Mutation of SLC7A14 causes auditory neuropathy and retinitis pigmentosa mediated by lysosomal dysfunction.

Lysosomes contribute to cellular homeostasis via processes including macromolecule degradation, nutrient sensing, and autophagy. Defective proteins related to lysosomal macromolecule catabolism are known to cause a range of lysosomal storage diseases; however, it is unclear whether mutations in proteins involved in homeostatic nutrient sensing mechanisms cause syndromic sensory disease. Here, we show that SLC7A14, a transporter protein mediating lysosomal uptake of cationic amino acids, is evolutionarily conserved in vertebrate mechanosensory hair cells and highly expressed in lysosomes of mammalian cochlear inner hair cells (IHCs) and retinal photoreceptors. Autosomal recessive mutation of SLC7A14 caused loss of IHCs and photoreceptors, leading to presynaptic auditory neuropathy and retinitis pigmentosa in mice and humans. Loss-of-function mutation altered protein trafficking and increased basal autophagy, leading to progressive cell degeneration. This study implicates autophagy-lysosomal dysfunction in syndromic hearing and vision loss in mice and humans.

Diagnostic Errors in Initial Misdiagnosis of Foreign Body Aspiration in Children: A Retrospective Observational Study in a Tertiary Care Hospital in China.

Background: Foreign body aspiration (FBA) in children is a common emergency that can easily be missed, leading to delays in treatment. Few large cohort studies have focused on errors in diagnostic assessment. The main purpose of this study was to analyze factors contributing to the initial misdiagnosis of FBA in children. Methods: We retrospectively reviewed the charts of 226 children diagnosed with FBA at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2018 to November 2020. Cases were divided into two groups according to whether or not patients were initially misdiagnosed. The clinical characteristics of the two groups were then compared. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was applied to cases with initial misdiagnosis. Results: Of the 226 included children with a final diagnosis of FBA, 153 (67.7%) were boys. Ninety percent of patients were under 3 years old. More than half (61.9%) of the children were referred from primary institutions, and 38.1% visited tertiary hospitals directly. A total of 80 (35.4%) patients were initially misdiagnosed. More than half of misdiagnosed children received an alternative diagnosis of bronchiolitis (51.3%), the most common alternative diagnosis. Test failures (i.e., errors in test ordering, test performance, and clinician processing) were primarily responsible for the majority of initial diagnostic errors (76.3%), followed by failure or delay in eliciting critical case history information (20.0%). Characteristics significantly associated with initial misdiagnosis were: presentation over 24 h (OR 9.2, 95% CI 4.8-17.5), being referred from primary institutions (OR 8.8, 4.1-19.0), no witnessed aspiration crisis (OR 7.8, 3.0-20.3), (4) atypical signs or symptoms (OR 3.2, 1.8-5.7), foreign body not visible on CT (OR 36.2, 2.1-636.8), foreign body located in secondary bronchi (OR 4.8, 1.3-17.2), organic foreign body (OR 6.2, 1.4-27.2), and history of recurrent respiratory infections (OR 2.7, 1.4-5.3). Children with misdiagnosis tended to have a longer time from symptom onset to the definitive diagnosis of FBA (P < 0.001). Conclusions: More than one-third of children with FBA were missed at first presentation. Errors in diagnostic testing and history taking were the main reasons leading to initial misdiagnosis.

mTOR/NF-κB signaling pathway protects hippocampal neurons from injury induced by intermittent hypoxia in rats.

OBJECTIVE: To expound the roles of mTOR and NF-kB signaling pathway in intermittent hypoxia (IH)-induced damage of hippocampal neurons. METHODS: For rat experiments, mTOR inhibitor (Rapamycin, Rapa) and NF-κB signaling inhibitor (ammonium pyrrolidine dithiocarbamate, PDTC) were applied to inhibit mTOR and NF-κB signaling, respectively. For neuron experiments, hippocampal neurons from rat were successfully cultured. Different concentrations of Rapa and PDTC were added to the cultured hippocampal neurons. Rat or primary hippocampal neurons were exposed to normoxic or IH conditions after administration of Rapa and PDTC. The effects of Rapa and PDTC administration on learning and memory ability of rats and hippocampal injury after IH exposure were assayed by Morris water maze and H&E staining. Electron microscope was utilized to examine primary hippocampal neuron ultrastructure changes after IH exposure and Rapa or PDTC administration. The expressions of NF-κB-p65, IκBα, IKKß, BDNF, TNF-α, IL-1ß, PSD-95 and SYN in hippocampal neurons were examined. RESULTS: Compared with normal control rats or neurons, IH-treated group had elevated expression levels of NF-kB, TNF-α and IL-1ß and suppressed expression level of BDNF, PSD-95 and SYN. These results were reversed upon pre-treatment with Rapa and PDTC. Furthermore, IκBα and IKKß expressions were down-regulated in IH group. No notable difference was manifested in PDTC pre-treatment group, while a prominent increase was shown after Rapa pre-administration. CONCLUSION: The administration of PDTC and Rapa could prevent IH-induced hippocampal neuron impairment, indicating that inhibition of the mTOR and NF-κB pathway may likely act as a therapeutic target for obstructive sleep apnea.

