed a new microfluidics-based "SMART" platform that is Simple to operate, able to generate a Massive single-cell array and Multiplex drug concentrations, capable of keeping cells Alive, Retainable and Trackable in the microchambers. These features are achieved by integrating a Microfluidic chamber Array (4320 units) and a six-Concentration gradient generator (MAC), which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way., Results: A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity. The statistic results reveal that Imatinib (Ima) and Resveratrol (Res) combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment, indicated by the markedly reduced half maximal inhibitory concentration (IC 50 ). Additionally, single-cell derived clones demonstrate a higher IC 50 in each drug treatment compared to single cells. Moreover, primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC., Conclusion: This microfluidics-based "SMART" platform allows high-throughput single-cell capture and culture, dynamic drug-gradient treatment and cell response monitoring, which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers., (© 2022. The Author(s).)

Pantoea dispersa is a Gram-negative bacterium frequently found in plants, soil, and water. The genus Pantoea is a rare pathogen in human infectious diseases. The known susceptible populations include infants and postoperative and immunocompromised patients. To date, there have been no reports of nosocomial bloodstream infection due to P. dispersa following chest puncture. A 72-year-old Chinese woman suffering from chest distress was found to be blood culture positive for a Gram-negative bacterium. The organism was identified as P. dispersa through Vitek 2, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and 16S rRNA gene sequencing. Although cefoperazone-sulbactam and imipenem were used for treatment, the patient died four days later. To the best of our knowledge, this is the first case of nosocomial bloodstream infection caused by P. dispersa in China. We hope that this article might help clinicians understand better the potential pathogenicity of this pathogen., (Copyright © 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The gut microbiota can affect human metabolism, immunity, and other biologic pathways through the complex gut-kidney axis (GKA), and in turn participate in the occurrence and development of kidney disease. In this study, 39 patients with stage 4-5 chronic kidney disease (CKD) and 40 healthy individuals were recruited and 16S rDNA sequencing was performed to analyze the V3-V4 conserved regions of their microbiota. A total of 795 operational taxonomic units (OTUs) shared between groups or specific to each group were obtained, among which 255 OTUs with significant differences between the two groups were identified ( P <0.05). Adonis differential analysis showed that the diversity of gut microbiota was highly correlated with CKD stages 4-5. Additionally, 61 genera with differences in the two groups were identified ( P <0.05) and 111 species with significant differences in the phyla, classes, orders, families, and genera between the two groups were identified ( P <0.05). The differential bacterial genera with the greatest contribution were, in descending order: c&#95;Bacteroidia, o&#95;Bacteroidales, p&#95;Bacteroidetes, c&#95;Clostridia, o&#95;Clostridiales, etc. Those with the greatest contribution in stages 4-5 CKD were, in descending order: p&#95;Proteobacteria, f&#95;Enterobacteriaceae, o&#95;Enterobacteriales, c&#95;Gammaproteobacteria, c&#95;Bacilli, etc. The results suggest that the diversity of the microbiota may affect the occurrence, development, and outcome of the terminal stages of CKD., Competing Interests: None., (AJTR Copyright © 2021.)

Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of SLC12A3 encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto's thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried SLC12A3 compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC&#95;000016.10:g.56872655&#95;56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto's thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease., Competing Interests: The authors do not have any conflicts of interest to declare., (Copyright © 2021 Jian-hui Zhang et al.)

Acute myeloid leukemia (AML) is a malignant disease of hematopoietic stem/progenitor cells, and most AML patients are in a severe state. Internal tandem duplication mutations in FLT3 gene (FLT3-ITD) detected in AML stem cells account for 20-30 percent of AML patients. In this study, we attempted to study the impact of the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis in AML, and the possible mechanisms caused by the impact by bioinformatics. Gene set variation analysis (GSVA) revealed that the PI3K-Akt-mTOR pathway positively correlated with the status of FLT3-ITD mutation. Multiple survival analyses were performed on TCGA-AML to screen the prognostic-related genes, and RPS6KA1 and AP2M1 are powerful prognostic candidates for overall survival in AML. WGCNA, KEGG/GO analysis, and the functional roles of RPS6KA1 and AP2M1 in AML were clarified by correlation analysis. We found that the expression levels of RPS6KA1 and AP2M1 were significantly associated with chemoresistance of AML, and the CXCL12/CXCR4 axis would regulate RPS6KA1/AP2M1 expression. Besides, miR-138-5p, regulated by the CXCL12/CXCR4 axis, was the common miRNA target of RPS6KA1 and AP2M1. Taken together, the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis activated the PI3K-Akt-mTOR pathway, and the increased expression of RPS6KA1 and AP2M1 caused by hsa-miR-138-5p downregulation regulates the multi-resistance gene expression leading to drug indications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Chen, Liu, Yao, Li and Ruan.)

