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Objective:To analyze the disease spectrum of lysosomal storage disorders(LSDs) and explore the prevalent distributions of different LSD types in one center in Shanghai.Methods:A retrospective analysis was made.A total of 5 476 suspected LSD patients, including 3 415 males and 2 061 females, with a median age of 4 years(1 day to 72 years), were collected from Xinhua Hospital, Shanghai Jiaotong University School of Medicine from August 2008 to May 2022.The activity of different lysosomal enzymes was detected by fluorescent and biochemical methods.Results:A total of 1 520 patients were diagnosed with LSDs, including 972 males and 548 females, with a median age of 4 years(1 day to 59 years), involving 19 different subtypes.Mucopolysaccharidosis(MPS) was the most common type among LSDs, with a frequency of 45.46%(691/1 520), followed by sphingolipidoses [33.88%(515/1 520)] and glycogen storage disease type Ⅱ [16.05%(244/1 520)] successively.MPS Ⅱ was the most common type in MPS, with a frequency of 45.73%(316/691), followed by MPS ⅣA [22.87%(158/691)]. Niemann-Pick A/B, Gaucher, and Krabbe diseases were common in Sphingolipidoses patients, with frequencies of 37.09%(191/515), 34.37%(177/515), and 10.29%(53/515), respectively.Conclusions:LSDs are common genetic metabolic diseases, especially MPS and sphingolipidoses.Newborn screening for LSDs should be carried out timely so that the patients can be treated early and their prognosis can be improved.
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Objective:Nuclear magnetic resonance spectroscopy (NMR) was used to detect the species and content of metabolites in urine of patients with inherited metabolic diseases, and to explore the application value of NMR technology in the diagnosis of inherited metabolic diseases.Methods:Urine samples were collected from 20 patients with inherited metabolic diseases diagnosed in Xinhua Hospital, Shanghai Jiaotong University School of Medicine from March to June 2019, including 9 cases of methylmalonic acidemia (MMA). NMR pulse length-based concentration determination and Gas chromatography mass spectrometry (GC/MS) semi-quantitative method were used to detect the composition of metabolites in urine samples of patients with inherited metabolic diseases, and the levels of abnormal metabolites in the two methods were analyzed.Results:NMR technology can detect the levels of characteristic metabolites significantly increased in the urine of patients with MMA, isovalerinemia, glutaric acidemia, propionic acidemia, 3-methylcrotonyl-CoA carboxylase deficiency, ornithine carbamyltransferase deficiency, Citrin deficiency, Canavan disease, tyrosinemia and lysinuria protein intolerance. The average is 8 times of the upper limit of the reference value, and the highest is 545 times. Compared to GC/MS, NMR technology can detect the levels of various metabolites such as organic acids, amino acids and sugars. In 9 cases of untreated MMA,the median levels of methylmalonic acid and 3-hydroxypropionic acid in NMR [1 800 (180-12 000) and 50 (0-270) mmol/mol Cr] were higher than the reference values (0-31, 0-35). The median levels of methylmalonic acid and methylmalonic acid in GC/MS [136.56 (43.79-518.67) and 4.87 (1.52-7.52)] were higher than the reference values (0-4 and 0-0.7).Conclusions:NMR and GC/MS technologies are specific for the diagnosis of organic acidemia. The primary component detected by GC/MS is organic acid. NMR technology can break through this limitation and measure the level of various metabolites in urine, which provides a more theoretical basis for the diagnosis and research of inherited metabolic disease.
