Hemorrhagic Cerebrovascular Disease: An Unusual Presentation of Hyperhomocysteinemia / Accidente cerebrovascular hemorrágico: una inusual presentación de hiperhomocisteinemia / Acidente vascular cerebral hemorrágico: uma apresentação incomum da hiper-homocisteinemia

Introduction: Stroke is a major cause of morbidity and mortality worldwide, with hemorrhagic stroke being the deadliest form of acute stroke. Therefore, the cause of the event should be determined to direct the associated therapy and take preventive measures. Hyperhomocysteinemia has been described as a rare etiology of stroke. Although hyperhomocysteinemia has been associated with venous thrombotic events, altered endothelial function, and procoagulant states, its clinical role in stroke remains controversial. Case description: We present a case of a 60-year-old male patient with primary autoimmune hypothyroidism who presented with dysarthria, facial paresis, and left upper-limb monoparesis after sexual intercourse. A simple skull computed tomography scan showed hyperintensity in the right basal ganglion, indicating an acute hemorrhagic event. Etiological studies were performed, including ambulatory blood pressure monitoring, cerebral angiography, and transthoracic echocardiogram, which ruled out underlying vascular pathology. During follow-up, vitamin B12 deficiency and hyperhomocysteinemia were detected, without other blood biochemical profile alterations. Supplementation was initiated, and homocysteine levels gradually decreased, without new neurological deficits observed during follow-up. Conclusion: Quantification of homocysteine should be considered in patients with a cerebrovascular disease without apparent cause, as documenting hyperhomocysteinemia and correcting its underlying etiology are essential not only for providing appropriate management but also for preventing future events.

Introducción: el accidente cerebrovascular es una causa importante de morbilidad y mortalidad en todo el mundo, y el accidente cerebrovascular hemorrágico es la forma más mortífera de accidente cerebro- vascular agudo. La determinación de la causa del evento es esencial para dirigir la terapia asociada y poder tomar medidas preventivas. La hiperhomocisteinemia se ha descrito como una etiología poco frecuente de accidente cerebrovascular. Aunque esta se ha asociado con eventos trombóticos venosos, disfunción endotelial alterada y estados procoagulantes, sigue siendo controvertido su papel clínico en el accidente cerebrovascular. Descripción del caso: se presenta el caso de un hombre de 60 años con hipotiroidismo autoinmune primario que presentó disartria, paresia facial y monoparesia del miembro superior izquierdo después de un encuentro sexual. Una simple tomografía computarizada de cráneo mostró hipointensidad en la región del ganglio basal derecho, que indicaba un evento hemorrágico agudo. Se realizaron estudios etiológicos, incluyendo monitorización ambulatoria de la presión arterial, angiografía cerebral y ecocardiograma transtorácico, que descartaron patología vascular subyacente. Durante el seguimiento, se detectó deficiencia de vitamina B12 e hiperhomocisteinemia, sin otras alteraciones en el perfil bioquímico sanguíneo. Se inició la suplementación y los niveles de homocisteína disminuyeron gradualmente, sin observar nuevos déficits neurológicos durante el seguimiento. Conclusión: la cuantificación de homocisteína debe ser considerada en casos de enfermedad cerebrovascular sin causa aparente, dado que documentar la hiperhomocisteinemia y corregir su etiología subyacente es esencial no solo para proporcionar un manejo adecuado, sino también para prevenir eventos futuros.

Introdução: o acidente vascular cerebral (AVC) é uma das principais causas de morbidade e mortalidade em todo o mundo, sendo o AVC hemorrágico a forma mais letal de AVC agudo. A determinação da causa do evento é essencial para direcionar a terapia associada e poder tomar medidas preventivas. A hiperhomocisteinemia tem sido descrita como uma etiologia rara de acidente vascular cerebral. Embora a hiper-homocisteinemia tenha sido associada a eventos trombóticos venosos, disfunção endotelial alterada e estados pró-coagulantes, seu papel clínico no AVC permanece controverso. Descrição do caso: apresentamos o caso de um homem de 60 anos com hipotireoidismo autoimune primário que apresentou disartria, paresia facial e monoparesia do membro superior esquerdo após relação sexual. A tomografia computadorizada de crânio mostrou hipointensidade na região do gânglio da base direito, indicando evento hemorrágico agudo. Foram realizados estudos etiológicos, incluindo monitorização ambulatorial da pressão arterial, angiografia cerebral e ecocardiograma transtorácico, que descartaram patologia vascular subjacente. Durante o acompanhamento, foram detectados deficiência de vitamina B12 e hiper-homocistei- nemia, sem outras alterações no perfil bioquímico sanguíneo. A suplementação foi iniciada e os níveis de homocisteína diminuíram gradualmente, sem novos déficits neurológicos observados durante o acompanhamento. Conclusão: a quantificação da homocisteína deve ser considerada em casos de doença vascular cerebral sem causa aparente, pois documentar a hiper-homocisteinemia e corrigir sua etiologia subjacente é essencial não apenas para fornecer manejo adequado, mas também para prevenir eventos futuros.

