1.Effect of triptolide on airway remodeling and the expression of phosphoinositide 3-kinases in asthmatic rats.
Bi-Wen MO ; Chang-Ming WANG ; Zhen-Xiang ZHANG ; Yong-Jian XU ; Wei-Ning XIONG ; Xian-Sheng LIU ; Chun-Sheng FANG
Chinese Journal of Applied Physiology 2007;23(3):359-364
AIMTo explore the effect of Triptolide on airway remodeling and the expression of Phosphoinositide 3-Kinases in asthmatic rats.
METHODS40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 weeks group; (3) Asthmatic 6 weeks group; (4) Therapeutic 4 weeks group; (5) Therapeutic 6 weeks group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PI3K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS(1) The expression of PI3K p85alpha protein and mRNA in asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The WA/Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01). (3) The airway resistance of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01, P < 0.05).
CONCLUSIONThe proliferation of airway smooth muscle is a remarkable character of airway remodeling in asthma. The PI3K signal pathway may be involved in the process. Triptolide may reduce AHR and decrease the proliferation of ASMCs by inhibiting the expression of PI3K. It may have potential therapeutic effects in the asthmatic airway remodeling.
Airway Remodeling ; Animals ; Asthma ; metabolism ; physiopathology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Male ; Phenanthrenes ; pharmacology ; Phosphatidylinositol 3-Kinase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction
2.The effect of birth weight and early growth on body fat composition and insulin sensitivity.
Mu-Xue YU ; Xiao-Shan QIU ; Su-E FENG ; Qing-Ping MO ; Xiao-Ying XIE ; Zhen-Yu SHEN ; Yong-Zhou LIU
Chinese Journal of Preventive Medicine 2011;45(7):633-638
OBJECTIVETo investigate the effect of birth weight and early growth on body fat composition and insulin sensitivity.
METHODSThe birth and growth data of 258 children of 6 to 7 years old in Guangzhou were collected from Jun.2009 to Feb. 2010. Physical and laboratory examination were preformed, which included body weight, body height and body fat composition index (body mass index (BMI), percentage of body fat (PBF), waist circumference to height ratio (WtHR), etc). Fasting blood glucose and insulin were measured. The homeostasis model assessment model for insulin resistance index (HOMA-IR) was calculated. According to birth weight, the children were divided into three groups from light to heavy: BW-I, BW-II, BW-III group. Then according to change in weight SDS between 0 and 36 months, the children were divided into three groups: changers up (CU), non-changers (NC), changers down (CD) group. The effect of birth weight and early growth on body fat composition and insulin sensitivity were analyzed.
RESULTSChange in weight SDS between 0 and 36 months was higher in BW-I group (1.06 ± 1.29) than in the BW-II group (-0.19 ± 0.94) and BW-III group (-0.10 ± 1.20) (all P values < 0.01). Birth weight of the CU group ((2.90 ± 0.47) kg) was lower than that of the NC group ((3.22 ± 0.34) kg) and the CD group ((3.57 ± 0.37) kg) (all P values < 0.01). The body fat composition index of BMI, PBF and WtHR were higher in the BW-III group ((16.35 ± 2.13) kg/m(2), (17.03 ± 5.88)%, (0.479 ± 0.033)) than in the BW-I group ((15.46 ± 2.06) kg/m(2), (14.06 ± 5.25)%, (0.459 ± 0.032)) and BW-II group ((15.47 ± 1.58) kg/m(2), (14.09 ± 5.01)%, (0.460 ± 0.025)) (P < 0.01), while there was no significant difference between the BW-I group and the BW-II group (P > 0.05). The body fat composition index of BMI, PBF and WtHR were higher in the CU group ((16.44 ± 2.20) kg/m(2), (16.51 ± 5.78)%, (0.473 ± 0.034)) than in the NC group ((15.62 ± 1.74) kg/m(2), (14.49 ± 5.30)%, (0.463 ± 0.030)) and the CD group ((15.26 ± 1.85) kg/m(2), (14.24 ± 5.54)%, (0.462 ± 0.031)) (all P values < 0.05). In the CU group, BMI, PBF and WtHR were higher in the BW-III-CU group ((18.76 ± 2.56) kg/m(2), (22.19 ± 8.28)%, (0.512 ± 0.029)) than in the BW-I-CU group ((16.04 ± 2.14) kg/m(2), (15.54 ± 5.28)%, (0.467 ± 0.034)) and BW-II-CU group ((16.70 ± 1.36) kg/m(2), (17.12 ± 4.44)%, (0.474 ± 0.017)) (all P values < 0.05), while there was no significant difference between the BW-I-CU group and the BW-II-CU group (P > 0.05). HOMA-IR was higher in the CU group (1.27 ± 0.44) than in the NC group (1.08 ± 0.31) and the CD group (1.00 ± 0.36) (all P values < 0.01). In the CU group, HOMA-IR was higher in the BW-III-CU group (1.69 ± 0.48) than in the BW-I-CU group (1.21 ± 0.41) and the BW-II-CU group (1.27 ± 0.44) (all P values < 0.01), while there was no significant difference between the BW-I-CU and BW-II-CU group (P > 0.05).