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Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule（FTZ） on hemoglobin A1c（HbA1c）in patients with type 2 diabetes mellitus （T2DM） based on real-world data. Method:T2DM patients who were provided with FTZ （FTZ group） and those receiving conventional hypoglycemic drugs （control group） were extracted from the hospital information system （HIS） of the First Affiliated Hospital of Guangdong Pharmaceutical University， followed by propensity score matching （PSM） for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index， the difference in efficacy between the two groups was compared using <italic>t</italic>-test and <italic>χ</italic><sup>2</sup> test. For repeated measurement data of the same patient， the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation （GEE）. The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis （MLRA）， and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation， ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time， the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover， the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c ［<italic>β</italic>=-0.530，95% confidence interval（CI） -0.850～-0.209，<italic>P</italic><0.01］ or those who were complicated with hypertension （<italic>β</italic>=-0.918，95%CI -1.614～-0.222，<italic>P</italic><0.05）. Conclusion:In the real world， FTZ is able to control the blood sugar， and its effect is similar to those of conventional hypoglycemic drugs. Besides， it is capable of stabilizing the blood sugar for a long time.
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The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.
Subject(s)
Animals , Mice , Artemisinins , Intercellular Adhesion Molecule-1/genetics , Monocytes , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
OBJECTIVE@#To develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma and investigate the pharmacokinetics of atorvastatin and the changes in voriconazole concentration in rats after administration.@*METHODS@#Plasma samples were collected from rats after intragastric administration of atorvastatin alone or in combination with voriconazole. The samples were treated with sodium acetate acidification, and atorvastatin and voriconazole in the plasma were extracted using a liquidliquid extraction method with methyl tert-butyl ether as the extractant. The extracts were then separated on a Thermo Hypersil Gold C18 (2.1×100 mm, 1.9 μm) column within 6 min with gradient elution using acetonitrile and water (containing 0.1% formic acid) as the mobile phase; mass spectrometry detection was achieved in selective reaction monitoring (SRM) mode under the positive ion scanning mode of heated electrospray ion source (H-ESI) and using transition mass of m/z 559.2→440.2 for atorvastatin and m/z 350→280 for voriconazole, with m/z370.2→252 for lansoprazole (the internal standard) as the quantitative ion.@*RESULTS@#The calibration curves were linear within the concentration range of 0.01-100 ng/mL (=0.9957) for atorvastatin and 0.025-100 ng/mL (=0.9966) for voriconazole. The intra-day and inter-day precisions were all less than 13%, and the recovery was between 66.50% and 82.67%; the stability of the plasma samples met the requirements of testing. The AUC of atorvastatin in rat plasma after single and combined administration was 438.78±139.61 and 927.43±204.12 h·μg·L, CLz/F was 23.89±8.14 and 10.43±2.58 L·h·kg, C was 149.62±131.10 and 159.37±36.83 μg/L, t was 5.08±1.63 and (5.58±2.11 h, and T was 0.37±0.14 and 3.60±1.52 h, respectively; AUC, CLZ/F and T of atorvastatin in rat plasma differed significantly between single and combined administration. The HPLC-MS/MS system also allowed simultaneous determination of voriconazole concentration in rat plasma after combined administration.@*CONCLUSIONS@#The HPLC-MS/MS system we established in this study is simple, rapid and sensitive and allows simultaneous determination of atorvastatin and voriconazole in rat plasma. Some pharmacokinetic parameters of atorvastatin are changed in the presence of voriconazole, and their clinical significance needs further investigation.
