[A follow-up study of abnormal mutation in neonatal deafness gene screening].

Objective: To screen, diagnose and follow up the abnormal mutation in the gene screening of neonatal deafness. Methods: A total of 24161 newborns born in Zhuhai Maternal and Child Health Hospital from February 1, 2015 to January 31, 2008 were screened for hearing and deafness genes, and audiological screening, diagnosis and 1-3 years follow-up were carried out for the newborns with positive gene screening. Results: There were 991 cases of deafness gene mutation (533 males and 458 females), and the rate of abnormal mutation was 4.10%(991/24 161). Among them, 921 cases were single heterozygous mutation, 130 cases were failed in primary hearing screening, 11 cases were failed in secondary hearing screening, 8 cases were abnormal in audiological diagnosis finally. In these 8 cases, 3 were diagnosed as otitis media and passed audiological follow-up after cure, 2 cases of single ear sensorineural injury caused by high-risk factors, passed after close audiological follow-up, and the other 3 cases were closely audiological follow-up while none of them were successfully sequenced. All of them were moderate to severe sensorineural deafness, 1 case was heterozygous mutation at 3 loci of GJB2(c.235delC,c.408C>A,c.134G>A), 1 case was heterozygous mutation at 2 loci of GJB2(c.235delC, c.109G>A), and 1 case was single heterozygous mutation of GJB2(c.235delC). The remaining 913 cases who passed the primary screening, secondary screening or hearing diagnosis were followed up for 1 to 3 years. Three cases of multiple heterozygous mutation were found in gene screening(2 cases were SLC26A4 2168A>G, IVS7-2A>G, 1 case was GJB2 c.176_191del 16bp, c.299_300del AT), all of them passed both primary and secondary hearing screening. In these 3 cases, the final audiological diagnosis was moderate sensorineural deafness in both ears, with no improvement in the follow-up of 1-3 years. There were 9 monogenic homozygous mutations, 7 failed in primary hearing screening, 3 failed in secondary hearing screening and also failed in audiological diagnosis and 1-3 years' audiological follow-up, all of whom were GJB2 c.235 del C homozygous mutations, and one of whom had a definite family history of deafness. The remaining 6 cases of homozygous mutation diagnosed by primary screening, secondary screening or hearing diagnosis were GJB2 c109G>A homozygous mutation, and passed the 1-3 years' hearing follow-up. 58 children with mtDNA mutations, including 2 with 12S rRNA 1494C>T homozygous mutation, 47 with 1555A>G homozygous mutation, and 9 with 1555A>G heterozygous mutation, all passed the primary or secondary hearing screening, and were instructed to ban ototoxic drugs for the whole life, and passed the 1-3 years' hearing follow-up. Conclusions: The audiological follow-up of children with monogenic heterozygous mutations in deafness gene screening is generally normal. In case of abnormality, the influencing factors such as otitis media should be excluded at first. In case of unexplained moderate to severe sensorineural deafness, the whole-gene sequencing should be performed to find possible pathogenic factors. The children with homozygous mutation or compound heterozygous mutation in gene screening, most of whom show different degrees of hearing loss, should be followed up for a long time, and provide parents with scientific and reasonable genetic counseling according to the mutation genes and loci,. The hearing of drug-induced deafness gene carriers is normal after birth. Parents should be advised to strengthen prevention and follow-up is generally enough.

[Analysis of the incidence and mortality of leukemia in the cancer registration area of Zhejiang Province from 2010 to 2014].

The incidence and mortality rate of leukemia in the cancer registration areas of Zhejiang Province from 2010 to 2014 were analyzed to depict their epidemiological characteristics. From 2010 to 2014, 3789 new cases were diagnosed as leukemia in Zhejiang cancer registration areas, with a crude incidence rate of 6.47 per 100 000. The age-standardized incidence rate of males (standardized by China census data 2000) was 1.35 times that of females. The age-standardized incidence rate of urban areas was similar to that in rural areas (1.04∶1). From 2010 to 2014, 2 568 cases died due to leukemia, with a crude mortality rate of 4.38 per 100 000. The age-standardized mortality rate of males was 1.44 times that of females. The age-standardized mortality rate of urban areas was 0.99 times that of rural areas. The age-standardized incidence and mortality rate did not show any significant change from 2010 to 2014. The annual percent change of these two metrics was -2.36% (t=-0.62, P=0.579) and -3.46% (t=-2.41, P=0.095).