Intranasal fluticasone furoate in pediatric allergic rhinitis: randomized controlled study.

BACKGROUND: Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. METHODS: In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2-12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. RESULTS: Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2-6 years). Drug-related adverse events occurred in <20% of patients in all groups. FFNS was well tolerated at both doses. CONCLUSIONS: This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2-12 years), supporting its use in clinical treatment for AR children, including younger children aged 2-6 years. IMPACT: The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2-6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2-6 years.

A cross-sectional survey on occupational stress and associated dyslipidemia among medical staff in tertiary public hospitals in Wenzhou, China.

INTRODUCTION: Occupational stress is considered to be a harmful physical and emotional response to an individual's psychological and/or physiological state in the work environment and is highly prevalent among medical staff. However, few epidemiological studies have investigated occupational stress in medical staff. Our study aims to explore the characteristics of occupational stress and its relationship with dyslipidemia in Chinese medical staff at tertiary hospitals and establish the basis for future preventive strategies. METHODS: A cross-sectional study was conducted in three tertiary public hospitals in Wenzhou City, Zhejiang Province, China. Data were collected using random sampling procedures to examine demographic characteristics and job-related data. The participants completed the Occupational Stress Inventory-Revised (OSI-R) questionnaires and serum lipids tests. Partial correlation analysis was conducted to explore the relationship between occupational stress and dyslipidemia. RESULTS: A total of 1,176 medical staff responses to questionnaires were obtained. The occupational stress levels of medical staff were higher than those of normative populations, while their coping resources were lower. Most of the subscales of occupational stress demonstrated higher results for doctors and males than for nurses and females with crude analyses. Each subscale of OSI-R was found to be associated with a different type of blood lipid level. CONCLUSIONS: The occupational stress level of medical staff in tertiary public hospitals in Wenzhou was high, and occupational stress may contribute to dyslipidemia. An investigation into occupational stress levels and their association with dyslipidemia in this population could draw more attention to medical staff in tertiary public hospitals.

Predictors of the Prevalence of Dyslipidemia and Influencing Factors for Young Health Examination Cohort: A Cross-Sectional Survey.

Objectives: The objective of this study was to estimate the prevalence of dyslipidemia and associated influencing factors in young adults in the southeastern coastal area of China. Methods: This study adopted a cross-sectional survey and included 7,859 young people who underwent examinations at three hospitals in Wenzhou, Zhejiang Province, China. All subjects completed a questionnaire in the form of face-to-face interviews and underwent anthropometric measurements and biochemical tests. The continuous data are presented as the means ± standard deviations and were compared using Student's t-tests. The categorical variables are presented as proportions. The influencing factors associated with dyslipidemia were evaluated through a multivariate logistic regression. Results: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high with 7.1, 15.0, 22.9, and 4.0% for high-total cholesterol (TC), high-triglyceride (TG), low-high-density lipoprotein cholesterol (HDL-C), and high-low-density lipoprotein cholesterol (LDL-C). Among those with dyslipidemia, a statistically significant difference in sex was observed, and all types of dyslipidemia were associated with smoking and alcohol consumption. However, those with high-TG, high-LDL, and low-HDL levels did not significantly differ in education level or occupation. The presence of dyslipidemia was significantly associated with increased age, the male sex (OR: 1.85, 95% CI: 1.39-2.21), smoking (OR: 2.02, 95% CI: 1.98-2.13), alcohol consumption (OR: 1.33, 95% CI: 1.16-1.63), overweight or obesity (OR: 2.01, 95% CI: 1.79-2.41), and intellectual work (OR: 1.36, 95% CI: 1.11-1.72). Conclusion: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high. To prevent dyslipidemia at an early age, it is essential to conduct effective intervention programs targeting risk factors and to implement routine screening programs.

