Risk factors affecting the outcome of cerebral infarction / 解剖学报

Objective To explore the risk factors that affect the outcome of cerebral infarction. Methods The clinical data of 594 patients with cerebral infarction were retrospectively analyzed, and 351 healthy subjects matched with age were compared. Two groups of demographic, past history and clinical laboratory indicators were compared, and multivariate analysis was performed using non-conditional logistic regression to rebeal the risk factors that affect the outcome of cerebral infarction. Results Homocysteinemia level, lipoprotein (a) level, fasting blood glucose level, admission systolic blood pressure and hypertension history were the independent risk factors affecting the outcome of cerebral infarction. Conclusion The risk factors for the poor prognosis of cerebral infarction should be controlled early, so as to reduce and prevent the poor outcome and cerebral infarction recurrence.

Study Of Serum Homocysteine Levels In Cerebrovascular Accident

Background:Stroke is the second most common cause of death and major cause of disability worldwide. Plasma homocysteine concentration is one of the emerging modifiable risk factor for stroke. The objective of this study was to evaluate the fasting homocysteine level in different type of stroke (Ischemia & Hemorrhage). Material & Meth-ods:The present study is case control study in which 90 patients with diagnosis of stroke (intracerebral infarct & hemorrhage) were enrolled and fasting serum homocysteine were measured in all and its comparison was done with matched healthy controls. Result: In study group the mean serum homocysteine level is 31.47±39.89 μmol/L and in control group 16.62±22.08 μmol/L, it indicates that serum homocysteine level is highly significantly raised (P value < 0.0001) in cases of stroke compared with control patients. However there is no significant difference in homocyste-ine level between intracerebral infarct and intracerebral hemorrhage (P= 0.5817). There is significant relationship of raised serum homocysteine level with hypertension & smoking. Conclusion: The present study revealed that hyper-homocysteinemia appears to be an important risk factor for cerebrovascular accidents. It is therefore important to use serum homocysteine level as an important tool to investigate all cases of cerebrovascular accidents and also in those who are at risk of developing stroke.

Heterogeneous phenotypes, genotypes, treatment and prevention of 1 003 patients with methylmalonic acidemia in the mainland of China / 中华儿科杂志

Objective@#To analyz the current situation of the diagnosis, treatment and prevention of methylmalonic acidemia, the phenotypes, biochemical features and genotypes of the patients in the mainland of China, were investigated.@*Methods@#Tottally 1 003 patients of methylmalonic acidemia from 26 provinces and municipalities of the mainland of China were enrolled. The clinical data, biochemical features and gene mutations were studied. Blood aminoacids and acylcarnitines, urine organic acids, and plasma total homocysteine were determined for the biochemical diagnosis. Gene analyses were performed for the genetic study of 661 patients. The patients were treated with individual intervention and long-term follow up. Prenatal diagnoses were carried out for 165 fetuses of the families.@*Results@#Among 1 003 patients (580 boys and 423 girls), 296 cases (29.5%) had isolated methylmalonic acidemia; 707 cases (70.5%) had combined homocysteinemia; 59 patients (5.9%) were detected by newborn screening; 944 patients (94.1%) had the onset at the ages from several minutes after birth to 25 years and diagnosed at 3 days to 25 years of age. The main clinical presentations were psychomotor retardation and metabolic crisis. Multi-organ damage, including hematological abnormalities, pulmonary hypertension, kidney damage, were found. MMACHC, MUT, MMAA, MMAB, HCFC1, SUCLG1, SUCLA2 mutations were found in 631 patients (96.6%) out of 661 patients who accepted gene analysis. MMACHC mutations were detected in 460 patients (94.7%) out of 486 cases of methylmalonic acidemia combined with homocysteinemia. MUT mutations were found in 158 (90.3%) out of 169 cases of isolated methylmalonic acidemia. The development of 59 patients detected by newborn screening were normal; 918 cases (97.2%) were diagnosed after onset accepted the treatment. Forty-five of them completely recovered with normal development. Twenty-six patients (2.7%) died; 873 (92.5%) patients had mild to severe psychomotor retardation. Methylmalonic acidemia were found in 35 out of 165 fetuses by metabolites assay of amniotic fluid and amniocytes gene analysis.@*Conclusion@#Combined methylmalonic acidemia and homocysteinemia is the common type of methylmalonic acidemia in the mainland of China. CblC defect due to MMACHC mutations is the most common type of methylmalonic acidemia combined with homocysteinemia. MUT gene mutations are frequent in the patients with isolated methylmalonic acidemia. Newborn screening is key for the early diagnosis and the better outcome. Combined diagnosis of biochemical assays and gene analysis are reliable for the prenatal diagnosis of methylmalonic acidemia.

