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Genotype imputation is now fundamental for genome-wide association studies but lacks fairness due to the underrepresentation of references from non-European ancestries. The state-of-the-art imputation reference panel released by the Trans-Omics for Precision Medicine (TOPMed) initiative improved the imputation of admixed African-ancestry and Hispanic/Latino samples, but imputation for populations primarily residing outside of North America may still fall short in performance due to persisting underrepresentation. To illustrate this point, we imputed the genotypes of over 43,000 individuals across 123 populations around the world and identified numerous populations where imputation accuracy paled in comparison to that of European-ancestry populations. For instance, the mean imputation r-squared (Rsq) for variants with minor allele frequencies between 1% and 5% in Saudi Arabians (n = 1,061), Vietnamese (n = 1,264), Thai (n = 2,435), and Papua New Guineans (n = 776) were 0.79, 0.78, 0.76, and 0.62, respectively, compared to 0.90-0.93 for comparable European populations matched in sample size and SNP array content. Outside of Africa and Latin America, Rsq appeared to decrease as genetic distances to European-ancestry reference increased, as predicted. Using sequencing data as ground truth, we also showed that Rsq may over-estimate imputation accuracy for non-European populations more than European populations, suggesting further disparity in accuracy between populations. Using 1,496 sequenced individuals from Taiwan Biobank as a second reference panel to TOPMed, we also assessed a strategy to improve imputation for non-European populations with meta-imputation, but this design did not improve accuracy across frequency spectra. Taken together, our analyses suggest that we must ultimately strive to increase diversity and size to promote equity within genetics research.
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Gene Frequency , Genetics, Population , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Genome, Human , Genotype , White People/genetics , European People , Hispanic or Latino , African People , Black PeopleABSTRACT
Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus. The constructed pharmacophore model, Phar-VRPR-N3, demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC50 = 60.2 ± 4.0 µM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 µM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.
Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Staphylococcus aureus/drug effects , Drug Discovery , Microbial Sensitivity Tests , Drug Evaluation, Preclinical , Molecular Docking Simulation , Methicillin-Resistant Staphylococcus aureus/drug effects , Models, Molecular , PharmacophoreABSTRACT
The reprogramming of somatic cells to pluripotent stem cells has immense potential for use in regenerating or redeveloping tissues for transplantation, and the future application of this method is one of the most important research topics in regenerative medicine. These cells are generated from normal cells, adult stem cells, or neoplastic cancer cells. They express embryonic stem cell markers, such as OCT4, SOX2, and NANOG, and can differentiate into all tissue types in adults, both in vitro and in vivo. However, tumorigenicity, immunogenicity, and heterogeneity of cell populations may hamper the use of this method in medical therapeutics. The risk of cancer formation is dependent on mutations of these stemness genes during the transformation of pluripotent stem cells to cancer cells and on the alteration of the microenvironments of stem cell niches at genetic and epigenetic levels. Recent reports have shown that the generation of induced pluripotent stem cells (iPSCs) derived from human fibroblasts could be induced using chemicals, which is a safe, easy, and clinical-grade manufacturing strategy for modifying the cell fate of human cells required for regeneration therapies. This strategy is one of the future routes for the clinical application of reprogramming therapy. Therefore, this review highlights the recent progress in research focused on decreasing the tumorigenic risk of iPSCs or iPSC-derived organoids and increasing the safety of iPSC cell preparation and their application for therapeutic benefits.
Subject(s)
Cellular Reprogramming , Induced Pluripotent Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/cytology , Animals , Neoplasms/pathology , Neoplasms/metabolism , Carcinogenesis , Neoplastic Stem Cells/metabolism , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/geneticsABSTRACT
The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10-2.31 and AOR=1.60, 95%CI=1.06-2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.