Investigation of the prognostic role of neutrophil-to-lymphocyte ratio in Idiopathic Sudden Sensorineural Hearing Loss based on propensity score matching: a retrospective observational study.

INTRODUCTION: The aetiology, management and prognosis of idiopathic Sdden Sensorineural Hearing Loss (ISSNHL) are still uncertain despite adequate investigation. OBJECTIVE: We conducted the present study to investigate the possible relationship between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ISSNHL based on PSM. METHODS: This was a retrospective observational study. Data and statistical analyses were performed using the SPSS statistical program (SPSS 19.0). PSM was performed using STATA (15.0). RESULTS: NLR = 3.42 was the cut-off value. After PSM, 84 pairs of patients were successfully matched. The number of patients in the effective group with the NLR < 3.42 and NLR < 3.42 were significantly different (P < 0.001). CONCLUSION: The NLR is an inexpensive and reliable index to predict the ISSNHL. We hold the view that the NLR can be a reliable factor for clinical doctors to predict the prognosis in ISSNHL. To further prove that the NLR is a powerful prognostic factor in ISSNHL, larger prospective studies are required in the future.

Human papillomavirus infection among head and neck squamous cell carcinomas in southern China.

Human papillomavirus (HPV) related tumours account for a significant proportion of head and neck squamous cell carcinomas (HNSCCs) in developed countries. They respond better to chemo- and radio-therapy, and have a better stage specific prognosis. To establish their prevalence in China, we assessed a series of histology confirmed HNSCCs collected in Zhejiang and Guangdong provinces by PCR for HPV DNA and by immunohistochemistry for p16 protein status. Among 303 HNSCCs, HPV DNA was detected in 26.4%, with HPV16 DNA in 71% of these. Of HNSCC located in the oropharynx, 38.55% (32/83) were HPV+ve. In this series, p16 status was a relatively poor predictor of HPV status as detected by PCR. The stage specific survival time of HPV+ HNSCCs was significantly longer than for HPV- HNSCC. HPV status should be assessed for oropharyngeal cancers in China to assist with appropriate management, and prophylaxis against HPV infection should be considered to reduce the incidence of this disease.

Risk factors analysis of attention deficit/hyperactivity disorder and allergic rhinitis in children: a cross-sectional study.

BACKGROUND: To investigate the relationship between symptom of attention-deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in AR children of different genders and ages. METHODS: Four hundred and sixty-five allergic rhinitis children aged 6-12 years old were recruited in this study. Skin-prick test, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Total Nasal Symptoms Score (TNSS) and the Swanson, Nolan, and Pelham version IV scale (SNAP-IV) were recorded. Patients were divided into AR with ADHD and AR without ADHD, according to the SNAP-IV scale results. RESULTS: Children with the inattention/hyperactivity scale (IHS) > 1.25 accounted for 26.4% of all children with AR. The TNSS with IHS > 1.25 group were significantly higher than the IHS ≤ 1.25 group. Univariate analysis showed that age, gender, duration of AR symptoms, skin index, and PRQLQ subscales were associated with symptoms of hyperactivity and attention deficit (IHS > 1.25). After normalizing the age and gender factors, duration of AR symptoms and skin index correlated with IHS > 1.25. After stratifying age and gender, the correlation between IHS > 1.25 and skin index and PRQLQ subscales was mainly found in male children, and the association between the duration of AR symptoms and IHS > 1.25 was reflected in each group. CONCLUSIONS: ADHD in children with AR is associated with severity, duration, and skin index of AR, and this association is more pronounced in male children.

Clinical Analysis of Sphenoid Sinus Mucocele With Initial Neurological Symptoms.

BACKGROUND AND OBJECTIVES: Neurological manifestations associated with sphenoid sinus mucocele (SSM) are easily misdiagnosed due to nonspecific symptoms. The objective is to analyze and report the clinical features of SSM presenting with neurological manifestations, to allow an earlier diagnosis and more timely intervention for this disease. METHODS: This was a retrospective cross-sectional study including 19 patients. The detailed clinical information of 19 patients with the initial symptom of neurological manifestations caused by SSM presenting at the Second Affiliated Hospital of Wenzhou Medical University between January 2000 and May 2018 were retrospectively analyzed. Collected data including symptoms, signs, neuroimaging, and pathologic diagnoses. RESULTS: There were eleven males and 8 females, and their ages ranged from 23 to 71 years. Headache was the most frequent symptom, in 12 of the 19 patients presenting as the initial symptom. The visual disturbance included visual loss (4/19), diplopia (3/19), and another patient had both visual loss and diplopia. Neurophysical examination found that 4 patients presented with oculomotor nerve palsy, 4 patients had optic nerve or abducens nerve palsy, and 1 patient had optic neuropathy, oculomotor nerve palsy and abducens nerve palsy simultaneously. All patients underwent endoscopic surgery and had postoperative clinical symptom improvement. CONCLUSIONS: Headache is the most common symptom of SSM and should be on the differential diagnosis of patients presenting with headache, even if in isolation. The results suggest that CT and MRI are the best tools in diagnosis of SSM and endoscopic sphenoidotomy is a safe and effective method in the treatment of SSM.

