[Postoperative rehabilitation effect and influence factors of adult prelingual deafness with cochlear implant].

Objective: To investigate whether pre-lingual deafness adult caused by inadequate auditory compensation in childhood can benefit from cochlear implants and the related influencing factors. Methods: A total of 26 prelingual deafness as experimental group [11 males and 15 females, the age of operation was (24.5±5.7) years] and 13 postlingual deafness as control group [5 males and 8 females, the age at the time of operation was (42.2±11.4) years] were recruited. Objective assessment included hearing threshold and speech recognition rate tests while wearing cochlear implants. Subjective assessment used Nijmegen Cochlear Implant Questionnaire to assess hearing-related quality of life of subjects. The changes of hearing ability in the prelingual deafness group before and after operation and the differences with the postlingual deafness group were compared, and the correlation between speech recognition ability and the age diagnosed as severe or profound deafness, the age of hearing aid invalid, and duration of wearing cochlear implant were analyzed as factor indicators. All statistical results were analyzed by SAS 9.4 software. Results: In terms of objective indicators, the speech recognition rate of pre-lingual deafness was significantly lower than that of post-lingual deafness [(35.4±28.0)% vs (80.9±8.0)%,t=7.67, P<0.001], while there was no statistical difference in hearing threshold between the two groups [(34.8±4.0) dB HL vs (33.1±3.7) dB HL, t=1.30, P>0.05]. The indicators in the subjective questionnaire showed that the prelingual deafness group was only weaker in advanced sound perception, confidence and total mean score than the post-lingual deafness group (P<0.05), and there was no significant difference in other aspects(P>0.05), meanwhile, all indicators of the prelingual deafness group were significantly improved compared with the preoperative level (P<0.001). There was a moderate positive correlation between the hearing quality and the speech recognition rate in the prelingual deafness group(r=0.51, P=0.008). The regression analysis showed that the invalid age of hearing aid was the exact influencing factor of speech recognition rate. Conclusions: Certain prelingual deaf adults can adapt to cochlear implants and obtain different degrees of auditory assistance. Compared with the improvement of objective auditory ability assessment, the patient who received cochlear implantation gain more improvement in auditory related quality of life subjectively. The ineffective age of preoperative hearing aid is an important factor, which needs to be aroused sufficient preoperative attention.

[Coverage rate and adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy: a cross-sectional retrospective cohort study].

Objective: To investigate the coverage rate and the adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy (SMA). Methods: A cross-sectional retrospective cohort study was carried out from July 2016 to June 2019, 192 children (116 boys and 76 girls) with SMA registered by Capital Institute of Pediatrics and 191 healthy children (115 boys and 76 girls) vaccinated in Chaoyang Olympic Village Community Health Service Center from July 2016 to December 2018 were included. Questionnaire survey was designed to investigate the vaccination coverage rate and associated adverse events. The t-test and χ(2) test were used to compare the difference between SMA patients and healthy children. Results: The coverage rate of age-appropriate immunization in SMA children was 62.0% (119/192) in general, and were 52.2% (12/23), 55.7% (68/122), and 83.0% (39/47) for SMA type 1-3 patients, respectively (χ(2)=12.23, P=0.002). The vaccination coverage rates of Bacillus Calmette-Guerin (BCG) vaccine, the 3(rd) dose of hepatitis B, the 3(rd) dose of polio, the 3(rd) dose of diphtheria-pertussis-tetanus, the 1(st) dose of meningococcal polysaccharide group A, the 1(st) dose of measles or measles and rubella vaccine, the 1(st) dose of Japanese encephalitis vaccine, hepatitis A, measles-mumps-rubella, and group A+C meningococcal polysaccharide vaccine were 100.0% (192 cases), 94.3% (181 cases), 81.8% (157 cases), 88.5% (170 cases), 83.9% (161 cases), 76.6% (147 cases), 80.2% (154 cases), 68.2% (131 cases), 69.8% (134 cases), 54.7% (105 cases), respectively. Among the 73 patients who did not have their planned immunization completed, 57 cases (78.1%) gave up the vaccination due to parents' concern of potential aggravation of their disease, and 16 cases (21.9%) had the plan discontinued by the immunization department because of the disease. Fever, local redness and swelling were the most common side-effects after vaccination both in SMA patients and healthy children (19.8% (38/192) vs. 18.8% (36/191) , χ(2)=0.055, P=0.815). The main abnormal reactions of vaccination were rash and neurovascular edema, without significant difference between these two groups (2.6% (5/192) vs. 3.7% (7/191), χ(2)=0.355, P=0.551). The coverage rate of Influenza and pneumococcal vaccine in SMA patients were 22.4% (43 cases) and 31.8% (61 cases), respectively. The incidence of pneumonia in the SMA patients decreased from 59.0% (23/39) to 41.0% (16/39) after vaccination. And none of the Influenza vaccinated patients had the flu in the year of vaccination. Conclusions: The coverage rate of National Immunization Program vaccines in the SMA children is low, especially in type 1 SMA patients, which is mainly due to their guardians' concern of potential adverse events, even though the incidence of adverse reactions is similar in SMA patients and healthy children. Influenza and pneumococcal vaccine can reduce the risk of pneumonia and flu in children with SMA effectively.