Subject(s)
Animals , Rats , Administration, Oral , Atorvastatin , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , VoriconazoleABSTRACT
Objective To understand the infection status and risk factors of Entamoeba histolytica in inpatients in Tengchong City, Yunnan Province. Methods A cross-sectional study was conducted in the inpatients in Tengchong People’s Hospital, Yunnan Province. After obtaining the informed consent from the subjects, the stool samples were collected from 2016-07-01 to 2017-03-31, and nested polymerase chain reaction (PCR) was used to detect E. histolytica in the stool samples. Meanwhile, a structured questionnaire was used to record the demographic information and clinical symptoms for the patients. Results Totally 507 cases were recruited, and the detection rate of E. histolytica was 1.97% (10/507, 95% CI: 1.07%-3.59%) in all subjects. There were no significant differences between the inpatients with and without E. histolytica infection in the height (Z = -0.40, P = 0.69), weight (Z = -0.34, P = 0.73), body mass index (Z = -0.40, P = 0.69) and age (Z = -1.48, P = 0.14). Chronic diarrhea (OR = 21.43, 95% CI: 5.04-91.23) and daily drinking water (OR = 11.28, 95% CI: 2.79-45.56) were relevant to E. histolytica infection. No significant association was observed between E. histolytica infection and the clinical symptoms, such as abdominal distension (OR = 0.70, 95% CI: 0.09-5.56), inappetence (OR = 0.50, 95% CI: 0.06-4.02), itchy skin (OR = 0.79, 95% CI: 0.10-6.38), perianal pruritus (OR = 1.74, 95% CI: 0.21-14.07), and constipation (OR = 0.91, 95% CI: 0.13-7.33). Conclusion E. histolytica infection is high in inpatients in Tengchong City, Yunnan Province, and chronic diarrhea and drinking unboiled water were highly correlated with E. histolytica infection.
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OBJECTIVE@#To summarize the clinical, biochemical and molecular characteristics of 8 patients with beta-ketothiolase deficiency (BKD).@*METHODS@#Clinical characteristics, biochemical markers detected by tandem mass spectrometry (MS-MS) and gas chromatography-mass spectrometry (GC-MS), and variations of ACAT1 gene of the 8 patients were reviewed.@*RESULTS@#Three patients were diagnosed by newborn screening and were asymptomatic. Five patients showed dyspnea and metabolic acidosis through high risk screening. Blood methylcrotonyl carnitine (C5:1) were 0.43 (0.20-0.89) μmol/L and 3-hydroxyisovaleryl carnitine(C5-OH) were 1.37 (0.98-3.40) μmol/L. Both were significantly higher than those of healthy controls (PG (p.N375S) variant, which accounted for 28.6% of all 14 mutant alleles. Four novel variants, namely c.229delG (p.E77KfsTer10), c.373G>T (p.V125F), c.419T>G (p.L140R) and c.72+1G>A, were discovered. Pathogenicity assessment of two highly conservative missense variants (p.V125F) and (p.L140R) were 0.994 and 1.0 (Scores obtained from PolyPhen2), and PROVEAN scores were -4.652 and -5.399, respectively. c.72+1g>a was suspected (by Human Splicing Finder) to alter the wild type donor motif and most probably affect the splicing.@*CONCLUSION@#Clinicians should consider MS/MS and GC/MS testing for those with unexplained neurological symptoms and metabolic acidosis in order to attain early diagnosis of BKD. Genetic testing should be used to confirm the diagnosis.
Subject(s)
Humans , Infant, Newborn , Acetyl-CoA C-Acyltransferase , Amino Acid Metabolism, Inborn Errors , Carnitine , Retrospective Studies , Tandem Mass SpectrometryABSTRACT
Objective To understand the infection status and risk factors of Entamoeba histolytica in inpatients in Tengchong City, Yunnan Province. Methods A cross-sectional study was conducted in the inpatients in Tengchong People’s Hospital, Yunnan Province. After obtaining the informed consent from the subjects, the stool samples were collected from 2016-07-01 to 2017-03-31, and nested polymerase chain reaction (PCR) was used to detect E. histolytica in the stool samples. Meanwhile, a structured questionnaire was used to record the demographic information and clinical symptoms for the patients. Results Totally 507 cases were recruited, and the detection rate of E. histolytica was 1.97% (10/507, 95% CI: 1.07%-3.59%) in all subjects. There were no significant differences between the inpatients with and without E. histolytica infection in the height (Z = -0.40, P = 0.69), weight (Z = -0.34, P = 0.73), body mass index (Z = -0.40, P = 0.69) and age (Z = -1.48, P = 0.14). Chronic diarrhea (OR = 21.43, 95% CI: 5.04-91.23) and daily drinking water (OR = 11.28, 95% CI: 2.79-45.56) were relevant to E. histolytica infection. No significant association was observed between E. histolytica infection and the clinical symptoms, such as abdominal distension (OR = 0.70, 95% CI: 0.09-5.56), inappetence (OR = 0.50, 95% CI: 0.06-4.02), itchy skin (OR = 0.79, 95% CI: 0.10-6.38), perianal pruritus (OR = 1.74, 95% CI: 0.21-14.07), and constipation (OR = 0.91, 95% CI: 0.13-7.33). Conclusion E. histolytica infection is high in inpatients in Tengchong City, Yunnan Province, and chronic diarrhea and drinking unboiled water were highly correlated with E. histolytica infection.
