Objective To explore the lymphcyte subsets distribution in cerebrospinal fluid in patients with HIV infection ,and to investigate the clinical significance of the lymphocyte subsets in cerebrospinal fluid in HIV central nervous system complication . Methods 34 patients with HIV infection ,including 20 patients without nervous system symptoms (simple HIV group) and 14 pa‐tients with nervous system symptoms (neurological HIV group) ,and 15 cases of healthy people (control group) were selected . Flow cytometry was used to detect lymphocyte subsets ,and immunoturbidimetry was used to detect the level of IgG in cerebrospinal fluid .Results The percentage of CD8+ T cells was higher and percentage of CD4+ T cells was lower in the simple HIV group and neurological HIV group than those in the healthy control ,with statistically significant differences (P<0 .01) .The level of IgG in pa‐tients with HIV infection was higher than that in the healthy control group (P<0 .01) .While no significant difference were found in the percentage of B cells and NK cells among the there group (P>0 .05) .There were also no significant differece between the sim‐ple HIV group and neurological HIV group in the ratio of each lymphcyte subset in cerebrospinal fluid (P>0 .05) .Conclusion The immune disorder in cerebrospinal fluid in patients with HIV infection may appear in the early time before the nervous system com‐plication .The changing trends of lymphocyte subsets are consistent with the peripheral blood ,which demonstrate that the T lym‐phocyte subsets may be correlated with the nervous system symptoms of HIV .

Mitochondrial respiratory chain deficiency is a common cause of mitochondrial disease in children. This study aimed to review the clinical, enzymatic and genetic characteristics of a Chinese boy with progressive intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency. The boy developed diarrhea from the age of 13 months, followed by progressive body weight loss, jaundice and weakness. His urine organic acids, blood amino acids and acylcarnitines profiles were normal. Mitochondrial respiratory chain complexes I to V activities in peripheral leukocytes were measured using spectrophotometric assay. Complex I activity was reduced. 5821G>A mutation was indentified by gene sequencing on tRNA-cys of mitochondrial gene in the patient and his mother. Vitamin supplements, liver protection, antibiotics and plasma infusion were not effective in the patient. Unfortunately, the boy died at the age of 17 months. Mitochondrial respiratory chain complex I deficiency is the most common mitochondrial respiratory chain disorder. This was the first case of intrahepatic cholestasis due to complex I deficiency confirmed by mitochondrial respiratory chain enzyme activity assay and gene analysis in China. It was concluded that mitochondrial hepatopathy is one of major causes of metabolic hepatopathy. Biochemical assay, mitochondrial respiratory chain complex activities assay and genetic analysis are crucial for the etiological diagnosis of metabolic hepatopathy.
Cholestasis, Intrahepatic ; diagnosis ; etiology ; Diagnosis, Differential ; Electron Transport Complex I ; deficiency ; Humans ; Infant ; Male ; Mitochondrial Diseases ; complications

OBJECTIVETo explore the biological function of vascular endothelial cells from hypertrophic scar, and to analyze the relationship between them.

METHODSThe samples from human hypertrophic scar and normal skin tissue were harvested for histological examination. Then vascular endothelial cells were purified and isolated from the samples, and the level of transforming growth factor (TGF) beta1, platelet derived growth factor (PDGF), endothelin1 (ET)-1, fibroblast growth factor (FGF)2 and vascular endothelial growth factor (VEGF) were determined in a single cell with ELISA.

RESULTSFew capillary vessels were observed in normal skin under microscope, while an increased number of them were present in hypertrophic scar, with slender, tortuous in morphology and even occluded. The diameter of blood capillary in hypertrophic scar was tiny under electron microscope, and the exfoliation of endothelial cells was observed. The levels of TGF-beta1, PDGF, ET-1, bFGF and VEGF from vascular endothelial cells from hypertrophic scar were 60 +/- 8, 30 +/- 4, 0.12 +/- 0.03, 52 +/- 5, 18.1 +/- 1.2 microg/cell, respectively, which were obviously lower than those in normal skin (P < 0.05).