[Sanger sequencing for the diagnosis of spinal muscular atrophy patients with survival motor neuron gene 1 compound heterozygous mutation].

Objective: To detect the subtle variant of survival motor neuron gene 1(SMN1) by Sanger sequencing, and to assess the value of Sanger sequencing for the diagnosis of spinal muscular atrophy(SMA) with compound heterozygous mutation of SMN1. Methods: Fifty-two patients suspected SMA were recruited by the Capital Institute of Pediatrics from Jan.2014 to June.2016. PCR was used for amplifying exon7 of SMN1 and SMN2 in 52 patients. Natural different base peaks on the sequencing chromatogram in the SMN1 and SMN2 within the amplified segments were identified with Sanger DNA sequencing to detect the homozygous deletion or heterozygous deletion of SMN1. Then we screened the SMN1 subtle variants in heterozygous deletion patients by genomic Sanger sequencing for the other SMN exons. At last, multiplex ligation-dependent probe amplification(MLPA) was carried out to confirm the results of SMN1 heterozygous deletion, and T-A cloning confirmed the subtle variants were located in SMN1. Results: Forty-seven of 52 cases were homozygous deletion of SMN1, while 5 cases were heterozygous deletion which were confirmed by MLPA.Then, by genomic and T-A cloning sequencing, five SMN1 subtle mutations were separately identified in 5 cases of heterozygous deletion. Conclusion: Sanger sequencing is an effective method for the clinical diagnosis of compound heterozygous mutation of SMN1, and is meaningful for improving genetic diagnosis rate of SMA.

Polymorphisms in Toll-like receptor 3 are associated with asthma-related phenotypes in the Chinese Han patients.

Toll-like receptor (TLR) 3 mediates antivirus immunity and is involved in asthma exacerbation and development. However, the genetic association between TLR3 and asthma remains unclear. This study aimed to evaluate the effects of polymorphisms within TLR3 on asthma risk and asthma-related phenotypes in the Chinese Han population. A total number of 462 unrelated adult patients with asthma and 398 healthy volunteers were enrolled in this study. The genotypes of tagging single nucleotide polymorphisms (SNPs) in TLR3 gene were determined using multiplex SNaPshot SNP genotyping assays. Case-control and case-only studies were used to assess any links with asthma and asthma-related phenotypes. The results showed that the genetic variants in TLR3 were associated with asthma-related phenotypes, including eosinophil counts, serum immunoglobulin E levels and lung function. However, there was no obvious association between the TLR3 SNPs and asthma susceptibility or asthma severity. TLR3 polymorphisms may play a considerable role in the pathogenesis of asthma. It will help in better understanding the pathogenesis of asthma and development of more effective strategies for the prevention, prediction and treatment of asthma.

Multicenter, double-blind, randomized clinical trial of parenterally administered Cefoselis versus Cefepime for the treatment of acute bacterial infections.

AIM: This study aims to evaluate the clinical efficacy and safety of intravenous Cefoselis injection for the treatment of acute moderate and severe bacterial infections. PATIENTS AND METHODS: A multicenter, double-blind, randomized clinical trial was carried out using Cefepime as control. Patients received 1.0 g of either Cefoselis or Cefepime for moderate infections or 2.0 g for severe infections at an interval of 12 hours for 7 to 14 days. A total of 276 patients (138 with Cefoselis, 138 with Cefepime) with respiratory or urinary tract infections were enrolled in the study. Up to 137 and 124 patients receiving Cefoselis and 132 and 125 patients receiving Cefepime were eligible for the ITT (intent to treat) and PP (per protocol) analyses, respectively. RESULTS: At the end of the treatment, the cure rates and effective rates were 59.68% (74/124) and 93.55% (116/124) with Cefoselis, and 56.00% (74/124) and 90.40% (116/124) with Cefepime. The bacterial eradication rates of the two groups were 90.32% and 93.85%, respectively. No statistical differences were observed on the above-mentioned parameters between the two groups (all p > 0.05). Adverse events, mainly mild aminotransferase elevation and mild leukopenia, were observed in 11.59% (16/138) and 13.77% (19/138) of patients with Cefoselis and Cefepime, respectively (p > 0.05). CONCLUSIONS: Cefoselis is an effective and safe choice against acute moderate and severe respiratory infections and UTI (urinary tract infection).