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease with lesions confined to the lungs. To identify meaningful microRNA (miRNA) and gene modules related to the IPF progression, GSE32537 (RNA-sequencing data) and GSE32538 (miRNA-sequencing data) were downloaded and processed, and then weighted gene co-expression network analysis (WGCNA) was applied to construct gene co-expression networks and miRNA co-expression networks. GSE10667, GSE70866, and GSE27430 were used to make a reasonable validation for the results and evaluate the clinical significance of the genes and the miRNAs. Six hub genes (COL3A1, COL1A2, OGN, COL15A1, ASPN, and MXRA5) and seven hub miRNAs (hsa-let-7b-5p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-29c-3p, hsa-let-7c-5p, hsa-miR-29b-3p, and hsa-miR-26b-5p) were clarified and validated. Meanwhile, iteration network of hub miRNAs-hub genes was constructed, and the emerging role of the network being involved in non-small cell lung cancer (NSCLC) was also analyzed by several webtools. The expression levels of hub genes were different between normal lung tissues and NSCLC tissues. Six genes (COL3A1, COL1A2, OGN, COL15A1, ASPN, and MXRA5) and three miRNAs (hsa-miR-29c-3p, hsa-let-7c-5p, and hsa-miR-29b-3p) were related to the survival time of lung adenocarcinoma (LUAD). The interaction network of hub miRNAs-hub genes might provide common mechanisms involving in IPF and NSCLC. More importantly, useful clues were provided for clinical treatment of both diseases based on novel molecular advances., (Copyright © 2020 Yu, Ruan, Huang, Liu, Ma, Chen, Hu and Li.)

Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β -galactosidase positive staining rate (decreased 16%, p < 0.01). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3'UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease., Competing Interests: All authors have read and approved the final manuscript. And there is no conflict of interest. All authors declare of no financial interest. Our manuscript has not been published previously., (Copyright © 2020 Xue Jiang et al.)

Lung adenocarcinoma (LUAD) is a common malignancy; however, the majority of its underlying molecular mechanisms remain unknown. In the present study, weighted gene co-expression network analysis was applied to construct gene co-expression networks for the GSE19804 dataset, in order to screen hub genes associated with the pathogenesis of LUAD. In addition, with the aid of the Database for Annotation, Visualization and Integrated Discovery, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes, pathway enrichment analyses were performed on the genes in the selected module. Using the GSE40791 dataset and The Cancer Genome Atlas database, the hub genes were identified. It was discovered that the turquoise module was the most significant module associated with the tumor stage of LUAD. After performing functional enrichment analyses, it was indicated that the turquoise module was mainly enriched in signal transduction. Additionally, at the transcriptional and translational level, nine hub genes were identified and validated: Carbonic anhydrase 4 (CA4), platelet and endothelial cell adhesion molecule 1 (PECAM1), DnaJ member B4 (DNAJB4), advanced glycosylation end-product specific receptor (AGER), GTPase, IMAP family member 6 (GIMAP6), chromosome 10 open reading frame 54 (C10orf54), dedicator of cytokinesis 4 (DOCK4), Golgi membrane protein 1 (GOLM1) and platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3). CA4, PECAM1, DNAJB4, AGER, GIMAP6, C10orf54 and DOCK4 were expressed at lower levels in the tumor samples, whereas GOLM1 and PAFAH1B3 were highly expressed in tumor samples. In addition, all hub genes were associated with prognosis. In conclusion, one module and nine genes were recognized to be associated with the tumor stage of LUAD. These findings may enhance the understanding of the progression and prognosis of LUAD., (Copyright: © Yu et al.)

