In order to observe the role of genetically modified Schwann cell (SC) with pSVP0Mcat in the regeneration of injured spinal cord, the cells were implanted into the spinal cord. Ninety SD rats were used to establish a model of hemi-transection of spinal cord at the level of T8, and were divided into three groups, randomly, that is, pSVP0Mcat modified SC implantation (Group A), SC implantation (Group B) and without cell implantation as control (Group C). After three months the presence of axonal regeneration of the injured spinal cord was examined by means of horseradish peroxidase (HRP) retrograde labelling technique and stereography. The results indicated that HRP labelled cells in Group A and B could be found in the superior region of injured spinal cord and the brain stem such as the red nuclei and oculomotor nuclei. The density of ventral hom neurons of the spinal cord and the number of myelinated axons in 100 microns of the white matter was A gt; B gt; C group. In brief, the pSVP0Mcat modified SC intraspinal implantation could promote regeneration of the injured spinal cord.
Objective To search for the significant gene indicators in the diagnosis of pancreatic cancer. Methods Literatures about genetic diagnosis of pancreatic cancer were collected and reviewed. Results K-ras, p53, DPC4 and telomerase genes were considered to play important roles in the diagnosis of pancreatic cancer. Conclusion Detection of the genes related to pancreatic cancer may be of helpful in early diagnosis of pancreatic cancer.
The autograft and non-autograft cannot meet the needs of clinical vascular surgery. Since there are possibilities of thrombus formation in artificial vascular grafts, the methods for deposing the graft using physical and chemical ways or simply seeding with endothelial cells cannot produce satisfactory grafts for vascular operations until now. In order to increase the anticoagulative capacity of artificial vascular graft, it is rational to use genetic engineering methods modifying the endothelial cells to make it express anticoagulative factors stably. Although seeding artificial graft with the genetically engineered endothelial cells can possibly produce a satisfactory graft for vascular surgery, some problems still need to be solved.
ObjectiveTo establish a hereditary deafness genetic screening cohort and conduct prospective follow-up to evaluate the effectiveness of the Nantong newborn genetic deafness screening program. MethodsA study based on traditional screening of newborn hearing was conducted from January 2016 to June 2021. Newborns in six hospitals in Nantong were screened for 15 hotspot mutation loci in four common deafness genes. Cohort follow-up was conducted. ResultsA total of 40 403 newborns were included, with a carrier rate of 39.5 per 1 000 for the four common deafness genes. In total, 168 children with hearing loss (HL) were identified at screening and follow-up, of which 56.5% (95 cases) had severe or very severe HL. The detection rate of HL was significantly higher with combined screening than with traditional screening (3.0‰ vs. 3.9‰, P<0.001). All four carriers of pathogenic mutations with normal hearing developed late-onset HL within 2 years of age. At the end of follow-up, six of the polygenic heterozygous mutation carriers had congenital HL and five had late-onset HL. Carriers of polygenic heterozygous mutations were more common as compared to other carrier mutation populations (2.1% vs. 68.8%, P<0.001). In addition, 525 carriers of the SLC26A4 mutation and 118 carriers of the MT-RNR1 mutation were identified and their parents were counselled during the combined screening, and no children with HL was identified during the follow-up period. ConclusionGenetic screening for deafness improves the detection of HL at birth. It is recommended that carriers of pathogenic mutations with normal hearing at birth be followed up every 3 to 6 months until the age of 2 years. Carriers of polygenic heterozygous mutations should undergo extended screening for deafness genes and have their hearing monitored more intensively for early detection of late-onset or progressive HL.
Objective To summarize the advancement of hereditary thrombophilia. Methods Relevant literatures about hereditary thrombophilia published recently domestic and abroad were reviewed and analyzed. Results The hereditary risk factors of venous thromboembolism were different among different races. In western population, the main risk factors were activated protein C resistance (APC-R) and mutation of factor V Leiden, methylene tetrahydrofolate reductase polymorphism (C677T) and prothrombin G20210A. While in Chinese population, the disorder of protein C system and hyperhomocysteinemia were the major genetic risk factor. The existence of multiple genetic risk factors increased the incidence of primary and recurrent venous thromboembolism. Conclusion Further study on the relations between the hereditary risk factors and thrombophilia will be very important for prediction and prevention of the venous thromboembolism.
Objective To analyze the correlation between HLA-A and B genotypes and maculopapular exanthema (MPE) caused by Carbamazepine (CBZ) and Oxcarbazepine (OXC), and to explore the genetic risk factors of MPE. Methods Patients with MPE (rash group) and patients without MPE (non-rash group) after taking CBZ or OXC were retrospectively collected from January 2016 to October 2021 in the Second Affiliated Hospital of Guangzhou Medical University. DNA was extracted from peripheral blood. HLA-A and HLA-B alleles were sequenced by high resolution sequencing, and a case-control study was conducted to analysis the correlations between MPE and HLA genotypes. Results A total of 100 patients with CBZ-MPE, 100 patients with CBZ-tolerant, 50 patients with OXC-MPE, and 50 patients with OXC-tolerant were collected. There was no significant difference in age and sex between CBZ, OXC rash groups and non-rash groups The average latency of CBZ-rash group was (11.31±11.00) days and their average dosage was (348.46±174.10) mg; the average latency of OXC-rash group was (11.67±10.34) days and their average dosage was (433.52±209.22) mg [equivalent to CBZ (289.01±139.48 mg)], showing no significant difference in latency and dosage between CBZ and OXC (P>0.05). The positive rates of HLA-A*24:02 and A*30:01 in CBZ-rash group were 28% and 6%, respectively, which were significantly higher than those in CBZ-non rash group (16% and 0%, both P=0.04). The positive rate of HLA-B*40:01 in CBZ-rash group was 18%, which was significantly lower than that in CBZ-non rash group (40%, P<0.001). No association between HLA-A or B genotype and OXC-rash was found yet. When pooled, it was still found that the positive rates of HLA-A*24:02 and A*30:01 in the rash group were higher than those in the non-rash group, while the positive rate of HLA-B*40:01 in the rash group was lower than that in the non-rash group, and the difference was statistically significant (P<0.05). Conclusions HLA-A*24:02 and A*30:01 were associated with MPE caused by CBZ, and may be common risk factors for aromatic antiepileptic drugs.