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·Rodents have been used widely in the research of eye diseases to study visual function in animal models. Two methods of visual acuity testing in animals have been internationally recognized:the electrophysiological visual acuity test and the behavioral visual acuity test. Both of these methods have their advantages and limitations. The electrophysiology test (visual evoked potential) is invasive, and animals need recovery time after being implanted with electrodes. Also,the electrophysiological visual acuity test only reflects the electrical activity of a single cell or nuclei, it does not reflect the overall visual function of the animal. The widely used behavioral visual acuity test is able to compensate for these limitations. This paper gives a brief overview of the methods of the behavioral visual acuity test for rodents (rats, mice, guinea pigs,etc.).
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Objective To compare the phenylalanine(Phe)concentration in the sample of dried blood spot,measured by four different methods:fluorescence assay,tandem mass spectrometry(MS/MS), including MS/MS Derivatized,MS/MS Non-Derivatized and MS/MS-Standard Curve.Methods A total of 204 dried blood spot(DBS)samples of phenylketonuria(PKU)patients from Shanghai Xinhua Hospital were collected in this study.Phe concentration in DBS was measured by fluorescence assay and MS /MS assay,including MS/MS Derivatized, MS/MS Non-Derivatized and MS/MS-Standard Curve.The samples were divided into low, middle and high concentration groups according to Phe concentration, which were under the 360 μmol/L,between 360 and 600 μmol/L,and over 600 μmol/L respectively.The differences among the groups were analyzed by consistency check and non-parametric test.Results The within-day and between-day precisions of MS/MS-Standard Curve assay were 4.0%-7.2%,the recoveries were 93.2%-97.3%.Consistency check showed that less than 8.1%of Phe value were out of the 95%limit of agreement among these four methods.In the low and middle concentration groups,the quartile of Phe value measured by fluorescence assay,MS/MS Standard Curve and MS/MS Derivatized were 176(118,251)μmol/L,174 (94,273)μmol/L,153(94,242)μmol/L; and 540(478,578)μmol/L,485(414,529)μmol/L,466(402,513)μmol/L,respectively.Phe value measured by fluorescence assay was significantly higher than that by MS/MS Standard Curve,the difference was 4.8%-9.0%,(Z=-3.787 to -2.674,P<0.01). Phe value obtained from MS/MS Non-Derivatized was less than that by MS/MS-Standard Curve, the difference was 3.9%-5.2%,(Z=-7.474 to -5.747,P<0.01).In the high concentration group,the quartile of Phe value measured by MS/MS-Standard Curve, MS/MS Derivatized, MS/MS Non-Derivatized and fluorescence assay were 807(695,924)μmol/L,700(575,785)μmol/L,680(623,771)μmol/L and 711(674, 794)μmol/L, respectively.Phe value obtained from MS/MS Standard Curve was significantly higher than those from the other methods and the difference was 10.9% -16.2%,(Z=-4.458 to-4.356,P<0.01).Conclusions The MS/MS Standard Curve assay showed good specificity and accuracy.These four assays displayed good agreement.Although there was difference in measuring the Phe concentration among these methods, they could be used in blood Phe concentration monitoring for PKU patients.