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The high rate of aquatic mortality incidents recorded in Taiwan and worldwide is creating an urgent demand for more accurate fish mortality prediction. Present study innovatively integrated air and water quality data to measure water quality degradation, and utilized deep learning methods to predict accidental fish mortality from the data. Keras library was used to build multilayer perceptron and long short-term memory models for training purposes, and the models' accuracies in fish mortality prediction were compared with that of the naïve Bayesian classifier. Environmental data from the 5 days before a fish mortality event proved to be the most important data for effective model training. Multilayer perceptron model reached an accuracy of 93.4%, with a loss function of 0.01, when meteorological and water quality data were jointly considered. It was found that meteorological conditions were not the sole contributors to fish mortality. Predicted fish mortality rate of 4.7% closely corresponded to the true number of fish mortality events during the study period, that is, four. A significant surge in fish mortality, from 20% to 50%, was noted when the river pollution index increased from 5.36 to 6.5. Moreover, the probability of fish mortality increased when the concentration of dissolved oxygen dropped below 2 mg/L. To mitigate fish mortality, ammonia nitrogen concentrations should be capped at 5 mg/L. Dissolved oxygen concentration was found to be the paramount factor influencing fish mortality, followed by the river pollution index and meteorological data. Results of the present study are expected to aid progress toward achieving the Sustainable Development Goals and to increase the profitability of water resources.
Subject(s)
Deep Learning , Fishes , Water Quality , Animals , Taiwan/epidemiology , Environmental Monitoring/methods , Forecasting , Bayes TheoremABSTRACT
Purpose Cognitive function, particularly food-related cognition, is critical for maintaining a healthy weight and preventing the acceleration of obesity. High-Intensity Interval Exercise (HIIE) is an increasingly popular form of exercise and has been shown to improve physical fitness and cognitive function. However, there is limited research on the effects and underlying mechanisms of HIIE on general and food-related cognition among adults with obesity. The aim of the current study was to examine the influence of a single bout of HIIE on food-related cognition among young adults with obesity. Methods Fifteen young men with obesity (BMI = 33.88 ± 4.22, age = 24.60 ± 5.29 years) were recruited. Participants took part in a HIIE condition consisting of 30 minutes of stationary cycle exercise (5-min warm-up, 20-min HIIE and 5-min cool down), and a control session consisting of a time and attention-matched period of sedentary rest in a counterbalanced order. Behavioral (reaction time and accuracy) and event-related potential measures (P3 and the late positive potential, LPP) elicited during a food-related Flanker task were measured after the HIIE and control session. Results Shorter response times were observed following HIIE, regardless of congruency or picture type, with no change in accuracy. Increased P3 and LPP amplitudes were observed following HIIE relative to the control session. Conclusion The findings suggest a single bout of HIIE has a beneficial effect on general and food-related cognition among young adults with obesity, with increased recruitment of cognitive resources to support cognitive control. Future research is warranted to examine the dose-response relationship between acute bouts or longer participation in HIIE on food-related cognition in obesity.
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Both acute aerobic (AE) and resistance exercise (RE) have been acknowledged to be effective methods in enhancing executive function and brain-related P3 amplitudes. Nevertheless, the effect of acute concurrent exercise training (CET), combining both AE and RE, on executive function remains subject to speculation. Moreover, investigation of the mechanisms that underlie improvements in executive function would facilitate scientific understanding. Notably, lactate has emerged as a candidate among several potential mechanisms. Therefore, the main aim of the present study was to investigate the effect of acute CET on the cognitive flexibility dimension of executive function using behavioural and neuro-electric measures. A secondary aim was to determine the mediating effect of blood lactate in the acute exercise-executive function relationship. Seventy-eight young adults (38 women, 40 men; 22.8 ± 1.8 years) were randomly assigned to one of the following groups: CET, AE, or reading control (RC). Cognitive flexibility was evaluated using the Task-Switching Test and its derived electroencephalography (EEG) was assessed immediately prior to and following each treatment. Fingertip lactate assays were taken prior to, at the midpoint, and after each treatment. Both acute CET and AE shortened response time regardless of test conditions when compared to the RC group. Greater P3 amplitude was observed following CET in the heterogeneous condition and under AE in the switch condition. A significant mediation of blood lactate for response time emerged in both the CET and AE groups for the heterogeneous and switch conditions. The blood lactate mediation was not reflected in P3 amplitude. The present findings suggest that acute CET leads to positive behavioural and neuro-electric alterations of cognitive flexibility, and its effect is similar to AE. Additionally, blood lactate serves as a mediator of the effects of acute exercise on executive function from a behavioural, but not neuro-electric standpoint.