Molecular and clinical characterization of Angelman syndrome in Chinese patients.

Angelman syndrome (AS) is a neurobehavioral disorder caused by lack of function of the maternal copy of the ubiquitin-protein ligase E3A (UBE3A) gene. In our study, 49 unrelated patients with classic AS phenotypes were confirmed by methylation-specific PCR (MS-PCR) analysis, short tandem repeat linkage analysis, and mutation screening of the UBE3A gene. Among the Chinese AS patients, 83.7% (41/49) had deletions on maternal chromosome 15q11.2-13. Paternal uniparental disomy, imprinting defects, and UBE3A gene mutations each accounted for 4.1% (2/49). Two AS patients were confirmed by MS-PCR analysis, but the pathogenic mechanism was unknown because their parents' samples were unavailable. Of the two described UBE3A gene mutations, that is, p.Pro400His (c.1199C>A) and p.Asp563Gly (c.1688A>G), the latter has not been reported previously. Mutation transmission analysis showed that the p.Pro400His and p.Asp563Gly mutations originated from asymptomatic mothers. The patients with the maternal deletion showed AS clinical manifestations that were consistent with other studies. However, the incidence of microcephaly (36.7%, 11/30) was lower than that in the Caucasian population (approximately 80%), but similar to that of the Japanese population (34.5%). Our study demonstrated that the occurrence of microcephaly in AS may vary among different populations.

Polymorphisms in toll-like receptor 4 gene are associated with asthma severity but not susceptibility in a Chinese Han population.

BACKGROUND AND OBJECTIVES: The toll-like receptor 4 (TLR4) gene links human innate immunity and adaptive immunity via bacterial endotoxin recognition, and plays a considerable role in the pathogenesis of asthma. The effects of the genetic variants of TLR4 on asthma are still largely unknown. This study aimed to evaluate the effects of TLR4 polymorphisms on asthma risk and asthma-related phenotypes in a Chinese Han population. METHODS: We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers. Four tagging single nucleotide polymorphisms (SNPs) in the TLR4 gene were detected using GenomeLab SNPstream or TaqMans Genotyping. We conducted case-control and case-only studies to investigate the association between the selected tagging SNPs in TLR4 and asthma and asthma-related phenotypes. RESULTS: We found no evidence to support a significant association between TLR4 SNPs and asthma susceptibility. However, our results revealed that the TT homozygote of rs1927914 was associated with lower forced expiratory volume in the first second (percent predicted) in asthmatic patients. An evidently positive association was found between asthma severity and both the TT genotype of rs1927914 and the GG genotype of rs10983755 and rs1927907 (P = .024, P = .009, and P = .013, respectively), indicating that the C allele of rs1927914 and the A allele of rs10983755 and rs1927907 have a protective effect on asthma severity. CONCLUSION: TLR4 polymorphisms do not contribute to asthma susceptibility but they may influence the severity of asthma.

Polymorphisms in the toll-like receptor 2 subfamily and risk of asthma: a case-control analysis in a Chinese population.

BACKGROUND AND OBJECTIVE: Cell activation through toll-like receptors (TLRs) has robust bipolar effects on host immunity and the pathogenesis of asthma. The TLR2 subfamily is a pivotal member of the TLR family. We sought to determine whether mutations in TLR2 subfamily genes affect the risk of asthma. METHODS: A total of 318 asthmatic patients and 352 nonasthmatic controls were recruited. Eight single-nucleotide polymorphisms in TLR2 subfamily genes were detected using GenomeLab SNPstream (Beckman Coulter, Fullerton, California, USA). RESULTS: We found that patients with the TLR2/rs7656411 TT variant homozygote had a significantly reduced risk of asthma when compared with those with the GG wild-type homozygote (adjusted odds ratio [OR], 0.63; 95% confidence interval (CI], 0.41-0.98; P = .036). Furthermore, a positive association was observed between the T allele of rs2381289 in TLR6 and allergic rhinitis in asthma (OR, 1.79; 95% CI, 1.10-2.91; P = .025), while the A allele of rs11466651 in TLRIO was negatively associated with allergic rhinitis (OR, 0.49; 95% CI, 0.26-0.95; P = .046). CONCLUSION: Our results indicate that a genetic variant in the TLR2 subfamily may play a role in susceptibility to asthma.