12 results on '"Chen, Qi-Xing"'
Search Results
2. Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8.
- Author
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Feng J, Yang C, Zhu L, Zhang Y, Zhao X, Chen C, Chen QX, Shu Q, Jiang P, and Tong F
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- Acyl-CoA Dehydrogenase deficiency, Amino Acid Metabolism, Inborn Errors, China epidemiology, Genotype, Humans, Infant, Newborn, Mutation, Phenotype, Prognosis, Retrospective Studies, Neonatal Screening, Tandem Mass Spectrometry
- Abstract
Background: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD., Methods: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel., Results: The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann-Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3-108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4_5delCT, c.109C > T, c.110-2A > T, c.236G > A, c.259G > A, c.381-14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842-1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%)., Conclusion: The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future., (© 2021. The Author(s).)
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- 2021
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3. Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury.
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Chen QX, Song SW, Chen QH, Zeng CL, Zheng X, Wang JL, and Fang XM
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- Acute Lung Injury etiology, Animals, Coinfection, Colony Count, Microbial, Disease Models, Animal, Disease Progression, Epithelial Cells immunology, Epithelial Cells physiology, Hepcidins immunology, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Respiratory System, Sepsis complications, Survival Rate, Acute Lung Injury microbiology, Bronchoalveolar Lavage Fluid microbiology, Hepcidins physiology, Iron metabolism, Sepsis microbiology
- Abstract
Introduction: The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a β-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infectious and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury., Methods: Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the 7-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated., Results: The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased the mortality (53.33% in Ad-shHepc1 treated mice versus 12.5% in Ad-shNeg treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice., Conclusions: Airway epithelial cell-derived hepcidin plays an important role in CLP induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.
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- 2014
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4. Defensins and sepsis.
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Xie GH, Chen QX, Cheng BL, and Fang XM
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- Adaptive Immunity, Defensins genetics, Defensins immunology, Dendritic Cells immunology, Dendritic Cells metabolism, Dendritic Cells pathology, Humans, Immunity, Innate, Interleukin-1beta immunology, Neutrophils immunology, Neutrophils metabolism, Neutrophils pathology, Sepsis drug therapy, Sepsis pathology, T-Lymphocytes immunology, Defensins metabolism, Interleukin-1beta metabolism, Phagocytosis immunology, Sepsis immunology
- Abstract
Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins' effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.
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- 2014
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5. Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients.
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Li CX, Liang DD, Xie GH, Cheng BL, Chen QX, Wu SJ, Wang JL, Cho W, and Fang XM
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- Adult, Aged, Cryptochromes biosynthesis, Female, Gene Expression Regulation, Humans, Male, Melatonin metabolism, Middle Aged, Period Circadian Proteins biosynthesis, Sepsis genetics, Sepsis pathology, Circadian Rhythm genetics, Interleukin-6 biosynthesis, Melatonin genetics, Sepsis metabolism, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.
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- 2013
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6. Polymorphisms of the HTR3B gene are associated with post-surgery emesis in a Chinese Han population.
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Ma XX, Chen QX, Wu SJ, Hu Y, and Fang XM
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- Adult, Asian People genetics, Female, Gene Frequency, Genotype, Gynecologic Surgical Procedures adverse effects, Humans, Middle Aged, Polymorphism, Single Nucleotide, Young Adult, Postoperative Nausea and Vomiting genetics, Receptors, Serotonin, 5-HT3 genetics
- Abstract
What Is Known and Objectives: The serotoninergic receptor 5-hydroxytryptamine (serotonin) receptor 3 (HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 (HTR3A, HTR3B) are associated with the incidence of post-operative vomiting in a Chinese Han population., Methods: Two hundred and thirty-one female Chinese Han patients undergoing gynaecological surgery with standardized general anaesthesia were recruited for the study. Clinical symptoms after surgery were recorded and direct DNA sequencing was performed to detect polymorphisms of HTR3A and HTR3B., Results: Five single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B were found, with R(2) > 0·8 and minor allele frequency > 10%. One of these (rs3758987 in HTR3B) was statistically associated with vomiting, after adjusting for body weight, body mass index and duration of general anaesthesia in dominant and additive models (P = 0·047 and P = 0·034)., What Is New and Conclusion: The HTR3B rs3758987 SNP might serve as a predictor of post-operative vomiting in Chinese Han patients undergoing gynaecological laparoscopic surgery., (© 2013 Blackwell Publishing Ltd.)