[Incidence and mortality of thyroid cancer in cancer registries of Zhejiang Province, 2010-2014].

From 2010 to 2014, a total of 17 150 new cases of thyroid cancer (TC) reported in cancer registration areas of Zhejiang province, the crude incidence rate of TC was 29.28/100 000. Using the Chinese Census in 2000 and the World Segi's population as the standard population, the age-standardized incidence rate by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 24.11/100 000 and 20.65/100 000 respectively. 256 TC death cases reported in all, the crude mortality rate was 0.44/100 000, the age-standardized mortality rate by Chinese standard population (ASMRC) and by World standard population (ASMRW) were 0.23/100 000 and 0.23/100 000 respectively. The ASIRC had a upward trend [annual percent change (APC)=28.62%, 95%CI: 21.00%-36.72%, t=13.10, P=0.001], while the ASMRC trend seemed stable (APC=0.73%, 95%CI: -7.47%-9.66%, t=0.27, P=0.803).

[Congenital ear deformity screening and non-invasive correction effect analysis].

Objective:To synchronously perform external auricle examination during neonatal hearing screening, follow up auricle deformity with neonatal disease screening system, and calculate the incidence of auricle deformity, self-healing rate, correction rate, incidence of complications and the relationship with hearing loss in Zhuhai area. Method:According to the diagnostic criteria of auricle deformity, the newborns in Zhuhai Maternal and Child Health Hospital were examined on the spot within 2 months. The deformity auricle was registered and uploaded into the newborn hearing screening system. The newborns were followed up by short message notification 7 days after birth, and then compared with the photo uploading system again. At 14 days, the ears of those who could not self-heal were went on non-invasive correction, and collect of relevant data for summary analysis. Result:Among the 1 073 newborns(2 146 ears), 26(37 ears) with malformed ears were treated with auricular pattern correction.The corrective rates of newborns less than 14 days, 14-30 days and 31-60 days were 95%, 90% and 87% respectively, and the incidence of complications were 50%, 58% and 69%, respectively. Conclusion:The incidence of auricular deformities in neonates is high. The earlier correction the better. The ear deformity can be detected at the earliest stage and missed diagnosis can be avoided by simultaneous hearing screening and ear deformity screening. During the window period of 7-14 d, by monitoring the self-healing rate of the affected ear excessive medical correction can be avoided. By hearing screening system statistics, ear shape malformation is not directly related to hearing loss.

[Hearing assessment and follow-up study of aeonatal deafness gene screening homozygous mutation infants].

Objective:To analyze the hearing assessment characteristics and follow-up of some deafness gene screening homozygous infants in Zhuhai. Method:The clinical data of 28 newborns with homozygous mutations transferred to Zhuhai Maternal and Child Health Hospital from Feb. 1, 2015 to Oct. 25, 2018 in hospitals of Zhuhai City were retrospectively analyzed. All the children were screened for hearing. The hearing characteristics and long-term follow-up results of homozygous mutations at different gene sites were analyzed by auditory diagnosis and behavioral follow-up from 1 to 3 years. Result:Fourteen cases of GJB2 c.109G>A with a homozygous mutation, 11 cases passed the hearing screening, the audiological diagnosis was normal, and the behavior test and follow-up were normal from 1 to 3 years. Hearing screening was not passed in 3 newborns, mild to moderate abnormalities of single or bilateral ears were diagnosed by audiology, 1 000 Hz without positive, and middle ear lesions were diagnosed. Eight cases of GJB2 c.235del C homozygous mutation were followed up by behavioral audiometry and follow-up from 1 to 3 years after cure. Among them, 5 cases were diagnosed as severe hearing impairment of bilateral ears and 3 cases as mild and moderate hearing impairment. One case of GJB3 547G>A homozygous mutation was followed up for 1-3 years, and all of them failed to pass the follow-up of behavioral audiometry and follow-up. Four cases of SLC26A4 IVS7-2A>G, 1 case of SLC26A4 1229C>T homozygous mutation, all of them failed to pass the neonatal hearing screening. All the patients were diagnosed as severe hearing impairment of binaural hearing, and the follow-up of 1-3 years' follow-up did not pass the follow-up tests. Conclusion:GJB2 C.235del C, SLC26A4 IVS7-2A>G locus homozygous mutation infant hearing impairment was mainly severe hearing impairment in bilateral ears, and there was no change in 1-3 years follow-up. GJB2 C.109G A homozygous mutant infants had normal hearing, and it was suggested that they should be followed up closely. It is very important to give correct and reasonable genetic counseling to parents with GJB2 C.109G A homozygous mutation without unnecessary panic.