CONCLUSIONAccording to birth weight tertile, both lower birth weight individuals with more weight change-up growth postnatal early and higher birth weight individuals had greater body fat composition in childhood. They were high-risk people of insulin resistance.
Birth Weight ; Body Composition ; Body Mass Index ; Child ; China ; Female ; Humans ; Insulin ; metabolism ; Insulin Resistance ; Male ; Sensitivity and Specificity
3.Clinical and gene mutation analyses of three patients with ornithine carbamoyltransferase deficiency.
Wei-qian MO ; Li LIU ; Yao-yong CHEN ; Jing CHENG ; Xiu-zhen LI ; Zhi-hong ZHOU ; Xiao-jian MAO ; Wen ZHANG
Chinese Journal of Medical Genetics 2011;28(3):328-331
OBJECTIVETo analyze the clinical and genetic characteristics of three children with ornithine carbamoyltransferase deficiency(OTCD), and to provide a practical method for gene diagnosis and genetic counseling of the disease.
METHODSAll exons of the ornithine carbamoyltransferase (OTC) gene were screened by polymerase chain reaction-DNA direct sequencing in the three OTCD patients.
RESULTSOne patient firstly presented as vomiting at 6 month of age. A missense mutation of T262I was detected. His mother had the same mutation without any clinical symptoms. The second patient presented as restlessness, and had a missense mutation of R277W. Gene analysis of his parents was not available. The third patient presented as neonatal lethargy, harbored a missense mutation of I172M. His mother had the same mutation without any clinical symptoms.
CONCLUSIONGene mutation analysis is a feasible way for diagnosing OTCD. Patients with I172M mutation present symptom early, while those with T262I and R277W mutations manifest symptoms later. Gene mutation analysis will be important for asymptomatic and prenatal diagnosis and genetic counseling.
Base Sequence ; Child ; Exons ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; genetics ; Ornithine Carbamoyltransferase ; genetics ; Ornithine Carbamoyltransferase Deficiency Disease ; genetics ; pathology
4.Construction of quantitative real-time PCR detection system of transgenic tomato line Zeneca B,Da,F.
Rong-Jia MAI ; Min-Fang CHEN ; Qian-Zhen MO ; Liang-Yong HU ; Shi-Lun LI ; Min-Ran TANG ; Xiao-Min GU ; Yong-Hong CAI ; Lun-Bin ZHOU ; Xiao-Hong ZHOU
Journal of Southern Medical University 2011;31(4):587-594
OBJECTIVETo construct the plasmid reference molecules for detection of transgenic tomato line Zeneca B,Da,F using quantitative real-time PCR(qPCR).
METHODSThree plasmid reference molecules pEasy-T3-APX, pEasy-T3-16A and pEasy-T3-16S were cloned based on reverse genetics, which contain the target fragments of tomato endogenous reference gene apx (ERG-apx), gene-specific sequence of pg(GS-pg) and construct-specific sequence of vectors pJR16S/pJR16A (CS-16S/CS-16A) of Zeneca B,Da,F, respectively. Primers and Taqman probes were designed by Beacon Designer 7.5.The specificity, sensitivity, reproducibility and the limit of detection(LOD) of the qualitative and quantitative PCR system based on the plasmid reference molecules were evaluated. PicoGreen was used to measure the DNA concentration of the plasmid reference molecules. Two sets of samples containing 1% or 0.1% (w/w) pEasy-T3-16A or pEasy-T3-16S mixed with pEasy-T3- APX as background DNA were prepared for evaluating the efficacy of the qPCR system.
RESULTSThe target fragments for qPCR detection were anchored, ERG-apx 108 bp, GS-pg 108 bp , CS-16S 109 bp and CS-16A 102 bp. The three plasmid reference molecules were confirmed at the expected sizes by restriction enzyme digestion. The qPCR results showed that the RSD of reproducibility were 0.2% to1.5%, LOD was 25 copies, R2 values for these standard curves were 0.994 ~0.998 and amplification efficiencies were 93.3%~102.4%.The bias between the test and true values of two sets of mixed samples ranged from -9.3% to 14.7% after adjusting by conversion factors(Cf).
CONCLUSIONThe plasmid reference molecules and qPCR system for qualitative and quantitative detection of transgenic tomato line Zeneca B,Da,F have been established successfully.
