p120 regulates E-cadherin expression in nasal epithelial cells in chronic rhinosinusitis.

BACKGROUND: The epithelial barrier plays an important role in the regulation of immune homeostasis. The effect of the immune environment on E-cadherin has been demonstrated in previous studies. This discovery prompted new research on the targeting mechanism of E-cadherin in chronic rhinosinusitis (CRS). METHODS: E-cadherin and p120 expression was determined by quantitative RT-PCR, and western blot. The interaction between E-cadherin and p120 was assessed by immunofluorescence staining and coimmunoprecipitation assays. Human nasal epithelial cells (HNECs) were cultured with submerged methods and transfected with p120-specific small interfering RNA. In other experiments, HNECs differentiated with the air-liquid interface (ALI) method were stimulated with various cytokines and Toll-like receptor (TLR) agonists. The barrier properties of differentiated HNECs were determined by assessing fluorescent dextran permeability. RESULTS: E-cadherin and p120 expression was decreased in HNECs from patients with CRS, and the p120 protein expression level was positively correlated with that of E-cadherin. Two isoforms of p120 (p120-1 and p120-3) were expressed in HNECs, with p120-3 being the main isoform. Knocking down p120 in HNECs cultured under submerged conditions significantly reduced the E-cadherin protein expression. The Rac1 inhibitor NSC23766 reversed the protein expression of E-cadherin in p120 knockdown experiments. Inflammatory mediators, including IL-4, TNF-α, TGF- ß, LPS and IFN-Î, reduced E-cadherin and p120 protein expression and increased paracellular permeability. Dexamethasone abolished the downregulation of E-cadherin and p120 caused by inflammatory mediators. CONCLUSIONS: p120 is involved in regulating E-cadherin protein expression in CRS. Dexamethasone may alleviate the reduction in E-cadherin and p120 protein expression caused by inflammatory mediators.

[Clinical study on the effects of neoadjuvant chemotherapy on lymph node ratio, prognosis, and survival analysis of stage â ¢A-N2 non-small cell lung cancer].

Objective: To investigate the effect of neoadjuvant chemotherapy (NCT) on the lymph node ratio (LNR) of patients with stage ⅢA-N2 non-small cell lung cancer (NSCLC), and analyze the relationship between LNR and prognosis. Methods: The data of 128 patients with stage ⅢA-N2 NSCLC admitted to the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Hebei North University from January 2013 to December 2018 were retrospectively collected. The patients were divided into two groups according to the treatment method. The patients in the observation group (64 cases) were treated with NCT and surgery, and the patients in the control group (64 cases) were treated with surgery. Lymph node metastasis and survival were observed in the two groups. Subgroups were divided according to LNR and N2 lymph node status, and survival analysis was performed for each subgroup. Univariate and multivariate analysis were conducted for the observation group. Results: The number of metastatic lymph nodes, the proportion of patients with positive lymph nodes, and the rate of lymph node metastasis in the observation group were lower than those in the control group,3.8±2.1 vs 4.9±2.4,92.2% vs 100%,19.1% vs 22.4% respectively (all P<0.05). Progression-free survival (PFS) and overall survival (OS) in the observation group were better than those in the control group (both P<0.05). Both the observation and control subgroups with low LNR had better PFS and OS than the subgroups with high LNR (both P<0.05). Patients in the observation group with non-multi-site N2 lymph node metastasis had better PFS and OS (both P<0.05). Univariate analysis of observation group showed that patients with low LNR had better 2-year PFS and OS(both P<0.05). Multivariate analysis showed that the higher the LNR, the greater the risk of death (HR=2.178,95%CI: 1.025-4.626,P=0.043) and progression (HR=2.130,95%CI: 1.123-4.038,P=0.021). Conclusion: NTC could improve the prognosis and reduce LNR of patients with stage ⅢA-N2 NSCLC, and LNR was expected to be a prognostic indicator.

Use of the multiplier method to estimate the size of populations most at risk of human immunodeficiency virus infection in China: a systematic review.

