Clarithromycin and dexamethasone show similar anti-inflammatory effects on distinct phenotypic chronic rhinosinusitis: an explant model study.

BACKGROUND: Phenotype of chronic rhinosinusitis (CRS) may be an important determining factor of the efficacy of anti-inflammatory treatments. Although both glucocorticoids and macrolide antibiotics have been recommended for the treatment of CRS, whether they have different anti-inflammatory functions for distinct phenotypic CRS has not been completely understood. The aim of this study is to compare the anti-inflammatory effects of clarithromycin and dexamethasone on sinonasal mucosal explants from different phenotypic CRS ex vivo. METHODS: Ethmoid mucosal tissues from CRSsNP patients (n = 15), and polyp tissues from eosinophilic (n = 13) and non-eosinophilic (n = 12) CRSwNP patients were cultured in an ex vivo explant model with or without dexamethasone or clarithromycin treatment for 24 h. After culture, the production and/or expression of anti-inflammatory molecules, epithelial-derived cytokines, pro-inflammatory cytokines, T helper (Th)1, Th2 and Th17 cytokines, chemokines, dendritic cell relevant markers, pattern recognition receptors (PRRs), and tissue remodeling factors were detected in tissue explants or culture supernatants by RT-PCR or ELISA, respectively. RESULTS: We found that both clarithromycin and dexamethasone up-regulated the production of anti-inflammatory mediators (Clara cell 10-kDa protein and interleukin (IL)-10), whereas down-regulated the production of Th2 response and eosinophilia promoting molecules (thymic stromal lymphopoietin, IL-25, IL-33, CD80, CD86, OX40 ligand, programmed cell death ligand 1, CCL17, CCL22, CCL11, CCL5, IL-5, IL-13, and eosinophilic cationic protein) and Th1 response and neutrophilia promoting molecules (CXCL8, CXCL5, CXCL10, CXCL9, interferon-γ, and IL-12), from sinonasal mucosa from distinct phenotypic CRS. In contrast, they had no effect on IL-17A production. The expression of PRRs (Toll-like receptors and melanoma differentiation-associated gene 5) was induced, and the production of tissue remodeling factors (transforming growth factor-ß1, epidermal growth factor, basic fibroblast growth factor, platelet derived growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9) was suppressed, in different phenotypic CRS by dexamethasone and clarithromycin in comparable extent. CONCLUSIONS: Out of our expectation, our explant model study discovered herein that glucocorticoids and macrolides likely exerted similar regulatory actions on CRS and most of their effects did not vary by the phenotypes of CRS.

Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps.

RATIONALE: Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear. OBJECTIVES: To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP. METHODS: DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL-12, IL-6, and transforming growth factor-ß, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture. CONCLUSIONS: Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells.

Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis.

BACKGROUND: T(H)17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. OBJECTIVE: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T(H)17 responses in the setting of AR. METHODS: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. T(H)17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T(H)17 cells and CD11c(+) dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. RESULTS: Compared with those of control subjects, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-ß expression in DCs. Importantly, CC10 was able to inhibit T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. CONCLUSION: T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.

Overexpression of miR-125b, a novel regulator of innate immunity, in eosinophilic chronic rhinosinusitis with nasal polyps.

RATIONALE: Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS. OBJECTIVES: To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP. METHODS: Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR-125b functional assays were performed on airway epithelial cells and mice. MiR-125b expression regulation was studied by tissue and cell culture. MEASUREMENTS AND MAIN RESULTS: CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR-125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-α/ß production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-ß expression was increased, in eosinophilic CRSwNP. IFN-ß mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-ß stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL-10. CONCLUSIONS: The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP.

[Psychological trauma and crisis intervention in children after earthquake].

As a momentous disaster, earthquake would bring severe psychological trauma to children, with an adverse effect not only on the physiological functions, but also on their behaviors, emotions, and cognition, and the short-term and long-term consequences are much greater in children than in adults. The children of different ages have different psychological reactions, so psychological intervention varies with children's age. Psychological intervention is still important long afterwards to prevent permanent psychological trauma in children.

Clinical characteristics of pediatric patients with treatment-refractory Tourette syndrome: An evidence-based survey in a Chinese population.