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Neurological paroxysmal disease is a large group of clinical syndrome with a characteristic of sudden, recurrent, self-limiting. Clinically, routine biochemical or imaging examinations are usually with no significant abnormalities in the interictal period. However, magnetoencephalography (MEG), as an important electrophysiological tool in studying brain magnetic signals and monitoring brain electric activity, has highly temporal and spatial resolution for its noninvasive measurement of human brain with superconducting quantum interference. Therefore, it has been gradually used in researching for functional activities and mechanisms of the neuropsychiatric disorders and the advanced brain activity. There mainly reviewed the application and studies of MEG in epilepsy, paroxysmal kinesigenic dyskinesias and migraine.
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Objective To investigate the preparation method of dry blood spots (DBS) control materials for steroids used for internal quality control by liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods Whole blood was collected and the blood cells and plasma were separated. The blood cells were washed by saline. The activated charcoal was added to the plasma. Standard substance was added to make different concentrations (low, medium, and high) of DBS control materials for steroids. The precision, accuracy, stability, and differences among different blood spots were detected and analyzed by LC-MS/MS. Results The inter-day precision and accuracy of DBS control materials for steroids were 2.4%-7.0% and 102.0%-111.0%, respectively, and the intra-day precision and accuracy were 5.1%-9.8% and 99.0%-114.8% respectively. The DBS control materials for steroids were stored for 5 months, and there was no difference among the different months (P>0.05). The coefficients of variation among different blood spots were small, 3.3%-8.2%. Conclusions The DBS control materials for steroids has good precision, accuracy and stability. The difference among different blood spots is small and meet the requirements of indoor quality control products. They can be used for the internal quality control in steroids detection by LC-MS/MS.
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Objective Establish a method for measuring the activities of Galactocerebrosidase (GALC), α-Glucosidase(GAA), α-Galactosidase (GLA) and α-L-Iduronidase (IDUA) in dried blood spots specimen by tandem mass spectrometry ( MS/MS ).Methods A total of 2175 dried blood spot samples forinborn errors of metabolism in neonatalscreening center of Shanghai Xinhua hospital were collected in July and November, 2013.And twenty dried blood spot samples from patients withlysosomalstorage disorders( LSDs) of Shanghai Xin Hua Hospital were collected from September 2012 to January 2014.The extraction of DBS was incubated with enzyme substrates and internal standards.After liquid-liquid and solid-phase extraction, the extraction solution was dried under nitrogen and reconstituted.Then enzyme reaction products and internal standards were analyzed by MS/MS.Linearity, precision, accuracy and the limit of detection were evaluated.2175 dried blood spot samples were detected to establish the normal reference range for the activities of four enzymes according to 0.5th to 99.5th percentiles.20 specimens from patients withLSDs were detected to verify the reference range inclinical judgment.Results The intraassay and interassay precisions ranged from 1.7%to 11.8%, and the intraassay and interassay accuracies ranged from 85%to 115%.The linear coefficients for measured concentration of enzyme products/internal standards and theoretical concentration were 0.997-0.999.The limits of detection forGALC, GAA, GLA and GLA were 0.03 μmol/(L· h), 0.09 μmol/(L· h), 0.12 μmol/(L· h) and 0.16 μmol/(L· h) .The normal reference values for GALC, GAA, GLA and GLAwere 0.51-8.51μmol( L· h) ,1.99-22.22μmol/( L· h),1.68-41.59 μmol/(L· h) and 2.36-19.21 μmol/(L· h).The enzymes of 20 patients with LSDs were remarkably decreased compared to the normal range.The Krabbe, Pompe, Fabry, MPSⅠpatients can be effectively detected by this MS/MS method.Conclusions A MS/MS method for measuring GALC, GAA, GLA and IDUA enzyme activities in DBShas been established.