Subject(s)
Executive Function , Lactic Acid , Male , Young Adult , Humans , Female , Executive Function/physiology , Exercise/physiology , Electroencephalography , Brain/physiologyABSTRACT
An understanding of the risk of gene deletion and mutation posed by endocrine-disrupting chemicals (EDCs) is necessary for the identification of etiological reagents for many human diseases. Therefore, the characterization of the genetic traits caused by developmental exposure to EDCs is an important research subject. A new regenerative approach using embryonic stem cells (ESCs) holds promise for the development of stem-cell-based therapies and the identification of novel therapeutic agents against human diseases. Here, we focused on the characterization of the genetic traits and alterations in pluripotency/stemness triggered by phthalate ester derivatives. Regarding their in vitro effects, we reported the abilities of ESCs regarding proliferation, cell-cycle control, and neural ectoderm differentiation. The expression of their stemness-related genes and their genetic changes toward neural differentiation were examined, which led to the observation that the tumor suppressor gene product p53/retinoblastoma protein 1 and its related cascades play critical functions in cell-cycle progression, cell death, and neural differentiation. In addition, the expression of neurogenic differentiation 1 was affected by exposure to di-n-butyl phthalate in the context of cell differentiation into neural lineages. The nervous system is one of the most sensitive tissues to exposure to phthalate ester derivatives. The present screening system provides a good tool for studying the mechanisms underlying the effects of EDCs on the developmental regulation of humans and rodents, especially on the neuronal development of ESCs.
Subject(s)
Dibutyl Phthalate , Mouse Embryonic Stem Cells , Phthalic Acids , Animals , Humans , Mice , Dibutyl Phthalate/toxicity , Cell Differentiation , EstersABSTRACT
Polygenic scores (PGS) are promising in stratifying individuals based on the genetic susceptibility to complex diseases or traits. However, the accuracy of PGS models, typically trained in European- or East Asian-ancestry populations, tend to perform poorly in other ethnic minority populations, and their accuracies have not been evaluated for Native Hawaiians. Using body mass index, height, and type-2 diabetes as examples of highly polygenic traits, we evaluated the prediction accuracies of PGS models in a large Native Hawaiian sample from the Multiethnic Cohort with up to 5,300 individuals. We evaluated both publicly available PGS models or genome-wide PGS models trained in this study using the largest available GWAS. We found evidence of lowered prediction accuracies for the PGS models in some cases, particularly for height. We also found that using the Native Hawaiian samples as an optimization cohort during training did not consistently improve PGS performance. Moreover, even the best performing PGS models among Native Hawaiians would have lowered prediction accuracy among the subset of individuals most enriched with Polynesian ancestry. Our findings indicate that factors such as admixture histories, sample size and diversity in GWAS can influence PGS performance for complex traits among Native Hawaiian samples. This study provides an initial survey of PGS performance among Native Hawaiians and exposes the current gaps and challenges associated with improving polygenic prediction models for underrepresented minority populations.
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Taiwan is an island surrounded by sea and only 19 % of its freshwater usage is for domestic applications. A system dynamic model was developed to investigate interactions between household water use behaviors (toilet flushing, clothes washing, bathing/showering, and cleaning) and associated greenhouse gas emissions and environmental costs. Six hundred and fifty face-to-face interviews were conducted in 12 districts of Taipei. The results showed that the respondents' individual attributes were not significantly related to water use behaviors. The highest volume of water was used for cleaning (27.7 %), followed by clothes washing (26.2 %), bathing/showering (26.1 %), and toilet flushing (20.0 %). Five water management scenarios with 5 %-20 % reductions in water volume from different water use behaviors were simulated. The maximum reduction in water use (6.27 t) was found in the fifth scenario (20 % reduction), which reflected the priority the respondents gave to save water if its price increased. 27.2 % of respondents had water saving appliances; 20.5 % and 16.4 % of the appliances were toilets and shower heads, respectively. The environmental cost of GHG emissions associated with water use behavior was US$0.001/t, causing an 8% increase in water price. A better understanding of household water use behaviors is needed to develop bottom-up strategies or measures for sustainable water management. Water saving measures or strategies would lead to targets being met in a short time.