Structure of transmembrane subunits gp47 of the foamy virus envelope glycoproteins.

The successful foamy viruses (FVs) infection includes at least two essential events, attachment to the cell surface and fusion of the viral envelope with the cell membrane. For the FVs, membrane fusion between virus and cell is mediated by envelope glycoprotein (Env) transmembrane (TM) subunit gp47. Compared with other retroviruses, FV TM subunit shares a similar but not identical structural characteristic. This paper focuses on in sillico analyses of all 15 available FV TM subunits gp47 based on their amino acid sequences. The hydrophobicity analysis revealed that the 15 FVs gp47 had two prominent hydrophobic regions, the N-terminal fusion peptide (FP) and the C-terminal region, which included a membrane-spanning domain (MSD) and a membrane proximal ectodomain region (MPER). In most FVs gp47, two heptad repeats, the coiled coils characterized by repetition of 7-amino acid-motif, were found to be correspondently located downstream of FP (named "N-HR") and the upstream of MPER (named "C-HR"). Furthermore, the solvent accessibility and secondary structure were predicted for all FVs gp47. These observations suggested that FVs gp47 possessed several fusion domains, which were necessary in the process of lipid membrane fusion between FVs and the target cells.

Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcomes of patients with advanced non-small cell lung cancer.

We investigated the association between the polymorphisms GSTP1 rs1695 and XRCC1 rs1799782 and rs25487 and the clinical outcome of patients with non-small cell lung cancer (NSCLC) receiving cisplatin-based chemotherapy. Genotyping of GSTP1 rs1695 and XRCC1 rs1799782, and rs25487 was conducted by polymerase chain reaction-restriction fragment length polymorphism analysis. By conditional logistic regression analysis, patients carrying the GG genotype of GSTP1 rs1695 and the AA genotype of XRCC1 rs25487 were found to be more highly associated with response to chemotherapy than were those carrying the AA genotype; the ORs (95%CIs) were 0.13 (0.04-0.37) and 3.37 (1.44-8.53), respectively. Presence of the GG genotype of GSTP1 rs1695 and the GA and AA genotypes of XRCC1 rs25487 was associated with overall survival of NSCLC, and the hazards ratios (95%CI) were 4.35 (1.40-17.92), 0.53 (0.31-0.91), and 0.39 (0.18-0.83), respectively. The results of our study suggest that the GSTP1 rs1695 and XRCC1 rs25487 polymorphisms might affect the clinical outcome of patients with advanced NSCLC receiving cisplatin-based chemotherapy.

Immuno-inflammatory regulation effect of mesenchymal stem cell transplantation in a rat model of myocardial infarction.

BACKGROUND: Mesenchymal stem cells (MSC) have recently been shown to possess immunomodulatory properties in vitro and in vivo. The present study aimed to investigate the regulatory effect of MSC transplantation on the immuno-inflammatory response in myocardial infarction (MI). METHODS: MI was induced in Sprague-Dawley rats by left anterior descending coronary artery ligation, and the animals were randomly assigned into the following three groups: sham ( n=8); phosphate-buffered saline (PBS) injected (MI+PBS, n=8); and MSC transplantation (MI+MSC, n=8). BrdU-labeled MSC or PBS was transplanted into peri-infarct myocardium by direct myocardial injection. At 1 and 28 days post-transplantation, cardiac function was evaluated by echocardiography. Transplanted cells were investigated through immunohistochemistry. Lymphocyte cytotoxic activity was evaluated with the crystal violet method. The activity of NF-kappaB and protein expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-10 in myocardium were assessed by immunohistochemistry and Western blot. RESULTS: Echocardiographic examination revealed that the MSC transplantation prevented left ventricular dilation and dysfunction at 28 days after the operation. BrdU-stained cells were found living in host heart 4 weeks after transplantation. MSC transplantation attenuated the cytotoxic activity of spleen lymphocytes. Transplantation of MSC inhibited the activity of NF-kappaB, attenuated the protein production of TNF-alpha and IL-6, and increased the expression of IL-10 in peri-infarct myocardium. DISCUSSION: MSC transplantation modulated the immuno-inflammatory response in MI. The immuno-inflammatory regulatory effect of MSC transplantation might partly account for the cardiac protection in myocardial infarction.