Base Sequence ; DNA, Plant ; genetics ; Lycopersicon esculentum ; genetics ; Plants, Genetically Modified ; genetics ; Plasmids ; Real-Time Polymerase Chain Reaction ; methods
5.Validity of Glycated Hemoglobin in Screening and Diagnosing Type 2 Diabetes Mellitus in Chinese Subjects.
Yun YU ; Xiao Jun OUYANG ; Qing Lin LOU ; Liu Bao GU ; Yong Zhen MO ; Gary T KO ; Chun Chung CHOW ; Wing Yee SO ; Ronald MA ; Alice KONG ; Nicola BROWN ; Jennifer NAN ; Juliana CHAN ; Rong Wen BIAN
The Korean Journal of Internal Medicine 2012;27(1):41-46
BACKGROUND/AIMS: The application of glycated hemoglobin (HbA1c) for the diagnosis of diabetes is currently under extensive discussion. In this study, we explored the validity of using HbA1c as a screening and diagnostic test in Chinese subjects recruited in Nanjing, China. METHODS: In total, 497 subjects (361 men and 136 women) with fasting plasma glucose (PG) > or = 5.6 mmol/L were recruited to undergo the oral glucose tolerance test (OGTT) and HbA1c test. Plasma lipid, uric acid, and blood pressure were also measured. RESULTS: Using a receiver operating characteristic curve, the optimal cutoff point of HbA1c related to diabetes diagnosed by the OGTT was 6.3%, with a sensitivity and specificity of 79.6% and 82.2%, respectively, and the area under the curve was 0.87 (95% confidence interval, 0.83 to 0.92). A HbA1c level of 6.5% had a sensitivity and specificity of 62.7% and 93.5%, respectively. When comparing the HbA1c > or = 6.5% or OGTT methods for diagnosing diabetes, the former group had significantly higher HbA1c levels and lower levels of fasting and 2-hour PG than the latter group. No significant difference was observed in the other metabolism indexes between the two groups. CONCLUSIONS: Our results suggest that HbA1c > or = 6.5% has reasonably good specificity for diagnosing diabetes in Chinese subjects, which is in concordance with the American Diabetes Association recommendations.
Aged
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Analysis of Variance
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*Asian Continental Ancestry Group
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Biological Markers/blood
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Blood Glucose/analysis
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China/epidemiology
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*Chromatography, High Pressure Liquid/standards
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*Chromatography, Ion Exchange/standards
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Diabetes Mellitus, Type 2/blood/*diagnosis/ethnology
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Fasting/blood
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Female
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Glucose Tolerance Test/standards
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Hemoglobin A, Glycosylated/*analysis
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Humans
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Male
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Mass Screening/*methods/standards
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Middle Aged
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Predictive Value of Tests
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ROC Curve
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Reference Standards
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Reproducibility of Results
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Sensitivity and Specificity
6.Chondroblastoma occurring in atypical sites.
Zhi-Ming JIANG ; Hui-Zhen ZHANG ; Yun-Shan TAN ; Ru-Yong TANG ; Hui-Min LIU ; Shao-Hua LU ; Mo-Juan SHU ; Bing-Fang ZENG ; Shi-Xun YANG ; Jie-Qing CHEN ; Jin HUANG
Chinese Journal of Pathology 2004;33(6):503-507
OBJECTIVETo study the clinical, pathologic and radiologic features of chondroblastoma occurring in sites other than epiphysis and apophysis of long bones, and to investigate possible reasons for misdiagnosis.
METHODSThe clinical, pathologic and radiologic data of 18 chondroblastoma cases occurring in atypical sites were collected from 5 major hospitals in Shanghai during the past 12 years. S-100 immunostaining was performed to confirm the cartilaginous differentiation of the tumor cells.
RESULTSChondroblastoma occurred in small bones of feet in 10 of the 18 cases (55.6%) studied, being commonest in the talus and calcaneus bones. Mean age of the patients was 27.8 years, with 55.6% over 25 years of age. Radiologic examination revealed expansive, multilocular and well-demarcated radiolucent lesions in most cases. There was local cortical destruction in 5 cases (28%) and soft tissue infiltration in 1 case. In 10 cases (55.6%), the tumor was associated with aneurismal bone cyst or simple bone cyst formation. None of the cases studied was accurately diagnosed clinically before the operation. In 2 cases, the pathology was also misdiagnosed, often being diagnosed as aneurismal bone cyst or giant cell tumor.
CONCLUSIONSChondroblastoma occurring in atypical sites are often associated with atypical age, radiologic features and pathologic findings at presentation. Thorough understanding of the potential pitfalls is essential in order to avoid misdiagnosis.