Genetic Polymorphisms and Susceptibility to Sudden Sensorineural Hearing Loss: A Systematic Review.

BACKGROUND: Recently, genetic factors have been considered as an important risk factor for sudden sensorineural hearing loss (SSNHL). Many studies analyzed the association between SSNHL and polymorphisms. However, most of them gave inconclusive results. Key Message: We performed a systematic review to find out the association between polymorphisms and susceptibility to SSNHL. Finally, 47 studies involving 5,230 SSNHL patients and 68 genes were included for analysis and discussion of results. Polymorphisms in 26 genes have been suggested to be correlated with the susceptibility to SSNHL. SUMMARY: Although a great number of studies support that polymorphisms in genes are associated with susceptibility to SSNHL, we need large multicenter studies, which evaluate multiple single nucleotide polymorphisms in SSNHL patients, to find real genetic risk factors for susceptibility to SSNHL. This is very helpful in designing more effective prevention and treatment strategies for patients with SSNHL.

Safety and Immunogenicity of a Nonadjuvant Human Papillomavirus Type 6 Virus-like Particle Vaccine in Recurrent Respiratory Papillomatosis.

OBJECTIVES: To assess the safety and immunogenicity of a nonadjuvant human papillomavirus (HPV) type 6 L1 virus-like particle (VLP) vaccine in recurrent respiratory papillomatosis (RRP) in local Chinese patients. METHODS: Patients with RRP who had undergone surgical treatment before intramuscular administration of an escalating dose of HPV type 6 L1 VLPs (1, 5, and 25 µg at 4 weekly intervals) as part of their treatment were followed up for more than 10 years. Efficacy was assessed by detecting the vaccine-induced type-specific antibody titer, calculating the intersurgical interval, and observing recurrence or remission of papillomas after receiving the vaccine. RESULTS: Nonadjuvant HPV vaccine was generally well tolerated, with no serious vaccine-related adverse episodes. It induced seroconversion for each vaccine-related HPV type. At week 12 (4 weeks after injecting 25 µg), the vaccine-induced type-specific antibody titer was significantly high. Analysis of all patients found a significant increase in the intersurgical interval and decrease in the scores. One patient (16.7%; female) experienced complete remission. Five patients (83.3%) (two males and three females) experienced partial remission. In total, complete or partial remission was achieved in six (100%) patients. CONCLUSIONS: Administration of nonadjuvant HPV type 6 L1 VLPs vaccine to RRP was generally well tolerated and highly immunogenic.

Prognostic role of haematological indices in sudden sensorineural hearing loss: Review and meta-analysis.

BACKGROUND: Complete blood count (CBC) is an important blood test in clinical practice, and it has been recently used to predict the prognosis of patients with sudden sensorineural hearing loss (SSNHL). Some haematological indices of the CBC test have been reported to be associated with the clinical outcome of SSNHL. However, the prognostic value of these haematological indices in SSNHL is currently under debate. Here, we performed a meta-analysis to investigate the association between haematological indices of the CBC test and clinical outcomes in patients with SSNHL. METHODS: We conducted a meta-analysis of studies that evaluated the association between haematological indices and prognoses in patients with sudden hearing loss. Subgroup and sensitivity analyses were also performed to explore potential sources of heterogeneity. RESULTS: Ten studies that included 972 individuals were identified. Pooled analysis showed neutrophil-to-lymphocyte ratio (NLR) (weighted mean difference [WMD] = -1.69 and p < 0.001), platelet-to-lymphocyte ratio (PLR) (WMD = -38.45 and p < 0.001), neutrophil count (WMD = -1.57 × 109/L and p < 0.001) and lymphocyte count (WMD = 0.41 × 109/L and p < 0.001) to be the factors associated with the prognosis of SSNHL. CONCLUSIONS: Our findings indicated that NLR, PLR, neutrophil count and lymphocyte count are strongly associated with the prognosis of SSNHL. These four indices could be recommended as inexpensive markers to report treatment outcomes.