OBJECTIVE: United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome and World Health Organization believe that some of the benchmark numbers collected may be inaccurate when using the multiplier method to estimate the size of populations most at risk of acquiring HIV. Here, study data have been evaluated to characterize the inaccurate benchmark numbers. STUDY DESIGN: The study design used is a systematic review. METHODS: Studies published from 1 January 2004 to 1 December 2019 using the multiplier method to estimate the population proportions of men who have sex with men (MSM) and female sex workers (FSWs) in China were reviewed. Five electronic bibliographic databases were searched: Medline, the China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data, and the Chinese BioMedical Literature Database. RESULTS: In all eight studies of FSW, six of the estimated population proportions fell within the range of national estimates. However, the estimated MSM population proportions of all 18 studies fell outside the range of national estimates. CONCLUSIONS: When estimating the MSM population, the use of benchmark numbers from homosexual websites or MSM-frequented sites usually led to an inaccurate estimation. Therefore, benchmark numbers from services/programs that meet fundamental needs, such as those dealing with health and wellness, should be used.

[Association between single nucleotide polymorphism in promoter region of SIRT1 gene and senile degenerative heart valvular disease].

Objective: To investigate the correlation between single nucleotide polymorphisms (SNPs) of SIRT1 gene promoter sequence and senile degenerative heart valvular disease (SDHVD). Methods: A total of 236 SDHVD patients and 285 healthy controls who visited the Affiliated Hospital of Jining Medical University between February 2012 and October 2016 were enrolled. SNPs of SIRT1 gene promoter were detected by Sanger sequencing. Typing and correlation were analyzed by χ(2) test and Logistic regression analysis. Haplotype and linkage disequilibrium were analyzed by Haploview4.2 software and SHEsis online software. The effect of SNPs on the binding of transcription factors to SIRT1 gene promoter was analyzed by electrophoretic mobility shift assay(EMSA). The transcription factors affected by SNPs were predicted by Transfac online software. Results: The frequency distribution of GG genotype of rs3740051 in the SDHVD group was significantly higher than that in the control group (χ(2)=4.855, P=0.028). There was a correlation between GG genotype of the rs3740051 and SDHVD. After adjusting for age, the risk of SDHVD in the carrier of GG genotype was 3.079 times higher than that of AA genotype(OR=3.079, 95%CI: 1.156-8.201, P=0.024). The five SNPs (rs3740051, rs932658, rs35995735, rs3740053 and rs2394443) showed strong linkage disequilibrium(D'>0.8). The haplotype analysis of the five SNPs (haplotype frequency<0 was ignored in the analysis) showed that 11 haplotypes (P<0.05) were formed, and the frequency of *A**C, AA**C, *AG*C, AAG*C, AA*AC, *AGAC and AAGAC in SDHVD group were significantly higher than that in control group (P<0.05, OR>1, 95%CI does not contains 1). EMSA showed that the color of the binding bands incubated by wild type probe and nucleoprotein was darker than that incubated by DNA sequence variation probe and nucleoprotein. Conclusion: The GG genotype of rs3740051 is associated with SDHVD and may be a risk genotype for SDHVD. The haplotype AC (across rs932658 and rs2394443) may be a dangerous haplotype of SDHVD. rs3740051 may affect the occurrence and development of SDHVD by interfering with the binding of FOXC protein to SIRT1 gene promoter.

[Upregulation of PLOD2 promotes invasion and metastasis of osteosarcoma cells].

