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The clinical features, electroneurophysiology, neuroimaging and gene characteristics of one case of early adult-onset dentatorubral-pallidoluysian atrophy (DRPLA) with an onset of epilepsy were reported. The female patient had the onset manifestation of epilepsy. Whereafter, she progressively developed marked cerebellar ataxia, mental retardation and choreic movement. Electroencephalography showed that there were multiple complex slow waves in the whole brain cortex. Magnetic resonance imaging showed the patient had marked atrophies in the cerebral cortex, brainstem and cerebellum. Atrophin-1 gene detection revealed that the numbers of CAG repeats were 15/65 (the patient) and 14/54 (her father) respectively. Her father had no clinical manifestations until now. The mother and brother were normal. DRPLA has diverse clinical presentation,heterogeneous phenotypic spectrum, early adult-onset DRPLA is rare, and the specific gene detection can be helpful for a definitive diagnosis.
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Objective:To investigate the pathogen distribution and antimicrobial resistance among lower respiratory tract infections in patients with hematological malignancies.Methods:Sputum samples were collected from 967 patients with hematological malignancies and lower respiratory tract infections in Department of Hematology,the Second Hospital of Shanxi Medical University from January 2017 to July 2020. The pathogens and drug sensitivity reports were carried out by automatic bacterial identification instruments. WHONET 5.6 and SPSS 20.0 softwares were used for statistical analysis.Results:A total of 961 strains of pathogens were isolated, 516 (53.7%) pathogens were Gram-negative bacteria, mainly 118 strains of Klebsiella pneumonia (12.3%), 68 strains of Pseudomonas aeruginosa (7.1%), 67 strains of Acinetobacter baumannii (7.0%),52 strains of Stenotrophomonas maltophilia (5.4%), 43 strains of Escherichia coli (4.5%), and 42 strains of Enterbacter cloacae (4.4%). There were 171 (17.8%) strains of Gram-positive bacteria and 274 (28.5%) fungi. The drug resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem were 22.1%-31.3%. Stenotrophomonas maltophilia was sensitive to levofloxacin, compound sulfamethoxazole and minocycline. The antimicrobial resistance rates of these three enterobacteria to carbapenems, cefoperazone/sulbactam, piperacillin/tazobactam were low (<10%). The resistant Gram-positive bacteria to ticoplanin, vancomycin and linazolamide were not detected.Conclusion:The major pathogens related to lower respiratory tract infections in patients with hematological malignancies are gram-negative bacteria in our centre. Different pathogens appear different characteristics of antimicrobial resistance.
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Objective To analyze the clinical features and risk factors for an emerging infection during the first induction chemotherapy in elderly patients with acute leukemia.Methods A retrospective analysis of clinical data of 79 elderly patients with newly diagnosed acute leukemia was performed in Second Hospital of Shanxi Medical University from January 2014 to May 2016.Results The 70 cases among 79 elderly patients with acute leukemia were suffered from infection with infection incidence rate of 88.6％ (70/79)during first induction chemotherapy.The infection-related fatality rate was 8.6 ％ (6/70).Being clear about sites of infection accounted for 90.0 ％ (63/70),and the top three infection sites were the lungs,gastrointestinal tract and the bloodstream.113 pathogenic strains were detected,including gram-negative bacilli accounting for 42.5 ％ (48/113),Gram-positive cocci for 30.1％ (34/113),fungi for 24.8％ (28/113),the virus for 2.7％ (3/113).Based on clinically and confirmatively diagnosis,the invasive fungal diseases mostly as Candida accounted for 30.4 ％ (24/79),mixed infections accounted for 34.3％ (24/70).Univariate analysis showed agranulocytosis and AML were risk factors for infection.Logistic multivariate regression analysis showed that agranulocytosis was a risk factor for infection (OR=12.010,95％CI:2.346-107.973,P=0.000).The infection does not affect a complete remission rate of acute leukemia (x2 =0.001,P=0.983).Conclusions For newly diagnosed elderly acute leukemia patients,an emerging infection during the first induction chemotherapy is characterized by a high incidence,high fungal infection rate,most common site in lung,Gram-negative bacteria as most common pathogen,and an increased infection rate by agranulocytosis.The infection does not affect the remission rate of acute leukemia.
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A quantitative method for clopidogrel using online-SPE tandem LC-MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.5-C18-UHPLC for both methods. Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed for signal detection and a deuterated analogue (clopidogrel-d 4) was used as internal standard (IS). Adjustments in sample preparation, including introduction of an online-SPE system proved to be the most effective method to solve the analyte back-conversion in clinical samples. Pooled clinical samples (two levels) were prepared and successfully used as real-sample quality control (QC) in the validation of back-conversion testing under different conditions. The result showed that the real samples were stable in room temperature for 24 h. Linearity, precision, extraction recovery, matrix effect on spiked QC samples and stability tests on both spiked QCs and real sample QCs stored in different conditions met the acceptance criteria. This online-SPE method was successfully applied to a bioequivalence study of 75 mg single dose clopidogrel tablets in 48 healthy male subjects.
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Objective To explore the effect of dietary fat acids on incretin and islet function in healthy adults .Methods Before each test, healthy subjects received a 1-week pre-experiment eucaloric diet .Fifteen subjects consumed two meals containing different fat acids , including high saturated fat acid ( HSF) and high monounsaturated fat acid ( HMF) .On two separate occasions,they underwent a minimum of 1-week washout between meals .At 0,30,60,120,180 and 240 min following meal intake, the plasma concentrations of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(GLP-1) and serum concentrations of glucose, insulin, triglycerides ( TG) and free fatty acid ( FFA) were measured.Results Postprandial glucose did not increase significantly following HSF and HMF meals (P>0.05).Compared with HMF meal, significant increase in AUCins240min,AUCTG240min and AUCFFA240minwas observed following HSF meal (P0.05). AUCI/AUCG was significantly lower following HMF meal as compared with HSF meal (P<0.05).Conclusion This study demonstrates that the function of GIP ,GLP-1 andβcell is affected by the dietary fat acids in healthy adults .The HMF meal may stimulate GIP and GLP-1 secretion to a greater extent than HSF meal .
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The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line-ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 μmol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Westernblot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 μmol/L), the expression levels of PAI-1 mRNA and protein were 0.65±0.05 and 0.96±0.11 respectively, significantly lower than in the control group (0.78±0.03 and 1.21±0.15, respectively, P＜0.05). PAI-1 antigenie contents (24.52±8.39) in ECV304 cells treated with 10 μmol/L fenofibrate were significantly lower than those in the control group (6.98±5.12, P＜0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.
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The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 micromol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 micromol/L), the expression levels of PAI-1 mRNA and protein were 0.65 +/- 0.05 and 0.96 +/- 0.11 respectively, significantly lower than in the control group (0.78 +/- 0.03 and 1.21 +/- 0.15, respectively, P<0.05). PAI-1 antigenic contents (24.52 +/- 8.39) in ECV304 cells treated with 10 micromol/L fenofibrate were significantly lower than those in the control group (6.98 +/- 5.12, P<0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.