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Purpose Cognitive function, particularly food-related cognition, is critical for maintaining a healthy weight and preventing the acceleration of obesity. High-Intensity Interval Exercise (HIIE) is an increasingly popular form of exercise and has been shown to improve physical fitness and cognitive function. However, there is limited research on the effects and underlying mechanisms of HIIE on general and food-related cognition among adults with obesity. The aim of the current study was to examine the influence of a single bout of HIIE on food-related cognition among young adults with obesity. Methods Fifteen young men with obesity (BMI = 33.88 ± 4.22, age = 24.60 ± 5.29 years) were recruited. Participants took part in a HIIE condition consisting of 30 minutes of stationary cycle exercise (5-min warm-up, 20-min HIIE and 5-min cool down), and a control session consisting of a time and attention-matched period of sedentary rest in a counterbalanced order. Behavioral (reaction time and accuracy) and event-related potential measures (P3 and the late positive potential, LPP) elicited during a food-related Flanker task were measured after the HIIE and control session. Results Shorter response times were observed following HIIE, regardless of congruency or picture type, with no change in accuracy. Increased P3 and LPP amplitudes were observed following HIIE relative to the control session. Conclusion The findings suggest a single bout of HIIE has a beneficial effect on general and food-related cognition among young adults with obesity, with increased recruitment of cognitive resources to support cognitive control. Future research is warranted to examine the dose-response relationship between acute bouts or longer participation in HIIE on food-related cognition in obesity.(AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Obesity , Cognition , Exercise , Diet, Healthy , High-Intensity Interval Training , Psychology, ClinicalABSTRACT
Objective To explore the effects of miR-221 on tumor cell proliferation, migration and invasion in nonsmall cell lung cancer (NSCLC) xenograft model mice, and to preliminarily analyze its possible mechanism of regulating Akt/ mammalian target of rapamycin(mTOR) signaling pathway by targeting tissue inhibitor of metalloproteinase-2 (TIMP-2) on tumor cells in non-small cell lung cancer (NSCLC) through tumor-bearing nude mice. Methods The A549 cells were divided into control group, mimic group, TIMP-2 group and mimic+TIMP-2 group. The mimic group and TIMP-2 group were transfected with miR-221 mimic and TIMP-2 overexpression plasmids, respectively. The mimic + TIMP-2 group was simultaneously transfected with miR-221 mimic and TIMP-2 overexpression plasmids. The control group was transfected with the same amount of negative control plasmid. After transfection, the cells of each group were injected subcutaneously into the left forelimb to construct the corresponding 4 groups of NSCLC mouse models. The proliferation-related protein (Ki67) was detected by immunohistochemical staining to detected the effect of cell proliferation ability. Matrix metalloproteinase-2 (MMP-2) and N-cadherin proteins in each group were tested by Western blotting to assess and compare the abilities of migration and invasion. The levels of miR-221, TIMP-2 and Akt/ mTOR pathways in bone marrow and tumor tissues were detected by Real-time PCR and Western blotting. Results When co-transfected with wild type(WT)-TIMP-2 and miR-221 mimic, the relative luciferase activity in the cells reduced significantly (P<0. 05). Compared with the control group, the tumor mass, volume, Ki67, MMP-2 and N-cadherin protein expression levels, miR-221 and Akt/ mTOR pathway levels were increased significantly, while the levels of TIMP-2 mRNA and protein were significantly reduced in the mimic group (P<0. 05). Compared with the control group, the levels of TIMP-2 mRNA and protein in the TIMP-2 group increased significantly, while the other indicators decreased significantly (P<0. 05). Tumor tissue mass, volume, Ki67, MMP-2, Ncadherin, miR-221 and Akt/ mTOR pathway levels in mimic+TIMP-2 group were significantly lower than those in the mimic group and significantly higher than those in the TIMP-2 group, while TIMP-2 mRNA and protein levels were significantly higher than those in the mimic group and significantly lower than those in the TIMP-2 group (P<0. 05). Conclusion In the NSCLC transplanted tumor mouse model, miR-221 may mediate the Akt/ mTOR pathway by targeting the expression of TIMP-2 protein to promote cell proliferation, migration and invasion.
