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Objective:To analyse the clinical presentation and pathogenic gene mutations of a family diagnosed with primary familial brain calcification (PFBC).Methods:A pedigree with primary familial brain calcification was recruited. The clinical data of the proband who was admitted to the Affiliated Hospital of Guizhou Medical University in March 2020 and the family members were collected. The DNA sequence of myogenesis regulating glycosidase (MYORG) gene was detected by Sanger sequencing in the proband and some available family members.Results:The proband is a male, 30 years old. There was only one patient of PFBC in this family. The first symptom of the proband was vagueness of speech, and gradually extrapyramidal symptoms such as slow and flexible movement and advanced cognitive impairment appeared. The brain CT of the proband and his second brother showed extensive symmetrical calcifications, mainly located in the bilateral cerebellar hemispheres, basal ganglia and thalamus. A homozygous mutation in the exon 2 of the MYORG gene [c.1967T>C(p.I656T)] was identified in the proband and an asymptomatic patient. The heterozygous mutation of MYORG gene was also detected in four healthy family members.Conclusions:All patients with homozygous mutations of MYORG gene showed calcification in CT scan, and most of the lesions were located in basal ganglia, cerebellum, subcortical white matter and thalamus. Compared with the patients with autosomal dominant gene mutation, the patients with MYORG gene mutation had more extensive intracranial calcification lesions, and the pontocerebellar lesions were more common. The most common symptoms of MYORG gene mutation patients were dyskinesia, mainly tremor paralysis and unclear speech.
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Objective: Chrysophanol (Chry) displays potent anticancer activity in human cancer cells and animal models, but the cellular targets of Chry have not been fully defined. Herein, we speculated whether mitochondria were a target involved in Chry-induced cytotoxicity. Methods: Human liver cancer cell line HepG2 was incubated. The cytotoxicity was evaluated by MTT assay. Mitochondria localization was evaluated by a confocal microscopy. Mitochondrial membrane potential ΔΨm was detected by TMRE staining and determined by the flow cytometer. The levels of ATP, mitochondrial superoxide anions, and GSH/GSSG were determined according to the assay kits. The apoptosis were evaluated through Hoechst33342/PI and Annexin V/PI staining, respectively. The expression of cyclophilin D (CyPD) was determined by immunoblot method, and the interaction between CyPD and Chry was analyzed by molecule docking procedure. Results: Chry itself mainly localized in mitochondria to cause mitochondrial dysfunction and cell death in HepG2 cells. As regard to the mechanism, cyclosporin A as the inhibitor for the formation of mitochondrial permeability transition pore (mPTP) moderately suppressed cell death, indicating mPTP involved in the process of cell death. Further, Chry enhanced the protein expression of Cyclophilin D (CyPD) which is a molecular componentry and a modulator of mPTP, while antioxidant N-acetyl-L-cysteine inhibited the expression of CyPD. Molecule docking procedure disclosed two hydrogen-bonds existed in CyPD-Chry complex with −11.94 kal/mol of the binding affinity value. Besides, the mtDNA-deficient HepG
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Objective@#To evaluate the feasibility of hepatitis C virus (HCV) infection by survey methods based on big data of hospital.@*Methods@#Inpatients data of anti-HCV was collected in 2016 and 2011. Patient’s data related to Department of Liver Diseases were excluded. The research population was divided into Surgical and Non-surgical Department. The characteristics of the two groups were analyzed and the changing trends of anti -HCV positive rate in different years was compared and analyzed.@*Results@#Patients in the surgical and non-surgical department of hospital were equally distributed across gender, urban and rural areas, and region, but the distribution of patients in surgical departments were relatively equal in all age groups. The positive rate of anti -HCV in hospitalized patients in 2016 was 0.82%, and anti -HCV positive rate was 0.58% in surgical department of 1~55 years old. Among them, anti-HCV was positive in 0.06% who underwent surgical procedure at the age of ≤25 (born after 1993 and screened for hepatitis C antibody), which was significantly lower than those in other age groups were. The anti -HCV positive rate of patients (all age groups) was lower in 2016 than that in 2011(0.75% vs. 0.97%). The anti-HCV positive rates of surgical department in both years had a decreasing trend with age.@*Conclusion@#The prevalence rate of anti-HCV, among patients population of operation departments, might reflect the prevalence rate of HCV infection among general population. Using the convenience of hospital data acquisition, we might dynamically understand the change of HCV infection.
