In the past few decades, the global obesity population has been increasing, and still has an upward trend. With obesity, the risk of cardiovascular and cerebrovascular diseases has increased. It’s found that an increase in body mass index is associated with the occurrence of some cardiovascular and cerebrovascular diseases Hypertension and hyperlipidemia, as common chronic cardiovascular diseases, are particularly affected by obesity, which has attracted extensive attention in recent years. Moreover, the occurrence of hypertension and hyperlipidemia under the influence of obesity is significantly related, and their synergy can also cause a variety of cardiovascular and cerebrovascular diseases. However, there is still less work to study these three factors at the same time. Therefore, on the basis of summarizing the molecular mechanisms of obesity affecting hypertension and hyperlipidemia, this paper summarizes the relevant molecular mechanisms of hypertension and hyperlipidemia under the influence of obesity, and points out the co-acting molecules, providing a reference for future research on cardiovascular and cerebrovascular diseases.

Objective:To summarize the clinical characteristics of SYNGAP1-related epilepsy in children.Methods:Data of 13 patients with SYNGAP1 gene variants diagnosed with epilepsy at Department of Neurology, Beijing Children's Hospital were collected retrospectively from March 2017 to October 2020 and the patients were followed up. The clinical features, electroencephalogram(EEG), brain imaging, gene results and treatment were summarized.Results:Twelve patients were followed up successfully among the 13 patients with SYNGAP1 variants. The last follow-up age was 5 years and 7 months (3 years and 1 month to 9 years).The onset age of seizures was 2 years (4 months to 3 years). Seizure types included eyelid myoclonia with or without absence (9 cases), myoclonic seizure (5 cases), atypical absence (4 cases), suspicious atonic seizures(4 cases),unclassified fall attack (6 cases), and the frequency of seizures varied from several times to more than 100 times per day. Four cases had the mimic phenotype of myoclonic astatic epilepsy. The seizures of 10 cases could be triggered by eating (5 cases), emotion (5 cases), fever (3 cases), voice (2 cases), fatigue (2 cases), etc. Electroencephalography (10 cases) showed interictal generalized or focal epileptiform discharges (9 cases), and atypical aphasia (4 cases), myoclonic seizure (2 cases) and eyelid myoclonic seizure (1 case) were monitored. Of the 12 cases, 9 were added with valproate, all of which were effective (the frequency of seizures reduced>50%). Five cases received combined levetiracetam, in 3 the treatments were effective. To last follow-up, 3 cases were seizure free from 6 months to 1 year and 1 month, but the remaining 7 cases still had seizures, one or several times per day. All 13 cases had developmental retardation (speech ability impaired mostly), 2 cases were severe, 10 cases were moderate, 1 case was mild. The SYNGAP1 gene variants of 13 patients were all de novo, including 12 variants. Among them, 4 were frameshift variants, 4 were nonsense variants, 2 were missense variants and 2 were splice site variants.Conclusions:Patients with SYNGAP1-related epilepsy have an early onset age and many seizure types. The main seizure type is eyelid myoclonia with or without absence, and other seizure types include myoclonic seizure, atypical absence, unclassified fall attack, etc. Valproate is effective in most patients, but seizures in some patients might be intractable. Most patients have developmental delay (mainly moderate and severe), speech ability impaired mostly.

Objective:To investigate the clinical and laboratory characteristics of subacute sclerosing panencephalitis (SSPE).Methods:The clinical, laboratory and electroencephalogram (EEG) data of eight patients with SSPE who admitted to the Department of Neurology, Beijing Children's Hospital, Capital Medical University, from May 2014 to February 2019 were retrospectively analyzed and followed up.Results:Four of the patients were male and four were female, who aged from two years and seven months to 13 years and five months with a median onset age of five years and six months. All of the eight cases had disease onset with progressive mental and physical regression, then developed periodic myoclonic seizures at the course of 11 days to 11 months. Video EEG examinations showed persistent generalized periodic complex waves with long interval (3-20 s). The IgG titers of measles virus in blood and cerebrospinal fluid of all cases were significantly increased. There was no significant abnormality in blood/urine metabolism screening nor head magnetic resonance imaging for the first time. Five cases performed head magnetic resonance imaging again, in which two cases with deepening hemispheric sulcus, two cases with cerebral white matter signal abnormalities. Antiepileptic drugs, gamma globulin, adrenocortical hormone and antiviral drugs were used after diagnosis though all were ineffective. All patients presented progressive deterioration. During the follow-up period of three months to two years and seven months, four patients died, of which three patients died at the time of five months, one year and two months, two years and six months after onset respectively, and the other one was unknown.Conclusions:The diagnostic clues of SSPE are progressive mental and physical regression, recurrent myoclonic seizures during period Ⅱ, as well as the extensive periodic complex waves of EEG. It is necessary to detect measles virus IgG antibody in blood and cerebrospinal fluid to make a definite diagnosis. There is no specific treatment for SSPE and its prognosis is very poor.

Objective: To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. Methods: The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children′s Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively. Results: Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively. Conclusions SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.