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OBJECTIVE@#To investigate the effect of chidamide on the killing activity of NK (Natural killer cell, NK) cells targeting K562 cells and its related mechanism.@*METHODS@#K562 cells were pretreated with chidamide at different concentrations and cocultured with NK cells at different effect-target ratios. The killing effect of chidamide on K562 cells by NK cells, the expression of natural killer group 2 member D (NKG2D) ligands and apoptosis rate of K562 cells were detected by flow cytometry.@*RESULTS@#The killing sensitivity of NK cells to K562 cells could be enhanced by chidamide. The expression of ULBP2 on K562 cell surface could be up-regulate, however, the expression of ULBP1 and MICA/MICB showed no statistically difference as compared with control group. Chidamide showed no obvious cytotoxicity to K562 cells.@*CONCLUSION@#Chidamide can significantly improve killing efficiency of NK cells on K562 cells, which may be related to the up-regulation of ULBP2 expression.
Subject(s)
Humans , Aminopyridines , Benzamides , GPI-Linked Proteins , Histocompatibility Antigens Class I , Intercellular Signaling Peptides and Proteins , K562 Cells , Killer Cells, Natural , Allergy and Immunology , NK Cell Lectin-Like Receptor Subfamily KABSTRACT
Objective To determine the spectrum of mutations responsible for Phenylalanine hydroxylase (PAH) deficiency on phenylketonuria (PKU) patients of Han Chinese people in the Huaihai region of central China.Methods One hundred and one patients diagnosed with PKU were referred to Xuzhou Maternity and Child Health Care Hospital for genetic counseling/analysis from January 2003 to December 2013.Thirteen exons of PAH gene mutations,as well as their flanking introns,were identified in 202 of chromosomes using polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and sequencing.Results (1) The spectrum was composed of 24 different mutation types,which had been submitted to the National Center for Biotechnology Information(NCBI) dbSNP databases under accession number SS#2137543837_SS#C2137543860.(2)The most commonly affected region was exon 7 and its flanking introns.The most prevalent mutations were c.728G > A (p.R243Q),followed by c.721C > T (p.R241C),c.1155G > C(p.L385L),c.1068C > A(p.Y356X),c.-71A > C(-71A > C) and c.60 + 62C > T (IVS1 +62C >T),accounting for 18.317%,8.416%,4.950%,3.960%,3.465% and 2.970% of the mutant chromosomes,respectively.(3)Two novel mutations were identified in PAH gene in PKU patients of Han Chinese people:c.60+62C>T(IVS1 +62C >T) and c.782G >T(p.R261L).Conclusions The vast majority of PAH mutations identified corresponded to those observed for the PKU populations in the other regions in China,whereas a few are considerably different from others.The mutational spectrum of PAH gene found in patients with PKU in the Huaihai region exhibit regional association.
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<p><b>OBJECTIVE</b>To detect the expression level of cyclooxygenase-1(COX-1) and cyclooxygenase-2(COX-2) in the platelet of iron deficiency anemia(IDA)women at childbearing age and to explore its correlation with the different indexes of anemia and platelets.</p><p><b>METHODS</b>Forty female IDA patients at childbearing age and 35 healthy controls were enrolled in this study. The Flow cytometry was used to detect the expression of platelet COX-1 and COX-2,the platelet aggregation function as examined by turbidimetric method,and the levels of serum ferritin were analyzed by electrochemical luminescence method,the leval of serum iron was determined by ELISA,and the correlation of different indexes was analyzed.</p><p><b>RESULTS</b>Compared with healthy controls,the levels of platelet COX-1 and COX-2 were significantly lower in female IDA patients at Childbearing age(P<0.05),but platelet count(Plt),mean platelet volume(MPV) and platelet aggregation rate(PAgT)were not statistically different between the 2 groups(P > 0.05). The expression level of platelet COX-1 positively correlated with those of Hb(r =0.623,P<0.01),serum iron(r =0.321,P<0.05) and HCT(r=0.305,P<0.05). but the platelet COX-2 expression did not corelate with these indexs.</p><p><b>CONCLUSION</b>The expression of platelet COX-1 and COX-2 in female IDA patients at Childbearing age markedly decrease,and the expression level of platelet COX-1 closely relates with the severity of anemia,that possesses reference value for clinical diagnosis of female IDA patients at Childbearing age..</p>
Subject(s)