Various microRNAs (miRNAs) are of importance in the development of colon cancer, but most of the mechanisms of the miRNAs are still unclear. In order to clarify the hub miRNAs and their roles in colon cancer development, GSE98406 was used to screen hub miRNAs by bioinformatics analysis. 46 DE-miRNAs (14 were upregulated and 32 were downregulated) and 1738 target genes of DE-miRNAs were ascertained. miRNAs-gene-networks and miRNAs-GO-networks were built to get more knowledge about the function of candidate miRNAs. After validation, three miRNAs (miR-17-5p, miR-182-5p and miR-200a-3p) were recognized to be hub miRNAs associated with the progression of colon cancer. More importantly, the hub miRNAs and the putative targets genes might be new diagnostic and therapeutic targets for colon cancer in the future., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Dong-Hu Yu et al.)

Purpose : The aim of this study was to evaluate microstructural changes of major white matter (WM) tracts in patients with vascular cognitive impairment (VCI). Method : Diffusion tensor imaging (DTI) data were obtained from 24 subjects with subcortical ischemic vascular disease (SIVD), including 13 subjects with VCI-no dementia (VCIND) and 11 subjects with normal cognition (as a control group). A tract-based spatial statistics approach was performed to investigate WM microstructure in VCIND by integrating multiple indices including fractional anisotropy (FA) and mean diffusivity (MD), which are intra-voxel metrics, and local diffusion homogeneity (LDH), which is an inter-voxel metric. Results : The VCIND group had decreased FA and increased MD values throughout widespread WM areas predominately in the corpus callosum, bilateral internal capsule/corona radiata/posterior thalamic radiation/inferior fronto-occipital fasciculus and right inferior/superior longitudinal fasciculus. There was a slight discrepancy between the distribution of areas with decreased FA and LDH. The FA, MD and LDH values were significantly correlated with cognitive test results. According to a WM tract atlas, 10 major tracts were identified as tracts of interest in which three diffusion metrics simultaneously differed between groups, including bilateral anterior thalamic radiation, forceps minor, right corticospinal tract, bilateral inferior fronto-occipital fasciculus, left inferior and superior longitudinal fasciculus, and bilateral uncinate fasciculus. Receiver operating characteristic (ROC) analysis demonstrated the feasibility of using diffusion metrics along the forceps minor and left anterior thalamic radiation for separating two groups. Conclusion : The results suggest WM microstructural abnormalities contribute to cognitive impairments in SIVD patients. DTI parameters may be potential biomarkers for detecting VCIND from SIVD.

Background and Aim of the Study: The prosthesis of choice for a tricuspid valve replacement is still unkown. This meta-analysis was undertaken to review the results of mechanical and bioprosthetic valves in the tricuspid position., Methods: We identified all relevant studies published in the past 20 years (from January 1, 1995 to December 31, 2014) through the Embase, Current Contents, and PubMed databases. The hazard ratio and its 95% confidence limits were utilized to evaluate time-to-event related effects of surgical procedures. The Q-statistic, Index of Inconsistency test, funnel plots, and Egger's test were used to assess the degree of heterogeneity and publication bias. Random effects models were used, and study quality was also assessed., Results: In our meta-analysis, 22 studies published from 1995 to 2014 were reviewed and 2630 patients and 14,694 follow-up years were analyzed. No statistically significant difference was identified between mechanical and biological valves in terms of survival, reoperation, and prosthetic valve failure. The respective pooled hazard ratio estimates were 0.95 (0.79 to 1.16, p = 0.62, I(2)  = 29%), 1.20 (0.84 to 1.71, p = 0.33, I(2)  = 0%), and 0.35 (0.06 to 2.01, p = 0.24, I(2)  = 0%). A higher risk of thrombosis was found in mechanical tricuspid valve prostheses (3.86, 1.38 to 10.82, p = 0.01, I(2)  = 0%)., Conclusions: No statistically significant difference was identified between mechanical and biological valves in terms of survival, reoperation, or prosthetic valve failure, but mechanical tricuspid valve prostheses had a higher risk of thrombosis. doi: 10.1111/jocs.12730 (J Card Surg 2016;31:294-302)., (© 2016 Wiley Periodicals, Inc.)