Adolescent ; Adult ; Bone Cysts, Aneurysmal ; diagnosis ; diagnostic imaging ; pathology ; Bone Diseases ; diagnosis ; diagnostic imaging ; pathology ; Bone Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; Calcaneus ; Child ; Chondroblastoma ; diagnosis ; diagnostic imaging ; pathology ; Diagnostic Errors ; Female ; Giant Cell Tumor of Bone ; diagnostic imaging ; pathology ; Humans ; Male ; Radiography ; Talus
7.Identification of a novel pathogenic mutation in PDHA1 gene for pyruvate dehydrogenase complex deficiency.
Mo-Ling WU ; Li LIU ; Xiao-Jian MAO ; Min-Zhi PENG ; Hong-Sheng LIU ; Hui-Ying SHENG ; Yan-Na CAI ; Hui-Fen MEI ; Chun FAN ; Yong-Lan HUANG ; Xiu-Zhen LI ; Jing CHENG
Chinese Journal of Contemporary Pediatrics 2015;17(8):775-779
OBJECTIVETo study the molecular genetic mechanism and genetic diagnosis of pyruvate dehydrogenase complex deficiency (PHD), and to provide a basis for genetic counseling and prenatal genetic diagnosis of PHD.
METHODSPolymerase chain reaction (PCR) was performed to amplify the 11 exons and exon junction of the PDHA1 gene from a child who was diagnosed with PHD based on clinical characteristics and laboratory examination results. The PCR products were sequenced to determine the mutation. An analysis of amino acid conservation and prediction of protein secondary and tertiary structure were performed using bioinformatic approaches to identify the pathogenicity of the novel mutation.
RESULTSOne novel duplication mutation, c.1111_1158dup48bp, was found in the exon 11 of the PDHA1 gene of the patient. No c.1111_1158dup48bp mutation was detected in the sequencing results from 50 normal controls. The results of protein secondary and tertiary structure prediction showed that the novel mutation c.1111 _1158dup48bp led to the duplication of 16 amino acids residues, serine371 to phenylalanine386, which induced a substantial change in protein secondary and tertiary structure. The conformational change was not detected in the normal controls.
CONCLUSIONSThe novel duplication mutation c.1111_1158dup48bp in the PDHA1 gene is not due to gene polymorphisms but a possible novel pathogenic mutation for PHD.
Amino Acid Sequence ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Pyruvate Dehydrogenase (Lipoamide) ; chemistry ; genetics ; Pyruvate Dehydrogenase Complex Deficiency Disease ; genetics
8.Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes.
Qing Lin LOU ; Xiao Jun OUYANG ; Liu Bao GU ; Yong Zhen MO ; Ronald MA ; Jennifer NAN ; Alice KONG ; Wing Yee SO ; Gary KO ; Juliana CHAN ; Chun Chung CHOW ; Rong Wen BIAN
Diabetes & Metabolism Journal 2012;36(6):433-442
BACKGROUND: To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009. METHODS: Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio > or =30 mg/g. RESULTS: We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9+/-12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively. CONCLUSION: In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.
Albuminuria
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Anemia
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Asian Continental Ancestry Group
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China
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Cross-Sectional Studies
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Diabetes Mellitus, Type 2
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Glomerular Filtration Rate
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Humans
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Hypertension
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Kidney Diseases
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Odds Ratio
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Renal Insufficiency, Chronic
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Risk Factors
9.Clinical characteristics of children with anti-neutrophil cytoplasmic antibody-associated vasculitis
Jing-Qi LIU ; Yong-Zhen LI ; Lan-Jun SHUAI ; Yan CAO ; Xiao-Yan LI ; Ying WANG ; Tian SHEN ; Shuang-Hong MO ; Xiao-Jie HE ; Xiao-Chuan WU
Chinese Journal of Contemporary Pediatrics 2024;26(8):823-828
Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.
10.The degree of HBV suppression with 24 week telbivudine- or lamivudine-treatment in hepatitis B patients predicts the efficacy of the treatment at week 52.
Ji-dong JIA ; Jin-lin HOU ; You-kuan YIN ; Dao-zhen XU ; De-ming TAN ; Jun-qi NIU ; Xia-qiu ZHOU ; Yu-ming WANG ; Li-min ZHU ; Yong-wen HE ; Hong REN ; Mo-bin WAN ; Cheng-wei CHEN ; Shan-ming WU ; Ya-gang CHEN ; Jia-zhang XU ; Qin-huan WANG ; Lai WEI ; Hong MA
Chinese Journal of Hepatology 2007;15(5):342-345
OBJECTIVESTo investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy.
METHODSIn this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again.
RESULTSAt week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition.
CONCLUSIONHBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.
Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Double-Blind Method ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Nucleosides ; therapeutic use ; Pyrimidinones ; therapeutic use ; Thymidine ; analogs & derivatives ; Treatment Outcome ; Young Adult