BACKGROUND: Tourette syndrome (TS) is a complex neurodevelopmental condition marked by tics, as well as a variety of psychiatric comorbidities, such as obsessive-compulsive disorders (OCDs), attention deficit hyperactivity disorder (ADHD), anxiety, and self-injurious behavior. TS might progress to treatment-refractory Tourette syndrome (TRTS) in some patients. However, there is no confirmed evidence in pediatric patients with TRTS. AIM: To investigate the clinical characteristics of TRTS in a Chinese pediatric sample. METHODS: A total of 126 pediatric patients aged 6-12 years with TS were identified, including 64 TRTS and 62 non-TRTS patients. The Yale Global Tic Severity Scale (YGTSS), Premonitory Urge for Tics Scale (PUTS), and Child Behavior Checklist (CBCL) were used to assess these two groups and compared the difference between the TRTS and non-TRTS patients. RESULTS: When compared with the non-TRTS group, we found that the age of onset for TRTS was younger (P < 0.001), and the duration of illness was longer (P < 0.001). TRTS was more often caused by psychosocial (P < 0.001) than physiological factors, and coprolalia and inappropriate parenting style were more often present in the TRTS group (P < 0.001). The TRTS group showed a higher level of premonitory urge (P < 0.001), a lower intelligence quotient (IQ) (P < 0.001), and a higher percentage of family history of TS. The TRTS patients demonstrated more problems (P < 0.01) in the "Uncommunicative", "Obsessive-Compulsive", "Social-Withdrawal", "Hyperactive", "Aggressive", and "Delinquent" subscales in the boys group, and "Social-Withdrawal" (P = 0.02) subscale in the girls group. CONCLUSION: Pediatric TRTS might show an earlier age of onset age, longer duration of illness, lower IQ, higher premonitory urge, and higher comorbidities with ADHD-related symptoms and OCD-related symptoms. We need to pay more attention to the social communication deficits of TRTS.

Comparison of diagnostic validity of two autism rating scales for suspected autism in a large Chinese sample.

BACKGROUND: Autism is the most common clinical developmental disorder in children. The childhood autism rating scale (CARS) and autistic autism behavior checklist (ABC) are the most commonly used assessment scales for diagnosing autism. However, the diagnostic validations and the corresponding cutoffs for CARS and ABC in individuals with suspected autism spectrum disorder (ASD) remain unclear. Furthermore, for suspected ASD in China, it remains unclear whether CARS is a better diagnostic tool than ABC. Also unclear is whether the current cutoff points for ABC and CARS are suitable for the accurate diagnosis of ASD. AIM: To investigate the diagnostic validity of CARS and ABC based on a large Chinese sample. METHODS: A total of 591 outpatient children from the ASD Unit at Beijing Children's Hospital between June and November 2019 were identified. First, the Clancy autism behavior scale (CABS) was used to screen out suspected autism from these children. Then, each suspected ASD was evaluated by CARS and ABC. Receiver operating characteristic (ROC) curve analysis was used to compare diagnostic validations. We also calculated the area under the curve (AUC) for both CARS and ABC. RESULTS: We found that the Cronbach alpha coefficients of CARS and ABC were 0.772 and 0.426, respectively. Therefore, the reliability of the CARS was higher than that of the ABC. In addition, we found that the correlation between CARS and CABS was 0.732. Next, we performed ROC curve analysis for CARS and ABC, which yielded AUC values of 0.846 and 0.768, respectively. The cutoff value, which is associated with the maximum Youden index, is usually applied as a decision threshold. We found that the cutoff values of CARS and ABC were 34 and 67, respectively. CONCLUSION: This result indicated that CARS is superior to ABC in the Chinese population with suspected ASD.

Decreased interoceptive accuracy in children with autism spectrum disorder and with comorbid attention deficit/hyperactivity disorder.

Interoception refers to the awareness of internal physiological state. Several previous studies reported that people with autism spectrum disorders (ASD) and adults with attention-deficit/hyperactivity disorder (ADHD) have diverse patterns of interoception, but the extent of literature is limited and inconsistent. This study aimed to investigate the interoceptive accuracy (IA) in children with ASD, children with comorbid ASD and ADHD, and typically developing (TD) children with high and low levels of autistic traits. We administered the eye-tracking interoceptive accuracy task (EIAT) to 30 children with ASD, 20 children with comorbid ASD and ADHD, and 63 TD controls with high and low levels of autistic traits. Parent-report scales concerning ASD and ADHD symptoms were collected. ASD children with and without comorbid ADHD both exhibited lower IA than TD children. Reduced IA was also found in TD children with high-autistic traits relative to those with low-autistic traits. IA was negatively correlated with autistic and ADHD symptoms. Atypical cardiac interoception could be found in children with ASD. Difficulties in sensing and comprehending internal bodily signals in childhood may be related to both ASD and ADHD symptoms. LAY SUMMARY: The present study examined interoceptive accuracy (IA) in children with autism spectrum disorders (ASD), children with comorbid ASD and attention-deficit/hyperactivity disorder (ADHD), and typically developing (TD) children with high and low levels of autistic traits. ASD children with and without comorbid ADHD both exhibited lower IA than TD children. TD children with high-autistic traits exhibited decreased IA compared to those with low-autistic traits. These results have implications for understanding sensory atypicality found in ASD and ADHD.

