Objective To study the correlation between the changes of matrix metalloproteinase-9(MMP-9)and neutrophil/lymphocyte ratio(NLR)before and after the revascularization of acute ischemic stroke(AIS),so as to find biomarkers to predict the bleeding transformation risk of AIS patients.Methods From February 2022 to December 2022,161 patients admitted to the Stroke Center of Qujing Hospital Affiliated to Kunming Medical University with AIS werre divided in to the hemorrhagic transformation group and the non-hemorrhagic transfor-mation groupand treated with revascularization(intravenous thrombolysis,endovascular treatment,combined the intravenous thrombolysis with endovascular treatment).Among them,there were 46 cases in the hemorrhagic transformation group and 115 cases in the non hemorrhagic transformation group.And the general data,NLR value and MMP-9 before and after the revascularization were compared between the two groups.Results There was no statistical difference in general data between the two groups(all P>0.05)except for C-reactive protein in hemorrhagic transformation group and in non-hemorrhagic transformation group(P<0.001).The white blood cells,neutrophils,neutrophil percentage,neutrophil absolute value,lymphocyte absolute value,NLR and MMP-9 value in hemorrhagic transformation group were significantly higher than those in non-hemorrhagic transformation group before the treatment and there was a statistical significance(P<0.05).After revascularization,the indexes of blood routine and MMP-9 were significantly higher than those before the revascularization,and the increase in hemorrhagic transformation group was more obvious than that in non-hemorrhagic transformation group and there was a statistical significance(P<0.001),The ROC curve showed that the area under the curve(AUC)of NLR and MMP-9 predicting bleeding transformation after AIS revascularization were 0.74 and 0.90.Conclusion NLR,MMP-9 are associated with the risk of bleeding transformation in AIS patients after the revascularization and can they can be used as the predictive factors for bleeding transformation risk.

OBJECTIVE: To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD). METHODS: For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos. RESULTS: The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor. CONCLUSION Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.
Male ; Pregnancy ; Child ; Humans ; Female ; Muscular Dystrophy, Duchenne/diagnosis* ; Dystrophin/genetics* ; Mosaicism ; Exons ; Prenatal Diagnosis/methods* ; Nucleotides

OBJECTIVE: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women. RESULTS: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M. CONCLUSION Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.
China ; Dystrophin/genetics* ; Exons ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To analyze the (CGG)n repeats of FMR1 gene among patients with unexplained mental retardation. METHODS: For 201 patients with unexplained mental retardation, the (CGG)n repeats of the FMR1 gene were analyzed by PCR and FragilEase RESULTS: For the 201 patients with unexplained mental retardation, 15 were identified with full mutations of the FMR1 gene. The prevalence of fragile X syndrome (FXS) in patients with unexplained mental retardation was determined as 7.5% (15/201). Prenatal diagnosis was provided for 6 pregnant women with pre- or full mutations. Analysis revealed that women with mental retardation and full FMR1 mutations exhibited a skewed XCI pattern with primary expression of the X chromosome carrying the mutant allele. CONCLUSION FXS has a high incidence among patients with unexplained mental retardation. Analysis of FMR1 gene (CGG)n repeats in patients with unexplained mental retardation can facilitate genetic counseling and prenatal diagnosis for their families. FMR1 gene (CGG)n repeats screening should be recommended for patients with unexplained mental retardation.
Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo screen for FOXL2 gene mutations in 6 patients with blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlation.

METHODSPeripheral venous blood samples were collected from the patients for the extraction of genomic DNA. PCR and Sanger sequencing were employed to analyze the coding region and flanking sequences of the FOXL2 gene. Pathogenicity of the identified mutations was verified through literature review and bioinformatic analysis.

RESULTSA heterozygous c.672_701dup30 mutation was found in the probands from the two familial cases, while three heterozygous mutations (two were novel), namely c.462_468del (p.Pro156Argfs*113), c.251T to A (p.Ile84Asn) and c.988_989insG (p.Ala330Glyfs*204) were detected in the three sporadic cases. Literature review and bioinformatic analysis indicated that all these mutations are pathogenic.

CONCLUSIONIdentification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blepharophimosis ; diagnosis ; genetics ; China ; Female ; Forkhead Box Protein L2 ; Forkhead Transcription Factors ; genetics ; Genetic Association Studies ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Skin Abnormalities ; diagnosis ; genetics ; Urogenital Abnormalities ; diagnosis ; genetics ; Young Adult

Objective To explore mutation diagnosis and discuss the pathogenic and clinical characteristics of neurofibromatosis type 1 (NF1).Methods DNA sequencing combined with denaturing highperformance liquid chromatography (DHPLC) method was used to diagnose patients and parents.Results A new nonsense mutations c.503C ＞ G(p.S168 *) was identified.Conclusions NF1 is a rare autosomal dominant genetic disease.Most of them are caused by new mutations.Genetic diagnosis of sporadic cases is very important for treatment and the future generations.

OBJECTIVETo detect SCN4A gene mutation in a pedigree with paramyotonia congenita in order to facilitate genetic counseling and assisted reproduction.

