Familial hypercholesterolemia (FH) is an autosomal dominant hypercholesterolemia caused by mutation in the low density lipoprotein receptor gene (LDLR). The identification of the causative mutation provides definitive diagnosis so that the patient can be treated, their relatives tested and, therefore, premature heart disease prevented.
Methods
DNA of the proband with clinically diagnosed FH and other three familial members were analysed using polymerase chain reaction (PCR) and DNA direct sequencing for the LDLR gene (promoter region, the translated exon sequences, and the exon-intron boundaries), the apolipoprotein B-100 gene (APOB) (part exon 26). TA cloning was performed to confirm the deletion mutations of the exon 11 of LDLR of the proband. Splice site prediction tools were used to predict the effect of a genetic variant on splicing. In addition unaffected random controls (n = 100) were screened the deleltion mutations (c. 1587_1588delCT and c. 1587-2_1587-4delCCA) of LDLR using PCR and sequencing.
Results
In this Chinese family, two heterozygous novel mutation (c. 1587_1588delCT and c. 1587-2_1588-4delCCA) of the LDLR were found in the proband and his mother, but no deletion mutations were detected in his father and his sister. The two-bases deletion of CT (1587_1588del2) at exon 11 is a frameshift mutation which predicted to be pathogenic. The functional effect of another novel mutation at intron 10 (c. 1587-2_1588-4delCCA) are predicted as benign by splice site prediction tools.
Conclusions
Only mutation in exon 11 of LDLR gene (c. 1587_1588delCT) had been found to cause FH, which was novel, not described in other FH populations.
To explore the polymorphism angiotensin converting enzyme (ACE) in Han populations and its relevance to the severity of coronary atherosclerosis.The ACE genotype distribution was detected in 169 patients [aged (62.0 +/-9.9) years] with coronary artery disease (CAD) confirmed with angiography and in 168 normal controls [aged (61.0 +/-7.7) years]. The severity of coronary lesions in the patients was assessed by the number of major coronary arteries with more than 50% luminal obstructions and by the Gensini coronary score. Associations of the severity of coronary artery lesions with the ACE I/D polymorphism in the patients were analyzed.The frequencies of the ACE genotype in the CAD patients were 0.296 for DD, 0.391 for ID, and 0.314 for II genotypes, while in the normal controls the genotype distribution was in Hardy-Weinberg equilibrium (DD, 0.161; ID, 0.512; II, 0.327); a significantly excess of the DD genotype in CAD patients was found (P<0.01). No associations were observed between the ACE polymorphism and the number of significantly stenosed coronary arteries.The ACE gene polymorphism is a significant predictor for CAD in the Han population but is not a marker for the severity of coronary atherosclerosis.
Objective
To investigate the preventive and adverse effects of postnatal inhalation of Budesonide in early stage on bronchopulmonary dysplasia (BPD) in very low birth weight infants.
Methods
A total of 105 cases of high risk premature infants with BPD, who were born in the Neonatal Intensive Care Unit (NICU) from Shenzhen Maternity and Child Healthcare Hospital from July 15, 2015 to December 25, 2016, and their gestational age ≥27 weeks and < 32 weeks or birth weight ≥1 000 g and <1 500 g were collected for a prospective randomized controlled trial, and were randomly divided into 3 groups: early inhalation group(34 cases), late inhalation group(34 cases) and non-inhalation group(37 cases). The oxygen time, and the incidence of BPD, periventricular-intraventricular hemorrhage(IVH), retinopathy of prematurity (ROP), necrotizing enterocolitis of the newborns (NEC), patent ductus arteriosus in preterm infants (PDA), sepsis and hyperglycemia of infants in 3 groups were compared.
Results
The average oxygen time in early inhalation group was 9 days, while in late inhalation group and the non-inhalation group was 15 days and 18 days, respectively.The average oxygen time in early inhalation group was significantly lower than that in the late inhalation group and the non-inhalation group, with the difference being statistically significant (H=6.09, P 0.05).
Conclusions
Postnatal inhalation of Budesonide in early stage in high risk very low birth weight infants can reduce the incidence of BPD and the oxygen time, and the adverse reactions are not obvious.