Clinical characteristics and dietary factors of elderly type 2 diabetes mellitus complicated with hyperhomocysteinemia / 公共卫生与预防医学

Objective To analyze in elderly type 2 diabetes (diabetes mellitus type 2, T2DM) combined high homocysteine levels (Hyperhomocysteinemia, HHcy) clinical characteristics and dietary factors, provide theoretical basis for T2DM combined HHcy patient's diagnosis and treatment. Methods A total of 186 elderly T2DM patients admitted to our hospital from January 2020 to June 2022 were selected and divided into control group (without HHcy) and observation group (with HHcy) according to whether the patients were complicated with HHcy. The age, gender, body mass index (BMI), mean course of disease, SBP, fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) levels, whether complicated with carotid plaque were compared between the two groups. Univariate analysis and logistic regression analysis were used to analyze the dietary factors affecting HHcy in T2DM patients. Results Among the 186 T2DM patients, 47 (25.27%) had HHcy. The serum Hcy level in the experimental group was significantly higher than that in the control group (P0.05). In terms of dietary factors , there were significant differences between the two groups in daily vegetable intake, daily meat intake, daily quantity of soy products (P1050g (OR=3.652) were dietary independent risk factors for HHcy in T2DM patients (P1050 g. Dietary adjustment should be actively adopted to reduce the risk of HHcy in T2DM patients.

Papilledema and abducens nerve palsy associated with vitamin B12 deficiency

Papilledema is defined as optic disc swelling that is secondary to elevated intracranial pressure. Vision is usually well preserved with this condition. The optic discs appear blurred in papilledema. Elevation in intracranial pressure is due to variety of reasons of which intracranial hemorrhageis the most common. We present a case in which our patient developed papilledema due to vitamin B12 deficiency. Lateral rectus muscle palsy occurs due to abducens nerve palsy. The lateral rectus muscle is responsible for lateral movement of the eyeball, specificallyabduction. Its palsy results in sudden onset of horizontal double vision, which is worse when the patient looks to the affected side. There is also limited outward movement of the affected eye. Abducens nerve palsy can occur due to ischemia injury, stroke, infection, brain tumour, elevated intracranial pressure, or inflammation of the nerve. In our patient the abducens nerve palsy was due to homocysteinemia secondary to dietary vitamin B12 deficiency. Homocysteine is a potent atherosclerotic risk factor and can cause ischemic nerve palsy, as seen in our patient.

The Role of High Concentrations of Homocysteine for the Development of Fetal Growth Restriction / O papel de altas concentrações de homocisteína para o desenvolvimento da restrição de crescimento fetal

Abstract Objective To assess homocysteine (Hcy) levels in the three trimesters of pregnancy in women with fetal growth restriction (FGR) and to evaluate the role of Hcy as a possible predictor of FGR. Methods A total of 315 singleton pregnant women were included in the present prospective cohort study and were monitored since the 1st trimester of pregnancy before delivery. Newborns were monitored for the first 7 days of life. Patients who had risk factors for FGR were excluded. Fetal growth restriction was defined according to uterine fundal height (< 10 percentile), ultrasound fetometry (< 5 percentile), and anthropometry of newborns (<5 percentile). The concentrations of Hcy were detected at between 10 and 14, between 20 and 24, and between 30 and 34 weeks of pregnancy by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristics (ROC) curve test and diagnostic odds ratio (DOR) were performed to evaluate the results of ELISA. Results The concentration of Hcy in patients with FGR was 19.65 umol/L at between 10 and 14 weeks, compared with 9.28 umol/L in patients with normal fetal growth (p<0.0001). The optimal cut-off level for Hcy in the 1st trimester of pregnancy was>13.9 umol/L with AUC 0.788, sensitivity of 75%, specificity of 83.6%, and DOR of 15.2. Conclusion Assessment of serum Hcy concentration may be used as a predictor of FGR, with the highest diagnostic utility in the 1st trimester of pregnancy.