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Aim To develop a sensitive,specific and accurate method for quantifying a novel derivate of all-trans-retinoic acid, 4-amino-2-trifluoromethyl-phenyl retinate (ATPR)in rat tissues to investigate the tissue distribution of ATPR in rats.Methods Sprague-Daw-ley (SD)rats were killed by exsanguination at 2,4,7 h after a single intragastric administration with one dose of ATPR (20 mg·kg-1 )or at 5 min,1 h,5 h after a single intravenous administration with one dose of AT-PR (7 mg·kg-1 ).The concentration of ATPR in the tissues was determined by high performance liquid chromatography (HPLC)method.Results After the rats were administrated intragastrically, the highest concentration of ATPR was observed in intestine,fol-lowed by liver,spleen and lung,while the distribution in heart,kidney,fat and brain was very little.Howev-er,the highest concentration of ATPR was in liver after given intravenously,followed by spleen and lung,and very low in heart,kidney,intestines,fat and brain. Conclusion The distribution of ATPR is higher in liv-er after administrated both intragastrically and intrave-nously,suggesting the potential anti-proliferation and differentiation inducing effects of ATPR targeting at liv-er cancer.
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Objective To investigate whether Bushen-Huoxue compound adjuvant therapy can be effective on mild cognitive impairment in Parkinson's disease and the influence on plasma phospholipids(PLs) levels. Methods 87 PD patients were recruited and collected for the general information. The patients were evaluated by Unified Parkinson's Disease Rating Scale(UPDRS) Ⅲ and Montreal Cognitive Assessment(MoCA). According to MoCA scores, patients with PD-MCI were divided into a Bushen-Huoxue compound treatment group and a control group(basic L-dopa or dopamine agonist). Reevaluating cognitive function by MoCA and plasma phopholipids levels at posttreatment 12 month and 18 month. Plasma PLs was assayed by measuring its inorganic phosphorus after separation by chromatograph.Results 39 cases in 87 PD patients(44.8%)were with PD-MCI.After 12 months or 18 months treatment period, MoCA scores was significantly higher in Bushen-Huoxue compound treatment group than in controls(P<0.05 or 0.01 respectively). Plasma PLs levels were significantly decreased in Bushen-Huoxue compound treatment group than in controls(P<0.01 or 0.01 respectively). Conclusions Bushen-Huoxue compound could be effective in the adjuvant treatment of PD-MCI, and could delay cognitive rate of decline in patients with PD. Meanwhile, Bushen-Huoxue compound could significantly decrease plasma PLs levels in PD-MCI. The evidence from present study suggested that Bushen-Huoxue compound have neuroprotective effects on patients with PD-MCI.
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Objective To understand the variation of thyroid hormones in each trimesters of pregnancy in women.Methods A total of 1 839 pregnant women in different trimesters were enrolled and thyroid hormones including FT3,FT4,TT3, TT4,TSH,TGAb and TPOAb were measured.The reference range of hormone in each trimester was calculated.Results There were statistically differences in all thyroid hormones among all trimesters of pregnancy women (P<0.05 )except for TT4 between the early and middle trimesters (P>0.05 ).The median of FT3 and FT4 were gradually reduced as the pregnant trimester grew up while the median of TSH had the adverse tendency.The median of TT3 was highest during the middle trimester (1.47 nmol/L).TT4 median was lowest during the late trimester (80.67 nmol/L).The TSH level of pregnant women over 30 years old was significantly lower than that of below 30 age group during all trimesters(P<0.05 ). There were significant differences in FT4,TT3 and TT4 level among early and middle trimesters among different ages groups(P<0.05 ).The positive rates of TGAb and TPOAb during late trimester (4.74% and 1.63%)were significantly lower than those of early trimester (1 4.40% and 5.56%)and middle trimester (1 4.40% and 5.56%)(P<0.05 ). Conclusion Significant differences of thyroid hormones are found not only in different stages of pregnancy,but also in different ages.Therefore,establishing trimester-specific reference data of thyroid hormones during different pregnency may be important for clinical practice.