Key words:
Infant, premature; Very low birth weight infant; Bronchopulmonary dysplasia; Glucocorticoid; Budesonide; Inhalation
To investigate the association of thrombospondin-1 (TSP- 1) gene A8831G (N700S) polymorphism with coronary artery disease (CAD).This study was conducted with a case-control design including 178 patients with CAD (55 AMI) and 158 healthy subjects. The TSP-1 N700S polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism analysis.No significant difference of the AG genotype in CAD group and control group (1.7% compared with 0.6%, P=0.375) was detected. None of the homozygotes was detected for the G allele. The prevalence of the G allele was not significantly different between CAD group and controls (0.8% compared with 0.3%, P=0.376). No significant difference of the AG genotype in AMI group and control group (3.6% compared with 0.6%, P=0.104). The prevalence of G allele was not significantly different between AMI patients and controls (1.8% compared with 0.3%, P=0.364).There are TSP-1 N700S polymorphisms in Chinese Zhejiang Han people, but the TSP-1 N700S variant shows a much lower prevalence compared with Western populations and may be not a potential risk for CAD and AMI.
Bacillus amyloliquefacien BS-3 is an endophytic bacterium isolated from the root tissue of a healthy rubber trees with strong antifungal activity against a variety of plant fungal diseases. In order to clone the antibacterial TasA gene of BS-3 and study its prokaryotic expression and antifungal activity. TasA gene was amplified from the genomic DNA of BS-3 by PCR method, the prokaryotic expression vectors pET28a/TasA and pCZN1/TasA were constructed and the fusion expression was obtained. The growth rate method was used to detect the antifungal properties of purified recombinant protein against various pathogens. The results showed that TasA gene contained a complete open reading frame of 483 bp, encoding 160 amino acids. 1-27 amino acids sequence that resembles signal peptides and 7-29 amino acids are transmembrane domains. The prokaryotic expression vectors pET28a-TasA and pCZN1-TasA were successfully constructed by removing the signal peptide and transmembrane domain of the TasA gene. The recombinant protein pET28a-BL21-TasA was expressed as an inclusion body at 37℃. Whereas the recombinant protein pCZN1-Arctic Express-TasA was successfully expressed in the supernatant at 15℃. The recombinant protein obtained from pCZN1-Arctic Express-TasA was purified and its antifungal activity was detected. It was found that the recombinant protein had inhibitory effects on Colletotrichosa acutatum, Alternaria heveae and Petrichospora microspora, with inhibitory rates of 99.38%, 66.17% and 30.88%, respectively. The TasA gene derived from BS-3 was the shortest reported with antifungal activity. The study broadens the understanding of the antifungal spectrum of the protein TasA of B. amyloliquefaciens, provides a theoretical basis for the application of protein TasA in plant disease control, and also provides a basis for the development and utilization of new antifungal proteins.
Objective
To investigate the efficacy and adverse effects of sustained lung inflation (SLI) combined with pulmonary surfactant (PS) in the treatment of neonatal respiratory distress syndrome (NRDS).
Methods
This prospective randomized controlled trial included 124 premature infants (gestational age <34 weeks and birth weight <2 000 g) diagnosed with NRDS and in need of PS treatment in Shenzhen Maternity & Child Healthcare Hospital affiliated to Southern Medical University from July 1, 2016 to October 31, 2018. They were randomly divided into experimental or control group, with 62 cases in each. Infants in the experimental group were treated with SLI using T-piece and intratracheal PS, while those in the control group were given PS only. Blood gas analysis and measurement of fraction of inspiration O2 (FiO2) and ratio of partial pressure of oxygen (PO2) over FiO2 were performed before and 1 h after PS injection. Results of the treatments and incidence of complications were compared. Paired samples t-test, two independent samples t-test, rank-sum test and Chi-square test were used for statistical analysis.
Results
There were 56 participants in the experimental group and 54 in the control group who were eventually analyzed. In the experimental group, the pH value, partial pressure of carbon dioxide (PCO2), FiO2 and PO2/FiO2 at 1 h after PS injection were all improved compared with those before treatment [pH value: 7.26±0.09 vs 7.19±0.09, t=3.814; PCO2: (51.5±12.6) vs (59.8±16.3) mmHg (1 mmHg=0.133 kPa), t=2.610; FiO2: 26.0 (21.0-31.5)% vs 40.5 (38.5-51.5)%, U=392.000; PO2/FiO2: (284.6±117.9) vs (173.4±59.7) mmHg, t=6.427; all P 0.05).
