TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway.

Tripartite Motif 14 (TRIM14) is an oncoprotein that belongs to the E3 ligase TRIM family, which is involved in the progression of various tumors except for non-small cell lung carcinoma (NSCLC). However, little is currently known regarding the function and related mechanisms of TRIM14 in NSCLC. Here, we found that the TRIM14 protein was downregulated in lung adenocarcinoma tissues compared with the adjacent tissues, which can suppress tumor cell proliferation and migration both in vitro and in vivo. Moreover, TRIM14 can directly bind to glutamine fructose-6-phosphate amidotransferase 1 (GFAT1), which in turn results in the degradation of GFAT1 and reduced O-glycosylation levels. GFAT1 is a key enzyme in the rate-limiting step of the hexosamine biosynthetic pathway (HBP). Replenishment of N-acetyl-d-glucosamine can successfully reverse the inhibitory effect of TRIM14 on the NSCLC cell growth and migration as expected. Collectively, our data revealed that TRIM14 suppressed NSCLC cell proliferation and migration through ubiquitination and degradation of GFAT1, providing a new regulatory role for TRIM14 on HBP.

High Mobility Group Box-1 Protein and Interleukin 33 Expression in Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is characterized by an inflammatory reaction. High mobility group box 1 (HMGB1) protein and interleukin (IL)-33 are damage-associated molecular pattern molecules and have many characteristics similar to pro-inflammatory cytokines. However, the role of IL-33 and HMGB1 in AR remains unclear. The aim of this study is to explore the role of HMGB1 and IL-33 in AR. METHODS: Twenty patients with AR (AR group) and 10 normal controls (normal group) were enrolled in this study. HMGB1 and IL-33 expression were analyzed by immunohistochemistry in epithelial cells of the inferior turbinate mucosa samples. Then, the human nasal mucosa epithelial cells (HNECs) were cultured in vitro, and the house dust mite allergen (Derp1) was used to stimulate the cells. Quantitative real-time PCR and ELISA assay were performed to detect HMGB1 and IL-33 expression in HNECs. RESULTS: The expression of HMGB1 and IL-33 in the nasal mucosa was higher in the AR group than in the normal group, with a statistically significant difference (p < 0.05). In HNECs of AR, the expression of both HMGB1 and IL-33 in stimulated groups was higher than that in non-stimulated groups. The differences were statistically significant (p < 0.05). In addition, they increased gradually with the prolonging time and the concentration of the added Derp1. CONCLUSIONS: The expression of HMGB1 and IL-33 were both increased in AR. HMGB1 and IL-33 may have a close relationship in AR.

H3N2 influenza virus infection enhances oncostatin M expression in human nasal epithelium.

Tight junctions (TJs) alteration is commonly seen in airway inflammatory diseases. Oncostatin M (OSM) is an inflammatory mediator associated with chronic rhinosinusitis with nasal polyps (CRSwNP). We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for influenza A virus (IAV). However, its role in TJs alteration and the effects of IAV on inducing OSM expression in nasal epithelium remains to be further investigated. In this study, OSM and TJs expression was measured and compared between inferior turbinate from healthy controls and nasal polyps from CRSwNP. Additionally, hNECs cultured at air-liquid interface (ALI) were infected with H3N2 influenza virus to study the role of influenza virus in inducing epithelial OSM expression as a possible means of exacerbation. The expression of ZO-1, claudin-1, and occludin was markedly decreased and correlated negatively with that of OSM in CRSwNP. By using the in vitro hNEC model, H3N2 infection resulted in significantly increased OSM expression (2.2-, 4.7- and 3.9-fold higher at 8, 24, and 48 h post-infection vs. mock infection). Furthermore, OSM is found to co-localize with ciliated and goblet cells in hNECs infected with H3N2 influenza virus. Our findings demonstrated that increased OSM expression is implicated in CRSwNP as a possible mechanism of TJs' impairment, which can be further augmented following influenza infection via epithelial OSM expression, possibly contributing to exacerbations.

GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis.

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.

Effects of Pendrin Protein in Nasal Epithelial Cells on Mucin Production in the Context of Type 2 Inflammation.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease. The pathogenesis of chronic sinusitis is still unclear; however, the nasal cavity and paranasal sinuses are commonly affected by type 2 inflammation, which is caused by Th2 cytokines such as interleukin (IL)-5, IL-4, and IL-13. Previous studies have shown that pendrin promotes local infiltration of neutrophils through the production of human neutrophil elastase (HNE), which is essential for the secretion of mucin 5AC (MUC5AC) in chronic inflammatory diseases of the lower respiratory tract. This study investigated pendrin expression and its relationship to mucin in type 2 inflammation. METHODS: A total of 40 patients (10 CRS patients with nasal polyps,10 CRS patients without nasal polyps, and 20 nasal septum deviation patients) were included in this study and were divided into the CRS group and the NC group. A normal nasal mucosa tissue culture model was established in vitro. IL-13 was used to stimulate primary cultures of human nasal epithelial cells (HNECs). Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of pendrin, MUC5AC, and MUC5B. After transfecting HNECs with siRNA pendrin or negative control (NC), EGF receptor (EGFR), HNE, MUC5AC, and MUC5B expression were analyzed using qRT-PCR, WB, or ELISA in terms of their relationships with pendrin. Pendrin expression in the tissue was also analyzed. RESULTS: After IL-13 stimulation, pendrin, MUC5AC, and MUC5B expression levels were upregulated; the optimal concentration of IL-13 was 50 ng/mL. The expression levels of HNE, EGFR, MUC5AC, and MUC5B were downregulated after transfection with siRNA pendrin-1650. Pendrin expression in the NC group was lower than in the CRS group. CONCLUSION: IL-13 is implicated in the inflammation of nasal mucosa, and pendrin is closely related to the excessive secretion of mucin. The expression of mucin is downregulated after transfection with siRNA pendrin. There is a positive relationship between pendrin and EFGR/HNE. Moreover, pendrin plays an important role in type 2 inflammation.

