OBJECTIVETo map the gene locus in a Chinese pedigree with autosomal dominant nonsyndromic hearing loss.

METHODSA genome wide screening was performed with 394 microsatellite markers distributed with an average spacing of 10 cM (ABI Prism Linkage Mapping Set 2, Applied Biosystems, Foster City, CA, U.S.A.).

RESULTSAffected family members showed a bilateral, symmetrical, progressive neurosensory deafness. Significant linkage was found to marker D1 S937 (maximum two point LOD score of 5. 71 at theta = 0.05) on chromosome 11q. The position of the novel deafness locus, DFNA11, was delimited by analysis of the recombinant haplotypes (D11S165-D11S1874). This analysis placed DFNA11 between the proximal marker D11S1314 and the distal marker D11S898, which define a critical interval of 25.34 cM.

CONCLUSIONSMapping of the DFNA11 locus further confirms the great genetic heterogeneity underlying the autosomal dominant forms of hereditary deafness. Reports of more families with hearing impairment linked to this locus should contribute to the identification of the responsible gene, providing insights into the auditory function and the molecular pathophysiology of age related hearing loss.

Adult ; Aged ; Chromosome Mapping ; Deafness ; congenital ; genetics ; Female ; Genes, Dominant ; Haplotypes ; Humans ; Male ; Microsatellite Repeats ; Middle Aged ; Myosins ; genetics ; Pedigree ; Young Adult

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

OBJECTIVETo characterize the audiological features in the infants with otitis media with effusion (OME) and to investigate the utility of variety of objective audiometry methods in diagnosis and intervention on OME.

METHODSFifty six infants (40 males and 16 females) were investigated, who were referred to our clinic at the General Hospital of Chinese People's Liberation Army by the other hospitals from December 2004 to June 2007 when the infants were diagnosed or highly suspected of OME. The ages at the initial diagnosis ranged from 42 days to three years, with an average of five months. The infants, after receiving the conventional otolaryngological exams, were subjected to the tests of auditory brainstem response (ABR), otoacoustic emission (OAE), tympanometry (226 Hz and 1000 Hz) and behaviors audiometry.

RESULTSAmong 56 affected infants, 87 ears were diagnosed with OME, of which 31 infants were affected bilateral and 25 with monaural. For the 49 infants who received hearing screening at birth, 36 infants were referred at the initial screening. For the 52 infants who received repeated screening, all subjects were referred. Six infants without receiving hearing screening came to clinic when their parents observed their kids' hearing impairment. Among the 52 cases (104 ears) who received tympanometry test, 20 subjects (28 ears) showed B or C type tympanometry curve. Thirty-nine cases (78 ears) were given tympanometry test at 1000 Hz, of which 38 cases (55 ears) showed abnormal hearing. Among 56 infants (112 ears) with ABR test, 49 subjects (74 ears) exhibited prolonged ABR type I curve. All 56 infants (112 ears) received OAE test, of which 55 subjects (81 ears) were referred. Four infants (8 ears) accepted the behavior test and all of them showed A-B Gap.

CONCLUSIONSThe combined tympanometry test at both 226 Hz and 1000 Hz, ABR latency or threshold test, infant's behavior test and OAE, used jointly, enable characterizing better OME in infants, thus helping early diagnosis of this hearing disorder.

Acoustic Impedance Tests ; Child, Preschool ; Evoked Potentials, Auditory, Brain Stem ; Female ; Humans ; Infant ; Male ; Otitis Media with Effusion ; physiopathology

OBJECTIVETo discuss and analyze the feasibility and strategy for perform the newborn gene screening in the process of newborn hearing screening in order to supply the defects or limitation in the hearing screening.

METHODSFour hundreds and sixty newborn babies from December 2006 to April 2007 accepted the simultaneous hearing and gene screening. Otoacoustic emission (OAE) was used for the first step hearing screening and OAE combined with auto auditory brainstem response (AABR) detection for the second step screening. Newborn genetic disease screening cards were used for collecting the blood spot from the umbilical cord within the moment of newborn. The cards could be directly performed the polymerase chain reaction (PCR) for screening the mitochondrial 12SrRNA 1555G and GJB2 as well as SLC26A4 genes mutations. The restriction enzyme Alw26I was used to recognize the point mutation of 12SrRNA A1555G. The samples with the possible 12SrRNA A1555G mutation were then sequenced to verify. The PCR products from the GJB2 coding region and SLC26A4 IVS7-2A > G hot spot region were sequenced directly. The software of DNAStar was used to analysis the sequence.

RESULTSThe first step of hearing screening of 460 newborn babies showed " refer" on the left ear of nine babies and on the right ear of three babies. Seven showed "refer" on bilateral with the the total of babies 19. After 42 days, they accepted the second step for hearing screening. 16 of the 19 were showed "pass" with OAE and AABR. One baby showed "pass" on the left ear, "refer" on the right ear with the OAE detection but bilateral "pass" with AABR. Two babies failed to accept the re-examination. The newborn gene screening showed five of the 460 babies had the positive response on the A1555G restriction enzyme assay. Of the five babies, one was proved to be the 12SrRNA A1555G mutation and three were the C1556T mutations and one sequence was normal. For the SLC26A4 gene screening, five were the heterozygote of IVS7-2A > G mutation were found and one was carrier the polymorphism of IVS7-18T > G and another was IVS6-62_63insGT heterozygote carrier. For the GJB2 gene screening, eight were 235delC heterozygote carriers, four were G109A heterozygote carriers. All the gene screening found 23 newborn babies of the 460 harbored the changes in the three genes. Of those, one was the 12SrRNA A1555G. pathogenic mutation and 13 were pathogenic heterozygote carriers, nine were the polymorphisms. It was worth to pay more attentions that A1555G mutation was found in the baby whose hearing screening was "pass" in the hearing screening as well as the 13 heterozygote carrier for GJB2 and SLC26A4 gene.