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- 2013
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7. Small molecules in treatment of sepsis.
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Hu Y, Xie GH, Chen QX, and Fang XM
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- Animals, Humans, Molecular Targeted Therapy, Sepsis metabolism, Sepsis physiopathology, Sepsis drug therapy
- Abstract
Sepsis is a common and frequently a fatal syndrome. Though, there is steady progress in the management of sepsis, further reduction of its mortality is still hampered by the lack of specific remedies. Recent advances in the understanding of the pathophysiology of sepsis and innovations in drug design have enabled researchers to develop new strategies for the treatment of this complicated condition in a more efficient way. Among these, a variety of small synthetic compounds with the molecular weight lower than 1000Da are emerging rapidly. This review highlights the advances of these small molecules in the treatment of sepsis, which are categorized into the following seven groups according to their pharmaceutical targets: LPS sequestrants and TLR4 antagonists, C5a receptor antagonists, inhibitors of macrophage migration inhibitory factor, inhibitors of QseC signaling, A3 adenosine receptor agonists and A2A adenosine receptor antagonists, estrogen receptor β agonists and caspase inhibitors. Most of the compounds have shown effectiveness in preclinical studies and displayed little or no toxicity. These small molecular compounds are potential candidates for further therapeutic development of sepsis.
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- 2011
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8. [Construction and evaluation of recombinant plasmid containing human triggering receptor expressed on myeloid cells-1 gene].
- Author
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Hu Y, Shu LQ, Chen QX, and Yao HP
- Subjects
- Cells, Cultured, Humans, Transfection, Triggering Receptor Expressed on Myeloid Cells-1, Genetic Vectors, Membrane Glycoproteins genetics, Plasmids genetics, Receptors, Immunologic genetics
- Abstract
Objective: To construct a eukaryotic expression plasmid containing human triggering receptor expressed on myeloid cells-1(TREM-1) gene., Methods: The entire gene coding region of human TREM-1 was amplified from total RNA of human peripheral blood by means of RT-PCR. The fragment of TREM-1 was cloned to vector pUCm-T. After digestion by restriction endonuclease BamH I and Pst I, the fragment was subcloned into the eukaryotic expressing vector pEGFP-C3. This recombinant vector was transfected into 293 cells using liposome. The expression level of TREM-1 was determined by fluorescence microscope and Western blot assay. The recombinant TREM-1 vector was transfected into THP-1 cells. After stimulation with 100 ng/ml LPS for 24 h, the mRNA levels of TNF-α and IL-1β were measured using RT-PCR., Result: The expression vector was constructed, and the result of the DNA sequencing showed that the constructed plasmid containing the TREM-1 gene. Fluorescence microscope and Western blot analysis showed that TREM-1 protein was expressed in 293 cells successfully. After transfection into THP-1 cells, recombinant TREM-1 could upregulate the mRNA levels of TNF-α and IL-1β., Conclusion: Eukaryotic expression plasmid pEGFP-TREM-1 is successfully constructed and showed biological activity.
- Published
- 2010
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9. Predictive value of expression and promoter hypermethylation of XAF1 in hepatitis B virus-associated hepatocellular carcinoma treated with transplantation.