OBJECTIVETo explore the application value of next generation sequencing (NGS) in the diagnosis of mitochondrial disorders.

METHODAccording to mitochondrial disease criteria, genomic DNA was extracted using standard procedure from peripheral venous blood of patients with suspected mitochondrial disease collected from neurological department of Beijing Children's Hospital Affiliated to Capital Medical University between October 2012 and February 2014. Targeted NGS to capture and sequence the entire mtDNA and exons of the 1 000 nuclear genes related to mitochondrial structure and function. Clinical data were collected from patients diagnosed at a molecular level, then clinical features and the relationship between genotype and phenotype were analyzed.

RESULTMutation was detected in 21 of 70 patients with suspected mitochondrial disease, in whom 10 harbored mtDNA mutation, while 11 nuclear DNA (nDNA) mutation. In 21 patients, 1 was diagnosed congenital myasthenic syndrome with episodic apnea due to CHAT gene p.I187T homozygous mutation, and 20 were diagnosed mitochondrial disease, in which 10 were Leigh syndrome, 4 were mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome, 3 were Leber hereditary optic neuropathy (LHON) and LHON plus, 2 were mitochondrial DNA depletion syndrome and 1 was unknown. All the mtDNA mutations were point mutations, which contained A3243G, G3460A, G11778A, T14484C, T14502C and T14487C. Ten mitochondrial disease patients harbored homozygous or compound heterozygous mutations in 5 genes previously shown to cause disease: SURF1, PDHA1, NDUFV1, SUCLA2 and SUCLG1, which had 14 mutations, and 7 of the 14 mutations have not been reported.

CONCLUSIONNGS has a certain application value in the diagnosis of mitochondrial diseases, especially in Leigh syndrome atypical mitochondrial syndrome and rare mitochondrial disorders.

Child ; DNA, Mitochondrial ; genetics ; High-Throughput Nucleotide Sequencing ; Homozygote ; Humans ; Leigh Disease ; Mitochondrial Diseases ; diagnosis ; Mitochondrial Encephalomyopathies ; Mutation ; Optic Atrophy, Hereditary, Leber ; Phenotype ; Point Mutation ; Sequence Analysis, DNA

OBJECTIVE: To observe the pathological changes of major organs in rats with acute Dysosma versipellis poisoning and investigate the toxic mechanism and the injuries of target tissues and organs. METHODS: Forty Sprague-Dawley (SD) rats were randomly divided into three experimental groups, which were given the gavage with 0.5, 1.0 and 2.0 LDo doses of Dysosma versipellis decoction, and one control group, which was given the gavage with 1.0 LD0 dose of normal saline. The rats were sacrificed 14 days after Dysosma versipellis poisoning and samples including brain, heart, liver, lung, and kidney were taken. After pathological process, the pathological changes of the major organs and tissues were observed by light microscope and electron microscope. The experimental data were statistical analyzed by chi2 test. RESULTS: The observations of light microscopy: loose cytoplasm of neurons with loss of most Nissl bodies; swelling of myocardial cells with disappearance of intercalated disk and striations; hepatocellular edema with ballooning degeneration; and swelling epithelial cells of renal proximal convoluted tubule with red light coloring protein-like substances in the tube. The observations of electron microscopy: the structures of cell membrane and nuclear membrane of neurons were destroyed; cytoplasm of neurons, obvious edema; and most organelles, destroyed and disappeared. The mortalities of rats after acute poisoning of the four groups increased with doses (P < 0.05). CONCLUSION Acute Dysosma versipellis poisoning can cause multi-organ pathological changes. There is a positive correlation between the toxic effect and the dosage. The target tissues and organs are brain (neurons), heart, liver and kidney.
Animals ; Berberidaceae/poisoning* ; Brain/pathology* ; Dose-Response Relationship, Drug ; Female ; Kidney/pathology* ; Liver/pathology* ; Male ; Microscopy, Electron, Transmission ; Myocardium/pathology* ; Neurons/pathology* ; Plant Extracts/poisoning* ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effects of bushen tongmai recipe (BSTMR) on mRNA and protein expressions of phosphatidylinositol-3-kinase (PI-3K) p85alpha in hepatic, adipose, muscular and ovarian tissues in PCOS rats with insulin resistance (IR).

METHODTwenty-three-day-old female SD rats were injected subcutaneously with sodium prasterone sulfate (90 mg x kg(-1) x d(-1)) for 20 days, and fed with high-fat forage for 80 days to induce PCOS rats with IR Then the rats were randomly divided into the model group and the treated group. Meanwhile, a group of fifteen rats of the same age was considered as the normal control group. The treated group were administered with BSTMR. The ovulation condition was examined by hematoxylin-eosin (HE) staining. Fasting blood glucose (FBG) was determined using glucose oxidase method. Serum fasting insulin (Fins) was determined by radioimmunoassay (RIA). The mRNA level of PI-3K p85alpha was measured by reverse transcription polymerase chain reaction(RT-PCR). Immunohistochemistry staining was wtilised to detect protein expression of PI-3K p85alpha in ovary.