Clinical Efficacy of Folic Acid Intervene in Hyper-homocysteinemia Patients Combining Coronary Artery Disease and Heart Failure / 中国循环杂志

Objective: To observe clinical efficacy of oral folic acid (FA) intervene in hyper-homocysteinemia (HHcy) patients combining coronary artery disease (CAD) and heart failure (HF), to study the effect of blood level of Hcy on cardiac function. Methods: A total of 126 relevant patients with blood level of Hcy>15 μmol/L were randomly divided into 2 groups:Routine group, the patients received anti-platelet therapy, statins, beta-blockers, diuretics, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonist and FA group, in addition to above mentioned therapies, the patients also received FA 5 mg/day. n=63 in each group and all patients were treated for 3 months. Fasting blood levels of Hcy, BNP and left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), 6-minute walk test (6MWT) were compared between 2 groups at pre- and 3 months post-treatment. Results: ① Based on NYHA classification, the patients with cardiac function at II, III, IV had accordingly increased blood levels of Hcy, BNP and LVEDD, while decreased LVEF and 6MWT, all P<0.05. ② Blood levels of Hcy were positively related to BNP (r=0.733, P<0.001) and LVEDD (r=0.511, P<0.001), negatively related to LVEF (r=-0.382, P<0.001) and 6MWT (r=-0.410, P<0.001). ③ With 3 months treatment, FA group and Routine group showed decreased Hcy level as (8.43 ± 1.87) μmol/L vs (3.29 ±1.68) μmol/L and BNP (891.84 ± 456.10) pg/ml vs (682.24 ± 463.79) pg/ml, reduced LVEDD (4.33 ± 1.231) mm vs (2.06 ± 1.73) mm, while elevated LVEF (6.59 ± 2.28) % vs (2.52 ± 2.37) % and 6MWT (142.97 ± 55.15) m vs (86.35 ± 59.06) m, all P<0.05. Conclusion: Increased blood level of Hcy is risky for HF occurrence, FA may treat HHcy and further improve the cardiac structure and function in HF patients.

The relationship of plasma homocysteine level and apolipoprotein E gene polymorphism with Alzheimer's disease / 中华老年医学杂志

Objective To investigate the correlations of plasma homocysteine(Hcy)level and apolipoprotein E gene polymorphism with Alzheimer' s disease(AD)and mild cognitive impairment (MCI).Methods A case-control study in 66 AD patients(AD group),64 MCI patients(MCI group) and 54 healthy controls(control group)was conducted.Plasma Hcy level and ApoE polymorphism were determined and analyzed.Results Plasma Hcy levels were significantly higher in AD and MCI groups than in control subjects(both P＜0.001).AD patients also showed increased plasma Hcy levels as compared with MCI patients(P＜0.001).Logistic regression analysis indicated that the increased plasma Hcy level was a risk factor for AD and MCI(OR＝ 1.435 and 1.312,both P＜0.001).ApoE ε3/3 was the most common genotype in AD,MCI and control groups,and ε3/4 and ε4/4 genotypes were more common in AD group and MCI group than in control group(both P＜0.05).The ε4 allele frequency of ApoE was 24.2％ and 23.4％ in AD or MCI group respectively,and 6.5％ in control group(AD or MCI vs.control,P＜0.05).The analysis by multiplicative interaction model showed that the odd ratio for MCI was 23.3 in patients with only hyperhomocysteinemia(Hhcy,Hcy＞ 15 μmol/L),12.6 in patients with carrying ε4 allele,and 46.7 in patients with both Hhcy and carrying ε4 allele,which indicated that there was interaction between hyperhomocysteinemia and carrying e4 allele.Conclusions Hyperhomocysteinemia and ApoE ε4 allele are correlated with dementia and also have additive interactions.

