1.Clinical study of docetaxel plus nedaplatin combined with concurrent intensity-modulated radiotherapy for locally-advanced nasopharyngeal carcinoma
Yuwei FAN ; Liwei QI ; Jia LI ; Xiaodong JIANG ; Peng DAI ; Yawen YUAN
Chinese Journal of Clinical Oncology 2014;(17):1115-1119
Objective:To investigate the differences in efficacy, survival outcomes, and acute and late toxicities for patients with local/regional advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT) in combination with che-motherapy (CT) and by IMRT alone. Methods:A total of 72 newly diagnosed local/regional advanced NPC patients were randomly subjected to IMRT/RT+adjuvant CT (after radiotherapy, RT) (n=42) or IMRT+adjuvant CT (after RT) (n=30). The Kaplan-Meier meth-od was used to analyze the two-year local/regional control rates, distant metastasis-free survivals, and overall survivals. The acute and late radiation toxicities were evaluated based on the toxicity criteria of the Radiation Therapy Oncology Group and European Organiza-tion for Research and Treatment of Cancer. Results:A median follow up period of 13.5 months was included in the study. The one-year and two-year local/regional control rates, distant metastasis-free survivals, and overall survival in the IMRT group were 95.0%, 80.0%, and 95.0%, and 80%, 60.0%, and 75.0%, respectively. For the IMRT+CT group, such rates were 100%, 96.4%, and 96.4%, and 100%, 92.9%, and 92.9%, respectively. The two-year local/regional control rate and distant metastasis-free survivals in the IMRT+CT group were higher than those in the IMRT group (P<0.05). Most patients had grade 1 to grade 2 acute radiation toxicities and grade 0 to grade 1 late radiation toxicities (P>0.05). No patient showed a grade 4 acute or late toxicity. The blood and gastrointestinal toxicity rates were high in the IMRT+CT group (P<0.05). Conclusion:The IMRT+CT treatment has potential advantages over the IMRT in the treatment of local/regional advanced NPC patients in terms of local/regional control and overall survival. The blood and gastrointestinal toxicity rates in the IMRT+CT group were higher than in the IMRT group but still within a tolerable range.
2.Association of CYP2C19 and CYP3A5 gene polymorphisms with myocardial infarction.
Lin QI ; Wei LIANG ; Hui QIAO ; Ruimin WANG ; Jingxian HAN ; Xiaofei XING ; Yuwei HU
Chinese Journal of Medical Genetics 2021;38(1):87-91
OBJECTIVE:
To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction.
METHODS:
Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power.
RESULTS:
The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%.
CONCLUSION
CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.
Cytochrome P-450 CYP2C19/genetics*
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Cytochrome P-450 CYP3A/genetics*
;
Gene Frequency
;
Genotype
;
Humans
;
Myocardial Infarction/genetics*
;
Polymorphism, Genetic
;
Polymorphism, Single Nucleotide
3.Genetic analysis of a patient with late infantile metachromatic leukodystrophy
Ke YANG ; Yuwei ZHANG ; Guiyu LOU ; Na QI ; Ling WANG ; Hongjie ZHU ; Bing ZHANG ; Dan WANG ; Shixiu LIAO
Chinese Journal of Medical Genetics 2020;37(2):153-155
Objective To detect variants of ARSA gene in a child featuring late infantile metachromatic leukodystrophy (MLD).Methods PCR and Sanger sequencing was carried out for the patient and her parents.Results The patient had typical features of MLD including ARSA deficiency,regression of walking ability,and demyelination.Compound heterozygous variants of the ARSA gene,namely c.960G>A and c.244C>T,were detected in the patient,for which her mother and father were respectively heterozygous carriers.ARSA c.960G>A was known to be pathogenic,while ARSA c.244C>T was a novel variant.The same variants were not detected among 50 healthy controls.Conclusion The compound heterozygous variants c.960G>A and c.244C>T of the ARSA gene probably underlie the MLD in this patient.