CONCLUSIONThe biological function of vascular endothelial cells was attenuated in the hypertrophic scar, which mightbe the result of the production of large amounts of collagen in the scar tissue, as well as hypoxia.

Adolescent ; Adult ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Collagen ; metabolism ; Endothelial Cells ; metabolism ; Endothelin-1 ; metabolism ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Male ; Platelet-Derived Growth Factor ; metabolism ; Skin ; blood supply ; Transforming Growth Factor beta1 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; Young Adult

This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
Animals ; Antihypertensive Agents ; chemistry ; pharmacology ; Calcium Channel Blockers ; chemistry ; pharmacology ; Calcium Channels, L-Type ; genetics ; metabolism ; Drug Repositioning ; methods ; Molecular Structure ; Myocardium ; metabolism ; Rabbits

cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine organic acids and genetic features of the patient were reported. The boy presented with fever, feeding difficulty and lethargy at the age of 2 months. Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis and liver damage. His blood propionylcarnitine and urinary methylmalonic acid levels increased significantly, but the plasma total homocysteine level was in the normal range, which supported the diagnosis of isolated methylmalonic aciduria. Gene analysis was performed by direct sequencing. No mutation in the MUT gene was found. However, a reported mutation c.577G>A (p.E193K) and a novel mutation c.562G>A (p.V188M) in the MMAB gene were identified, which confirmed the diagnosis of methylmalonic aciduria cblB type. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 3 years and 11 months old and has a normal development condition. The phenotypes of the patients with cblB defect are nonspecific. Metabolic analysis and MMAB gene analysis are keys for the diagnosis of the disorder.
Alkyl and Aryl Transferases ; genetics ; Amino Acid Metabolism, Inborn Errors ; genetics ; Humans ; Infant ; Male ; Mutation

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine.
Adolescent ; Base Sequence ; Homocystinuria ; complications ; diagnosis ; drug therapy ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; deficiency ; Molecular Sequence Data ; Muscle Spasticity ; complications ; diagnosis ; drug therapy ; Psychotic Disorders ; complications ; diagnosis ; drug therapy ; Schizophrenia ; etiology

Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.
Diagnosis, Differential ; Electron Transport Complex II ; deficiency ; Humans ; Infant ; Leigh Disease ; diagnosis ; etiology ; therapy ; Male ; Mitochondrial Diseases ; complications

OBJECTIVEMethylmalonic aciduria is the most common disorder of organic acidurias in the mainland of China. It is also the one of treatable metabolic disorders. The clinical spectrum of the patients varies from severe neonatal-onset forms with neonatal brain injury and high mortality to milder forms with adult-onset. The clinical manifestations of neonates with methylmalonic aciduria are non-specific. Early diagnosis and adequate treatment contribute a lot to improving the prognosis of the patients. In this study, the abnormal clinical and laboratory findings in neonatal period of 160 Chinese patients with early-onset methylmalonic aciduria were investigated.

METHODFrom 1996 to 2011, a total of 398 patients with methylmalonic aciduria were diagnosed in our hospital; 286 (71.9%) patients had early-onset before 1 year of age. Among 286 patients, 160 (55.9%) presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by liquid chromatography tandem mass spectrometry. Serum and urine total homocysteine were measured using a fluorescence polarization immunoassay. In some patients, gene analysis was performed. Based on the disease types and general condition, individual dietary and medical interventions were started soon after diagnosis.