ObjectiveTo evaluate the association between the Single Nucleotide Polymorphism (SNP) BsmI (rs1544410) in the vitamin D receptor gene and the susceptibility of coronary artery disease. MethodsDatabases including PubMed, Web of Science, CNKI, WanFang Data, VIP and CBM were searched from inception to May, 2016 to collect case-control studies about SNP BsmI (rs1544410) in the vitamin D receptor gene and the susceptibility of coronary artery disease. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then Meta-analysis was performed by using RevMan 5.3. ResultsA total of seven studies were included, which involved 2182 patients and 5925 controls. The results of meta-analyses showed that the B allele and BB genotype in rs1544410 was associated with the risk of coronary artery disease (B vs. b:OR=1.36, 95%CI 1.03 to 1.79, P=0.03; BB vs. bb:OR=1.70, 95%CI 1.06 to 2.72, P=0.03; BB+Bb vs. bb:OR=1.52, 95%CI 1.00 to 2.30, P=0.05). Subgroup analysis by age showed that rs1544410 was associated with the risk of coronary artery disease in the age <65(B vs. b:OR=1.65, 95%CI 1.00 to 2.73, P=0.05; BB vs. Bb+ bb:OR=1.79, 95%CI 1.08 to 2.97, P=0.02; BB vs. bb:OR=2.64, 95%CI 1.12 to 6.25, P=0.03). Subgroup analysis by ethnicity showed that rs1544410 was associated with the risk of coronary artery disease in Caucasians (B vs. b:OR=1.47, 95%CI 1.10 to 1.97, P=0.01; BB+Bb vs. bb:OR=1.71, 95%CI 1.09 to 2.68, P=0.02; BB vs. Bb+bb:OR=1.39, 95%CI 1.01 to 1.92, P=0.05; BB vs. bb:OR=1.80, 95%CI 1.10 to 2.95, P=0.03). Subgroup analysis by genotyping methods showed that rs1544410 was associated with the risk of coronary artery disease in the TaqMan (B vs. b:OR=2.18, 95%CI 1.06 to 4.45, P=0.03; BB+Bb vs. bb:OR=3.32, 95%CI 1.06 to 10.40, P=0.04; BB vs. bb:OR=3.31, 95%CI 1.06 to 10.30, P=0.04). Subgroup analysis by diagnostic criteria for cases showed that rs1544410 was associated with the risk of coronary artery disease in the ECG (B vs. b:OR=1.15, 95%CI 1.02 to 1.29, P=0.02; BB+Bb vs. bb:OR=1.22, 95%CI 1.02 to 1.45, P=0.03; BB vs. bb:OR=1.31, 95%CI 1.03 to1.67, P=0.03). ConclusionBsmI (rs1544410) B allele may have a significant association with the high risk of coronary artery disease especially the Caucasians and the ones with age <65.
Inherited eye disease is a heterogeneous group of eye disorders caused by genetic defects, which has many genetic characteristics, such as multiple inheritance modes and numerous gene variation types. Over the past few decades, genetic testing has improved significantly, with more and more known disease-causing gene variants identified. With the rapid development of high-throughput sequencing technology, clinical diagnosis and treatment of eye genetic diseases have been accelerated, and molecular diagnosis of eye genetic diseases has become an important step in accurate diagnosis and treatment. How to correctly select and evaluate each kind of genetic testing technology, reasonably standardize the use of genetic testing technology, and provide patients with more accurate genetic counseling are problem that clinicians need to seriously consider.
Objective To investigate the relationship between p53 codon 72 polymorphism and susceptibility to keloid. Methods The p53 genotypes were detected by polymerase chain reactionreverse dot blot(PCRRDB) and DNA direct sequencing among 15 healthy controls and 15 patients with keloid. Results The frequency of the Proallele(P=0.035) and Pro/Pro genotype(P=0.030) in patients was significantly higher than that in the controlls. There was no significant difference in the frequency of Pro/Arg and Arg/Arg genotypes between patients and controls. Conclusion The p53 gene codon 72 polymorphism may play a role in susceptibility to keloid.
ObjectiveTo identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6). MethodsA retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations. ResultsThe proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6wt mRNA, the relative expression levels of HPS6L22fs and HPS6L383fs mRNA were significantly decreased (t = 3.549, 4.560; P＜0.05). Western blot analysis demonstrated that the HPS6L383fs protein was truncated, whereas the HPS6L22fs protein was not detected. ConclusionsThis family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.