Background: Many studies have reported that the p53 codon 72 polymorphism is associated with acute myeloid leukemia (AML) susceptibility; however, the conclusions are inconsistent. Therefore, we performed this meta-analysis to obtain a more precise result., Material and Methods: We searched PubMed to identify relevant studies, and 6 published case-control studies were retrieved, including 924 AML patients and 3832 controls. Odds ratio (OR) with corresponding 95% confidence interval (95%CI) was applied to assess the association between p53 codon 72 polymorphism and AML susceptibility. The meta-analysis was performed with Comprehensive Meta-Analysis software, version 2.2., Results: Overall, no significant association between p53 codon 72 polymorphism and AML susceptibility was found in this meta-analysis (Pro vs. Arg: OR=0.94, 95%CI=0.81-1.10; Pro/Pro vs. Arg/Arg: OR=0.93, 95%CI=0.71-1.22; Arg/Pro vs. Arg/Arg: OR=0.79, 95%CI=0.55-1.13; (Pro/Pro + Arg/Pro) vs. Arg/Arg: OR=0.84, 95%CI=0.62-1.13; Pro/Pro vs. (Arg/Arg + Arg/Pro): OR=1.06, 95%CI=0.83-1.35). Similar results were also found in stratified analysis according to ethnicity and source of controls., Conclusions: Our meta-analysis demonstrates that p53 codon 72 polymorphism may not be a risk factor for AML, which should be verified in future studies.

The purpose of this meta-analysis was aimed to evaluate the association of tumor protein p53 (TP53) gene codon 72 polymorphism with leukemia susceptibility. We searched PubMed to identify relevant studies, and 16 case-control studies from 14 published articles were identified as eligible studies, including 2062 leukemia patients and 5826 controls. After extracting data, odds ratio (OR) with the corresponding 95% confidence interval (95%CI) was applied to assess the association between TP53 codon 72 polymorphism and leukemia susceptibility. The meta-analysis was performed with the Comprehensive Meta-Analysis software, version 2.2. Overall, no significant association between TP53 codon 72 polymorphism and leukemia susceptibility was found in this meta-analysis (Pro vs Arg: OR = 1.05, 95%CI = 0.90-1.21; Pro/Pro vs Arg/Arg: OR = 1.13, 95%CI = 0.84-1.52; Arg/Pro vs Arg/Arg: OR = 0.94, 95%CI = 0.76-1.15; [Pro/Pro + Arg/Pro] vs Arg/Arg: OR = 0.99, 95%CI = 0.80-1.21; Pro/Pro vs [Arg/Arg + Arg/Pro]: OR = 1.19, 95%CI = 0.93-1.51). Similar results were also found in subgroup analysis by ethnicity, source of controls, and types of leukemia (either acute myeloid leukemia or acute lymphocytic leukemia). Our meta-analysis demonstrates that TP53 codon 72 polymorphism may not be a risk factor for acute leukemia; however, due to the limitations of this study, it should be verified in future studies.

The aim of this study was to compare plasmakinetic resection of the prostate (PKRP) with transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) in terms of efficacy and safety. Published RCTs were searched from PubMed, Embase, Science Citation Index, and Cochrane Library up to April 10, 2014. After methodological quality assessment and data extraction, meta-analysis was performed using the STATA 12.0 software. 18 reports of 16 RCTs were included in this analysis. Meta-analyses showed that PKRP significantly improved Qmax at 12 months, but no significant difference was found for other efficacy outcomes. In terms of safety, treatment of PKRP was associated with reduced drop in serum sodium, lower TUR syndrome, reduced need of blood transfusion, clot retention, and shorter catheterization time and hospital stay; in contrast, there were no significant differences in the analysis of operative time, postoperative fever, and long-term postoperative complications. In summary, current evidence suggests that, although PKRP and TURP are both effective for BPH, PKRP is associated with additional potential benefits in efficacy and more favorable safety profile. It may be possible that PKRP may replace the TURP in the future and become a new standard surgical procedure.