Resumo Objetivo Avaliar os níveis de homocisteína (Hcy) em três trimestres da gravidez em mulheres com restrição de crescimento fetal (FGR, na sigla em inglês) e avaliar o papel da Hcy como possível preditor de FGR. Métodos Um total de 315 gestantes solteiras foram incluídas no presente estudo de coorte prospectivo e monitoradas desde o 1° trimestre de gravidez antes do parto. Os recém-nascidos foram acompanhados durante os primeiros 7 dias de vida. Pacientes que apresentam fatores de risco para FGR foram excluídos. A FGR foi definida de acordo com a altura do fundo do útero (< percentil 10), ultrassonografia fetometria (< percentil 5) e antropometria dos recém-nascidos (< percentil 5). As concentrações de Hcy foram detectadas entre 10 e 14, entre 20 e 24 e entre 30 e 34 semanas de gravidez por ensaio de imunoabsorção enzimática (ELISA, na sigla em inglês). O teste da curva das características de operação do receptor (ROC, na sigla em inglês) e a razão de chances de diagnóstico (DOR, na sigla em inglês) foram realizados para avaliar os resultados do ELISA. Resultados A concentração de Hcy em pacientes com FGR foi de 19,65 umol/L entre 10 e 14 semanas, em comparação com 9,28 umol/L em pacientes com crescimento fetal normal (p<0,0001). O nível de corte ideal para Hcy no 1° trimestre da gravidez foi>13,9 umol/L com AUC 0,788, sensibilidade de 75%, especificidade de 83,6%, e DOR 15,2. Conclusão A avaliação da concentração sérica de Hcy pode ser usada como um preditor de FGR, com maior utilidade diagnóstica no 1° trimestre de gravidez.

Association between MTHFR gene polymorphism and primary hypertension in children / 中国当代儿科杂志

OBJECTIVES@#To study the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in children with primary hypertension, and to explore the association between MTHFR C677T gene polymorphism and H-type hypertension in children.@*METHODS@#A total of 121 children with primary hypertension who were hospitalized in the department of cardiovascular medicine from January to July 2021, newly diagnosed, and untreated were retrospectively selected as the subjects. The children were divided into three groups: CC genotype (19 children), CT genotype (51 children), and TT genotype (51 children). According to the serum homocysteine (Hcy) level, they were divided two groups: H-type hypertension (47 children) and simple hypertension (74 children). The medical data were compared between the groups. The association between MTHFR C677T gene polymorphism and H-type hypertension was evaluated.@*RESULTS@#The mutation frequency of T allele in children with primary hypertension was significantly higher than that in healthy adults in Beijing and Chinese Han adults (P<0.001). The serum Hcy level in the TT genotype group was significantly higher than that in the CC and CT genotype groups (P<0.001). The serum Hcy level in the H-type hypertension group was significantly higher than that in the simple hypertension group (P<0.001), and MTHFR C677T was mostly TT genotype, which was associated with the risk of H-type hypertension (OR=12.71, P<0.001). There was no significant difference in the incidence rate of target organ damage between the H-type hypertension and simple hypertension groups (P>0.05). However, multiple organ involvement was observed in the H-type hypertension group at diagnosis, accounting for 11% (5/47).@*CONCLUSIONS@#The mutation rate of MTHFR C677T T allele in children with primary hypertension is high and associated with the serum Hcy level. TT genotype is an independent risk factor for H-type hypertension in children, and it may be related to the severity of early target organ damage.

Cerebral infarction complicated with multiple arterial thrombosis caused by cystathionine beta-synthase gene mutation in youth: a case report / 中华神经科杂志

Hyperhomocysteinemia (HHcy) is one of the independent risk factors for youth cerebral infarction. Gene mutation of key enzymes in homocysteine metabolism is the main cause of HHcy. Few cases of cystathionine beta-synthase (CBS) compound heterozygous mutation complicated with pulmonary embolism and lower extremity artery embolism have been reported. This article reported a young cerebral infarction patient complicated with pulmonary embolism and lower extremity artery embolism, who was subsequently detected with significantly elevated blood Hcy, and finally etiologically diagnosed with CBS 833 T>C/1082C>T compound heterozygous mutation. With the treatment of folic acid, methyl cobalt amine, vitamin B 6 and anticoagulant, the blood Hcy has been gradually declined, and no new thrombotic events occurred during the follow-up period of a year.

