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Abstract Background Aminoglycoside ototoxicity is one of the common health problems. Mitochondrial 12S rRNA mutations are one of the important causes of aminoglycoside ototoxicity. However, the incidences of 12S rRNA mutations associated with aminoglycoside ototoxicity are less known. Methods A total of 440 Chinese pediatric hearing-impaired subjects were recruited from two otology clinics in the Ningbo and Wenzhou cities of Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of mitochondrial 12S rRNA. Resultant mtDNA variants were evaluated by structural and phylogenetic analysis. Results The study samples consisted of 227 males and 213 females. The age of all participants ranged from 1 years old to 18 years, with the median age of 9 years. Ninety-eight subjects (58 males and 40 females) had a history of exposure to aminoglycosides, accounting for 22.3% cases of hearing loss in this cohort. Molecular analysis of 12S rRNA gene identified 41 (39 known and 2 novel) variants. The incidences of the known deafness-associated 1555A > G, 1494C > T and 1095T > C mutations were 7.5%, 0.45% and 0.91% in this entire hearing-impaired subjects, respectively, and 21.4%, 2% and 2% among 98 subjects with aminoglycoside ototoxicity, respectively. The structural and phylogenetic evaluations showed that a novel 747A > G variant and known 839A > G, 1027A > G, 1310C > T and 1413T > C variants conferred increased sensitivity to aminoglycosides or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants were polymorphisms. Of 44 subjects carrying one of definite or putative deafness-related 12S rRNA variants, only one subject carrying the 1413T > C variant harbored the 235DelC/299DelAT mutations in the GJB2 gene, while none of mutations in GJB2 gene was detected in other 43 subjects. Conclusions Mutations in mitochondrial 12S rRNA accounted for ~30% cases of aminoglycoside-induced deafness in this cohort. Our data strongly support the idea that the mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity. These data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.

To investigate the role of mitochondrial modifiers in the development of deafness associated with 12S rRNA A1555G mutation.Four Chinese families with nonsyndromic and aminoglycoside-induced deafness were studied by clinical and genetic evaluation, molecular and biochemical analyses of mitochondrial DNA (mtDNA).These families exhibited high penetrance and expressivity of hearing impairment. Penetrances of hearing loss in WZD31, WZD32, WZD33, and WZD34 pedigrees ranged from 50 to 67% and from 39 to 50%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Matrilineal relatives in these families developed hearing loss at the average of 14, 13, 16, and 15 years of age, respectively, when aminoglycoside-induced deafness was excluded. Mutational analysis of entire mtDNA in these families showed the homoplasmic A1555G mutation and distinct sets of variants belonging to haplogroup B5b1. Of these, the tRNAThr G15927A mutation locates at the fourth base in the anticodon stem (conventional position 42) of tRNAThr. A guanine (G42) at this position of tRNAThr is highly conserved from bacteria to human mitochondria. The lower levels and altered electrophoretic mobility of tRNAThr were observed in cells carrying A1555G and G15927A mutations or only G15927A mutation but not cells carrying only A1555G mutation. The abolished base pairing (28C-42G) of this tRNAThr by the G15927A mutation caused a failure in tRNA metabolism, worsening the mitochondrial dysfunctions altered by the A1555G mutation.The G15927A mutation has a potential modifier role in increasing the penetrance and expressivity of the deafness-associated 12S rRNA A1555G mutation in those Chinese pedigrees. [ABSTRACT FROM AUTHOR]

It remains unclear whether the Glutathione S-transferase M1 (GSTM1) null genotype influence laryngeal cancer development. This study aimed to investigate the interactions among GSTM1 genotype with regard to laryngeal cancer development. We searched online electronic databases (PubMed, EMBASE and CNKI). The strength of association between the GSTM1 genotype and laryngeal cancer risk was assessed by calculating OR with 95% CI. Finally, a total of 25 case-control studies with 2999 cases and 4942 controls on the association between GSTM1 genotype and laryngeal cancer risk were included in this meta-analysis. The overall result showed that the GSTM1 null genotype was related to an increased risk of laryngeal cancer (OR = 1.34; 95% CI, 1.09-1.63). Subgroup analysis was performed according to ethnicity. The results showed that Asians had an increased risk of laryngeal cancer (OR = 1.90; 95% CI, 1.40-2.57), while no significant increased risk was observed in Caucasians (OR = 1.15; 95% CI, 0.97-1.36). In conclusion, this meta-analysis suggested that GSTM1 null genotype was significantly associated with increased laryngeal cancer risk.