Association of pediatric allergic rhinitis with the ratings of attention-deficit/hyperactivity disorder.

BACKGROUND: Allergic rhinitis (AR) is currently the most prevalent allergic disease in children and adolescents. OBJECTIVE: Surveys conducted by population-based studies of East Asia revealed an increased prevalence of behavioral disorders in patients with AR. Thus, in this study, we explored the prevalence of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients with AR. METHODS: A total of 333 children (6-12 years of age) with AR and a total of 322 age-matched controls were included in this study. An otorhinolaryngologist diagnosed all AR cases and evaluated the severity of the disease. Skin-prick test results for 18 major allergens, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Child Behavior Checklist (CBCL), and Swanson, Nolan, and Pelham version IV (SNAP-IV) scores were recorded. RESULTS: In total, 320 age-matched controls and 323 children with AR completed the study. With respect to the Total Nasal Symptom Score and the PRQLQ, the condition of the experimental group was more serious than that of the controls. The scores on the hyperactivity/impulsivity and inattention subscales, which evaluate ADHD symptoms, and those on the CBCL subscales were significantly higher in patients with AR than in the controls (all p values were <0.01). From the results of the Pearson correlation, we deduced that there were significant positive correlations between the AR-related data and each subscale of the CBCL and SNAP-IV in the AR group. Moreover, two basic characteristics (males and environmental exposure to tobacco smoke) present significant positive and age showed a significant negative correlations affect ADHD symptom in both the AR group and the control group. Also, in the "pure AR" group, hierarchical regression analyses were performed to determine the subtests of the PRQLQ, which are significant predictors of SNAP-IV and CBCL. CONCLUSIONS: Apart from AR per se, the possible comorbidities of impulsivity and inattention are important when managing children with AR. It is essential to evaluate the symptoms of ADHD in children and adolescents with AR.

Efficacy of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Allergic rhinitis (AR) has become a global issue for a large part of the general population. Sublingual immunotherapy (SLIT) has been used extensively to treat persistent allergic rhinitis (PAR). Although systematic reviews have confirmed the effectiveness of SLIT for the treatment of AR, a considerable number of studies using extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic treatment parameters and questioned the efficacy of SLIT. METHODS: In this study, we evaluated SLIT for PAR by a meta-analysis of randomized controlled trials (RCTs). Medline, Embase, and Cochrane Library database searches were performed for RCTs on the treatment of PAR by SLIT that assessed clinical outcomes related to efficacy through May 2016. Descriptive and quantitative information was abstracted. An analysis was performed with standardized mean differences (SMDs) under a fixed or random effects model. Subgroup analyses were performed. Heterogeneity was assessed using the I² metric. RESULTS: In total, 25 studies were eligible for inclusion in the meta-analysis for symptom scores and 15 studies for medication scores. SLIT was significantly different from the controls for symptom scores (SMD=1.23; 95% confidence interval [CI]=1.74 to 0.73; P<0.001). For medication scores, significant differences for SLIT were also observed versus the controls (SMD=-1.39; 95% CI=-1.90 to -0.88; P<0.001). CONCLUSIONS: Our meta-analysis indicates that SLIT provided significant symptom relief and reduced the need for medications in PAR. In this study, significant evidence was obtained despite heterogeneity with regard to the use of mite extract. Specifically, the mite extract used was provided by the patients with PAR. Furthermore, to confirm both the objective outcomes and the effective doses of HDM allergen extracts, experimental data should be obtained from large high-quality population-based studies.

Efficacy and safety of sublingual immunotherapy for allergic rhinitis in pediatric patients: A meta-analysis of randomized controlled trials.