A pedigree of a rare Cb1X type X-linked methylmalonic acidemia due to transcriptional co-regulator HCFC1 ;mutation / 临床儿科杂志

Objective To explore the clinical and genetic features in the pedigree of Cb1X type X-linked methylmalonic aciduria. Methods Clinical data of one child with X-linked methylmalonic aciduria diagnosed by blood and urine analysis were analyzed retrospectively. Targeted next-generation sequencing has been performed to detect the mutation of methylmalonic aciduria-related genes. Results The boy started presenting with seizures and severe mental retardation at 2 months of age. At 5 months of age, he had the manifestations of seizures, severe mental retardation, increased methylmalonic acid in urinary, increased propionylcarnitine in blood and increased plasma homocysteine, and met the requirements for the diagnosis of methylmalonic aciduria complicated with hyperhomocysteinemia. No mutation was detected in his MMA-related autosomal genes. However, a hemizygote mutation c.344C?>?T (p.Ala115Val) was identiifed in exon 3 of HCFC1 in X chromosome, which conifrmed the CblX type methylmalonic aciduria. His parents were healthy. His elder brother also manifested severe psychomotor retardation with intractable epilepsy, and died at 6 months of age with unknown cause. His mother carried the same mutation and had slightly elevated urine methylmalonic acid and plasma total homocysteine. His father did not carry the mutation. Conclusion A pedigree of a rare Cb1X type X-linked methylmalonic acidemia is ifrstly diagnosed in China by the new generation sequencing technology.

Value of homocysteine in patients with acute cerebral infarction / 国际检验医学杂志

Objective To study value of homocysteine (Hcy) in patients with acute cerebral infarction for prevention ,early diag‐nosis and treatment .Methods A total of 88 patients with acute cerebral infarction from August 2012 to October 2014 were collect‐ed in study group ,50 healthy persons were recruited in control group .Enzyme cycle method was used to measure levels of Hcy in the study group before and after treatment and the control group .Results The levels of Hcy in the study group before and after treatment were significant higher than that of the control group ,the level of Hcy in the study group after treatment were significant lower than that before treatment ,the differences had statistical significance(P < 0 .05) .There was 42 .27% patients in the study group had hyper‐homocysteinemia ,which was significant higher than 14 .00% in the control group (P< 0 .05) .Conclusion For pa‐tients with acute cerebral infarction ,Hcy levels are closely correlated with their condition ,detection of Hcy could provide effective measure for diagnosis and treatment of acute cerebral infarction .

Application of gene capture technology combined with next generation sequencing technology on methylmalonic acidemia / 中华实用儿科临床杂志