Objective: To investigate the relationship of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression and the clinical characteristics of osteosarcoma, and explore the potential mechanism of tumour metastasis promoted by PLOD2. Methods: The expression of PLOD2 in osteosarcoma tissues and paired adjacent tissues were detected by immunohistochemistry and qRT-PCR. Correlation of PLOD2 expression in osteosarcoma with the clinical pathologic features was analyzed by Chi square test and Kaplan-Meier analysis.Fibrillar collagen formation and collagen deposition in the tumor tissues were detected by picrosirius red staining. We transfected U-2OS cells with LV-vector, LV-over/PLOD2, sh-NC and sh-PLOD2. The expression of PLOD2 was detected by qRT-PCR. The impact of POLD2 on U-2OS cell invasion was determined by wound-healing assay and Transwell migration assay. The expressions of PLOD2/FAK/JAK2-STAT3 signal pathway related proteins were detected by western blotting. Results: The high expression level of PLOD2 in osteosarcoma tissues was 72.5%, significantly higher than 0% in paired adjacent noncancerous tissues (P<0.01), the expression of PLOD2 was positively correlated with lymph node metastasis, pulmonary metastasis and poor outcome (P<0.01). The same results were also observed in qRT-PCR assay. The median survival time of patients with high expression of PLOD2 protein was 13 months, significantly shorter than 32 months of patients with low expression of PLOD2 (P<0.05). The result of picrosirius red staining showed that the percentage of collagen fiber deposition in the osteosarcoma tissue with high level of PLOD2 was (74.43+ 9.63)%, significantly higher than (9.67±1.28)% in tissue with low expression of PLOD2 (P<0.001). The result of wound-healing and Transwell migration assay showed that over-expression of PLOD2 markedly promoted the invasion, however, knockdown of PLOD2 suppressed the invasion of U-2OS cells (both P<0.01). The result of western blotting showed that over-expression of PLOD2 significantly increased the expression levels of p-FAK, p-JAK2, p-STAT3, but knockdown PLOD2 decreased the levels of p-FAK, p-JAK2, p-STAT3 in U-2OS cells. Conclusions: Up-regulation of PLOD2 in osteosarcoma is correlated with lymphatic and distant metastasis. PLOD2 promotes invasion and metastasis of osteosarcoma might through FAK/JAK2-STAT3 signal pathway.

[Mechanism of MALAT1 induced osimertinib resistance in HCC827 lung cancer cells].

Objective: To test the effect of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) and/or osimertinib on the proliferation and apoptosis of HCC827 cells, and explore the potential mechanism of MALAT1 induced resistance to osimertinib. Methods: We transfected HCC827 cells with LV-vector or LV-over/MALAT1. Stable transfected cells (HCC827/Vector, HCC827/MALAT1) were selected by adding puromycin. HCC827/MALAT1 cells were further transfected with the shRNA-negative control (NC) or shRNA-human epidermal growth factor receptor 3 (ERBB3) plasmid. The effects of overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib on the proliferation of HCC827 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. Cell apoptosis induced by MALAT1 overexpression, knockdown of ERBB3 and/or osimertinib treatment were analyzed by flow cytometry analysis. The expressions of EGFR and ERBB3 signal pathway related proteins in HCC827 cells treated with overexpression of MALAT1, knockdown of ERBB3 and/or osimertinib treatment were detected by western blot. Results: The MTT assay showed that sensitivity to osimertinib of HCC827/MALAT1 cells were significantly repressed. The 50% inhibitive concentration (IC(50)) of osimertinib >4 000 nmol/L in HCC827/MALAT1 cells. However, knockdown of ERBB3 facilitated the anti-proliferation effect of osimertinib, and the IC(50) of osimertinib in shRNA-ERBB3 cells was (17.27±3.21) nmol/L. The results of flow cytometry analysis showed that the apoptotic rate of HCC827/MALAT1 cells induced by 10 nmol/L osimertinib was (8.38±0.92)%, significantly lower than (27.17±5.83)% of knockdown of ERBB3 (P<0.01). Western blotting showed that the expression of p-ERBB3, p-AKT and p-extracellular regulated protein kinases (ERK) in HCC827/MALAT1 cells was markedly up-regulated, while the expression of p-epithelial growth factor receptor (EGFR) was inhibited. The expressions of p-ERBB3, p-AKT and p-ERK were marginally affected by osimertinb. However, osimertinib downregulated the expressions of p-EGFR, p-ERBB3, p-AKT and p-ERK in ERBB3 deleted cells. Conclusions: MALAT1 confers resistance to osimertinb in HCC827 cells by activating of the ERBB3/PI3K/AKT and ERBB3/MAPK/ERK signaling pathways.

[Mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1 induced invasion and metastasis of esophageal cancer cell EC-109].

Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay. The expressions of components of epithelial-msenchymal transition pathway in EC-109 cells were determined by immunofluorescence array and western blotting. The expression relationship between MALAT1 and miR-200a in EC-109 cells was detected by dual-luciferase reporter assay. Results: The result of qRT-PCR showed that the expressions levels of MALAT1, ZEB1 and ZEB2 in shRNA-MALAT1 group were 0.43±0.06, 0.64±0.04 and 0.51±0.04, respectively, significantly lower than 0.97±0.08, 1.06±0.07 and 0.98±0.05 in shRNA-control group and 1 in control group, respectively(all P<0.05). Transwell assay showed that the number of invaded cells in shRNA MALAT1 group was (96.81±10.43) per low-power field, markedly lower than that of (278.44±13.28) per low-power field in shRNA-control group (P<0.01). Immunofluorescence staining and Western blotting showed that MALAT1 downregulation significantly reduced the expressions of proteins related to EMT signal pathway in EC-109 cells.Dual luciferase reporter assay showed that compared to negative control, the activities of luciferase reporter in EC-109 cells co-transfected with pmirGLO-MALAT1-wt and miR-200a were significantly down-regulated. While co-transfected pmirGLO-MALAT1-mut with miR-200a mimics had no effect on the luciferase reporter activities of MALAT1. Conclusion: LncRNA MALAT1 functions as a competing endogenous RNA to regulate the expressions of ZEB1 and ZEB2 by sponging miR-200a and promotes invasion and migration of esophageal cancer cells through inducing epithelial-mesenchymal transition.

[Ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus].

Objective: To explore the ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus (CIN). Methods: Case-control study. Ten extraocular muscle samples were collected from five CIN children who underwent nystagmus surgeries in Beijing Children's Hospital from March 2015 to March 2016. Another ten extraocular muscle specimens were collected from five strabismus children in surgery at the same period as normal contrast. There were 3 male patients and 2 female patients of CIN with age of 61-147 months (median age: 91 months). The ultrastructure of extraocular muscle proprioceptors was compared between these two groups by transmission electron microscope. Results: Twenty-three proprioceptors were found in extraocular muscle specimens of CIN children, whereas thirty-three proprioceptors were detected in strabismus children. The ultrastructure of extraocular muscle proprioceptor of CIN altered greatly comparing with that of the control. Fourteen extraocular muscle proprioceptors of CIN were discovered much smaller and vacuolated not only at inner capsules but also at the space between inner and outer capsules with lipofuscins and myeloid bodies in the intrafusal muscle fibers. Sensory nerve fibers degenerated greatly with a lot of lipofuscins and myeloid bodies in these sensory nerve fibers. Demyelination also appeared in some severe cases. Nine extraocular muscle proprioceptors of CIN showed significant dissolving degeneration of myofibrils and proliferation of collagen fibrils. The normal structures could not be distinguished in these proprioceptors. And these structural disorders also appeared in extrafusal muscle fibers and nerve endings. Conclusion: The ultrastructure of extraocular muscle proprioceptor in CIN turned much smaller and had significantly structural disorder.(Chin J Ophthalmol, 2017, 53: 136-139).

Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns.