Female , Humans , Anemia, Iron-Deficiency , Blood Platelets , Cyclooxygenase 1 , Cyclooxygenase 2 , Ferritins , Platelet Aggregation , Platelet CountABSTRACT
AIM To investigate the protective effects of Dahuang Zhechong (DHZC) Pills (Rhei Radix et Rhizoma,Eupolyphaga seu Steleophaga,Hirudo,etc.) against alcoholic liver fibrosis (ALF) injury in mice and to explore the underlying mechanisms.METHODS C57BL/6 male mice were used to build up ALF injury model,intervened with DHZC Pills.The serum of mice was examined for changes in alanine transaminase (ALT),aspartate aminotransferase (AST),interleukin-6 (IL-6),interleukin-10 (IL-10),interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α).Simultaneously,the deposit of collagen 1 (COL-1) and apoptotic cell death in liver tissues were analyzed by immunofluorescent and TUNEL assay,respectively.The expressions of cleaved caspase-3 (CC3) in livers were measured by Western blot.RESULTS Compared with the model group,the levels of serum ALT,AST,IL-6,IFN-γand TNF-α of mice in DHZC group were decreased significantly.And the level of serum IL-10 of mice in DHZC group was increased significantly.Mice in DHZC group had higher rates of COL-1 deposition and apoptotic cell death in liver tissues than those in the model group.Mice treated with DHZC Pills showed lower expression of CC3.CONCLUSION DHZC Pills confers protection against ALF injury in mice by inhibiting the generation of COL-1 and down-regulating apoptosis of liver cells death as a result of adjusting the levels of inflammatory factors.
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Objective To discuss the common deviation in TCM dispensing and corresponding measures. Methods Totally 103 cases of TCM deviation happened in the TCM dispensary of outpatient clinic in our hospital from September 2012 to September 2014 were selected. Retrospective analysis was conducted to analyze case related data collation and factors that affect the quality of TCM dispensing. Corresponding measures for each factor were designed.Results Age and gender of all the 103 cases showed no influence on the statistics of TCM deviation in the study. Among the 103 cases of TCM deviation, 41 cases were caused by factors about medicine. Among the 41 cases, 9 cases were about similar packaging; 12 cases were about similar medicine names; 2 cases were about quality problems; 18 cases were about lack of standardization in medicine placement. 33 cases were caused by factors about deployment, among which, 8 cases were about dosage error, 8 cases were about waste in the preparation process of TCM decoction pieces, 17 cases were about replacement of TCM decoction pieces. 29 cases were caused by factors about prescriptions, among which, 13 cases were about errors of prescription entering deviation, 11 cases were about prescription examining deviation, 5 cases were about ignorance of prescription footnotes. Conclusion Common deviation in TCM dispensing and the reasons are complicated. Timely and correct measures targeting them should be taken to improve the quality of TCM dispensing and guarantee safety.
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Objective To develop a dual real-time fluorescent RT-PCR method for rapid detection of enterovirus(EV)and en terovirus type 71(EV71).Methods Specific primers and probes were designed and the dual real-time fluorescent RT-PCR reaction system was established.The quantitative standard curve was drawn;its sensitivity and precision were evaluated.Feces and throat swab specimens of 109 clinical patients with hand foot and mouth disease were collected and tested by using this method.Then the obtained results were compared with those detected by commercial EV71 PCR kit.Results The relative coefficient(2)of EV and EV71 standard curve established by the dual real-time fluorescent RT-PCR method were both 0.998.Its sensitivity reached 0.5 TCID50/mL for detecting EV and 0.05 TCID50/mL for detecting EV71.The within-run precision for detecting EV and EV71 was <3% and total precision≤4%.The results showed good specificity for the detection of enterovirus and non-enterovirus.In 109 detected clinical samples,84 cases of EV positive samples were detected,in which 56 cases were EV71 positive with the total positive rate of 51.4 %,which was consistent with the result of simple fluorescent RT-PCR commercialization kit(P=1.000).Conclusion The established dual real-time fluorescent RT-PCR method has high sensitivity and good stability,which has an important significance for early high throughput rapid diagnosis of hand foot and mouth disease.
