OBJECTIVE: Porcine stress syndrome (PSS) is one kind of molecular genetics defect diseases of pig which will cause malignant hyperthermia syndrome (MHS) and is the first index should be excluded in screening of a pig species for xenotransplantation. It was reported that mutation of pig rynodine receptor(RYR1) gene is the main reason for PSS. In this study, RYR1 genotypes of the Chinese Banna mini pig inbred line and inbreeding closed colony Wuzhishan pig were investigated with polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) technique. METHODS: Antevenocaval whole blood samples were collected from 50 Banna mini-pig inbred-line(BMI), 15 inbreeding Wuzhishan pig (WZSP) and 25 Neijiang pigs (NJP) as negative control, the primer were designed and synthesized, PCR reaction was conducted following the sequence of 94 degrees C (1 min), 58 degrees C (1 min) and 72 degrees C (1 min) for 30 cycles. The PCR products were digested with restriction endonuclease HhaI and then electrophoresis check. RESULTS: A 659 bp DNA fragment was amplified with these two primers, the HALNN sample fragment was cut into fragments as 493 bp and 166 bp individually after the digestion, indicates no point mutation at site 1,843 in RYR1 gene in all tested BMI pig and WZSP. Namely, the RYR1 genotype of 50 cases of BMI and 15 cases of WZSP were HALNN, therefore their phenotype is PSS negative. CONCLUSION: It indicates that the genotype of Banna mini pig inbred line and inbreeding Wuzhishan pig are HALNN therefore PSS absolutely negative, the group penetrance is 0. This is consistent with experimental observation. It suggests that Banna mini pig inbred line and inbreeding Wuzhishan pig may be the alternative donor for xenotransplantation.
ObjectiveTo analyze the drug-resistant phenotype and genotype characteristics of carbapenem-resistant Enterobacteriaceae (CRE) in a traditional Chinese medicine hospital from 2016 to 2018, to provide guidance for clinical rational drug use and effective anti-infection treatment.MethodsA total of 2 901 Enterobacteriaceae bacteria strains isolated from January 2016 to December 2018 were selected, and CRE strains were screened by microdilution test and Kirby-Bauer methods. CRE strains with successful seed preservation and detailed clinical data were selected for carbapenemase phenotype confirmation test, drug-resistant gene amplification, and sequencing comparison.ResultsThe 101 CRE strains collected between 2016 and 2018 were mainly Klebsiella pneumonia (73.27%, 74/101) and Escherichia coli (14.85%, 15/101), and the specimens were mainly from sputum (63.37%, 64/101) and catheter urine (11.88%, 12/101). The phenotypic test results of carbapenemase showed that 94 strains were positive in modified Hodge test, with a positive rate of 93.07%, 96 strains were positive in Carba NP test, with a positive rate of 95.05%, and 98 strains were positive in modified carbapenem inactivation method test, with a positive rate of 97.03%. Drug-resistant genes were detected in 92 (91.01%) of the 101 CRE strains, sequencing results showed that 66 (65.35%) carried blaKPC-2 gene, 4 (3.96%) carried blaKPC-19 gene, 9 (8.91%) carried blaNDM-1 gene, and 13 (12.87%) carried blaNDM-5 gene. No CRE strains carrying two resistance genes were detected. Among them, Klebsiella pneumoniae strains mainly carried blaKPC-2 gene (82.43%, 61/74), and Escherichia coli strains mainly carried blaNDM-5 gene (86.67%, 13/15), which were consistent with the main epidemic genotype in China.ConclusionsIn recent three years, the CRE strains in this hospital mainly included Klebsiella pneumoniae with blaKPC-2 gene and Escherichia coli with blaNDM-5 gene. According to the results of this test, we can reasonably select antimicrobial agents in combination with the drug sensitivity report from the microbial laboratory, so as to delay the growth of drug-resistant strains and prevent hospital transmission of multidrug-resistant bacteria.