4.An investigation on avian influenza virus distribution in poultry-related environment in Nanping city
Yating ZHANG ; Jingjing WU ; Qi LIN ; Yuwei WENG
Chinese Journal of Experimental and Clinical Virology 2024;38(2):138-143
Objective:To profile the distribution of avian influenza virus in poultry-related environment in poultry industry developed area in Fujian province, an investigation was conducted in Nanping city from Dec.2021 to Dec.2023.Methods:The samples from multiple types of external environment related to poultry in Nanping city were collected from Dec. 2021 to Dec. 2023, and the real-time fluorescence quantitative RT-PCR used to detect and subtype the influenza A virus (FluA). SPSS 26.0 software was used to analyze the distribution characteristics of FluA in poultry-related environment and the differences in time, places and sample types.Results:The overall positive rate of FluA in samples from poultry-related environment was 49.16% (1 435/2 919). The positive rates of H3, H5, H9 and H10 subtypes were 0.72% (21/2 919), 9.42% (275/2 919), 33.20% (969/2 919), 0.89% (26/2 919) respectively, and no H7 subtype was detected. The positive rate of mixed type (more than one subtype of FluA detected in a same sample) was 6.51% (190/2 919), and the positive rate of unknown subtype (positive for FluA but negative for H3/5/7/9/10) was 11.58% (338/2 919). The higher positive rate of FluA mainly occurred in autumn-winter season (September to February of the following year). In live poultry markets and slaughterhouses, the positive rates of FluA, H9 subtype, mixed type and unknown subtype were significantly higher than that in poultry farms. The positive rate of FluA in poultry drinking water and feces was higher than samples of other types, most of the positive samples were H9 subtype.Conclusions:The positive rate of FluA in poultry-related environment in Nanping city was higher in autumn-winter season. The investigation also showed that higher FluA positive rate in drinking water and feces sample and diversity of the virus existed in the place of multiple types of poultry clustered, such as live poultry markets and slaughterhouses.
5. Clinical characteristics and pathogenic gene analysis in a large pedigree with multiple epiphyseal dysplasia
Guiyu LOU ; Na QI ; Ke YANG ; Litao QIN ; Yuwei ZHANG ; Shixiu LIAO
Chinese Journal of Orthopaedics 2020;40(2):97-102
Objective:
To provide experimental evidence for genetic counseling and prenatal molecular diagnosis by analyzing the clinical characteristics and screening for pathogenic genes of a five-generation suspected multiple epiphyseal dysplasia (MED) family (17 patients).
Methods:
The family members' medical history, general physical examination and hip joint X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA were extracted from these samples. The exons of clinical genes from probands' DNA were sequenced by High throughput sequencing method. Next Gene software was used to compare and analyze the sequence and INGENUITY software was further used to annotate the mutations in order to find the pathogenic mutations in probands. The suspicious mutations were confirmed in pedigree members by PCR and Sanger sequencing.
Results:
The family consisted of 5 generations and 38 members. Pedigree analysis was consistent with autosomal dominant inheritance. There were 17 patients in the family, and their clinical manifestations showed abnormal walking posture in childhood, pain in hip and knee joints, and typical pathological changes of epiphyseal dysplasia on X-ray. Cartilage oligomeric matrix protein (COMP) gene c.1153G>A (p.Asp385Asn) missense heterozygous mutation was screened in proband, which was genotypically and phenotypically segregated in the pedigree.
Conclusion
A missense mutation of the comp gene has been identified in a pedigree affected with MED which was the first reported in a big family. Our result is conducive to the further diagnosis and treatment and also provides a molecular basisfor the future prenatal diagnosis.
6.A novel compound heterozygous mutation of GNPTAB gene underlying a case with mucolipidosis type II α/β.
Ke YANG ; Guiyu LOU ; Na QI ; Yuwei ZHANG ; Hongjie ZHU ; Li WANG ; Xijuan WANG ; Bing ZHANG
Chinese Journal of Medical Genetics 2019;36(6):606-609
OBJECTIVE:
To analyze the clinical features and genetic mutations in a patient with mucolipidosis type II α/β by using next generation sequencing.