In this study, magnetic single-walled carbon nanotubes (MSWCNTs) were prepared by impregnating magnetic Fe3O4 nanoparticles onto the surfaces of carboxylic single-walled carbon nanotubes based on electrostatic interactions. The prepared MSWCNTs were used as the adsorbent for the dispersive solid-phase extraction (DSPE) of paraquat from human urine. After adsorption, the paraquat was quantitatively desorbed with 5%TFA in acetonitrile and determined by HPLC-MS. Extraction parameters such as the type of CNT adsorbent, extraction time, sample volume, wash solvent, and the type and volume of desorption solvent were optimized to obtain high DSPE recoveries and extraction efficiencies. Under the optimized conditions, the calibration curve was linear in the range 3.75-375.0 μg/L with a correlation coefficient of 0.999 45. The LOD (S/N=3) and LOQ (S/N=10) were 0.94 and 2.82 μg/L, respectively. The recoveries ranged from 92.89 to 108.9% for spiked real urine samples with RSDs below 3.21%. Finally, the new method was successfully used to determine paraquat in urine samples of suspected paraquat poisoning patients. The MSWCNTs exhibited suitable properties and a high adsorption capacity for the extraction of paraquat., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Holmium laser enucleation (HoLEP) in surgical treatment of benign prostate hyperplasia (BPH) potentially offers advantages over transurethral resection of the prostate (TURP)., Methods: Published randomized controlled trials (RCTs) were identified from PubMed, EMBASE, Science Citation Index, and the Cochrane Library up to October 10, 2013 (updated on February 5, 2014). After methodological quality assessment and data extraction, meta-analysis was performed using STATA 12.0 and Trial Sequential Analysis (TSA) 0.9 software., Results: Fifteen studies including 8 RCTs involving 855 patients met the criteria. The results of meta-analysis showed that: a) efficacy indicators: there was no significant difference in quality of life between the two groups (P>0.05), but compared with the TURP group, Qmax was better at 3 months and 12 months, PVR was less at 6, 12 months, and IPSS was lower at 12 months in the HoLEP, b) safety indicators: compared with the TURP, HoLEP had less blood transfusion (RR 0.17, 95% CI 0.06 to 0.47), but there was no significant difference in early and late postoperative complications (P>0.05), and c) perioperative indicators: HoLEP was associated with longer operation time (WMD 14.19 min, 95% CI 6.30 to 22.08 min), shorter catheterization time (WMD -19.97 h, 95% CI -24.24 to -15.70 h) and hospital stay (WMD -25.25 h, 95% CI -29.81 to -20.68 h)., Conclusions: In conventional meta-analyses, there is no clinically relevant difference in early and late postoperative complications between the two techniques, but HoLEP is preferable due to advantage in the curative effect, less blood transfusion rate, shorter catheterization duration time and hospital stay. However, trial sequential analysis does not allow us to draw any solid conclusion in overall clinical benefit comparison between the two approaches. Further large, well-designed, multicentre/international RCTs with long-term data and the comparison between the two approaches remain open.

The association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and bladder cancer (BC) susceptibility was investigated by two meta-analyses, however, their results were contrary. We conjecture the reason might be the sample size, thus we performed this updated and cumulative meta-analysis using the Comprehensive Meta-Analysis software. We searched PubMed up to August 25th, 2013 and yielded 20 published articles with 21 case-control trails including 6,836 BC patients and 8,251 controls. The meta-analysis results showed that XPD Lys751Gln polymorphism was borderline significantly associated with BC susceptibility for overall population [Gln vs. Lys: OR 1.07, 95% CI 1.01-1.12, P = 0.01; Gln/Gln vs. Lys/Lys: OR 1.15, 95% CI 1.03-1.29, P = 0.01; Gln/Gln vs. (Lys/Gln + Lys/Lys): OR 1.13, 95% CI 1.02-1.26, P = 0.02]. The cumulative meta-analysis according to the publication year showed the CI became increasingly narrower and tended to have statistical significance for the studies incessantly accumulated. In the subgroup analysis according to ethnicity, there was a significant association in Asian population and no association in Caucasian population. There was no publication bias detected. However, due to the limitations and cumulative analysis result of this meta-analysis, more well-designed and larger studies with risk factors adjusted are suggested to be performed to obtain a conclusive result on this topic.