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Zhang F, Wu LM, Zhou L, Chen QX, Xie HY, Feng XW, and Zheng SS
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- Adaptor Proteins, Signal Transducing, Adult, Aged, Apoptosis Regulatory Proteins, Azacitidine pharmacology, Carcinoma, Hepatocellular complications, Carcinoma, Hepatocellular surgery, Female, Gene Expression Regulation, Neoplastic, Hepatitis B complications, Hepatitis B virology, Hepatitis B virus genetics, Humans, Immunoenzyme Techniques, Intracellular Signaling Peptides and Proteins, Liver Neoplasms complications, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Proteins metabolism, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local surgery, Prognosis, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Tumor Cells, Cultured, Zinc Fingers, Carcinoma, Hepatocellular genetics, DNA Methylation, Hepatitis B genetics, Liver Neoplasms genetics, Liver Transplantation, Neoplasm Proteins genetics, Promoter Regions, Genetic genetics
- Abstract
Background: Transcriptional regulation of the putative tumor suppressor gene X-linked inhibitor of apoptosis protein-associated factor 1 (XAF1) by promoter methylation has been related to tumor progression in gastric and bladder cancer. The aim of this study was to investigate the methylation status and expression level of XAF1 in human hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) treated with liver transplantation (LT), and to evaluate potential predictive value for tumor recurrence., Methods: The expression level and methylation status of XAF1 in three liver cancer cell lines (SMMC-7721, HepG2, and Hep3B) and 65 cases of HBV-associated HCC following LT were analyzed by RT-PCR (RT, reverse-transcriptase), immunohistochemistry, and methylation-specific polymerase chain reaction (PCR)., Results: XAF1 transcripts were not observed or present at low levels in liver cancer cell lines and were restored by treatment with demethylating agent 5-aza-2'-deoxycytidine (5-Aza-dC). In vivo, methylation status was associated with protein level of XAF1 (P < 0.001) and serum level of alpha-fetoprotein (AFP) (P = 0.009). The expression pattern of XAF1 was associated with portal vein tumor thrombi (PVTT), preoperative AFP level, tumor size, and recurrence. Multivariate analysis revealed that expression level of XAF1 was an independent factor for predicting recurrence-free survival [hazard ratio 0.237, 95% confidence interval (CI) 0.095-0.592, P = 0.002]. However, no significant association was found between methylation status and the risk of tumor recurrence., Conclusion: Promoter hypermethylation is a critical, but not the sole, mechanism for gene silencing of XAF1 in HCC. Protein level of XAF1 may serve as a potential biomarker for tumor recurrence after LT.
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- 2008
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10. Protein C -1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis in Chinese Han population.
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Chen QX, Wu SJ, Wang HH, Lv C, Cheng BL, Xie GH, and Fang XM
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- Alleles, China epidemiology, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Promoter Regions, Genetic genetics, Haplotypes genetics, Multiple Organ Failure genetics, Protein C genetics, Sepsis genetics
- Abstract
Activation of protein C plays an important role in modulating coagulation as well as inflammation during severe sepsis. The baseline of activated protein C level in patients with severe sepsis showed interindividual variability between survivors and nonsurvivors, and the decreased level of protein C correlated with organ dysfunction and poor outcome. However, there are limited data concerning the genetic predisposition of individuals carrying two functional polymorphisms -1641A>G and -1654C>T within protein C gene to sepsis. Here we investigated the impact of these two variations on the development of severe sepsis in 240 patients with severe sepsis and 323 healthy controls using direct sequencing. After Bonferroni correction for multiple comparisons, -1641A/-1654C haplotype was significantly associated with the fatal outcome of severe sepsis (P = 0.008, OR 1.739, 95% CI 1.165-2.595), which was confirmed by multiple logistic regression analysis (P = 0.024, OR 2.090, 95% CI 1.101-3.967). Compared to patients without carrying -1641A/-1654C haplotype, the -1641A/-1654C haplotype carriers showed higher SOFAmax scores (10.3 +/- 5.2 vs. 9.0 +/- 4.5; P = 0.014) and more hepatic dysfunction (P = 0.004, OR 2.270, 95% CI 1.312-3.930). These findings suggest that protein C haplotype -1641A/-1654C is associated with organ dysfunction and is an independent risk factor for the fatal outcome of severe sepsis in Chinese Han population.