ObjectivesTo compare different formula calculated dosages with the actual doses of warfarin from patients in Beijing Hospital so as to investigate suitable warfarin dosing models for Chinese patients.MethodsOne hundred and three Chinese patients with long-term prescription of warfarin were randomly selected from Beijing Hospital from July 2012 to May 2013. The CYP2C9 and VKROC1 genotypes and basic statistical information were collected. SPSS 18.0 software was used to compare the differences between different formula calculated dosages and the actual dosages of warfarin.ResultsFive genotypes were found in 103 patients, including: CYP2C9 AA genotype + VKORC1 AA genotype (n=72, 69.9%), CYP2C9 AA genotype + VKORC1 AG genotype (n=17, 16.5%), CYP2C9 AC genotype + VKORC1 AA genotype (n=10, 9.7%), CYP2C9 AC genotype + VKORC1 AG genotype (n=3, 2.9%) and CYP2C9 AA genotype + VKORC1 GG genotype (n=1, 1%). Compared with the actual dosages of warfarin, the degree of coincidence was highest for dosages calculated by Jeffrey’s formula.Conclusions Using Jeffrey’s formula to calculate warfarin dosages may be more suitable for Chinese patients with using long-term warfarin. Due to limited sample size, prospective and large sample size studies are required to verify the above conclusion.
Online Mendelian Inheritance in Man (OMIM) is a knowledge source and data base for human genetic diseases and related genes. Each OMIM entry includes clinical synopsis, linkage analysis for candidate genes, chromosomal localization and animal models, which has become an authoritative source of information for the study of the relationship between genes and diseases. As overlap of disease symptoms may reflect interactions at the molecular level, comparison of phenotypic similarity may indicate candidate genes and help to discover functional connections between genes and proteins. However, the OMIM has used free text to describe disease phenotypes, which does not suit computer analysis. Standardization of OMIM data therefore has important implications for large-scale comparison of disease phenotypes and prediction of phenotype-genotype correlations. Recently, standard medical language systems, term frequency-inverse document frequency and the law of cosines for document classification have been introduced for mining of OMIM data. Combined with Gene Ontology and various comparison methods, this has achieved substantial successes. In this article, we have reviewed various methods for standardization and similarity comparison of OMIM data. We also predicted the trend for research in this direction.
Objective To summarize the gastrointestinal manifestations and diagnostic and therapeutic experience of hereditary angioedema (HAE), enhancing early recognition of this rare disease. Methods The clinical data, genotype analysis results, treatment process, and follow-up data of HAE patients who visited the Department of Gastroenterology and Hepatology of West China Hospital of Sichuan University between May 2023 and December 2024 due to abdominal pain were retrospectively collected and summarized for analysis. Results A total of 10 patients with abdominal HAE were included, including 2 males and 8 females. The age range of the patients was 30-71 years old, and 6 patients were found to have HAE through family screening. Most patients first developed the disease during adolescence or youth, and there was a significant time interval between the onset and diagnosis, ranging from 3 to 42 years. Patients mainly presented with gastrointestinal symptoms, with the first symptoms usually being abdominal pain (the most common) and vomiting, accompanied by nausea and other symptoms. Five patients were hospitalized multiple times due to severe gastrointestinal symptoms, and all patients had significantly reduced levels of complement C4, with a C1-esterase inhibitor function of less than 7%. Three patients had a C1-esterase inhibitor concentration below the normal range. All patients were detected with SERPING1 gene mutations. During the follow-up period, 6 patients received preventive treatment. Conclusion Gastrointestinal symptoms are one of the important clinical manifestations of HAE and are often misdiagnosed as other gastrointestinal diseases.