The addition of the DNA methyltransferase inhibitor 500 μM 5-azacytidine to the culture medium of a plant endophytic fungus, Pestalotiopsis crassiuscula, obtained from the leaves of Fragaria chiloensis, dramatically altered the profiles of its metabolites and resulted in the isolation of one new coumarin (1), along with six known compounds (2-7). HPLC profiles revealed that only compounds 3, 4, and 7 belonged to the new induced secondary metabolites. The structures of all isolated compounds were elucidated on the basis of extensive analysis of NMR spectra.

Banana wilt disease, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense 4 (Foc4), is regarded as one of the most devastating diseases worldwide. Cavendish cultivar 'Yueyoukang 1' was shown to have significantly lower disease severity and incidence compared with susceptible cultivar 'Brazilian' in greenhouse and field trials. De novo sequencing technology was previously performed to investigate defense mechanism in middle resistant 'Nongke No 1' banana, but not in highly resistant cultivar 'Yueyoukang 1'. To gain more insights into the resistance mechanism in banana against Foc4, Illumina Solexa sequencing technology was utilized to perform transcriptome sequencing of 'Yueyoukang 1' and 'Brazilian' and characterize gene expression profile changes in the both two cultivars at days 0.5, 1, 3, 5 and 10 after infection with Foc4. The results showed that more massive transcriptional reprogramming occurs due to Foc4 treatment in 'Yueyoukang 1' than 'Brazilian', especially at the first three time points, which suggested that 'Yueyoukang 1' had much faster defense response against Foc4 infection than 'Brazilian'. Expression patterns of genes involved in 'Plant-pathogen interaction' and 'Plant hormone signal transduction' pathways were analyzed and compared between the two cultivars. Defense genes associated with CEBiP, BAK1, NB-LRR proteins, PR proteins, transcription factor and cell wall lignification were expressed stronger in 'Yueyoukang 1' than 'Brazilian', indicating that these genes play important roles in banana against Foc4 infection. However, genes related to hypersensitive reaction (HR) and senescence were up-regulated in 'Brazilian' but down-regulated in 'Yueyoukang 1', which suggested that HR and senescence may contribute to Foc4 infection. In addition, the resistance mechanism in highly resistant 'Yueyoukang 1' was found to differ from that in middle resistant 'Nongke No 1' banana. These results explain the resistance in the highly resistant cultivar and provide more insights in understanding the compatible and incompatible interactions between banana and Foc4.

Background: Many studies indicated the human cytochrome P450 2D6 (CYP2D6) gene polymorphism was associated with acute leukemia (AL) susceptibility, however, the results were inconsistent. So we performed this meta-analysis to evaluate the relationship between CYP2D6*3 or CYP2D6*4 polymorphism and AL susceptibility., Methods: We searched PubMed database up to February 20, 2013, and finally yielded 9 case-control studies including 1343 cases and 1843 controls which tested the association between CYP2D6*3 or *4 polymorphism and AL. After data extraction, we conducted a meta-analysis using the Comprehensive Meta Analysis software., Results: Overall, no significant association between CYP2D6*3 or *4 polymorphism and AL risk was found in this metaanalysis (+ vs. -: OR = 1.13, 95% CI = 0.79-1.63; +/+ vs. -/-: OR = 1.73, 95% CI = 0.99-3.02; -/+ vs. -/-: OR = 1.03, 95% CI = 0.68-1.56; (-/+ and +/+) vs. -/-: OR = 1.08, 95% CI = 0.72-1.63; +/+ vs. (-/+ and -/-): OR = 1.76, 95% CI = 0.98-3.17). Similar results were also been found in stratified subgroup analysis. There was no publication bias., Conclusion: CYP2D6*3 or *4 polymorphism might not be associated with AL susceptibility. However, the results need to be further confirmed by well-designed and high quality randomized controlled trials with larger sample sizes.