Correlation between MTHFR gene C677T polymorphism, homocysteine and early neurological deterioration in Han population with acute ischemic stroke in Chengdu area / 国际脑血管病杂志

Objective:To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and early neurological deterioration (END) in Han population with acute ischemic stroke in Chengdu area, and the interaction with other traditional risk factors.Methods:Consecutive Han patients with acute ischemic stroke admitted to the Department of Neurology, the Third People's Hospital of Chengdu from January 2017 to June 2019 were enrolled prospectively. Using the candidate gene association study method, MTHFR gene C677T polymorphism was used as a genetic marker to analyze the correlation between END and MTHFR gene polymorphism, and analyze the interaction of gene-END traditional risk factors.Results:A total of 434 patients with acute ischemic stroke were enrolled in the study, and 129 had END (29.7%). Multivariate logistic regression analysis showed that hyperglycemia (odds ratio [ OR] 2.410, 95% confidence interval [ CI] 1.436-4.046; P<0.001), hyperhomocysteinemia ( OR 2.570, 95% CI 1.229-5.376; P=0.012) and moderate to severe neurological deficit (baseline National Institutes of Health Stroke Scale score >5) ( OR 2.158, 95% CI 1.337-3.484; P=0.002) at admission were independently correlated with END. There was a correlation between C677T polymorphism and END. TT genotype ( OR 1.710, 95% CI 1.021-2.863; P=0.002) and A allele ( OR 1.583, 95% CI 1.181-2.121; P=0.002) could significantly increase the risk of END. Interaction analysis showed that there was interaction effect between C677T polymorphism and hyperglycemia at admission, alcohol drinking and moderate to severe neurological deficit. Interaction could increase the risk of END, but it did not reach statistical significance ( OR 1.237, 95% CI 0.227-6.734; P=0.806). Conclusion:MTHFR gene C677T polymorphism and hyperhomocysteinemia are associated with END in Han population with acute ischemic stroke in Chengdu area.

Hyperhomocysteinemia is a risk factor for intracranial aneurysms / 国际脑血管病杂志

Objective:To investigate the correlation between hyperhomocysteinemia (HHcy) and the onset of intracranial aneurysm (IAs).Methods:Patients with IA visited the Department of Neurosurgery, the First People's Hospital of Kashgar from February 2017 to November 2020 were retrospectively included as a case group, while patients with trigeminal neuralgia visited the hospital at the same time were selected as a control group. Demographic data, vascular risk factors and laboratory findings were compared between the two groups. Multivariate logistic regression analysis was used to determine the correlation between HHcy and IAs. Results:A total of 150 patients with IA (case group) and 112 patients with trigeminal neuralgia (control group) were included. Univariate analysis showed that there were significant differences in age, hypertension, drinking, triglyceride, low-density lipoprotein cholesterol, total Hcy and HHcy between the two groups (all P<0.05). Multivariate logistic regression analysis showed that there were significant independent correlation among males (odds ratio [ OR] 0.320, 95% confidence interval [ CI] 0.167-0.613; P=0.001), hypertension ( OR 4.915, 95% CI 2.674-9.036; P<0.001), triglycerides ( OR 1.342, 95% CI 1.030-1.750; P=0.030), total Hcy ( OR 1.171, 95% CI 1.082-1.268; P<0.001), HHcy ( OR 3.574, 95% CI 1.522-8.391; P=0.003) and IAs. Conclusion:HHcy is an independent risk factor for the increased risk of IAs.

Mechanism of hyperhomocysteinemia induced renal injury in CBS+/- mice / 中国组织工程研究

BACKGROUND: In chronic kidney disease, there is often an increase in the level of homocysteine, which can lead to podocyte apoptosis, but the specific mechanism is not clear. OBJECTIVE: To investigate the mechanism of hyperhomocysteinemia-induced renal injury in Cbs+/- mice. METHODS: Cbs+/+ mice (control group) and Cbs+/- mice (model group) with similar body weight were selected, with 10 mice in each group, and were fed with high methionine diet. After 8 weeks, the mice were killed, the serum was separated and the kidney tissue was obtained. The levels of serum homocysteine, urea nitrogen and creatinine were measured by automatic biochemical analyzer. The renal injury was observed by Periodic Acid-Schiff staining and transmission electron microscope. TUNEL staining was used to observe the apoptosis of glomeruli. The protein expression levels of Bax, Bcl-2 and caspase12 were detected by western blot. RESULTS AND CONCLUSION: Compared with Cbs+/+ mice, the level of serum homocysteine, urea nitrogen and creatinine in Cbs+/- mice were significantly increased (P < 0.01). The Periodic Acid-Schiff staining results showed that the glomerular basement membrane of Cbs+/+ mice was clear and the thickness was uniform, while the Cbs+/- mouse glomerular basement membrane showed varying degrees of uneven thickness, widening of membrane area and thickening of matrix. Under the transmission electron microscope, the glomerular basement membrane of Cbs+/+ mice was clear and the foot process was regular, while the glomerular basement membrane of Cbs+/- mice was locally thickened and the foot process was irregular fusion. TUNEL staining showed that the number of apoptotic cells in glomeruli of Cbs+/- mice was significantly increased compared with Cbs+/+ mice; meanwhile, western blot detection showed that the protein levels of Bax/Bcl-2 and caspase12 were significantly increased (P < 0.05). To conclude, podocyte apoptosis plays an important role in hyperhomocysteinemia-induced renal injury in Cbs+/- mice.