The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis.

BACKGROUND: The involvement of secretoglobins (SCGBs) other than SCGB1A1 (Clara cell 10-kDa protein, CC10) in human airway diseases remains unexplored. Among those SCGBs, SCGB3A2 (uteroglobin-related protein 1, UGRP1) is particularly interesting, given its structure and function similarities with SCGB1A1 (CC10). The aim of this study was to investigate the expression regulation of SCGBs other than SCGB1A1 (CC10) in human upper airway, and their potential involvement, particularly that of SCGB3A2 (UGRP1), in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). METHODS: Eight SCGB family members including SCGB3A2 (UGRP1), SCGB1C1 (ligand binding protein RYD5), SCGB1D1 (lipophilin A), SCGB1D2 (lipophilin B), SCGB1D4 (interferon-γ inducible SCGB), SCGB2A1 (mammaglobin 2), SCGB2A2 (mammaglobin 1), and SCGB3A1 (uteroglobin-related protein 2) were studied. The regulation of SCGBs mRNA expression in normal nasal mucosa by proinflammatory, Th1, and Th2 cytokines was studied through nasal explant culture. SCGBs mRNA expression levels in CRSsNP and CRSwNP patients and controls were compared. The mRNA levels were detected by means of quantitative reverse transcriptase-polymerase chain reaction. The protein expression of SCGB3A2 (UGRP1) was analyzed using immunohistochemistry. RESULTS: The expression of SCGBs except SCGB1D2 (lipophilin B) could be found in upper airway and be differentially regulated by different cytokines. SCGB3A2 (UGRP1) mRNA expression was induced by Th1 cytokine, but suppressed by proinflammatory and Th2 cytokines. SCGBs mRNA expression was altered in CRS; particularly, SCGB3A2 (UGRP1) protein and mRNA expression was markedly decreased in both CRSsNP and CRSwNP and its protein levels inversely correlated with the number of total infiltrating cells, preoperative sinonasal CT scores, and postoperative endoscopy and symptom scores. CONCLUSION: SCGBs except SCGB1D2 (lipophilin B) are expressed in human upper airway and their expression can be differentially regulated by inflammatory cytokines. SCGBs mRNA expression is altered in CRS. Reduced production of UGRP1, which is likely due, at least in part, to a local cytokine environment, may contribute to the hyper-inflammation in CRS and correlates with response to surgery.

Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis.

RATIONALE: Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS). OBJECTIVES: To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model. METHODS: Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line. MEASUREMENTS AND MAIN RESULTS: Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1beta, tumor necrosis factor-alpha, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation. CONCLUSIONS: These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.

Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. OBJECTIVE: To investigate the immunopathologic profiles of CRSwNP and CRSsNP in adult Chinese. METHODS: Histologic characteristics of surgical samples were analyzed in 50 controls, 94 CRSsNP patients, and 151 CRSwNP patients. Tissue samples from 17 controls, 36 CRSsNP patients, and 45 CRSwNP patients were stained for CD3, CD4, CD8, CD20, CD68, myeloperoxidase, and dendritic cell lysosome-associated membrane protein. Expression profiles of transcription factors of T-cell subsets in relation to cytokines and a marker of natural killer T cell (Valpha24) were examined by means of quantitative RT-PCR. RESULTS: Over half of CRSwNP patients presented noneosinophilic inflammation. CRSwNP had a higher number of eosinophils, plasma cells, and CD3(+), CD8(+), CD20(+), and CD68(+) cells and a lower myeloperoxidase expression rate than CRSsNP. Expression levels of transcription factors and cytokines of T(H)1/T(H)2/T(H)17 were increased, whereas the expression rate of Forkhead box p3 and TGF-beta1 was decreased in both CRSsNP and CRSwNP compared with controls. Comparing CRSsNP and CRSwNP, CRSsNP had higher levels of IFN-gamma expression, whereas only eosinophilic CRSwNP demonstrated an enhanced expression of GATA-3 and IL-5. Compared with noneosinophilic CRSwNP, an exaggerated T(H)2/T(H)17 reaction and Valpha24 expression were found in eosinophilic CRSwNP. CONCLUSION: Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced T(H)1/T(H)2/T(H)17 responses. CRSsNP is confirmed to be a predominant T(H)1 milieu, whereas T(H)2 skewed inflammation with predominant T(H)17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.