The aim of this study was to evaluate the recurrence rate of simultaneous transurethral resection of bladder cancer and prostate (TURBT+TURP) in the treatment of non-muscle invasive bladder cancer (NMIBC) with benign prostatic hyperplasia (BPH). We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ISI Web of Knowledge databases from their establishment until March 2012, to collect all the original studies on TURBT+TURP vs. TURBT alone in the treatment of NMIBC with BPH. After screening the literature, methodological quality assessment and data extraction was conducted independently by two reviewers and meta-analysis was performed using the RevMan 5.1 software. The quality of data was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Eight studies, including seven non-randomized concurrent controlled trials (NRCCTs) and one randomized controlled trial (RCT), involving a total of 1,372 patients met the criteria. Meta-analyses of NRCCTs showed that in the TURBT+TURP group, overall recurrence rates were lower [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.60-0.96; P=0.02] and the difference was statistically significant. The postoperative recurrence rate in the prostatic fossa/bladder neck (OR, 0.96; 95% CI, 0.64-1.45; P=0.86) and bladder tumor progression rates (OR, 0.96; 95% CI, 0.49-1.87; P=0.91) were similar between the TURBT+TURP and TURBT groups, but the difference was not significant. According to the GRADE approach, the level of evidence was moderate or low. Only one RCT demonstrated that overall postoperative tumor recurrence rates, recurrence rates at prostate fossa/bladder neck and bladder tumor progression rates between simultaneous groups and control groups were almost equal. There was no significant difference (P>0.05), and the level of evidence was moderate. For patients with NMIBC and BPH, simultaneous resection did not increase the overall recurrence rate of bladder tumors, it also did not cause metastasis and tumor progression, but it may reduce the recurrence rate. However, due to the low quality of investigations included in the present study, careful selection was necessary, and more large-scale and high-quality randomized controlled trials are also required for further confirmation.

Transgenic rice (Oryza sativa) plants expressing the Pns11 protein of rice gall dwarf virus (RGDV) displayed multiple abnormal phenotypes, some of which were highly reminiscent of the symptoms observed in RGDV-infected rice. Further analysis indicated that the apparent alterations in plant growth and morphology were correlated with the expression levels of microRNA160, microRNA162, microRNA167, microRNA168, and the microRNA target OsARF8. Especially, the striking dwarfing phenotype depended on the high expression level of microRNA167. By analogy to other categories of plant viruses, the RNA silencing suppressors encoded by plant dsRNA viruses function as pathogenicity determinants. These findings significantly deepen our current mechanistic understanding of the RNA silencing suppressor (VSR) encoded by a dsRNA virus and provide additional evidence that interference with microRNA expression is a VSR function utilized by a diverse range of viruses.

Some persistent organic pollutants (POPs) have been found in human semen but until this point it was unclear whether polybrominated diphenyl ethers (PBDEs) could be detected in human semen. In this study, PBDEs were found for the first time in human semen samples (n=101) from Taizhou, China. The concentrations of total PBDEs (∑PBDEs) varied from 15.8 to 86.8 pg/g ww (median=31.3 pg/g ww) and 53.2 to 121 pg/g ww (median=72.3 pg/g ww) in semen and blood samples, respectively. The ∑PBDE level in semen was about two times lower than in human blood, which was different in the distribution in the two matrices from other POPs. A correlation of ∑PBDE concentration was found between paired semen and in blood. The results suggest that semen could be used to detect PBDE burden in human body as a non-invasive matrix. In addition, the levels of BDE-209 and BDE-153, especially the latter, were much higher in blood than in semen, while the levels of BDE-28, BDE-47 and BDE-99 were comparable in the two matrices, suggesting that low brominated congeners could be more easily transferred to semen than high brominated congeners. Considering different toxicities among the PBDE congeners, it might be more significant to measure PBDEs in semen than in blood for evaluating male reproduction risks of PBDEs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