RESULTOut of the 160 patients, 131 (81.9%) had combined methylmalonic aciduria and homocysteinemia. Isolated methylmalonic aciduria was found in 29 cases (18.1%). The common presentations in neonatal period were feeding difficulty, seizures, lethargy and dyspnea. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent findings in the routine laboratory test. The most common initial clinical diagnosis was suspected hypoxic-ischemic encephalopathy. Even in 36 cases with abnormal family history, only 3 patients were admitted with suspected inborn errors of metabolism. Five cases (3.1%) were diagnosed by postmortem metabolic examination; 7 cases (4.4%) were detected by newborn screening. In 148 cases (92.5%), the diagnosis was much delayed to the age of one month to 8 years and 5 months (mean 13 months). Methylmalonic aciduria combined with homocysteinemia (MMACHC) gene analyses were performed in 31 cases with combined methylmalonic aciduria. CblC defect was confirmed. The patients with isolated methylmalonic aciduria were treated with protein-restricted diet, cobalamin and L-carnitine. The patients of methylmalonic aciduria combined with homocysteinemia were treated with cobalamin, L-carnitine, calcium folinate, betaine and common diet. Seven patients died without treatment. Clinical improvement was observed in 153 patients. Only 2 patients detected by newborn screening had normal mental and physical development. Mild to severe psychomotor retardation was observed in 151 cases.

CONCLUSIONHigh mortality and disability rates were observed in the patients with early-onset methylmalonic aciduria. Combined methylmalonic aciduria and homocysteinemia is the common type of methylmalonic aciduria. The clinical manifestation in neonatal period of the patients with early-onset methylmalonic aciduria is complex. Feeding difficulty, seizures, lethargy and dyspnea are the common symptoms in neonatal period of the patients. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent laboratory findings.

Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; genetics ; therapy ; Carnitine ; therapeutic use ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Folic Acid ; therapeutic use ; Gas Chromatography-Mass Spectrometry ; Homocysteine ; blood ; urine ; Humans ; Hyperhomocysteinemia ; diagnosis ; etiology ; therapy ; Infant ; Infant, Newborn ; Male ; Methylmalonic Acid ; urine ; Neonatal Screening ; Retrospective Studies ; Vitamin B 12 ; therapeutic use

OBJECTIVETo study the clinical and enzymological characteristics of the children with mitochondrial respiratory chain complex III deficiency.

METHODThe clinical manifestations of five patients (3 males, 2 females) were summarized. Spectrophotometric assay was used for the analysis of respiratory chain complex I to V enzyme activity in peripheral blood leukocytes, after obtaining venous blood.

RESULT(1) Five patients were hospitalized at the age of 1 month to 15 years. Three patients had Leigh syndrome with progressive motor developmental delay or regression and weakness. One had severe liver damage and intrahepatic cholestasis. One presented muscle weakness. (2) Deficient complex I + III activity was identified in five patients. Their complex I + III activities in peripheral blood leukocytes were 3.0 to 14.2 nmol/min per mg mitochondrial protein (control: 84.4 ± 28.5 nmol/min per mg mitochondrial protein). The ratio of complex I + III to citrate synthase decreased to 3.5 to 22.9% (normal control 66.1 ± 14.7%). The activities of complex III decreased to 10.4 to 49.3% of the lowest control value, while complex I, II, IV and V activities were normal. The results supported the diagnosis of isolated respiratory chain complex III deficiency.

CONCLUSIONComplex III deficiency is a kind of disorder of energy metabolism with various manifestations. The complex I + III activities and the ratio of complex I + III to citrate synthase were lower than those of the control. The activities of complex I, II, IV and V were normal.

Adolescent ; Child ; Child, Preschool ; Electron Transport Complex I ; metabolism ; Electron Transport Complex II ; metabolism ; Electron Transport Complex III ; metabolism ; Female ; Humans ; Infant ; Leigh Disease ; Leukocytes, Mononuclear ; enzymology ; Male ; Mitochondrial Diseases ; diagnosis ; metabolism ; physiopathology

Adult ; Aged ; Carcinoma, Hepatocellular ; etiology ; pathology ; prevention & control ; therapy ; Female ; Hepatitis B ; pathology ; therapy ; Humans ; Male ; Middle Aged ; Phyllanthus ; Phytotherapy ; Precancerous Conditions ; etiology ; pathology ; prevention & control ; therapy