METHODSClinical data of the family was collected. DNA was extracted from peripheral blood samples. Potential mutation of the SCN4A gene was screened using PCR-Sanger sequencing. Potential mutation was detected in 3 affected relatives, 4 unaffected relatives and 100 unrelated healthy controls. Bioinformatics software was used to predict the effect of mutation on the protein function and conservation of the sequence at the mutation site across various species.

RESULTSA novel missense mutation c.4427T>C (p.Met1476Thr) was detected in the exon 24 of the SCN4A gene in the proband and other 3 affected relatives, but not in 4 unaffected relatives and 100 unrelated controls. Bioinformatic analysis indicated that the codon is highly conserved across various species, and that the mutation has caused damage to the structure and function of SCN4A protein.

CONCLUSIONThe c.4427 T>C (p.Met1476Thr) mutation of the SCN4A gene may contribute to the paramyotonia congenita. Detection of SCN4A gene mutation is an effective method for the diagnosis of paramyotonic congenita.

Adult ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Exons ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Myotonic Disorders ; genetics ; NAV1.4 Voltage-Gated Sodium Channel ; genetics ; Pedigree ; Point Mutation ; Sequence Alignment

OBJECTIVETo study the prediction performance evaluation with five kinds of bioinformatics software (SIFT, PolyPhen2, MutationTaster, Provean, MutationAssessor).

METHODSFrom own database for genetic mutations collected over the past five years, Chinese literature database, Human Gene Mutation Database, and dbSNP, 121 missense mutations confirmed by functional studies, and 121 missense mutations suspected to be pathogenic by pedigree analysis were used as positive gold standard, while 242 missense mutations with minor allele frequency (MAF)>5% in dominant hereditary diseases were used as negative gold standard. The selected mutations were predicted with the five software. Based on the results, the performance of the five software was evaluated for their sensitivity, specificity, positive predict value, false positive rate, negative predict value, false negative rate, false discovery rate, accuracy, and receiver operating characteristic curve (ROC).

RESULTSIn terms of sensitivity, negative predictive value and false negative rate, the rank was MutationTaster, PolyPhen2, Provean, SIFT, and MutationAssessor. For specificity and false positive rate, the rank was MutationTaster, Provean, MutationAssessor, SIFT, and PolyPhen2. For positive predict value and false discovery rate, the rank was MutationTaster, Provean, MutationAssessor, PolyPhen2, and SIFT. For area under the ROC curve (AUC) and accuracy, the rank was MutationTaster, Provean, PolyPhen2, MutationAssessor, and SIFT.

CONCLUSIONThe prediction performance of software may be different when using different parameters. Among the five software, MutationTaster has the best prediction performance.

Computational Biology ; methods ; DNA Mutational Analysis ; methods ; Gene Frequency ; Humans ; Mutation, Missense ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Reproducibility of Results ; Software

blood of patients.

BACKGROUND: Due to the trouble of body image and self-esteem, more and more women hope to reduce their body mass.OBJECTIVE: To assay the characters and correlation between body image and self-esteem in women who reduce weight positively.DESIGN: Transect investigation.SETTING: Department of Dermatology of Xiangya Hospital and Xiangya Second Hospital of Central South University. PARTICIPANTS: Totally 100 patients for weight loss was collected in Department of Acupuncture and Moxibustion of Xiangya Hospital Affiliated to Central South University from November 2002 to September 2003 and they were included in experimental group. Severe physical disorders or other chronic physical disorders were excluded, such as cardiac vascular disease and diabetes and various metal disturbances were excluded too. In addition,the patients did not taken psychoactive drugs recently. Those were in over-body-mass group if body mass index(BMI) ≥ 24 and those were in normal body mass group if BMI＜24. In the control, there were 100 healthy women participating in the study in volunteer at the same time. The exclusive standards for them were same as the experimental group and they did not taken psychoactive drugs recently and had done nothing for weight loss in 5 years.METHODS: After instructed, the receptors filled up the following questionnaire: a self-rating scale of body image(SRSBI) and the self-esteem scale (SES). SRSBI is the subjective assessment on the beauty and strength of the body individually. SES is the assessment on holistic perception of self-value and self-acceptance.MAIN OUTCOME MEASURES: Results of SRSBI and SES in weight loss women.RESULTS: According to intention, general results of SRSBI: The score in experimental group(15.14±9.99) was higher than that in the control (7.89±6.18) (t= 6.15, P＜0.001) . The score was(15.65±10.36) in normal body mass group and was(13.81 ±10.03) in over-body-mass group. By the comparison between both, no difference presented(t=0.91, P ＞0.05) . Results of SES: the score in experimental group (27.01±4.19)was lower than that in the control(28.23±3.65) (t= 2.16, P＜0.05).The score was(27.31±4.50) in normal body mass group and was (26.86±3.82) in over-body-mass group. By the comparison between both,no difference presented (t=0.54, P＞0.05) . It was indicated in linear correlation analysis on SRSBI and SES in experimental group that the correlation coefficient between SRSBI and SES was-0. 088(P＞0.05).CONCLUSION: The people who seek for weight loss actively present inferior subjective perception of body image and low level of self-esteem, and there is no correlation between both of them and neither of them is relevant t.o obesity.