Objective To assess the efficiency and reliability of clinical genetic diagnosis of methylmalonic acidemia(MMA) using new generation sequencing platform (HiSeq2000).Methods 1.Nine patients diagnosed with clinical signs of MMA were recruited.DNA library from the patients were mixed with designed gene capture probe.The whole exons region of 48 genes related to organic acid metabolism were screened using the gene capture combined with high-throughput sequencing.2.The joints were removed and the low quality data were filtered,the data were analyzed by means of SNP and InDel.To avoid the false positive,the abnormal sites were verified using the Sanger sequencing method.3.The detection of the organic acid in the urine was performed through gas chromatography-mass spectrometry and other auxiliary examinations.Results 1.Gene mutation:7 gene mutations of MMACHC were identified in 7 patients.Seven mutations:c.482G ＞ A,c.567_568insT,c.609G ＞ A,c.440_441del,c.80A ＞ G,c.315C ＞ G,c.90G ＞ Awere screened.The mutation c.440_441del had not been reported before,and others were all related to the disease.Two gene mutations of mutase apoenzyme(MUT) were identified in 1 case,all of which were introns:.c.754-1G ＞ C,c.1677-1G ＞ A.The novel mutation was c.754-1G ＞ C.No gene mutation was identified in 1 patient.2.Clinical manifestation:all of the patients were development delay,but the degrees were different;3 patients with convulsion; 1 patient with headache and central facial paralysis;1 patient with repeated intractable metabolic acidosis;1 patient with repeated hemolysis.Electroencephalogram of the all patients were abnormal;the result of cranial MRI of the 8 patients were abnormal;In all patients,urine level of methylmalonic acid significantly increased (273.4-146 022.8 times).Blood homo cysteine of 8 patients were significantly increased(27.13-396.84 μmol/L,normal ＜ 20 μmol/L).3.Sanger sequencing:there were no false positive exists.Conclusions 1.There were not a correlation between the clinical manifestation and gene mutation of the patients with MMA.The c.609G ＞ A was the hotspot mutation of MMACHC gene in Chinese patients with MMA and homocysteinemia.2.The mutations c.440_441del and c.754-1G ＞ C were presumed to be novel mutations.3.Gene capture technology combined with next-generation sequencing technology could be used to interrogate the wealth of data available in the human genome and lay the foundations for counseling of gene.This platform can be readily and timely adopted by clinical molecular diagnosis of MMA and represents a high throughput,high sensitivity,high efficiency and other characteristics approach for screening common genetic diseases.

Investigation of relationship between hyper-homocysteinemia and experiment au-toimmune encephalomyelitis mice / 中国免疫学杂志

Objective:To investigate the relationship between hyper-homocysteinemia ( HHcy) and experiment autoimmune en-cephalomyelitis (EAE) mice,and to study the cause and effect of HHcy in multiple sclerosis (MS).Methods: Four groups were included in this study:healthy C57BL/6 mice and EAE mice fed with chow(HC and EAE group),healthy mice and EAE mice supple-mented with 4%(w/v) methionine in the drinking water (HC+Hcy and EAE+Hcy group).Clinical symptoms,the levels of Hcy and cytokines ( TNF-α,IFN-γand IL-17) were evaluated at different time points.Results:EAE group had no greater Hcy than HC group ( P>0.05 ).The clinical scores and weight loss of mice from EAE+Hcy group were more severe than those from EAE group during the course of EAE ( P<0.05 ).EAE+Hcy group had higher levels of TNF-αand IFN-γthan EAE group ( P<0.05 ) ,while IL-17 was about the same.Conclusion:Mice do not have gradually increased Hcy during the course of EAE.HHcy worsen the symptoms of EAE by pro-moting the production of TNF-αand IFN-γ,but not IL-17.

Livedoid Vasculopathy with Hyperhomocysteinemia due to MTHFR Mutation / 대한피부과학회지

Livedoid vasculopathy is a hyalinizing vascular disease characterized by thrombosis and ulceration of the lower extremities. It can be caused by an alteration in control of coagulation with the formation of thrombi within dermal blood vessels. We report a case of livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation, which is treated by folic acid and which also showed very unusual clinical manifestations. A 38-year-old male visited the department of dermatology with a 1 year history of purplish-brown purpura with punched-out ulcers on both lower legs. He had a history of homocysteinemia due to methylene tetrahydrofolate reductase (MTHFR) mutation. The histopathologic findings of the lesional skin revealed dense superficial and deep perivascular and perifollicular infiltrates of lymphocytes and fibrin deposition within the vessels in the dermis. On the basis of clinical and pathological findings, livedoid vasculopathy with hyperhomocysteinemia due to MTHFR mutation was diagnosed and improved by the treatment of 1 mg of folic acid daily.

Clinical and gene mutation analysis in patients with methylmalonic acidemia and homocystelnemia / 中华内分泌代谢杂志

ld have an improved outcome after reasonable treatments. The gene mutation detection suggests that 609G>A (W203X) may be the hot spot mutation of MMACHC gene in Chinese patients.