METHODS:
Clinical data of the patient was collected. Genomic DNA of the patient and her parents was extracted by a standard method. The patient was subjected to targeted sequencing using an Ion Ampliseq panel, which included genes related to mucolipidosis and mucopolysaccharidosis. Suspected mutations were verified by Sanger sequencing.
RESULTS:
Compound heterozygous mutations, namely c.1284+1G>T and c.1090C>T (p.Arg364*), were detected in the patient, which were respectively inherited from her mother and father. No other disease-causing mutation was detected in the patient. GNPTAB c.1090C>T was known to be pathogenic, while GNPTAB c.1284+1G>T is a novel mutation. The same mutations were not detected among 50 healthy controls.
CONCLUSION
The compound heterozygous mutations c.1284+1G>T and c.1090C>T (p.Arg364*) of GNPTAB gene probably account for the mucolipidosis type II α/β in the patient. NGS has a great value for the molecular diagnosis and typing of mucolipidosis.
Female
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High-Throughput Nucleotide Sequencing
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Humans
;
Mucolipidoses
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genetics
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Mutation
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Transferases (Other Substituted Phosphate Groups)
;
genetics
7.Genetic analysis of a pedigree affected with Bartter's syndrome.
Ke YANG ; Xiaodong HUO ; Yuwei ZHANG ; Mengting ZHANG ; Yue GAO ; Dong WU ; Guiyu LOU ; Na QI ; Bing ZHANG ; Dan WANG
Chinese Journal of Medical Genetics 2019;36(7):701-703
OBJECTIVE:
To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS).
METHODS:
Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members.
RESULTS:
No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion.
CONCLUSION
The loss of the MAGED2 gene may underlie the BS in this pedigree.
Adaptor Proteins, Signal Transducing
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genetics
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Antigens, Neoplasm
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genetics
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Bartter Syndrome
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genetics
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Female
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Genetic Testing
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Heterozygote
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Humans
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Male
;
Mutation
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Pedigree
;
Sequence Deletion
8.Analysis of a Chinese pedigree affected with dyschromatosis symmetrica hereditaria due to a novel variant of ADAR gene.
Ke YANG ; Qiaofang HOU ; Yuwei ZHANG ; Guiyu LOU ; Na QI ; Bing KANG ; Bing ZHANG ; Shixiu LIAO
Chinese Journal of Medical Genetics 2022;39(1):64-67
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).
METHODS:
PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.
RESULTS:
The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.
CONCLUSION
The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics*
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China
;
Female
;
Humans
;
Mutation
;
Pedigree
;
Pigmentation Disorders/congenital*
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RNA-Binding Proteins/genetics*
9.Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene.
Ke YANG ; Yuwei ZHANG ; Guiyu LOU ; Na QI ; Bing ZHANG ; Bing KANG ; Xingxing LEI ; Shixiu LIAO
Chinese Journal of Medical Genetics 2022;39(3):305-308
OBJECTIVE:
To analyze the clinical features and genetic variant in a patient with Usher syndrome.
METHODS:
Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.
RESULTS:
The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.
CONCLUSION
The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
Cadherin Related Proteins
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Cadherins/genetics*
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Child
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China
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Female
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Genetic Testing
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Humans
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Infant, Newborn
;
Pedigree
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Pregnancy
;
Prenatal Diagnosis
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Usher Syndromes/genetics*
10.Efficacy of postoperative radiotherapy based on modified clinical target volume according to high-frequency recurrence regions in patients with esophageal squamous cell carcinoma
Puyuan WU ; Liang QI ; Tao WANG ; Minke SHI ; Yuwei SUN ; Lifeng WANG ; Baorui LIU ; Jing YAN ; Wei REN
Journal of International Oncology 2022;49(8):464-472
Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.