Current Status, Diagnosis, and Treatment Recommendation for Tic Disorders in China.

Tic disorders (TD) are a group neuropsychiatric disorders with childhood onset characterized by tics, i.e. repetitive, sudden, and involuntary movements or vocalizations; and Tourette syndrome (TS) is the most severe form of TD. Their clinical manifestations are diverse; and are often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders. Individual severity and response to treatment are highly variable, and there are some refractory cases, which are less responsive to conventional TD treatment. TD/TS are also common in the Chinese pediatric population. To help improve the understanding of TD for pediatricians and other health professionals, and to improve its diagnosis and treatment in China, the Chinese Child Neurology Society (CCNS) has developed an Expert Consensus on Diagnosis and Treatment of TD in China, which is based on our clinical experience and the availability therapeutic avenues. It is focused on clinical diagnosis and evaluation of TD and its comorbidities, psychological and educational intervention, nonpharmacological therapy, pharmacological treatment, including traditional Chinese medicine and acupuncture, as well as prognosis in children with TD in China. A summary of the current status of TD and up-to-date diagnosis and treatment recommendations for TD in China is presented here.

Let-7a microRNA functions as a potential tumor suppressor in human laryngeal cancer.

MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs, which are involved in the gene expression regulation. Lethal-7a (let-7a) is a founding member of miRNA family and recently it was found to be associated with several cancers, such as lung and colon cancers. In the present study, we found that let-7a miRNA expression was significantly downregulated both in human laryngeal squamous cancer tissues and in Hep-2 cells, a laryngeal cancer cell line, as compared with adjacent normal tissues and BEAS-2B cells, respectively. Moreover, we found that let-7a expression levels were significantly further decreased in non-differentiated (G3) cancer tissues as compared with moderately and well differentiated cancer tissues (G2 and G1), although no significant difference in let-7a expression levels between the cancer specimens with different T stages or specimens from patients with different lymph node metastasis status was revealed. In Hep-2 cells, let-7a mimics transfection markedly suppressed proliferation and induced apoptosis of Hep-2 cells under the treatment of diamminedichloroplatinum or not and downregulated RAS and c-MYC protein expression without affecting the mRNA levels. In parallel, RAS and c-MYC protein levels were found significantly upregulated only in cancer tissues with downregulated let-7a expression. Thus, we propose that let-7a may be a tumor suppressor in laryngeal cancer by inhibiting cell growth, inducing cell apoptosis and downregulating the oncogenes expression.

Increased serum complement component 3 and mannose-binding lectin levels in adult Chinese patients with chronic rhinosinusitis.

OBJECTIVE: To study the immune function of adult Chinese patients with chronic rhinosinusitis (CRS) to elucidate its potential role in the pathogenesis of CRS. METHODS: A prospective three-arm case-control study. The study population comprised 72 CRS patients without nasal polyps (NPs), 95 CRS patients with NPs, and 110 healthy controls. The concentrations of serum immunoglobulin A (IgA), M (IgM), G (IgG), IgG subclasses (IgG1-4), complement component 3 (C3), and complement component 4 (C4) were measured by nephelometry. Serum mannose-binding lectin (MBL) levels were analyzed by enzyme-linked immunosorbent assay. All CRS patients had a complete blood count with differential, atopic status evaluation, coronal computed tomographic (CT) scan of the sinuses, and nasal endoscopy. RESULTS: Frequency of immunoglobulin, C3, C4, or MBL deficiency showed no difference among groups. The prevalence of coexistence of MBL and immunoglobulin or complement component deficiency did not differ significantly among groups either. However, compared with controls, decreased IgG3 levels were found in CRS patients without NPs, and increased C3 and MBL levels was found in both CRS patients with and without NPs. Moreover, MBL levels were significantly higher in CRS patients with NPs than in CRS patients without NPs, which positively correlated with extent of disease seen on CT scan and endoscopy, and peripheral eosinophil count. CONCLUSIONS: Immunoglobulin, C3, C4, and MBL deficiency is not the main cause of CRS in adult Chinese patients. However, on the contrary, increased C3 and MBL levels in serum might play a modulatory role in CRS development.