RESULTCompared with the model group, the mean number of corpus luteum and the rate of ovulation in the treated group increased significantly (P <0. 01). The level of Fins in the treated group was much lower than that in the model group (P < 0.01). Both mRNA and protein expressions of PI-3K p85alpha in target tissues were up-regulated significantly in the treated group (P < 0.01 or P < 0.05).

CONCLUSIONBSTMR could improve IR and ovulation dysfunction in PCOS rats accompanying with IR and its molecular mechanisms might be closely related with the elevation of mRNA and protein levels of PI-3K p85alpha in target tissues of the model rats.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Gene Expression ; drug effects ; Humans ; Insulin Resistance ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Polycystic Ovary Syndrome ; drug therapy ; enzymology ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo estimate the clinical effect of the maltitol chewing gums in plaque control.

METHODSThirty 13-15 years old susceptible adolescent were divided into three groups randomly, group A (maltitol chewing gums), group B (xylitol chewing gums) and group C (gum base chewing gums). Subjects chewed gums 5 times each day, 10 min each time. At baseline and at 4-week, subjects were evaluated for supragingival plaque. SPSS 17.0 software package was used for statistical analysis.

RESULTSFour weeks later, plaque index of the three groups continuously step down. Significant difference was observed between baseline and 4-week (P = 0.000, 0.000, 0.006). Four weeks later, there was statistically significant difference in clearance rate of plaque among the three groups (P = 0.015). There was still no statistically significant difference between group A and group B (P = 0.687), but they were both different from C group(P = 0.019, 0.007).

CONCLUSIONMaltitol chewing gum can lead to similar effect on reduction of plaque as xylitol chewing gum.

Adolescent ; Chewing Gum ; Dental Plaque ; Dental Plaque Index ; Humans ; Hydrogen-Ion Concentration ; Maltose ; analogs & derivatives ; Sugar Alcohols ; Xylitol

Progesterone has nongenomic effects on inducible nitric oxide synthase(iNOS),which is mediated by mitogen activated protein kinase(MAPK)pathways.This effect is supposed to have some potential association with asymptomatic gonococcal infections in women by immunological depression.In this study,polymorphonuclear leukocytes(PMNs)challenged by gonococci were used to study the nongenomic effects of progesterone.The activation of iNOS was assessed by measuring[3H]L-arginine converses to[3H]L-citruiline,and the activity of MAPK was detected by Western blot.It was found that the activity of iNOS and the yields of NO were enhanced significantly in gonococci-challenged PMNs compared with the controls(P<0.01).Progesterone could repress the activation of iNOS through P38MAPK pathway within PMNs(P<0.05),which could be blocked by SB203580(P<0.01),but not by actinomycin D(P>0.05).It was also found subsequently that in the serum specimens collected from gonococci-infected but asymptomatic women,the progesterone level was higher than that in women with severe symptoms(P<0.01).Moreover,the yield of NO had an inverse correlation with progester-one.With these results it suggested that the rapid nongenomic effects of progesterone may inhibit iNOS activation and NO yields mediated by P38MAPK pathways,which were supposed to be concerned with asymptomatic women infected with gonococci.

OBJECTIVETo investigate the effect of astragalus (As) on calcium accumulation and SERCA2a gene expression in left ventricular tissues in rats with pressure overload-induced cardiac hypertrophy.

METHODcardiac hypertrophy was induced by clipping the abdominal aorta in rats. Male SD rats were allocated to six groups: sham-operrated (Sham), aortic stenosis (Model), model +As-L (5 g x kg(-1) x d(-1)), model+As-M (10 g x kg(-1) x d(-1)), model+As-H (20 g x kg(-1) x d(-1)) and model + captopril (0.05 mg x kg(-1) x d(-1), a positive control). The drugs were administered orally from the 13 th week after surgery. Rats were examined after 12 week treatment with drugs. The cardiac hypertrophy was evaluated by left ventricular mass index (LVMI, left ventricular weight/ body weight). The calcium content in left ventricular tissue was measured by atomic absorption spectrometry. SERCA2a mRNA and protein expressions in left ventricular tissues were determined by half-quantitative RT-PCR and Western blot normalized to abundance of GAPDH mRNA and protein, respectively.

RESULTThe increase of LVMI was dose-dependently lessened by As (P < 0.01, P < 0.001). The effect of As-H was similar to that of Captopril. As markedly attenuated calcium accumulation in myocardial tissure (P < 0.01). RT-PCR and Western blot results demonstrated that SERCA2a gene expressions were downregulated (P < 0.05) significantly in model group compared with sham group. As-H upregulated SERCA2a gene expressions (P < 0.05), whereas Captopril had no effect on that.

CONCLUSIONThe inhibition of As on left ventricular hypertrophy induced by pressure overload in rats may partly contribute to its attenuation of calcium accumulation and up-regulation of SERCA2a gene expressions in left ventricular tissues.

Animals ; Astragalus Plant ; chemistry ; Blotting, Western ; Calcium ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gene Expression Regulation ; drug effects ; Heart ; drug effects ; Hypertrophy, Left Ventricular ; metabolism ; physiopathology ; Male ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; genetics ; metabolism