E-waste recycling resulted in serious pollution of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in Taizhou of Zhejiang Province, China. The aims of this study were to assess dual body burdens of the two pollutants and potential health risk for local residents. Blood samples were collected from two e-waste recycling sites, Luqiao (where PCBs-containing e-wastes were recycled) and Wenling (where PBDEs-containing e-wastes were recycled). The mean summation SigmaPCBs (CB-105, 118, 153, 183, and 180) and summation SigmaPBDEs (BDE-28, 47, 99, 100, 153, 154, 180, and 209) were 204.20 and 117.58 ng g(-1) lipid in the blood from Luqiao, respectively, while they were 83.80 and 357.44 ng g(-1) lipid from Wenling, respectively. The PCBs levels among Luqiao residents were comparable to the values reported for US populations, while the PBDEs levels among two study populations were higher than the values from US populations. This is the first report to present dual body burdens of PCBs and PBDEs at so high levels. Based on previous epidemiologic data, it is suggested that dual burdens of PCBs and PBDEs at so high levels might pose health risk for local residents. In addition, no correlation between PCBs or PBDEs concentrations and the ages of the volunteers was observed in the two populations, which was explained by similar exposure time. No correlation of PBDEs with PCBs concentrations suggested different pathways of human exposures to PCBs and PBDEs. Our findings have raised concern about human health risk of dual exposure to PCBs and PBDEs resulting from e-waste recycling., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 (CYP) epoxygenases that have vasodilatory and anti-inflammatory properties. Here we report that EETs have additional fibrinolytic properties. In vascular endothelial cells, physiological concentrations of EETs, particularly 11,12-EET, or overexpression of the endothelial epoxygenase, CYP2J2, increased tissue plasminogen activator (t-PA) expression by 2.5-fold without affecting plasminogen activator inhibitor-1 expression. This increase in t-PA expression correlated with a 4-fold induction in t-PA gene transcription and a 3-fold increase in t-PA fibrinolytic activity and was blocked by the CYP inhibitor, SKF525A, but not by the calcium-activated potassium channel blocker, charybdotoxin, indicating a mechanism that does not involve endothelial cell hyperpolarization. The t-PA promoter is cAMP-responsive, and induction of t-PA gene transcription by EETs correlated with increases in intracellular cAMP levels and, functionally, with cAMP-driven promoter activity. To determine whether increases in intracellular cAMP levels were due to modulation of guanine nucleotide-binding proteins, we assessed the effects of EETs on Galpha(s) and Galpha(i2). Treatment with EETs increased Galpha(s), but not Galpha(i2), GTP-binding activity by 3.5-fold. These findings indicate that EETs possess fibrinolytic properties through the induction of t-PA and suggest that endothelial CYP2J2 may play an important role in regulating vascular hemostasis.

The mechanism by which moderate alcohol ingestion lowers the risk of cardiovascular disease is unknown but may be due, in part, to the ability of alcohol to increase the level of tissue-type plasminogen activator (t-PA). Human endothelial cells were treated with low concentrations of ethanol (0.25-25 mM, 0-24 h), which are associated with moderate alcohol consumption. Although treatment with ethanol alone did not affect t-PA gene transcription or mRNA expression, it augmented isoproterenol (ISO)-stimulated t-PA gene transcription and mRNA levels by 3.4- and 2.8-fold, respectively, and decreased plasminogen activator inhibitor-1 mRNA levels by 65%. These effects of ethanol correlated with 2.5- and 6.9-fold increases in ISO-stimulated cyclic AMP levels and 4x-cyclic AMP response element heterologous promoter activity, respectively. To determine whether alcohol-induced changes in agonist-stimulated cyclic AMP levels were because of modulation of guanine nucleotide-binding proteins (G proteins), we assessed the effects of ethanol on Galphas and Galphai2. Although ethanol did not affect the expression of Galphas or Galphai2, it increased ISO-stimulated Galphas GTPase and GTP binding activity by 2.2- and 2.9-fold and decreased UK14304-stimulated Galphai2 GTPase and GTP binding activity by 38 and 80%. These results indicate that treatment with relatively low concentrations of ethanol enhances agonist-stimulated cyclic AMP-dependent t-PA gene transcription in vascular endothelial cells through differential modulation of G protein.