BACKGROUND: The remodeling patterns in different types of chronic rhinosinusitis (CRS) have rarely been compared, particularly the difference between eosinophilic and noneosinophilic CRS with nasal polyps (CRSwNP). Moreover, whether there is a link between remodeling and inflammation remains controversial. OBJECTIVE: To directly compare the remodeling features of different CRS and to explore their relationship with inflammation in Chinese patients. METHODS: Histologic characteristics of surgical samples were analyzed in 33 controls, 72 eosinophilic and 76 noneosinophilic CRSwNP, and 72 CRS without nasal polyps (CRSsNP) patients. Tissue samples from 38 controls, 26 eosinophilic and 26 noneosinophilic CRSwNP, and 32 CRSsNP patients were measured for mRNA and/or protein expression of profibrotic growth factors, metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), hypoxia-inducible factor (HIF)-1α, interleukin (IL)-8, eosinophil cationic protein (ECP), and myeloperoxidase (MPO). RESULTS: The amount of collagen decreased, whereas the edema scores increased, from CRSsNP to noneosinophilic CRSwNP and to eosinophilic CRSwNP. Transforming growth factor (TGF)-ß2 protein levels were enhanced in CRSsNP compared with CRSwNP. TIMP-4 protein levels decreased in eosinophilic CRSwNP compared with noneosinophilic CRSwNP and CRSsNP. The number of neutrophils decreased from CRSsNP to noneosinophilic CRSwNP and to eosinophilic CRSwNP. ECP levels were only up-regulated in eosinophilic CRSwNP. ECP levels and neutrophil number correlated positively with the severity of edema and fibrosis, respectively. Neutrophils were the major sources of TGF-ß2 in CRSsNP and noneosinophilic CRSwNP. CONCLUSION: Distinct remodeling patterns are revealed for different types of CRS, particularly for eosinophilic and noneosinophilic CRSwNP. Tissue remodeling associates with inflammation in CRS.

Transcriptional activity of an ovarian-specific promoter from rat in dairy goat granulosa cells.

Ovarian-specific promoter 1 (OSP-1) is a retrovirus-like element isolated from the complementary DNA library of rat that has been thought to be specifically expressed in ovary. To exploit this promoter in dairy goat ovary granulosa cells (GCs), OSP-1 from rat was used to construct the reporter vector pOSP-1-EGFP, in which egfp coding for enhanced green fluorescent protein (EGFP) was used as a reporter to examine the activity of OSP-1 in GCs. EGFP was successfully expressed in dairy goat GCs transfected with pOSP-1-EGFP. Reverse transcriptase-polymerase chain reaction analysis confirmed the tissue-specific transcription of EGFP messenger RNA in dairy goat GCs transfected with pOSP-1-EGFP. We concluded that OSP-1 promoter from rat can specifically drive foreign gene expression in dairy goat GCs. Thus, we obtained a tissue-specific regulation element and provided a potential tool for the research of regulation and development of the ovary in dairy goats.

[Diagnosis and management of orbital and cranial complications of pediatric acute rhinosinusitis].

Objective: To review the clinical characteristics, to illustrate diagnosis and management experience of orbital and cranial complications of pediatric acute rhinosinusitis. Methods: The clinical data of 24 children with orbital and cranial complications of acute rhinosinusitis who received endoscopic sinus surgery combined with drug treatment in Beijing Children's Hospital from January 2017 to December 2021 were retrospectively reviewed. There were 19 boys and 5 girls. The age varied from 13 to 159 months, with a median 47.5 months. The following diagnoses were obtained: 12 isolated subperiosteal orbital abscess, 2 associated with preseptal abscess, 2 associated with intraorbital abscess, 7 associated with optic neuritis, and 1 associated with septic cavernous sinus thrombosis. Clinical characteristics, organism isolated and outcomes were analyzed through descriptive methods. Results: All 24 patients presented with fever; 9 presented with nasal congestion and purulent discharge. The clinical manifestations of orbital infection included orbital edema, pain, proptosis and displacement of globe in all patients, while visual impairment was recognized in 7 children. Purulent drainage was cultured in 17 patients, among which 12 were positive. All patients underwent nasal endoscopic surgical interventions uneventfully, excluding one patient who required a second surgical procedure. Follow-up period ranged from 5 to 64 months. All patients resolved fully, with the exception of 2 children who got permanent blindness with visual loss preoperative. There was no recurrence or death. Conclusions: Orbital and cranial complications of pediatric acute rhinosinusitis could be severe with an occult onset. For patients with vison impairment, any signs of intracranial complications and a lack of response to conservative management, an urgent endoscopic intervention is needed.

Polymorphism identification in the goat KITLG gene and association analysis with litter size.

This study reported the analysis of KIT ligand (KITLG) gene polymorphisms in 681 goats of three breeds: Xinong Saanen (SN), Guanzhong (GZ), and Boer (BG). In addition, the study identified three allelic variants: g.769T>C and g.817G>T in SN and GZ breeds, and g.9760G>C in the three goat breeds. The g.769T>C and g.817G>T loci were closely linked (r(2) > 0.33). All the single nucleotide polymorphism loci were in Hardy-Weinberg disequilibrium (P < 0.05). Significant associations were found for litter size with all three loci. Therefore, these results suggest that the KITLG gene is a strong candidate gene affecting litter size in goats.