Objective: This study was designed to explore the risk factors associated with severity of juvenile onset recurrent respiratory papillomatosis., Method: A retrospective study was conducted to study determinants of severe forms of juvenile recurrent onset respiratory papillomatosis. The patients were separated into different groups based on the onset age, the first recurrence of age, the first recurrence of period, gender and incision of tracheal respectively. The relationship among the lesion severity score,the involvement of the subregion, operation period and the next operation period were also explored., Result: It was observed that some children who recurred before 4 years old required more surgery, shorter operation period(the average, longest or shortest operation period) than those elder children, the differences were statistically (P=0. 029, 0. 003, 0. 010, 0. 039, respectively). The severity score of lesion was correlated positively with the involvement of the subregion and negatively with operation period (r=0. 914, -0. 451, respectively). Some children who diagnosed before 4 years old had to endure more severity score and shorter operation period than those older children, the differences were statistically (P= 0. 036, 0. 000, respectively). 8 cases accepted incision of tracheal, they accepted more surgery too. But the differences in the onset age, the first recurrence of age, and the operation period were not statistically., Conclusion: The results showed that the clinical course of juvenile onset recurrent respiratory papillomatosis was closely related to the first recurrence age and period, while the severity of disease was associated to the onset age and the involvement of the subregion.

Objective: To investigate the correlation between nonsyndromic deafness and mitochondrial 12s rRNA A839G mutation., Methods: According to the clinical manifestations of mitochondrial DNA sequencing and analysis to find and determine family containing mitochondrial 12s rRNA A839G mutation. Harvested its family members blood and transferred their lymphocytes into lymphoblastoid cell lines, followed by cells cultured, cell doubling experiment, susceptibility testing, cellular oxygen consumption rate experiment, ROS and mitochondrial membrane potential experimental tests were progressed to explore the correlation between the A839G mutation and nonsyndromic deafness., Results: The mitochondrial 12s rRNA A839G mutation pedigrees were determined through the full sequence detections of the Mitochondrial DNA, further phylogenetic analysis showed that 839 point conservative index (CI) up to 78.6%; in RPMI-galactose medium containing A839G gene mutant cell line, the doubling time was significantly longer than the control group, and the difference was significant (P = 0.033). The effect to cell lines containing the A839G mutation of aminoglycoside drugs was not obvious. When compared with the control group, cell lines containing the A839G mutation significantly reduced cellular oxygen consumption rate(P = 0.033); compared with the control group, the ROS levels of cell lines containing the A839G mutation appeared more substantial elevated with significan difference (P < 0.01). The mitochondrial membrane potential of cells of experimental group was significantly reduced than the control group., Conclusion: The present study proved that the mitochondria 12s rRNA A839G mutations affect the function of the mitochondrial respiratory chain at the cell level, which might reduce the growth rate of the mutant cell lines, result in hearing.

Objective: To explore the relationship between serum IL-4, IFN-gamma, IL-10 levels and the aetiology of juvenile-onset recurrent respiratory papillomatosis., Method: Serum IL-4, IFN-gamma, IL-32 levels of 15 JORRP children were detected by use of enzyme-linked immunosorbent assay (ELISA) and compared with those of healthy control group., Result: Serum IL-4 levels were significantly higher in the JORRP children (P<0.01): (524.65 +/- 147.77)pg/ml in the JORRP children and (213.27 +/- 87.48) pg/ml in the healthy control group. Serum IFN-gamma levels were significantly lower in the JORRP children (P<0.01): (2.87 +/- 0.84) pg/ml in the JORRP children and (10.63 +/- 5.09) pg/ml in the healthy control group. Serum IL-32 levels were significantly lower in the JORRP children (P< 0.01): (2.47 +/- 1.60) pg/ml in the JORRP children and (9.08 +/- 2.66) pg/ml in the healthy control group., Conclusion: 1) While the concentration of Th2 like cytokine IL-4 in children with JORRP was higher than that in control group, the concentration of Th1 like cytokine IFN-gamma in children with JORRP was lower than that in controls, indicating that the polarization of Th1 /Th2 T cell in children with JORRP; 2) The polarization of Th1/Th2 T cell may cause the reduction of the serum IL-32 as a proinflammatory role in host immunity system that could not eradicate HPVs because of lacking enough inflammatory stimulation.

Objective: To study the safety and the immunogenicity of HPV6b virus-like particles (VLP) in children with juvenile laryngeal papilloma (JLP). The result of therapy is observed., Method: HPV6b VLP were expressed with HPV6b L1 recombinant baculovirus in sf-9 insect cells. Ten case of recurrent JLP were immunized with HPV6b VLP in 5, 10, 25 microg doses progressively and any local or systemic adverse events were recorded. By ELISA was used to detect the serum HPV6b VLP antibody (Ab) of JLPs samples in therapy different stage. Seven cases of JLP were used DTH test. To understand the effects of VLP on disease prognosis subjects will be examined by fibrolaryngoscope., Result: All subjects did not experience local or systemic adverse events and specific serum antibody against HPV6b L1VLP was produced in JLP immunized. The A value of sera antibody in the first dose group have completed (0.310 +/- 0.012) were higher than that of pro-immune (0.110 +/- 0.035) (t = 4.673, P < 0.01). There was a significant difference of serum mean HPV6b Ab A value between JLP's patients immunized (0.772 +/- 0.013) and the control group (0.153 +/- 0.014) (t = 15.45, P < 0.01), 7 samples have male response of DTH test. All patients didn't recurrent papilloma after receiving treatment., Conclusion: HPV6b VLP have immunogenicity and safety as therapy for JLP patients, and HPV6b VLP may be used in prophylactic and therapeutic vaccine for JLP.