Reliability and Validity of Simplified Chinese STOP-BANG Questionnaire in Diagnosing and Screening Obstructive Sleep Apnea Hypopnea Syndrome.

The main purpose of this study was to assess the reliability and validity of the simplified Chinese STOP-BANG Questionnaire (SBQ) as a diagnosing and screening tool for obstructive sleep apnea hypopnea syndrome (OSAHS). Two hundred and ten patients with suspected OSAHS were recruited in this study. The simplified Chinese SBQ was completed twice before and after polysomnography (PSG) monitoring. SPSS 20.0 was used to analyze the test-retest reliability, discriminant validity, comparative validity and predictive validity of the SBQ. Fourteen patients were excluded on account of fragmentary data, and valid 196 were divided into four groups: non-OSAHS group (n=28, 14.29%), mild OSAHS group (n=28, 14.29%), moderate OSAHS group (n=31, 15.81%) and severe OSAHS group (n=109, 55.61%). The test-retest coefficient for the first four items was 0.810, 0.679, 0.775, 0.963 respectively and the total score of the STOP questionnaire was 0.854. The analysis of discriminant validity revealed that there were significant differences among four groups in the total score of the SBQ and scores of item 1, 3, 7 and 8, which were also validated between patients with normal blood oxygen saturation and different degrees of hypoxemia. The SBQ evaluation showed low consistency with diagnostic gold standard PSG (κ=0.303, P<0.05). When taking apnea hypopnea index (AHI) ≥5/h, ≥15/h and ≥30/h as cut-offs to evaluate the SBQ predictive value, the areas under ROC curve were 0.77, 0.81 and 0.78, the sensitivity was 90.48%, 93.57% and 93.33%, and corresponding negative predictive values were 40.74%, 66.67% and 85.19%, respectively. It was suggested that the simplified Chinese version of SBQ had good reliability, and could distinguish the severity of OSAHS. Despite its limited diagnostic accuracy, the SBQ can be considered as an ideal tool for screening OSAHS with superior predictive validity.

Premonitory urges located in the tongue for tic disorder: Two case reports and review of literature.

BACKGROUND: Premonitory urges (PUs) was defined as the uncomfortable physical sensations of inner tension that can be relieved by producing movement responses. Nearly 70%-90% patients with Tourette syndrome reported experiences of PUs. CASE SUMMARY: In this paper, we present two cases of young patients with PUs located in their tongue, which is very rare and easily misdiagnosed in clinical work. Both two young patients complained of an itchy tongue and cannot help biting their tongue. These two cases were worth reporting because it was rare that PUs was the initial symptom and located in the tongue. The results indicated that PUs seem to play an important role in the generation of tics. CONCLUSION: Thus, PUs may be the first process, and an essential part, of the formation of tics.

Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis.

BACKGROUND: After establishing a murine model of aminoglycoside antibiotic (AmAn) induced ototoxicity, the sensitivity of AmAn induced ototoxicity in three murine strains and the effect of kanamycin on the expression of Na-K-2Cl cotransporter-1 (NKCC1) in stria vascularis were investigated. METHODS: C57BL/6J, CBA/CaJ, NKCC1(+/-) mice (24 of each strain) were randomly divided into four experimental groups: A: kanamycin alone; B: kanamycin plus 2, 3-dihydroxybenzoate; C: 2, 3-dihydroxybenzoate alone; and D: control group. Mice were injected with kanamycin or/and 2, 3-dihydroxybenzoate twice daily for 14 days. Auditory brainstem response (ABR) was measured and morphology of cochlea delineated with succinate dehydrogenase staining. Expression of NKCC1 in stria vascularis was detected immunohistochemically. RESULTS: All three strains in groups A and B developed significant ABR threshold shifts (P < 0.01), which were accompanied by outer hair cell loss. NKCC1 expression in stria vascularis was the weakest in group A (A cf D, P < 0.01) and the strongest in groups C and D (P < 0.05). CBA/CaJ mice had the highest sensitivity to AmAn. CONCLUSIONS: Administration of kanamycin established AmAn induced ototoxicity. Kanamycin inhibited the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate attenuated AmAn induced ototoxicity-possibly by enhancing the expression of NKCC1. Age related hearing loss did not show additional sensitivity to AmAn induced ototoxicity in murine model.