[Transoral robotic surgery for treatment of lingual thyroglossal duct cyst].

Objective: To investigate the feasibility, safety and efficacy of transoral robotic surgery (TORS) in the treatment of lingual thyroglossal duct cyst (LTGDC). Methods: The clinical data of 10 patients with LTGDC treated with TORS in Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2017 to November 2020 were analyzed retrospectively,including 6 males and 4 females, aged 5-44 years. The cysts were fully exposed, and resection usually started from the cephalic side of lesions. The range of resection was 3 to 5 mm away from the lesions, and partial hyoid bone was removed if necessary. Intra-operative robotic set-up time,operation time and estimated blood loss,and post-operative local bleeding, dyspnea and recovery time for oral intake were analyzed. SPSS 12.0 software was used for statistical analysis. Results: The cysts in all 10 patients were successfully resected by TORS with da Vinci Si surgical system. The mean robotic set-up and exposure time, operation time, estimated intraoperative blood loss and recovery time for oral intake were (15.5±7.1) min, (17.6±7.4) min, (8.9±6.4)ml and (2.3±2.2)days, respectively. No patient required tracheostomy intra-or post-operatively, and no symptoms of airway obstruction, postoperative bleeding, pharyngeal fistula, hoarseness and neurological impairment occurred after operation. The patients were followed up for 5 to 47 months, with median follow-up time of 17 months, and no recurrence was observed. Conclusion: TORS is safe and feasible for resection of LTGDC, with rapid recovery and low recurrence rate.

A new approach for cloning hLIF cDNA from genomic DNA isolated from the oral mucous membrane.

Complementary DNA (cDNA) is valuable for investigating protein structure and function in the study of life science, but it is difficult to obtain by traditional reverse transcription. We employed a novel strategy to clone human leukemia inhibitory factor (hLIF) gene cDNA from genomic DNA, which was directly isolated from the mucous membrane of mouth. The hLIF sequence, which is 609 bp long and is composed of three exons, can be acquired within a few hours by amplifying each exon and splicing all of them using overlap-PCR. This new approach developed is simple, time- and cost-effective, without RNA preparation or cDNA synthesis, and is not limited to the specific tissues for a particular gene and the expression level of the gene.

The expression of osteopontin and its association with Clara cell 10 kDa protein in allergic rhinitis.

BACKGROUND: Osteopontin (OPN) is a multifunctional protein that has recently been linked to allergic diseases. Clara cell 10 kDa protein (CC10) is another protein linked to allergy, and has been suggested to have an inhibitory role in inflammatory airway diseases. At this time, it is not known whether OPN is involved in allergic rhinitis (AR) or if there is any association between CC10 and OPN in AR. OBJECTIVE: To study the expression of OPN and its potential association with CC10 in AR. METHODS: The expression of CC10 and OPN in nasal mucosa of AR patients was investigated. AR animal models were established by using wild-type and CC10-knockout mice. In some experiments, human recombinant CC10 protein was given to AR mice during either sensitization or challenge. The phenotypic changes were examined by histology and real-time RT-PCR. The direct effect of CC10 on the OPN expression in spleen mononuclear cells and on the OPN-induced inflammatory cytokine expression in BEAS-2B cells was measured through in vitro cell culture. RESULTS: OPN expression was up-regulated, with a concomitant down-regulation of CC10, in AR patients, showing a significant negative correlation between their expression. Compared with control mice sensitized with PBS, the OPN expression was significantly increased in AR mice; such an increase was more prominent in CC10-knockout mice, compared with wild-type. Administration of CC10 during both sensitization and challenge could markedly ameliorate Th2-skewed inflammation and OPN expression in nasal mucosa. CC10 administration at the sensitization phase could also reduce spleen OPN expression. The in vitro study showed that CC10 directly down-regulated the OPN expression in spleen mononuclear cells stimulated with OVA and suppressed the OPN-induced expression of Th2 cytokines and pro-inflammatory cytokines in BEAS-2B cells. CONCLUSION: In the context of allergic airway responses, CC10 can inhibit OPN expression and suppress the Th2-promoting function of OPN, resulting in CC10's inhibitory biological effects.