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<p><b>OBJECTIVE</b>To investigate the relationship of bilirubin/albumin (B/A) ratio and acidosis with abnormal brainstem auditory evoked potentials (BAEPs) in neonates with severe hyperbilirubinemia and its clinical significance.</p><p><b>METHODS</b>A total of 967 neonates with severe hyperbilirubinemia between November 2008 and October 2009 were enrolled in the study. They were divided into two groups according to their BAEPs: normal BAEP group (n=799) and abnormal BAEP group (n=168). Univariate analysis and age-stratified Chi-square test were used to determine the relationship of B/A ratio and acidosis with BAEP.</p><p><b>RESULTS</b>The univariate analysis showed that the abnormal BAEP group had significantly lower pH and base excess values and a significantly higher B/A ratio compared with the normal BAEP group (P<0.05). The age-stratified Chi-square test showed that neonates with acidosis or with a B/A ratio greater than 1.0 had a significantly higher incidence of abnormal BAEPs than those without acidosis or with a B/A ratio less than 1.0 in any age (days) group of neonates with severe hyperbilirubinemia (P<0.05).</p><p><b>CONCLUSIONS</b>High B/A ratio and acidosis are the risk factors for abnormal BAEPs in neonates with severe hyperbilirubinemia, which is the case for those in any age group. In order to reduce the incidence of hearing loss in any age group of neonates with severe hyperbilirubinemia, we should correct the acidosis and lower the B/A ratio as soon as possible.</p>
Subject(s)
Humans , Infant, Newborn , Acidosis , Bilirubin , Blood , Evoked Potentials, Auditory, Brain Stem , Hyperbilirubinemia , Blood , Serum AlbuminABSTRACT
<p><b>OBJECTIVE</b>To investigate the number of peripheral blood CD5(+) B cells and their ability of secreting IL-10 in patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Peripheral blood lymphocytes were isolated from 57 pre-treated, 40 post-treated ITP patients and 25 controls using Ficoll-Hypaque density centrifugation and then stained with PE-CD5/FITC-CD19 for flow cytometric analysis. After 24-hour culture, lymphocytes were stained with APC-IL-10 for intracellular cytokine detection. ELISA assay was employed to determine IL-10 concentration in supernatants.</p><p><b>RESULTS</b>The percentage and absolute number of CD5(+) B cells in peripheral blood from pre-treated ITP patients were significantly higher than that from normal controls (3.75 ± 2.37)% vs (2.10 ± 1.08)%, P < 0.01; (6.29 ± 5.77)× 10(7)/L vs (3.06 ± 1.90)× 10(7)/L, P < 0.01. CD5(+) B cells expressed more intracellular IL-10 than other lymphocyte subsets both in ITP patients and normal controls. The percentages of IL-10(+) cells within CD5(+) B cells in pre-treated ITP patients and normal controls were (29.51 ± 20.73)% and(15.90 ± 9.58)%, respectively(P < 0.01). Intracellular mean fluorescence intensity (MFI) of IL-10 in CD5(+) B cells was 27.95 ± 13.99 in pre-treated patients, which was significantly higher than that in controls (P < 0.01). In contrast, IL-10 concentration in supernatants was (173.05 ± 102.50) ng/L in pre-treated ITP group, which was lower than that (230.61 ± 76.96) ng/L in controls. In patients who achieved remission, the number of CD5(+) B cells decreased to level comparable to normal controls. While intracellular IL-10 MFI of CD5(+) B cells in post-treated ITP patients remained as high as in pre-treated ones, the IL-10 concentration in supernatants increased to level similar to controls.</p><p><b>CONCLUSION</b>The significantly increased number of CD5(+) B cells and accumulated IL-10 in CD5(+) B cells suggested impaired IL-10 secretion in ITP patients. The number and the ability of secreting IL-10 of CD5(+) B cells could be restored after effective treatments in patients with ITP.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , B-Lymphocytes , Allergy and Immunology , Metabolism , CD5 Antigens , Metabolism , Case-Control Studies , Interleukin-10 , Blood , Purpura, Thrombocytopenic, Idiopathic , Blood , Allergy and ImmunologyABSTRACT