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Objective To investigate the association between the level of polymorphism of APOE gene and cognitive impairment in patients with CNS demyelinating diseases. Methods 56 patients with central nervous system demyelinating disease were applied APOE genotyping,MoCA and expanded disability status (EDSS) scale score. Patients with MOCA scores <26 were divided into cognitive impairment group, and those with MOCA scores ≥26 were divided into normal cognitive preserved group. Results The probability of cognitive dysfunction in patients with central nervous system demyelinating diseases was 53.57%. There was no significant difference in age, gender, and disease duration between the CI group and the CP group(P>0.05), the difference in age and education among groups is statistically significant (P<0.05). There was no statistical significance in the difference in age, sex, education years and EDSS score between APOEε4 gene positive group and APOEε4 gene negative group (P<0.05). The difference of visual space and attention between different cognitive domains is statistically significant(P<0.05). Years of schooling is a risk factor for cognitive dysfunction in patients with central nervous system demyelinating disease(P<0.01). Conclusion The central nervous system demyelinating disease is impaired cognitive function. Patients with APOEε4 gene positive are more severely impaired in visual space and attention than patients with negative APOEε4 gene.Years of education are the risk factors of cognitive dysfunction in patients with central nervous system demyelinating disease. The course of disease and disabled function may not be significant related to cognitive impairment.
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Objective To investigate the clinical significance of cortactin antibody in myasthenia gravis (MG).Methods Cortactin antibody in the serum of 100 MG patients, 40 normal controls and 40 other neuroimmune diseases patients was examined by Western blotting and ELISA using purified recombinant human protein cortactin as antigen .Acetylcholine receptor antibody ( AchR-ab ) and muscle specific kinase antibody (MuSK-ab) were parallely measured by ELISA.Results Antibodies to cortactin were found in nine (9％) serum samples of 100 MG patients.Four of the nine cortactin antibody positive sera were also positive for AChR-ab.The rest five MG patients only had antibodies against cortactin ( no detectable AChR-ab or MuSK-ab).None of the control subjects (including 40 normal controls and 40 other neuroimmune diseases patients ) had cortactin antibodies.Most (7/9) of the cortactin antibody positive MG patients presented with early-onset subgroup.Patients only with cortactin antibodies did not appear to have thymoma.Patients with MG who had both AChR and cortactin antibodies showed maximum involvement of muscles and severe Osserman's classification ( three cases of type ⅡB and one case of type Ⅳ) . Conclusion Cortactin antibody may be a new antibody for MG , which can provide clues for further exploring the potential pathogenic mechanisms of the disease .
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Objective To investigate the clinical characteristics of children with medulloblastoma (MB). Methods The correlations amongst MB histopathological subtype,age at diagnosis,gender,primary tumor locations, relapsed tumor and relapsed tumor locations were analyzed retrospectively in 83 children who were diagnosed as MB by histopathology subtypes from February 2012 to April 2015 in Beijing Shijitan Hospital Affiliated to Capital Medical Uni-versity.The data was conducted by using SPSS 22.0 statistical software.Results Among the 83 cases (53 boys and 30 girls),there were 14 patients younger than 3 years old (9 boys and 5 girls)and 69 patients (44 boys and 25 girls)ol-der than 3 years old,including 28 relapsed (19 boys and 9 girls)and 55 non -relapsed cases (34 boys and 21 girls). The median age was 80.2 (13.1 -184.7)months at diagnosis.Of these 83 cases,48.2% (40 /83 cases)was classic medulloblastoma (CMB)(2 cases less than 3 years old),24.1 % (20 /83 cases)was desmoplastic /nodular medullo-blastoma (DMB)(6 cases less than 3 years old),12.1 % (10 /83 cases)was large cell/anaplastic medulloblastoma (LC /AMB)(1 case less than 3 years old),3.6% (3 /83 cases)was extensive nodular medulloblastoma (MBEN)(1 case less than 3 years old),and 12.1 % (10 /83 cases)(3 cases less than 3 years old)was mixed subtype.The rela-tionships between age at diagnosis and histopathological subtype,gender and primary tumor location were all statistically significant (χ2 =0.014,0.013,all P <0.05).Conclusions The incidence of boys with MB is higher than girls.CMB is the main histopathologic subtype in children over 3 years old.The primary tumor location involving the cerebellar vermis or cerebellar vermis and the fourth ventricle is higher in girls with MB.The primary tumor location involving the fourth ventricle,the fourth ventricle and other parts of the central nervous system,Cerebellar vermis and other parts of the central nervous system or other parts of the central nervous system is higher in boys with MB.