[Investigation on the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children].

Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

[Safety and effectiveness of transoral robotic surgery for oropharyngeal cancer: a pilot study].

Objective: To evaluate the indication, safety and effectiveness of transoral robotic surgery (TORS) for oropharyngeal cancer based on our preliminary experience. Methods: Twelve patients, including six with tonsil cancer, five with tongue base cancer and one with posterior pharyngeal wall cancer, who underwent TORS with Da Vinci Si surgical system from March 2017 to October 2018 at Tongji Hospital of Huazhong University of Science Technology were respectively analyzed. And the surgical time, intraoperative blood loss, postoperative local bleeding, dyspnea, nerve function injury, oral intake time, whether or not to receive chemoradiotherapy were analyzed. Results: All tumors in the 12 patients were en bloc removed by TORS. Surgical time ranged from 25 to 80 min with an average of 34.2 min. The blood loss ranged from 10 ml to 50 ml with an average of 20.8 ml. The recovery time for oral intake ranged from 1 day to 30 days with an average of 8.4 days. No patient underwent tracheostomy after TORS. Also, no patient manifested with airway obstruction, bleeding or nerve injury symptoms after operation. All 12 patients reached pathologically negative surgical margins. The patients were followed up for 4 to 22 months, with a median of 12 months. All patients who combined with more advanced than T3 stage, or more advanced than N2 stage were recommended to oncologist, then, followed with radiotherapy or chemoradiotherapy if no relevant contradictions occurred. No local recurrence or distant metastasis case was found. Conclusion: With proper indications, the application of TORS in oropharyngeal cancer is a relatively safe, effective and minimal invasive therapy, which merits more clinical applications.

Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipper.

BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. OBJECTIVE: Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-gamma, IL-4, IL-13, IL-1beta, and TNF-alpha on GILZ mRNA expression in normal sinonasal mucosa. RESULTS: The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1beta, TNF-alpha, IL-4, and IL-13 reduced, whereas IFN-gamma enhanced GILZ mRNA levels in the sinonasal mucosa. CONCLUSION: Down-regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines.

Clara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosa.

BACKGROUND: Clara cell 10-kDa protein (CC10) is a multifunction protein with anti-inflammatory and immunomodulatory effects; hence we compared the CC10 expression between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NPs), analyzed its association with disease severity and response to surgery, and explored its regulation via cytokines. METHODS: The plasma and tissue CC10 levels were compared between controls and CRS patients with and without NPs by means of quantitative RT-PCR, ELISA, and immunohistochemistry. Computed tomography (CT) scan and endoscopy findings and symptoms were scored. Nasal explant culture was used to explore the effect of TNF-alpha, IL-1beta, IL-4, INF-gamma, and IL-10 on CC10 gene regulation. RESULTS: Compared with controls, the CC10 expression in sinonasal mucosa was significantly inhibited in both CRS patients with and without NPs. There was a significant further decrease of CC10 expression in patients with NPs and asthma. No difference in CC10 plasma levels was found between controls and patients. CC10 levels inversely correlated with preoperative CT scores, and postoperative endoscopy and symptom scores. TNF-alpha, IL-1beta and IL-4 inhibited, whereas INF-gamma and IL-10 promoted CC10 production in nasal mucosa. A significantly faster decay of CC10 transcripts was seen after IL-1beta treatment. IL-1beta and IL-10 induced thyroid transcription factor-1 expression. INF-gamma increased, whereas IL-4 inhibited hepatocyte nuclear factor-3alpha expression. CONCLUSION: CC10 may take part in the pathogenesis of CRS and correlates with disease severity and response to surgery. Different cytokines can regulate CC10 expression in nasal mucosa differentially through modulating mRNA stability and certain transcriptional factors expression.