A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults.

OBJECTIVE: The aim of the study was to investigate the efficacy and safety of St John's wort extract and selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. METHODS: Databases were searched for studies comparing efficacy and/or safety of St John's wort extract with SSRIs in depression from 1966 to April 2015. Stata software was used for statistical analysis. RESULTS: Twenty-seven studies met the study entry criteria. A total of 3,126 patients with depression were included. St John's wort extract did not differ from SSRIs in clinical response, remission, and mean reduction in Hamilton Rating Scale for Depression score. St John's wort extract had a significantly lower rate of adverse events compared to SSRIs (summary relative risk: 0.77; 95% confidence interval: 0.70, 0.84, P=0.00) and had fewer withdrawals due to adverse events. St John's wort extract had superior safety in the management of patients with depression. CONCLUSION: Both St John's wort extract and SSRIs are effective in treating mild-to-moderate depression. St John's wort extract is safer than SSRIs.

Changes in endolymphatic hydrops visualized by magnetic resonance imaging after sac surgery.

The purpose of the study was to observe changes in endolymphatic hydrops by using intratympanic injection of gadolinium and magnetic resonance imaging (MRI) before and after endolymphatic sac surgery in patients with unilateral Meniere's disease. Thirteen patients with unilateral Meniere's disease undergoing endolymphatic sac surgery were retrospectively and prospectively analyzed. Three-dimensional fluid-attenuated inversion recovery or three-dimensional real inversion recovery MRI was performed 24 h after an intratympanic injection of gadolinium to grade the presence of endolymphatic hydrops. Among the 13 patients with hydrops confirmed by preoperative MRI, vestibular hydrops had no significant change in all patients; cochlear hydrops became negative in 2 patients, and remained unchanged in the other 11 patients after surgery. Definite vertigo attacks were substantially controlled in one patient and completely controlled in 12 patients during a follow-up period of 8-34 months after surgery. The hearing levels were improved in 3 patients, remained unchanged in 7 patients, and decreased in 3 patients. In conclusion, endolymphatic sac surgery does not always alleviate endolymphatic hydrops in patients with Meniere's disease. Relief from vertigo cannot always be attributed to the remission of hydrops. A change in hearing levels cannot be explained by hydrops status alone.

Distinct mucosal immunopathologic profiles in atopic and nonatopic chronic rhinosinusitis without nasal polyps in Central China.

BACKGROUND: The role of atopy to aeroallergens in chronic rhinosinusitis without nasal polyps (CRSsNP) remains unclear. This study aimed to investigate the mucosal immunopathologic characteristics of CRSsNP with and without atopy to inhalant allergens. METHODS: Thirteen nonatopic CRSsNP patients, 9 atopic CRSsNP patients, and 11 nonatopic control subjects were enrolled in this study. The expression of type 1, 2, and 17 cytokines, growth factors, and chemokines for T cell subsets and granulocytes in sinonasal mucosa was detected using Bio-Plex suspension chip technology or enzyme-linked immunosorbent assay (ELISA). Subjective symptoms were scored on a visual analogue scale (VAS), while disease severity on computed tomography (CT) was graded by the Lund-Mackay CT scoring system. RESULTS: There was no significant difference in VAS and CT scores between atopic and nonatopic CRSsNP. Compared with control, both atopic and nonatopic CRSsNP demonstrated increased interferon γ (IFN-γ) levels in sinonasal mucosa. In contrast, although no difference in interleukin 5 (IL-5), IL-13 and eotaxin-1 expression, or mucosal eosinophil infiltration, was found between the control and whole CRSsNP group, atopic CRSsNP manifested an increased expression of IL-5, IL-13 and eotaxin-1, as well as an enhanced infiltration of mucosal eosinophils in comparison with control and nonatopic CRSsNP. Mucosal eosinophil infiltration correlated with IL-5 and eotaxin-1 expression. No difference in IL-12, IL-4, IL-6, IL-17A, IL-8, myeloperoxidase, "regulated upon activation normal T cell expressed and presumably secreted" (RANTES), or chemokine (C-X-C motif) ligand 10 (CXCL10) protein expression was found among control, atopic CRSsNP, and nonatopic CRSsNP. CONCLUSION: Atopic and nonatopic CRSsNP have distinct mucosal immunopathologic profiles. CRSsNP is a heterogeneous disorder consisting of multiple groups of biological subtypes, or "endotypes," which may argue for different therapeutic strategies.