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Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.
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Objective To analyze the susceptibility of serotonin promoter single nucleotide polymorphism (SNP)rs956304 to chemotherapy-induced nausea and vomiting(CINV)in colorectal cancer.Methods Rs956304 genotypes and the clinical pathological data of 166 patients with colorectal cancer from September 2009 to April 2014 were retrospectively analyzed. Rs956304 genotype was analyzed by sequencing. The correlations between rs956304 genotype,factors of clinical pathology and CINV were analyzed by chi-square test. Unconditional logistic regression model was used to analyze the independent effect of rs956304 genotype on colorectal cancer CINV. Results Chi-square test showed that moderate to severe CINV was associated with rs956304 AG+GG genotype (P=0.011). Unconditional logistic regression model showed that the patients with AG+GG genotype had a signifi-cant higher risk of moderate to severe CINV than AA genotype(OR=3.215,95% CI:1.202 to 8.599,P=0.020). Conclusion Rs956304 AG+GG genotype is an independent risk factor for moderate to severe colorectal cancer CINV.
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<p><b>OBJECTIVE</b>To examine the association between the genotype (LL, LS and SS) of serotonin transporter promoter gene polymorphism(5-HTTLPR) and clinicopathological factors, and to investigate the effect of 5-HTTLPR on the prognosis of colorectal cancer patients.</p><p><b>METHODS</b>Data of peripheral blood samples of 161 colorectal cancer patients at the Second Affiliated Hospital of Guangzhou Medical University from October 2009 to January 2014 were collected retrospectively. The genotyping of 5-HTTLPR was determined by PCR and agarose gel electrophoresis. Coincidence Chi-square test was used to examine the 5-HTTLPR genotype with Hardy-Weinberg law. Chi-square test and Cox multifactor model were used to analyze the association of 5-HTTLPR genotype with clinicopathology and prognosis. All the patients were informed and agreed to participate in the study. This study was approved by the Hospital Ethics Committee (2015056).</p><p><b>RESULTS</b>Of 161 colorectal cancer patients, 89 were male and 72 were female; the median age was 64 (25-85) years; 86 (53.5%) cases were colon cancer and 75 (46.5%) were rectal cancer. Genotype was LL in 12 cases, LS in 59 cases and SS in 90 cases, which complied with the law of Hardy-Weinberg genetic balance (χ²=0.288, P=0.592). Univariate analysis showed that 5-HTTLPR gene polymorphism was only associated with lymph node metastasis [lymph node metastasis rate: LL and LS genotype 21.1% (15/71);SS genotype 40.0% (36/90), χ²= 6.532, P=0.011]. The 3-year and 5-year overall survival rates of whole patients were 71% and 63% respectively. Multivariate analysis revealed that the SS genotype was an independent risk factor affecting the overall survival of colorectal cancer patients(HR=1.933, 95%CI:1.090-3.428, P=0.024).</p><p><b>CONCLUSION</b>Among genotypes of 5-HTTLPR gene, colorectal cancer patients with SS genotype have higher risk of lymph node metastasis and poorer prognosis.</p>
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Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Colorretais , Genética , Patologia , Genótipo , Polimorfismo Genético , Prognóstico , Estudos Retrospectivos , Proteínas da Membrana Plasmática de Transporte de Serotonina , GenéticaRESUMO
Objective To determinate the effects of sodium tanshinone ⅡA sulfonate(STS)on cardiomyocyte hypertrophy and explore the relative effects of STS on mitogen-activated protein kinase signal transduction system in rats with cardiomyocyte hypertrophy through constricting the thoracic aorta.Methods The models of cardiomyocyte hypertrophy were established in vivo,and the thoracic aorta was partially tied between the right innominate and the left common carotid arteries.The rats were randomly divided into 6 groups(n=8/group)as follows:①sham,②transverse aortic constriction(TAC),③TAC+low-dose Tan(TAC+LT)(5 mg/kg),④TAC+middle-dose Tan(TAC+MT)(10 mg/kg),⑤TAC+high-dose Tan(TAC+HT)(20 mg/kg),and ⑥ TAC+Val(10 mg/kg).After treatment for 8 weeks,echocardiography was performed to observe the changes in hypertrophy and heart function,and heart samples were cut into transverse sections and stained with hematoxylin and eosin(H&E).The MAPKs protein expression in the cardiomyocytes was detected by Western blot.Results The heart weight index(HWI),left ventricular mass index(LVMI)and cross-sectional diameter of cardiomyocytes(CD),left ventricular posterior wall thickness(LVWT),and interventricular septal thickness(IVS)were significantly increased in TAC group as compared with sham group.The relative parameters in STS groups and Val group were reduced as compared with those in TAC group.Western blot analysis revealed the p-ERK and p-p38 expression was significantly decreased in TAC group as compared with sham group(P＜0.01).The p-ERK expression was significantly decreased in STS groups and Val group as compared with TAC group(P＜0.05).The TAC+HT group,TAC+MT group and Val group had significantly higher p-p38 expression than TAC group(P＜0.05).Conclusion Tanshinone ⅡA could regulate the expression of protein in MAPK pathway to exert its inhibitory effects on hypertrophy of cardiomyocytes.
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Objective To examine the expression and the significance of mdr 1 mRNA in guinea pig cochlea lateral wall at different developmental stages.Methods Thirty white guinea pigs with red eye including three developmental stages were used in this study. The expression of mdr 1mRNA in the cochlear lateral wall was measured in situ hybridization and analyzed by the softeware of MPLAS-500.Results mdr 1mRNA was detected mainly in the endothelial cells.The expression intensity of mdr 1mRNA was different in guinea pig cochlea lateral wall at different developmental stages, mdr 1mRNA in 1～2 weeks group was significantly lower than that of 3-week-group and 4-week-group(P0.05).Conclusion mdr 1mRNA is found in the normal cochlea lateral wall cells. The expression intensity is different with the development of guinea pig cochlea lateral wall.
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Objective To study the relationship between the expression of MDR 1 gene in cochlea lateral wall and the accumulation of adriamycin in endolymph of guinea pig.Methods Twenty four white guinea pigs with red eyes were randomly chosen,and administered an intravenous injection of 30 mg/kg adriamycin or N.S.The animals were sacrificed 24 hours later,the cochlea lateral wall was then immediately removed after the endolymph was drawn by the siphon from the basal turn of cochlea. The expression of the MDR 1 mRNA in cochlea lateral wall of guinea pigs were observed by RT-PCR.The ADM concentration in endolymph was measured by high performance liquid chromatography.Results The accumulation of adriamycin in endolymph negatively correlated with the expression of MDR 1 gene in cochlea lateral wall(r s=-0.901, P
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Objective To create a method to assay adriamycin in endolymph of guinea pig cochlea,and provide methodology background to study the accumulation of ototoxicity substance in inner ear.Methods 12 normal guinea pig were killed quickly after 24 hours following adriamycin injection.The concentrate of adriamycin in endolymph of guinea pig cochlea was assayed by high performance liquid chromatography(HPLC).Results The linear relation of concentration of adriamycin in endolymph was well when the concentration was from 2.56 ng/mL to 1398.00 ng/mL.Correlation coefficient of linearity was 0.999 (n=10).The percentage of retrieve for adriamycin in endolymph was 96.3%.Relative standard deviation (RSD) was 2.61%.The lowest limitation was 1.9 ng/ml .Conclusion The sensibility of HPLC is high,and it can accurately detect the concentration of adriamycin in endolymph of guinea pig cochlea,especially the adriamycin is administrated in vein.