The present study was aimed to explore the relationship of transforming growth factor (TGF) β3 gene SfaNI polymorphism (rs3917201 locus) and non-syndromic cleft lip with or without cleft palate (NSCL/P) in people of the Uygur's Nationality and Han's in Xinjiang, China. TGFβ3 gene fragment including SfaNI was amplified and purified as the template of the primer extension reaction thenafter. The single base extension reaction was carried out using SNP specific extension primer. The products were purified and analyzed by MALDI-TOF. The test showed that there were not significantly different frequencies of AA, AG, GG genotypes and alleles between the whole NSCL/P group and the whole control group (P>0.05).Within the Uygurs or Hans, the frequencies of genotypes between the whole NSCL/P group and the whole control group were not significantly different(P>0.05). The distributions of the A, G alleles between the NSCL/P group and the control group were not significantly different within the Uygurs (P>0.05), but significant different within the Hans (P<0.05). In all the NSCL/P patients, frequencies of genotypes and alleles were not significantly different between Uygurs and Hans (P>0.05), and not significantly (P>0.05) either between Uygurs and Hans in all the healthy persons. The results proved that TGFβ3 gene SfaNI polymorphism may not be related to NSCL/P in Xinjiang Uygur people, while the occurrence of NSCL/P in Han population may be related to frequency of the A and G allele of SfaNI polymorphism.
【Abstract】 Objective To analyze the correlations between the mt5351G and mt6680C genotypes in mitochondrial DNA ( mtDNA) haplogroup M and susceptibility to high altitude pulmonary edema ( HAPE)among the Hans. Methods Specimens from206 Hans cases of HAPE and 144 matched Hans controls were collected. Then PCR-RFLP method was used to determine haplogroup M and N of mtDNA, and PCR-LDR was used to genotype mt5351G and mt6680C in the haplogroup M in these samples. Results The frequencies of haplogroup Mand N were 49. 0% and 51.0% in the HAPE patients, and 47. 2% and 52. 8% in the controls, respectively, with no significant difference between the HAPE patients and the controls. In the haplogroup M, the genotype of mt6680C and mt5351G frequencies in the HAPE patients were both significantly higher than the controls ( both 12. 0% vs. 1. 5% , P = 0. 016) . Conclusion The existence of mt5351G and mt6680C genotypes in the haplogroup Mis a risk factor for HAPE among the Hans.
Objective To summarize the significance of CYP3A5 in individualized immunosuppressive treatment with tacrolimus (FK506) after liver transplantation. Methods Relevant literatures about the effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in liver transplant recipients, which were published recently domestic and abroad, were reviewed and analyzed. Results Tacrolimus was used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variation in pharmacokinetics made it difficultly to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters influenced the plasma concentration of tacrolimus. CYP3A5 genotype had an effect on the tacrolimus dose requirement in liver transplant recipients.Conclusion Genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing liver transplantation
ObjectiveTo investigate the clinical characteristics and genetic phenotype of mitochondrial myopathy associated with lactic acidemia and stroke-like seizure syndrome (MELAS) in DNA A3243G mutation, and to improve the clinical understanding and diagnosis.MethodsThe clinical data and imaging characteristics of 4 patients with DNA A3243G mutation-related MELAS syndrome who were diagnosed and treated in the Department of Pediatric Neurology, Henan Provincial People's Hospital from June 2017 to June 2018 were retrospectively reviewed.ResultsOf the 4 patients, 3 were caused by convulsions, 1 was caused by dizziness, and the MELAS syndrome caused by mitochondrial DNA A3243G mutation was confirmed by genetic testing. The patients were treated with anti-epilepsy drugs. The patients were followed up for at least 1 year, and 2 of 4 patients were stable, 1 patient still had seizures, and 1 patient did not improved.ConclusionsThe clinical phenotypic heterogeneity of patients with DNA A3243G mutation-related MELAS syndrome is caused by the " heterogeneity” and " threshold effect” of DNA mutation. The mutation rate of DNA A3243G is as high as 80%. In the era of promoting precision medicine, genes examination can help early diagnosis and early treatment of MELAS syndrome as well as improve the quality of life of patients and improve the prognosis.