CONCLUSIONSIt might be one of the powerful strategy for adding the concept of newborn gene screening into the hearing screening for the purpose of early diagnosis and discovery the prelingual or late-onset or the high risk as well as the pathogenic carriers. On the basis of the research progress, it was necessary to develop the national newborn gene screening into the process of newborn hearing screening.

Connexins ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Disorders ; diagnosis ; genetics ; prevention & control ; Hearing Tests ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; Point Mutation

OBJECTIVETo investigate the prevalence of the mitochondrial DNA (mtDNA) A1555G mutation in nonsyndromic hearing impairment (NSHI) patients from Gansu province.

METHODSSubjects included 802 students selected from five Deaf-Mute Schools in Gansu. DNA was extracted from peripheral blood of all patients. The mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). The Mutations were detected by AIw26I digestion and sequence analysis.

RESULTSThe homoplasmic A1555G mutation was found in 67 individuals from 802 patients (8.4%). Fifteen of these 67 patients had family histories.

CONCLUSIONSThe mtDNA A1555G mutation had a higher incidence in Gansu population with nonsyndromic hearing impairment than other studies. The data not only gaven more evidences that the prevalence of mtDNA A1555G mutation in china was higher than that in Europe and America, but also gaven valuable information for gene diagnosis, genetic counseling and would improve the safety of aminoglycoside antibiotic therapy.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Female ; Humans ; Male ; Mutation ; Young Adult

BACKGROUNDThere are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI), including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI). Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI.

METHODSTo decipher the genetic code of a Chinese family (family 686) with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years.

RESULTSWe identified a pathogenic missense mutation, c. 2081G>A (p.G694E), in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL). The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136* and p.G45E in the GJB2 gene may account for the phenotype shown in this patient.

CONCLUSIONSWe identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

Adult ; Aged ; Asian Continental Ancestry Group ; Connexins ; genetics ; Exome ; genetics ; Female ; Genetic Linkage ; genetics ; Haplotypes ; genetics ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; genetics ; Pedigree ; Young Adult ; Zonula Occludens-2 Protein ; genetics

Objective: To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis. Methods: The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score <2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test. Results: The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ²=14.57, P<0.01). Conclusions: Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission.
8-Hydroxy-2'-Deoxyguanosine ; Aged ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions (i.e. frontoinsular cortex), and ECN-related brain regions (i.e. frontal middle gyrus and frontal inferior); (2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control (HC) groups, but no significant difference was observed between the aMCI and HC groups; and (3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination (MMSE) and Montreal Cognitive Scale (MOCA) scores and their factor scores in the AD, aMCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the aMCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.
Aged ; Aged, 80 and over ; Alzheimer Disease/physiopathology* ; Brain/diagnostic imaging* ; Brain Mapping ; Cognitive Dysfunction/physiopathology* ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory ; Middle Aged ; Models, Neurological ; Nerve Net

Objective::To study the protective effect of astragalus polysaccharide (APS) on micronucleus and sister chromatid exchange (SCE) in human bone marrow mesenchyml stem cell (BMSCs) exposed to formaldehyde, in order to initially explore the potential mechanism. Method::BMSCs were cultured in vitro, cells were randomly divided into five groups: control group, formaldehyde group, and APS 40, 100, 400 mg·L^-1 groups. BMSCs were infected with 120 μmol·L^-1 formaldehyde, meanwhile, APS 40, 100, 400 mg·L^-1 groups were co-cultured with 40, 100, 400 mg·L^-1 APS. Cell morphology was observed by inverted phase contrast microscope, micronucleus were detected by micronucleus test, SCE was detected by SCE test, and mRNA and protein expressions of proliferating cell nuclear antigen (PCNA), xeroderma pigmentosum B, D, F, G (XPB, XPD, XPF, XPG) were detected by quantitative real-time fluorescence polymerase chain reaction(Real-time PCR)and Western blot. Result::Compared with control group, cell counts decreased, and cell morphology of BMSCs in formaldehyde group significantly changed, they were all recovered gradually in 40, 100, 400 mg·L^-1 APS groups. Compared with control group, the micronucleus and SCE increased significantly (P<0.01), PCNA mRNA and protein expressions down-regulated significantly (P<0.05), while XPB, XPD, XPF, XPG mRNA and protein expressions up-regulated significantly (P<0.05, P<0.01). Compared with formaldehyde group, BMSCs were treated with APS at 40, 100, 400 mg·L^-1, micronucleus and SCE decreased significantly (P<0.01), and mRNA and protein expressions of PCNA, XPB, XPD, XPF and XPG up-regulated significantly (P<0.05, P<0.01). Among them, the 100 mg·L^-1 APS group had the most obvious effect. Conclusion::APS can protect formaldehyde-induced BMSCs micronucleus and SCE, especially 100 mg·L^-1 APS has the most obvious effect. The mechanism may be associated with the up-regulation of expressions of PCNA, XPB, XPD, XPF and XPG in the nucleotide exicision repair pathway (NER), which promoted the damage repair.