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Objective To investigate the prevalence,clinical classification,treatment and prognosis of neonatal hyperphenylalaninemia(HPA) in Xuzhou area,China.Methods Infants born between July 1,2003 and July 1,2015 in Xuzhou area were investigated.Heel blood samples of neonates were collected at 72 hours after birth,and the concentration of blood phenylalanine(Phe) was determined by fluorescent quantitative method in Xuzhou Maternity and Child Health Care Station Neonatal Disease Screening Center.Differential diagnosis was performed in all 265 cases diagnosed as HPA by urinary pterin analysis and dihydropteridine reductase activity determination.The blood Phe concentration and mental development were followed up regularly in infants with HPA.Mutations of phenylalanine hydroxylase (PAH) gene were analyzed by gene sequencing.The relationship between blood Phe concentration and mental development was analyzed by Bivariate correlation analysis.Results (1) The prevalence of HPA in neonates in Xuzhou was 1/4 635.Among the 265 confirmed HPA cases,260 cases(98.11%) had PAH deficiency,including 90(33.96%) classical phenylketonuria(PKU),84(31.70%) mild PKU and 86(32.45%) mild HPA.The other five patients(1.89%) diagnosed with tetrahydrobiopterin (BH4) deficiency all had 6-pyruvoyl tetrahydropteim synthase(PTPS) deficiency.(2) Among the 265 HPA cases,26 cases refused any treatment,including five cases of PTPS deficiency and 21 cases of PKU.Of the five patients with PTPS deficiency,two died and the other three had normal mental and physical development.Twenty-one PKU patients who refused treatment had mental retardation of various degrees.Among 153 PKU patients who received medical treatment,three died and 12 were lost to follow-up.(3) For 138 PKU patients who received dietary treatment and follow-up,the ages at the last visit were two months to 12 years,116 of them had normal mental development,the remaining 22 patients had mental retardation,and a negative correlation was observed between mental development and the average Phe concentration.(4) Thirty-five patients with PAH deficiency underwent gene sequencing,and 22 kinds of mutations of PAH gene were detected.Conclusions The prevalence of HPA in Xuzhou area is higher than the average national level.With early diagnosis and standard treatment,most of PKU neonates can have normal mental development.Phe level control is an important factor for mental development.
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Objective To investigate the levels of trace element in calcium, magnesium, zinc, iron and copper in maternal blood of pregnant women of different pregnancy and ages of pregnant women , and its relation to the pregnancy the age of pregnant women. Methods Calcium, magnesium, zinc, iron and copper in serum in 10 131 cases of pregnant women (3 565 cases in the first pregnancy, 6 566 cases in second pregnancy) were measured. All cases (both first pregnancy and second pregnancy) were analysed according to three age periods (less than or equal to 25, 25 to 35 years old, more than or equal to 35). Results (1)Comparing to the cases in second pregnancy, Copper in serum of the cases in first pregnancy was lower, while zinc, magnesium and iron were higher (P 0.05). (2) For the cases in the first pregnancy in different age periods, all 5 kinds of trace elements were compared. Only the zinc level in serum in the groups of 25 ~ 35 years old and more than or equal to 35 years old was higher than that in the group of less than or equal to 25 years old (P 0.05). (3) For the cases in the first pregnancy in different age stages , all 5 kinds of trace elements were compared basis on the age periods. the zinc and iron levels in serum in the groups of 25 to 35 years and more than or equal to 35 years old were higher than those in less than or equal to 25 years old (P 0.05) was found in the other three kinds of trace elements in different age periods. Conclusions (1)There are differences in trace elements, magnesium, zinc, iron and copper, and no difference in calcium in the first and second pregnancy. (2)Trace elements in serum of pregnant women in different age periods are different. (3)According to the characteristics of various trace elements in serum of pregnant women of different pregnancy and age periods, trace elements shall be supplemented to meet the needs of the pregnant women and fetus.