The relationship of hyperhomocysteinemia and diabetic neuropathy / 中国糖尿病杂志

Objective To investigate the level of homocysteinemia in type 2 diabetes mellitus with neuropathy,and observe the effect of medical intervention of hyperhomocysteinemia on diabetic neuropathy.Methods 200 patients with type 2 diabetes mellitus plus neuropathy and 200 control were collected.Patients with diabetic neuropathy plus hyperhomocysteinemia were divided into two groups:medical intervention group(15mg/d folic acid,20mg/d vitamin B6)and control group.The level of homocysteinemia in plasma was measured,and neuropathy score was evaluated by clinical and electrobiological methods before and three months after treatment.Results The morbidity of hyper-homocysteinemia in type 2 diabetes mellitus with neuropathy was 40%,and the levels of homocysteinemia was higher in treatment group than in control(P<0.05).Compared with the control,the levels of homocysteinemia in group of medical intervention was lower(P<0.01),and neuropathy score and nerve conductive velocity showed an obviously improvement after 3-month-treatment(P<0.05).Conclusions Hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in humans.Efficiently intervening the levels of homocysteinemia could improve the electrobiological activity and neuropathy score.

Study on the relationship between serum homocysteinemia and the level of serum uric acid,blood glucose,lipoproteins in aged patients with coronary heart disease and stroke / 中国医师进修杂志

15.6 ?mol/L. Group B, 55 cases, Hcy≤15.6 ?mol/L). The Hcy, FBG, TC, TG, HDL-C, LDL-C, LP(a) and UA of both groups were compared. Results The concentration of FBG,LP(a) and UA of group A was higher than that of group B (P

Etiology, Pathology and Medical Treatment of Carotid Artery Stenosis / 国际脑血管病杂志

Carotid artery stenosis is one of the major causes of ischemic stroke. Recent studies have found that homocysteinemia and matrix metalloproteinase and its endogenous tissue inhibitor play important roles in carotid artery stenosis. The interventional strategies that aim at the 2 new risk factors may have extensive prospects of application in the future prevention and treatment of ischemic cerebrovascular disease.

Therapeutic action of Taurine in patients with cerebral infarction induced by hyperhomocysteinemia / 临床神经病学杂志

Objective To investigate the therapeutic action of Taurine in patients with cerebral infarction(CI)induced by hyperhomocysteinemia(Hhcy).Methods The 100 CI patients induced by Hhcy were randomly divided to two therapy groups.One group was administered Taurine,the other group was administered Folacin combined with Vitamine B12 for 8 weeks.Before and after treating,the serum levels of homocysteic acid(Hcy),Folacin and Vitamine B12 were detected,NIHSS and BI were evaluated.Results The serum levels of Hcy were significantly decreased after administering in both two groups(all P

Puerarin results in down-regulation of apoptosis in cultured human aortic endothelial cells induced by homocysteinemia / 中成药

AIM: To select differentially the expressed gene,glucose regulated protein 78(GRP78),to observe the expression of GRP78 in atherosclerosis tissue and to elucidate the mechanism for anti-atherosclerosis of puerarin.METHODS: The model was established by using homocysteinemia in vitro.The vascular endothelial cells were incubated with various concentrations of puerarin(10 -7 mol/L,10 -6 mol/L,10 -5 mol/L) for 48 h.The apoptosis rate was detected by flow cytometry using Annexin/PI-staining.GRP78 gene was amplificated by PCR.These differentially expressed fragments were cloned,selected,confirmed,and sequenced.Digoxigenin-labeled DNA Probe and cholesterol-rich rabit model were prepared,GRP78 mRNA was determined by in situ hybridization in atherosclerotic lesions and normal tissue.RESULTS: Three concentrtions of puerarin significantly inhibited the apoptosis of endothelial cells.The early apoptosis rate was decreased magnificently in a dose dependent manner compared with that of HCY group (P