Conclusions
SLI combined with PS for NRDS babies can increase the rate of extubation within 24 h and promote the down-regulation of FiO2 without causing significant complications.
Key words:
Respiratory distress syndrome, newborn; Continuous positive airway pressure; Pulmonary surfactants; Treatment outcome
With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.
To investigate the association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with coronary atherosclerotic heart disease (CHD) in Chinese Han nationality.For 106 patients with CHD and 108 unrelated health individuals, the G894T mutation at exon 7 of the endothelial nitric oxide synthase gene was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.(1) Among the normal subjects of Chinese Han nationality, the frequencies of the eNOS/GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. The G and T allele frequencies were 0.9537 and 0.0463. (2) The authors assumed the effects of the T allele to be dominant (GT and TT combined vs GG). The GT+TT genotype frequencies in CHD and myocardial infarction (MI) subgroup were 0.2219 and 0.2387, respectively. The frequencies of eNOS/GT+TT genotypes in CHD patients, as well as MI subgroup were significantly higher than that of the normal subjects (P<0.05), respectively. The frequencies of T allele in CHD, MI subgroup were significantly higher than that in the normal subjects (P<0.01), respectively. (3) This mutation was not related to the number of affected vessels in the 58 patients who had angiographically documented artery narrowing (P>0.05).The G894T mutation of the endothelial nitric oxide synthase gene may be a marker for genetical predisposition of CHD in Chinese Han population.
OBJECTIVE To evaluate the influence of the angiotensinogen(AGT) gene M235T variant on the prevalence and severity of hypertrophic cardiomyopathy(HCM). METHODS The authors conducted a case-control study on 152 subjects, including 72 HCM patients and 80 normal controls. Polymerase chain reaction(PCR) combined with restriction fragment length polymorphism(RFLP) was used to detect the M235T variant of AGT gene. Interventricular septum thickness, left ventricular posterior wall thickness and apical wall thickness were measured by means of M-mode echocardiography under two-dimensional guidance in the parasternal long-axis plane and apical two- and four-chamber views. RESULTS (1) The genotype distributions of AGT gene in both groups were in agreement with Hardy-Weinberg equilibrium. (2) The genotype distributions of the M235T variant differed significantly in HCM patients and controls(chi-square=6.090 P<0.05). The frequencies of TT genotype and T235 allele in HCM patients were higher than did the patients in controls(TT genotype 0.63 vs 0.45 OR=2.037 95%CI 1.064-7.899 P<0.05 T235 allele 0.78 vs 0.64 OR=1.990 95%CI 1.197-3.308 P<0.01). (3)The patients with the TT genotype had significantly greater mean left ventricular maximal wall thickness than did the patients with the MM and MT genotypes [(19.1+/-4.8) mm vs(15.3+/-2.6)mm and(16.2+/-5.1)mm F=4.261 P<0.05]. CONCLUSION The variant M235T of the AGT gene is significantly associated with HCM in this population. The genotype TT or allele T might be a genetic risk factor for the development and extent of hypertrophy in HCM patients.
Objective To assess the association of haptoglobin (HP)1/2 polymorphism with coronary heart disease (CHD) in Chinese Hans. Methods One hundred and eighty-nine CHD patients and 242 healthy controls confirmed with angiography were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was utilized to genotype the HP1 and HP2 alleles and genotype frequencies in cases and controls were compared. Results The frequency of HP2-2 genotype was significantly higher in CHDs than in controls (0. 54 vs. 0.35, P=0.000). The HP2-2 genotype significantly increased the risk for CHD in univariable analysis (OR= 2. 165, 95% CI: 1. 467-3. 196). Multifactor Logistic regression analysis indicated that HP2-2 genotype is an independent risk factor to CHD (P=0.002;OR=2. 101, 95% CI: 1. 311-3. 367). Similarly, the HP2 allele frequency in the CHD group was significantly higher than that in the control subjects (0.74 vs. 0. 61, P= 0. 000). Conclusion The HP2-2genotype is associated with CHD in Chinese. HP2-2 genotype may be an independent risk factor to CHD,and HP2 allele may be a genetic susceptibility factor to CHD in Chinese.
Key words:
haptoglobin gene; polymorphism; coronary heart disease
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