Correlation of homocysteine levels with gene polymorphisms of homocysteine metabolic enzymes in physical examination in Nan Chong / 公共卫生与预防医学

Objective To study the correlation of plasma homocysteine (Hcy) levels with the gene polymorphisms of homocysteine metabolic enzymes in physical examination in Nan Chong. Methods A cross-sectional study design was adopted. A total of 470 Han people who received physical examination in the outpatient clinic of Nanchong Central Hospital were enrolled in this study. Blood samples were collected from the research subjects, and general clinical data of the subjects were collected. The plasma Hcy level was determined by a commercial homocysteine assay kit. Genomic DNA was extracted, and a newly-developed technology (improved Multiplex Ligation Detection Reaction, iMLDR) was used to detect target genes and SNPs. The gene polymorphism of Hcy metabolism enzymes MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G was detected, and its correlation with plasma levels of Hcy was analyzed. Results (1) The distribution frequency of the heterozygous genotype of MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G was 46.38%, 35.32%, 17.45%, and 40.85%, while the distribution frequency of the homozygous genotype was 12.13%, 4.04%, 1.49%, and 7.66%, respectively. There was no statistically significant difference in allele frequencies between male and female populations by chi-square test (2) The detection rate of hyperhomocysteinemia (HHcy) was 34.68%. There was significant difference in the levels of plasma Hcy among the three genotypes of MTHFR C677T, and the heterozygous genotype and homozygous genotype of MTHFR C677T increased the risk of HHcy by 2.97 times and 1.917 times, respectively. The genotypes of MTHFR A1298C, MTR A2756G, and MTRR A66G were not found to be correlated with the risk of HHcy. Conclusion MTHFR C677T CT and TT genotypes elevate the plasma Hcy level. The gene polymorphisms of MTHFR A1298C, MS A2756G and MTRR A66G are not risk factors for HHcy.

Status of hyperhomocysteinemia in China: results from the China Stroke High-risk Population Screening Program, 2018 / 医学前沿

A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia (Hhcy) and its influencing factors in China. A standardized questionnaire was used to collect information. Hhcy was defined as the level of serum homocysteine (HCY) ⩾ 15.0µmol/L. The H-type hypertension (HHYP) was defined as hypertension with an elevated serum HCY 15.0µmol/L). Finally, 110 551 residents ⩾ 40 years of age from 31 provinces in the mainland of China were included. Overall, the median serum HCY level was 10.9µmol/L (interquartile range 7.9-15.1). A total of 28 633 participants (25.9%) were defined as Hhcy. The Hhcy prevalence ranged from 7.9% in Shanghai to 56.8% in Tianjin. The data showed that serum HCY levels were associated with age, male gender, cigarette smoking, hypertension, diabetes, ethnicity, endurance in exercise (inverse), and fruit and vegetable intake (inverse). In addition, 15 486 participants were defined as HHYP, and the rate was 14.0%. HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752 (95% CI 1.338-2.105). The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences, and national strategies should be carried out to further improve the care of patients with Hhcy across China.

Methylmalonic acidemia involving high cervical spinal cord leading to respiratory failure: a case report / 中国综合临床

Late onset methylmalonic acidemia (MMA) is a rare genetic metabolic disease.This case is a 46 year old adult patient with MMA complicated with hyperhomocysteinemia.It starts with progressive limb weakness and mental abnormality, and has dysuria and respiratory failure.Neurological examination showed decreased muscle strength of limbs and pyramidal tract sign.The levels of blood homocysteine and urinary methylmalonic acid increased significantly.Head, neck, thoracolumbar magnetic resonance imaging showed abnormal signals in the spinal cord from the level of foramen magnum to the level of lumbar 1 vertebral body.Two heterozygous variants of mmachc were found by gene detection: c: 609G>A, c: 349G>A, consistent with cobalamin C deficiency.Treat with L-carnitine, vitamin B12 and betaine.The patients′ mental symptoms, limb muscle strength and respiratory failure were improved, and the level of blood homocysteine also decreased significantly.