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In order to develop agents with superior chemopreventive and chemotherapeutic properties against hepatocellular carcinomas, mitochondria-targeted hydroxycinnamic acids (MitoHCAs) were synthesized by conjugation with a triphenylphosphonium cation. These synthetic compounds were evaluated for their antioxidant activities in hepatic mitochondria, including against OHand ROOinduced lipid peroxidation. HOproduction was decreased significantly by increasing glutathione peroxidase and catalase activities. In addition, cell proliferation data from three cell lines (HepG2, L02 and WI38) indicated that the MitoHCAs were selective for cancer cells. Interestingly, the MitoHCAs both with or without Catriggered mitochondrial dysfunction by inducing mitochondrial swelling, collapsing the mitochondrial membrane potential and causing cytochromerelease. In particular, an inhibitor of the mitochondrial permeability transition pore (mPTP), cyclosporin A, attenuated mitochondrial damage and cell apoptosis, indicating that mPTP may be involved in the antiproliferative activity of MitoHCAs. Further studies focused on structural optimization of these compounds are onging.
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Complexes containing cobalt and carbon monoxide ligands, CO releasing molecules (CORMs), have the potential of anti-tumor and anti-inflammatory. In this paper, three hybrid CORMs 1-3 were synthesized and tested for their toxicology in vivo and bioactivities. The results suggest that the complexes have a long half-life in the range of 43-53 min; their oral LD50 to mouse are between 1 500 mg·kg-1 and 5 000 mg·kg-1. After the successive administration, complex 1 exhibited a toxic activity in rats' liver, and induced an injury to liver cells. Complex 1 had a strong growth inhibition activity (IC50 36.20 μmol·L-1 and 39.25 μmol·L-1) in both HeLa cells and HepG2 cells, complex 2 displayed a lower activity in the inhibition of HeLa cells proliferation than the control 5-FU (IC50 114.19 μmol·L-1), but had a higher activity in the inhibition of HepG2 cells than the control 5-FU (IC50 171.34 μmol·L-1). The anti-inflammatory study suggests that all of them reduce intracellular nitrite level, complexes 1 and 2 have a stronger activity than complex 3. Their anti-inflammatory activity attributes to the CO molecules of the CORMs, which was confirmed by comparison with the corresponding ligand.
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Objective To investigate the factors affecting the vaginal birth after cesarean (VBAC). Methods Totaly 298 women who underwent trial of labor after cesarean section (TOLAC) from Jan 2015 to Dec 2015 were recruited from Beijing Obstetrics and Gynecology Hospital, FuXing Hospital, Tongzhou Maternal and Child Health Hospital of Beijing, the Second Affiliated Hospital of Chongqing Medical University and the People′s Hospital of Chengyang District of Qingdao. The maternal age, the interval from the last cesarean section, the body mass index (BMI) before pregnancy, the weight gain during pregnancy, the way into labor, the Bishop score before labor, the gestational age and the birth weight of the neonate were recorded in a self-made form. The factors affecting VBAC were analyzed by univariate analysis and multivariable logistic regression. Results (1)The incidence of VBAC, uterine rupture, postpartum hemorrhage and neonatal asphyxia were 70.5%(210/298), 2.7%(8/298), 9.4% (28/298) and 1.3% (4/298), respectively. No maternal death and perinatal death occurred. (2)The univariate analysis suggested that the maternal age, the BMI before pregnancy, the Bishop score before labor, the labor induction, the gestational age at delivery and the neonatal weight were factors affecting VBAC. The maternal age and the Bishop score before labor were significantly higher in the VBAC group than in the unsuccessful TOLAC group(P<0.05). While the BMI before pregnancy, the induction rate, the gestational weeks at delivery and the birth weight of the neonate were significantly lower in the VBAC group than in the unsuccessful TOLAC group (P<0.05). Multivariable logistic regression analysis showed that successful VBAC was affected by the maternal age, the BMI before pregnancy, the Bishop score before labor and the birth weight of the neonates(P<0.05). Conclusion The maternal age, the BMI before pregnancy, the Bishop score before labor and the birth weight of neonate are the main factors affecting VBAC.
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A series of 4-(2-acetoxybenzoylamino) butyrate derivatives were designed and synthesized. All of the novel 12 compounds (7a-7k) were synthesized from gamma-aminobutyric acid (1) as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that most of these title compounds possessed antiepileptic activity. Compounds 7i-7k displayed strong antiepileptic activity and are worth for further development. Compounds 4, 7d-7h showed moderate antiepileptic activity. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyrate derivatives is also discussed preliminarily.