This study was aimed to investigate the T cell (helper T cells) immune status in ITP patients and its relation with therapeutic response. 20 de novo ITP patients were enrolled (8 males, 12 females) with a median age of 41 (20 to 81). Real-time RT-PCR method was used to measure the gene expression of Th cells including T-bet, IFN-γ, GATA-3, TGF-β, Foxp3, IL-2, IL-4 in PBMNC of ITP patients before and after conventional dose of prednisone therapy [1 mg/(kg·d)] and in PBMNC of 20 normal controls. The results showed that T-bet, IFN-γ and IL-2 were significantly over-expressed in PBMNC of ITP patients before treatment compared with that in normal controls (p < 0.01), and compared with that before treatment, T-bet, IFN-γ, and IL-2 were markedly down-regulated in ITP patients after treatment. Before treatment, the expressions of Foxp3, TGF-β, GATA3 and IL-4 in ITP patients did not show difference from normal controls, while after treatment Foxp3 were more up-regulated than that before treatment (p < 0.05). After treatment, TGF-β expression showed a different pattern between old and young patients. TGF-β expression was down-regulated (p < 0.05) among ITP patients younger than 60, while up-regulated in older patients. It is concluded that there is an imbalance of Th1/Th2/Treg cytokines in ITP patients, which can be reversed by glucocorticoid treatment. The conventional dose of glucocorticoid may be regarded as effective therapy for de novo ITP patients, it may correlate with improvement of imbalance between Th1/The2/Treg cytokines.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Case-Control Studies , Forkhead Transcription Factors , Metabolism , Gene Expression , Gene Expression Regulation , Glucocorticoids , Therapeutic Uses , Interferon-gamma , Metabolism , Interleukin-2 , Metabolism , Purpura, Thrombocytopenic, Idiopathic , Drug Therapy , Metabolism , Pathology , T-Box Domain Proteins , Metabolism , T-Lymphocytes, Helper-Inducer , Metabolism , Transforming Growth Factor beta , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical significance of MAIPA test in diagnosis of idiopathic thrombocytopenic purpura (ITP) and in the differential diagnosis of antoimmune thrombocytopenias from nonimmune thrombocytopenias.</p><p><b>METHODS</b>A total of 321 thrombocytopenic patients (118 males, 203 females) from 14 centers were studied. A modified monoclonal antibody immobilization of platelet antigen (MAIPA) method was used to detect the platelet glycoprotein-specific autoantibodies (anti-GP IIb/IIIa, anti-GPIb/IX) to double-blindly evaluate its sensitivity and specificity for the diagnosis of ITP and to investigate the impact of the antibodies on platelet count.</p><p><b>RESULTS</b>The results showed that for the diagnosis of ITP, anti-GPIIb/IIIa, anti-GPIb/IX and both of them had the sensitivity of 39.75%, 32.64% and 55.23%; the specificity of 97.56%, 93.94% and 92.68%; the positive predictive value of 97.94%, 93.98% and 95.65%; the negative predictive value of 35.71%, 32.35% and 41.53%; and the total efficiency of 54.51%, 48.29% and 64.80%, respectively. The positivity of the autoantibodies in immune thrombocytopenias was incredibly higher than that in nonimmune thrombocytopenias. The platelet counts in the immune thrombocytopenias with autoantibody positivities were significantly lower than those without the autoantibodies. The platelet counts were negatively correlated with the concentration of the autoantibodies. The levels of anti-GPIIb/IIIa or anti-GPIb/IX or both of them dropped or disappeared in patients being responsive to steroid therapy.</p><p><b>CONCLUSION</b>MAIPA assay is proved to be of great value for the diagnosis of ITP and for differential diagnosis of immune thrombocytopenias from nonimmune thrombocytopenias.</p>