Clinical outcomes of drug-eluting balloons and drug-eluting stents for the treatment of in-stent restenosis / 中国组织工程研究

BACKGROUND: A series of studies have shown that both drug-eluting balloons and drug-eluting stents are better than the other treatments for drug-eluting in-stent restenosis lesions, but both of them have limitations. OBJECTIVE: To evaluate the long-term therapeutic efficacy of drug-eluting balloons and drug-eluting stents in the treatment of coronary in-stent restenosis. METHODS: A total of 63 patients with in-stent restenosis who received treatment in the First Affiliated Hospital of Inner Mongolia Medical University between January 2016 and December 2017 were included in this study. Among these patients, 32 patients received treatment with drug-eluting balloons (drug-eluting balloon group) and 31 patients were treated with drug-eluting stents (drug-eluting stent group). Coronary artery status before and immediately after surgery, coronary angiography 1 year after surgery, adverse events, and the risk factors of in-stent restenosis were recorded in both groups. The study was approved and supported by the Medical Ethics Committee of Inner Mongolia Medical University. RESULTS AND CONCLUSION: All patients were followed up for 1 year. There were no significant differences in minimum in-stent diameter, target vessel diameter, in-stent lumen loss in the late period between patients receiving treatment with drug-eluting balloons and patients receiving drug-eluting stents (all P > 0. 05). There were no significant differences in secondary restenosis rate (18% vs. 16%, P=0. 216), target lesion revascularization rate (6% vs. 6%, P=0. 513), and incidence of adverse events (9% vs. 10%, P=0. 334) between drug-eluting balloon and drug-eluting stent groups. There were two cases of gastrointestinal bleeding in the drug-eluting stent group, and no gastrointestinal bleeding occurred in the drug-eluting balloon group. Significant difference in gastrointestinal bleeding occurred between these two groups (P < 0. 01). Multi-factor analysis showed that smoking, diabetes and hyperhomocysteinemia are the risk factors of in-stent restenosis. These results suggest that both drug-eluting balloons and drug-eluting stents are the ideal treatments of in-stent restenosis. In clinical practice, individualized treatment options should be considered based on multiple factors.

Research on compatibility rule of traditional Chinese medicine for treatment of hyperhomocysteinemia based on data mining / 中草药

Objective: To summarize the medication rules of traditional Chinese medicine for treatment of hyperhomocysteinemia (HHcy) by data mining. Methods: To collect the relevant literatures of TCM treatment of HHcy from CNKI, VIP, Wanfang Data, CBM from the establishment of the database to December 31, 2019. TCMSS V 2.5 was used to count the frequency of medication, common drug pairs and drug combinations; Association rules, improved mutual information method, complex system entropy cluster analysis were used to analyze drug association rules and core drug combinations; Unsupervised entropy hierarchical clustering was used to analyze the new prescriptions. Results: There were 156 prescriptions with 199 Chinese medicinal herbs and 46 Chinese medicinal herbs of them with functions of promoting blood circulation and removing blood stasis, promoting urination and draining dampness, pacifying liver and extingushing wind and tonic deficiency were used for more than 10 times,. A total of 33 high-frequency drug combinations were obtained through data mining, and the top five combinations were Poria-Gastrodiae Rhizoma, Chuanxiong Rhizoma-Angelicae Sinensis Radix, Chuanxiong Rhizoma-Astragali Radix, Carthami Flos-Chuanxiong Rhizoma and Chuanxiong Rhizoma-Gastrodiae Rhizoma. A total of 20 core drug combinations and 10 potential new prescriptions were obtained through evolution. Conclusion: In the treatment of HHcy in TCM, blood-activating and stasis-resolving medicines, urination-promoting and dampness-draining medicines, liver-pacifying and wind-extingushing medicines and tonic deficiency medicines were mostly used. These prescriptions show that the main methods of promoting blood circulation and removing blood stasis, and resolving phlegm and turbidity, as well as supplementing qi and invigorating spleen, promoting urination and draining dampness, removing phlegm and widening chest reflect the characteristics of addressing both the symptoms and root causes of TCM.

Effect of fatty acid binding protein 4 on the apoptosis of podocytes in mice with hyperhomocysteinemia / 医学研究生学报

Objective　To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy).　Methods　Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry.　Results　Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05).　FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05).　Conclusion　FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.