BACKGROUND: Allergic rhinitis (AR) has become a global health problem that constantly affects a large part of the general population, especially children. OBJECTIVE: Sublingual allergen immunotherapy (SLIT) has been used extensively for pediatric AR, although its efficacy and safety are often questioned. In this meta-analysis of randomized controlled trials (RCT), we evaluated the use of SLIT for pediatric AR. METHODS: A number of medical literature data bases were searched through January 2016 to identify RCTs that examined the use of SLIT for pediatric AR and that assessed clinical outcomes related to efficacy. Descriptive and quantitative information was abstracted. Standardized mean differences (SMD) were calculated by using fixed- and random-effects models. Subgroup analyses were performed. Heterogeneity was assessed by using the I2 metric. A network meta-analysis was used to estimate SMDs between two SLIT protocols for pediatric seasonal AR. All data were extracted from publications or received from the authors. RESULTS: Twenty-six studies were eligible for inclusion in the meta-analysis of rhinitis or rhinoconjunctivitis symptom scores, and 19 studies were eligible for the meta-analysis of medication scores. Descriptive and quantitative data were extracted. SLIT differed significantly from placebo in terms of symptom scores (SMD -0.55 [95% confidence interval {CI}, -0.86 to -0.25]; p = 0.0003, I2 = 90%) and medication scores (SMD -0.67 [95% CI, -0.96 to -0.38]; p < 0.00001, I2 = 83%). Oral pruritus was the adverse effect, which occurred most commonly in children who were receiving SLIT. Network meta-analysis revealed no significant difference between the pre-coseasonal and continuous SLIT protocols for seasonal AR in symptom scores (SMD -6.55 [95% CI, -25.38 to 12.29]; p = 0.496) and medication scores (SMD -8.83 [95% CI, -22.10 to 4.43]; p = 0.192). CONCLUSIONS: Our meta-analysis results indicated that SLIT provided significant symptom relief and reduced the need for medication in pediatric patients. Moreover, the safety of SLIT needs to be confirmed in RCTs with larger samples.

A Deafness- and Diabetes-associated tRNA Mutation Causes Deficient Pseudouridinylation at Position 55 in tRNAGlu and Mitochondrial Dysfunction.

Several mitochondrial tRNA mutations have been associated with maternally inherited diabetes and deafness. However, the pathophysiology of these tRNA mutations remains poorly understood. In this report, we identified the novel homoplasmic 14692A→G mutation in the mitochondrial tRNAGlu gene among three Han Chinese families with maternally inherited diabetes and deafness. The m.14692A→G mutation affected a highly conserved uridine at position 55 of the TΨC loop of tRNAGlu The uridine is modified to pseudouridine (Ψ55), which plays an important role in the structure and function of this tRNA. Using lymphoblastoid cell lines derived from a Chinese family, we demonstrated that the m.14692A→G mutation caused loss of Ψ55 modification and increased angiogenin-mediated endonucleolytic cleavage in mutant tRNAGlu The destabilization of base-pairing (18A-Ψ55) caused by the m.14692A→G mutation perturbed the conformation and stability of tRNAGlu An approximately 65% decrease in the steady-state level of tRNAGlu was observed in mutant cells compared with control cells. A failure in tRNAGlu metabolism impaired mitochondrial translation, especially for polypeptides with a high proportion of glutamic acid codons such as ND1, ND6, and CO2 in mutant cells. An impairment of mitochondrial translation caused defective respiratory capacity, especially reducing the activities of complexes I and IV. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These mitochondrial dysfunctions caused an increasing production of reactive oxygen species in the mutant cells. Our findings may provide new insights into the pathophysiology of maternally inherited diabetes and deafness, which is primarily manifested by the deficient nucleotide modification of mitochondrial tRNAGlu.

Autologous Olfactory Lamina Propria Transplantation for Chronic Spinal Cord Injury: Three-Year Follow-Up Outcomes From a Prospective Double-Blinded Clinical Trial.

We did a clinical trial to determine whether olfactory mucosa lamina propria (OLP) transplants promote regeneration and functional recovery in chronic human spinal cord injury (SCI). The trial randomized 12 subjects to OLP transplants (n = 8) or control sham surgery (n = 4). The subjects received magnetic resonance imaging (MRI), electromyography (EMG), urodynamic study (UDS), American Spinal Injury Association impairment scale (AIS), and other functional assessments. OLP-transplanted subjects recovered more motor, sensory, and bladder function compared to sham-operated subjects. At 3 years after OLP transplant, one patient improved from AIS A to C and another recovered from AIS A to B, two recovered more than three segmental sensory levels, two had less spasticity, two had altered H-reflexes and SSEP, two regained bladder and anorectal sensation and had improved bladder compliance on UDS. OLP-treated patients had partial or complete tissue bridges at the injury site compared to cavitary gaps in sham-operated patients. The limited recovery suggests that OLP transplants alone do not have significant benefits but may provide a rationale for larger randomized trials or combination therapies.

GSTM1 null genotype is a risk factor for laryngeal cancer.

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.

[Function study of non-syndromic deafness associated mitochondrial 12S rRNA A839G mutation].

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.