Subject(s)
Animals , Female , Male , Mice , 4-Aminopyridine , Anticonvulsants , Chemistry , Therapeutic Uses , Butyrates , Chemistry , Therapeutic Uses , Drug Design , Epilepsy , Drug Therapy , Lethal Dose 50 , Molecular Structure , Random Allocation , Structure-Activity Relationship , gamma-Aminobutyric Acid , ChemistryABSTRACT
A series of 4-(2-acetoxybenzoylamino) butyrate derivatives were designed and synthesized. All of the novel 12 compounds (7a-7k) were synthesized from gamma-aminobutyric acid (1) as starting material, and their structures were confirmed with IR, 1H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that most of these title compounds possessed antiepileptic activity. Compounds 7i-7k displayed strong antiepileptic activity and are worth for further development. Compounds 4, 7d-7h showed moderate antiepileptic activity. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyrate derivatives is also discussed preliminarily.
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Aim To establish an ideal hyperlipidemia animal model by a new way.Methods 30 mice were randomly divided into control group, positive control group and model group.The mice of control group were only fed with a standard diet.Those of positive control group were fed with high fat diet.Those of model group were fed with a standard diet and enough milk.After 30 days the TG, TC, HDL-C and LDL-C of serum and hepatic and LI were detected and pathological changes in the liver of mice were observed microscopically.Results Compared with the control group, the mice of model group developed hyperlipidemia with LI and the serum and the hepatic TG, TC, LDL-C elevated significantly, while HDL-C were significantly lower.The histopathological research showed hepatocellular macrovesicular steatosis and hepatitis in the model group.Conclusion An ideal model of hyperlipidemia is successfully established with standard diet and milk fed to mice for 30 days.
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Objective To explore the mutation and evolution of Yersiniapestis(Y. pestis) from the point of codon and 16S-ribosome. Methods Codon preference and 16S-ribosome of Y. pestis were analyzed by bioinformatics. Results Similar codon preference was found among 4 PCD1 Y. pestis, of the 3 old Y. pestis the codon preference between PMT1 and PCD1 was similar. There were some differences between PCD1, PCP1 and Yunnan 6 kb plasmid. Through the analysis of 16S-ribosome, the sequences were found similar in 11 strains of Y. pestis,Yersinia pseudotuberculosis was very close to Y. pestis, with only one nucleotide difference, mutated G-T, and corresponding amino acid methionine (M)-isoleucine (I). There were some differences in sequences of 16S-ribosome in Y. pestis, Escherichia coli and Pulex irritans. Conclusions The time for Y. pestis to obtain PCP1 is later than PMT1 does, in other words, the affinity of Y. pestis with PMT1 was closer than PCP1 with 6 kb plasmid;alteration of 16S-ribosomal nucleotide sites may cause changes in function and structure of 16S rRNA. The lower similarity between 16S-ribosomal sequences of Y. pestis and Pulex irritans indicates the time for co-evolution is very short,and the late emergence of Y. pestis.
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<p><b>OBJECTIVE</b>To study the genetic characterizations of VP1 region of Human enterovirus 71 (HEV71) isolated from clinical specimens of hand, foot and mouth disease (HFMD) patients in Beijing in 2008.</p><p><b>METHODS</b>285 clinical samples were collected from HFMD patients in hospitals and day-care centers in Chaoyang district. They were performed by reverse transcription-polymerase chain reaction (RT-PCR) specific for HEV71. 10 HEV71 isolates were selected for entire VP1 coding gene amplification and sequencing.</p><p><b>RESULTS</b>129 samples were RT-PCR positive, the positive rate is 45.26%. The homology of the nucleotide and the amino acid of the 10 strains were 94.6%-99.6% and 95.9%-100%. The phylogenetic tree revealed that 10 Beijing strains clustered within the C4a evolution branch of C4 subgenotype.</p><p><b>CONCLUSIONS</b>RT-PCR played an important role in identifying HFMD outbreak in Beijing in 2008. The HEV71 strains were all belong to C4a evolution branch of C4 subgenotype with several transmission chains, and it showed that C4 subgenotype HEV71 spread in mainland China widely after 1998. The molecular epidemiology surveillance and the research of genetic characterizations of HEV71 should be strengthened in mainland China.</p>