Deficiencia de cobalamina C de inicio temprano: presentación de caso clínico / Early onset cobalamin C deficiency: clinical case presentation

Cobalamin C (CblC) deficiency is an autosomal recessive disorder caused by mutations of the MMACHC gene that results in impaired synthesis of the methylcobalamin and adenosylcobalamin co-factors. This brings an impaired conversion of dietary cobalamin and therefore dysfunction of two key enzymes generating hyperhomocysteinemia, hypometionimemia and methylmalonic aciduria. It is the most common intracellular metabolism disorder of cobalamin. The early clinical form is the most frequent disorder and appears as a multisystemic disease with developmental delay, failure to thrive, and ocular, renal and hematological involvement during the first year of life. The thromboembolic events are associated with small vessel involvement, generating thrombotic microangiopathy responsible for renal involvement and pulmonary thromboembolism. The late-onset form is characterized by leukoencephalopathy, psychiatric disorders, subacute degeneration of the spinal cord, and thromboembolic events of medium to large vessels. The treatment currently available increases the survival of the patient and improves growth, neurological manifestations, biochemical, hematological profile and hydrocephalus. We present the neonatal debut of a case of CblC deficiency that appeared as a multisystem disease with initial neurological, ocular and hematological manifestations. The onset of symptoms was acute, a characteristic that is not frequent in CblC. The patient started treatment early, but in an unsatisfactory fashion, which led to increased neurological deterioration. Due to MRI images performed during the evolution of his condition, a superior and transverse sagittal sinus thrombosis, a rare manifestation of the disease, was observed.

La deficiencia de cobalamina C (CblC) es un defecto autosómico recesivo causado por la mutación del gen MMACHC, que resulta en la síntesis alterada de los cofactores metilcobalamina y adenosilcobalamina. Esto trae aparejado una disfunción de dos enzimas claves, lo cual genera hiperhomocisteinemia, hipometionimemia y aciduria metilmalónica. La presentación clínica de la deficiencia de CblC es heterogénea, y varía desde las formas de inicio temprano graves y potencialmente mortales, hasta los fenotipos más leves de inicio tardío. La forma clínica temprana es la más frecuente y se manifiesta como una enfermedad multisistémica, con restricción del desarrollo, restricción del crecimiento y alteraciones oculares, renales y hematológicas durante el primer año de vida. Las manifestaciones tromboembólicas están asociadas con el compromiso de pequeños vasos, lo que causa microangiopatía trombótica, responsable de compromiso renal y de tromboembolismo pulmonar. La forma tardía se caracteriza por leucoencefalopatía, trastornos psiquiátricos, degeneración subaguda de la médula espinal y eventos tromboembólicos de medianos o grandes vasos. El tratamiento disponible actualmente aumenta la supervivencia de la enfermedad y mejora el crecimiento, las manifestaciones neurológicas, el perfil bioquímico y hematológico y la hidrocefalia. Presentamos el debut neonatal de un caso de deficiencia de CblC que se manifestó con compromiso inicial neurológico, ocular y hematológico. El comienzo de los síntomas fue agudo, característica que no es frecuente en la deficiencia de CblC. El tratamiento se inició tempranamente, pero en forma insatisfactoria, con evolución de deterioro neurológico. En la evolución de su enfermedad en las imágenes de resonancia magnética, se puso de manifiesto trombosis de los senos sagital superior y transversos, una rara manifestación de la deficiencia de CblC.

Analysis of Clinical Features, Risk Factors and Laboratory Parameters in Cerebral Venous Thrombosis: A Study of 70 Cases

Introduction: Cerebral venous thrombosis (CVT) has variableclinical presentations mimicking other neurological disorders.There is variation in risk factors for CVT in different areas.Study was done with the aim of analyzing the clinical features,risk factors and laboratory parameters on patients diagnosedwith CVT on Magnetic Resonance Venography (MRV) andMRI.Material and Methods: In this retrospective study, data of70 consecutive patients attending a private neurology centerwith CVT confirmed on MRV and MRI from May 2016 toApril 2019 was analyzed. Laboratory parameters emphasizedwere hemoglobin content, serum homocysteine level and lipidprofile.Results: Out of 70 patients, 48 were men and 22 women inthe age range of 14 to 71 years. Most common presentingsymptom was progressive headache (63 cases,90%) aloneor in combination with other symptoms like vomiting (22cases, 31.42%), hemiparesis (17 cases, 24.28%), ataxia(17 cases, 24.28%) and seizures (15 cases, 21.42%).Hyperhomocysteinemia was seen in 15 cases (21.42%),anemia in total 30 cases (42.85%), and alcoholism in sevencases (10%). Twenty four patients (34.28%) had high densitylipoprotein (HDL) level of less than 40mg/dl, five patients(7.14%) had total cholesterol more than 200mg/dl and threepatients (4.28%) had triglycerides more than 200mg/dl. Onepatient (1.42%) had protein S deficiency.Conclusion: CVT is an uncommon but treatable cause ofstroke in young patients. Due to variety of clinical presentation,a high degree of clinical suspicion is neccessory for correctdiagnosis and early treatment.