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- 2008
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11. [IL-10 inhibits inducible expression pattern of beta-defensin-2 in human peripheral blood cells].
- Author
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Chen QX, Zhou JL, and Book M
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- Blood Cells cytology, Blood Cells metabolism, Cells, Cultured, Humans, Lipopolysaccharides pharmacology, RNA, Messenger biosynthesis, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Blood Cells drug effects, Interleukin-10 pharmacology, beta-Defensins genetics
- Abstract
Objective: To investigate the effect of IL-10 on the inducibility of human beta-defensin 2 (hBD-2) in human peripheral blood cells., Methods: Peripheral blood samples were collected from 22 healthy individuals and co-cultured with 0 ng/ml lipopolysaccharide (LPS), 100 ng/ml LPS, 10 ng/ml IL-10, or 100 ng/ml LPS plus 10 ng/ml IL-10 at 37 degree for 6 h. Total RNA was extracted from peripheral blood cells and the mRNA level of hBD-2 was detected by relative quantitative real-time PCR.., Result: No detectable level of hBD-2 mRNA was found in normal peripheral blood cells with stimulation of 0 ng/ml LPS or 10 ng/ml IL-10. The mRNA level of hBD-2 was increased to 166.9 +/- 35.14 after 100 ng/ml LPS challenge, while the mRNA level of hBD-2 was decreased to 30.40 +/- 9.18 after the co-stimulation of 100 ng/ml LPS plus 10 ng/ml IL-10; which was significantly lower than that with LPS alone (P<0.05)., Conclusion: The expression of hBD-2 gene can be induced by LPS.IL-10 inhibits the inducible expression of hBD-2.
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- 2006
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12. Interleukin 10.G microsatellite in the promoter region of the interleukin-10 gene in severe sepsis.
- Author
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Shu Q, Shi CC, Zhang XH, Shi Z, Shi SS, Fang XM, Chen QX, and Stuber F
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- Female, Genetic Predisposition to Disease, Humans, Male, Interleukin-10 genetics, Microsatellite Repeats, Promoter Regions, Genetic, Sepsis genetics
- Abstract
Background: The highly polymorphic interleukin 10.G (IL10.G) microsatellite located in the promoter region of the interleukin-10 (IL-10) gene exerts a positive transcriptional regulatory effect on IL-10 gene expression and correlates with the in vitro IL-10 secretion. This study was conducted to investigate whether IL10.G microsatellite is associated with the incidence and/or the outcome of severe sepsis., Methods: One hundred and fifteen patients with severe sepsis who had been treated at the intensive care unit of the university hospital were studied. One hundred and forty-one healthy individuals served as controls. IL10.G microsatellite genotyping was performed with the following two methods: fluorescent based polymerase chain reaction (PCR) techniques and silver staining of the amplified DNA fragment in polyacrylamide gel. Alleles were defined according to the size of the amplified DNA product., Results: Ten alleles and 36 genotypes were detected both in the patients with severe sepsis and in the healthy controls. Allele IL10.G9 and allele IL10.G13 were the commonest alleles with the frequencies of 32.6% and 21.3% respectively in the patients with severe sepsis, and 34% and 27% respectively in the healthy controls. The allele frequencies of IL10.G microsatellite were neither different between the patients with severe sepsis and the healthy controls (P > 0.05), nor between survivors and non-survivors (P > 0.05). However, the frequency of one common allele IL10.G13 was slightly lower in the patients with severe sepsis than in the healthy controls (21.3% vs 27%, P > 0.05), and the frequency of allele IL10.G9 was slightly higher in the non-survivors than in the survivors (37.1% vs 28.1%, P > 0.05)., Conclusion: IL10.G microsatellite may neither contribute to the susceptibility to severe sepsis nor to the fatal outcome of severe sepsis.
- Published
- 2006
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