Retinal Venous Occlusive Diseases and Study of their Risk Factors

Introduction: Retinal vein occlusion (RVO) is a major causeof vision loss. Of the two main types of RVO, Branch RetinalVein Occlusion (BRVO) is 4 to 6 times more prevalent thanCentral Retinal Vein Occlusion (CRVO), and is the mostcommon type of RVO. Risk factors evaluated in this studyinclude Age, Sex, Hypertension, Diabetes Mellitus, PrimaryOpen Angle Glaucoma (POAG), Tobacco consumption inany form, Dyslipidemia, Hyperhomocysteinemia and Irondeficiency Anaemia (IDA). Current research aimed to studythe risk factors associated with Retinal Venous Occlusivediseases and to study correlation of occurrence of lesions withthese risk factors.Material and methods: This was a hospital based crosssectional study involving 60 cases diagnosed with RetinalVenous Occlusions who were further evaluated for the abovementioned risk factors. Results were evaluated by Unpaired ttest, Fisher test, student ‘t’ test and Chi-Square test. ‘p’ valueless than 0.05 was taken as significant.Results: BRVO (n=49), CRVO (n=11). Most common comorbidity was hypertension, which was found to be significant(p<0.05). Diabetes, dyslipidemia, tobacco in any form,iron deficiency anaemia were not found to be significant.Hyperhomocystemia was found to be significant (p<0.05)under 40 years of age and insignificant risk factor above 40years. Presence of POAG with a duration of more than 5yearswas significant factor in CRVO but not in BRVO.Conclusion: Age and hypertension are significant risk factorsfor RVO. Hyperhomocysteinemia is a significant risk factorfor RVO in patients below 40 years on age. POAG is a riskfactor for development of CRVO. Presence of multiple riskfactors increases the chances of development of RVO.

A comparative and correlative study of serum homocysteine level in gestational diabetes mellitus and normal pregnancy

Background: An alarming increase in Gestational diabetes mellitus (GDM) cases worldwide elevates concern regarding the consequences including fetal macrosomia, preeclampsia and many more. Plasma homocysteine levels which has direct impact on to endothelial function of blood vessels. The relationship of homocysteine and GDM is yet to be clarified.Methods: This single centre prospective observational study was conducted in Department of Obstetrics and Gynaecology of Thanjavur medical college hospital among 50 pregnant primi and multi gravida patients with normal pregnancy and gestational diabetes mellitus to assess the association and comparison of serum homocysteine levels in both groups.Results: The mean value of homocysteine in control group was 3.8 ± 0.95 and in gestational diabetes patients was 16.30±6.09. On comparison, found that there was hyperhomocysteinemia among GDM patients with normal pregnancy and results were statistically significant (T= -9.024 Df=48.000 <0.05).Conclusions: In this comparative and correlative study, we found that patients with gestational diabetes mellitus have higher serum homocysteine levels in comparison with normal pregnant women. Hyperhomocysteinemia is found to be an independent risk factor for gestational diabetes mellitus patients. Further investigations are needed to follow up for these patients in the postpartum period and later in their life.

Clinical profile and serum homocysteine level in young patients with stroke: a prospective, observational study

Background: According to the WHO, stroke is the second most important cause of death in elderly people with age >60 years and fifth leading cause in the age group of 15 to 59 years. Hyperhomocysteinemia has been linked to increased incidence of ischemic strokes. Thus, the aim of the present study was to assess serum homocysteine levels as an individual risk factor of stroke in young patients.Methods: This was a prospective, cross-sectional, single center study performed in 50 patients admitted in the Department of Medicine, Thanjavur Medical College and Hospital, Thanjavur, over a period of 7 months (i.e., from December 2013 to June 2014). Young patients, aged 1545 years, and diagnosed with stroke were included in the study. Serum homocysteine was measured by fluorescein polarization immunoassay (FPIA). Significant difference between the patients with normal and elevated mean serum homocysteine levels was identified by using unpaired t-test. P value ?0.05 was considered as statistically significant.Results: Majority of the stroke patients were male (78%). Similarly, male patients dominated the total number of patients with elevated serum homocysteine levels (75%). Thirty-two (64%) patients had an elevated serum homocysteine level. There was a significant difference between the patients with increased homocysteine levels as compared to patients with normal homocysteine levels (p value <0.05). Out of 32 patients with hyperhomocysteinemia, 27 (84.38%) patients had ischemic stroke, 4 (12.50%) had cortical vein thrombosis and 1 (3.12%) had hemorrhagic stroke.Conclusions: Findings of the present study confirm that hyperhomocysteinemia is associated with an increased incidence of stroke in young patients. As healthcare providers, we must stress on prevention of stroke, especially by identifying treatable risk factors.