Diagnostic value and underlying mechanism of nasal nitric oxide in eosinophilic chronic rhinosinusitis with nasal polyps.

PURPOSE: Nitric oxide (NO) is an important messenger molecule widely present in the human body. However, the role of nasal NO (nNO) in eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) remain unclear. This study aimed to investigate the diagnostic value and underlying mechanism of nNO in Eos CRSwNP. METHODS: The medical records of 84 non-Eos CRSwNP patients, 55 Eos CRSwNP patients, and 37 control subjects were retrospectively reviewed. The diagnostic value of nNO for Eos CRSwNP was assessed. The expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and tight junctions (TJs) components claudin-1, occludin, and ZO-1 was detected in the nasal polyps. Primary human nasal epithelial cells (HNECs) were co-treated with eNOS inhibitor (L-NAME) or Akt inhibitor (MK-2206), interleukin (IL)-13, and dexamethasone (Dex). The level of NO and the expression of TJs and Akt/eNOS pathways were examined. RESULTS: The nNO levels of the CRSwNP group were significantly lower than those of the control group. Compared with the non-Eos CRSwNP group, the Eos CRSwNP group showed higher nNO level. The combination of nNO level, eosinophilic percentage, and posterior ethmoid score had a better predictive value for Eos CRSwNP (AUC = 0.855). The expression of iNOS, eNOS, and p-eNOS was higher in the CRSwNP groups than in the control group, and p-eNOS expression was higher in the Eos CRSwNP group than in the non-Eos CRSwNP group. The expression of TJs was lower in the Eos CRSwNP group than in the non-Eos CRSwNP and control group. IL-13 decreased TJ expression in HNECs, while Dex promoted Akt and eNOS phosphorylation, NO production and TJ expression. Furthermore, these effects of Dex were inhibited by L-NAME and MK-2206 in HNECs. CONCLUSION: nNO may have a high diagnostic value in Eos CRSwNP, and Akt/eNOS pathway may promote the generation of NO to protect TJs. NO may have a potentially important role in the diagnosis and treatment of Eos CRSwNP.

Hypoxia disrupts the nasal epithelial barrier by inhibiting PTPN2 in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Hypoxia is involved in inflammation and immune response; however, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is not fully understood. We aimed to investigate the mechanisms by which hypoxia disrupts the nasal epithelial barrier in CRSwNP. METHODS: The expression of hypoxia-inducible factor-1α (HIF-1α), protein tyrosine phosphatase non-receptor type 2 (PTPN2), and tight junction (TJ) components (claudin-4, occludin, and ZO-1) was detected in nasal polyps using immunohistochemistry, western blotting, and qRT-PCR. Primary human nasal epithelial cells (HNECs), BEAS-2B cells, and an eosinophilic CRSwNP (Eos CRSwNP) mouse model were used to explore the potential mechanisms by which hypoxia disrupts the nasal epithelial barrier. RESULTS: HIF-1α expression in the non-Eos and Eos CRSwNP groups was higher than in the control group, and the expression of PTPN2 and TJs in the non-Eos and Eos CRSwNP groups were lower than those in the control group. Hypoxia decreased the expression of PTPN2 and TJs and increased epithelial cell permeability in HNECs, which was blocked by the HIF-1α inhibitor PX-478. PTPN2 overexpression inhibited hypoxia-induced downregulation of TJ expression in BEAS-2B cells, whereas PTPN2-knockdown aggravated the effects of hypoxia. In the Eos CRSwNP mouse model, both PX-478 and PTPN2 overexpression reduced the formation of nasal polypoid lesions, permeability of the nasal epithelium, and restored TJ expression. CONCLUSIONS: Our data indicate that hypoxia-induced HIF-1α downregulates TJ expression by inhibiting PTPN2, thereby disrupting the nasal epithelial barrier and promoting CRSwNP development. HIF-1α and PTPN2 may be potential targets for the treatment of CRSwNP.

Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer.

Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan-Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.

Expression and clinical significance of TYRP1, ABCB5, and MMP17 in sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a lethal malignancy with poor prognosis. Treatment outcomes of SNMM are poor. Novel prognostic or progression markers are needed to help adjust therapy. METHODS: RNA-seq was used to analyze the mRNA expression of tumor tissues and normal nasal mucosa from primary SNMM patients (n= 3). Real-time fluorescent quantitative PCR (qRT-PCR) was used to validate the results of RNA-seq (n= 3), while protein expression was analyzed by immunohistochemistry (IHC, n= 31) and western blotting (n= 3). Retrospective studies were designed to determine the clinical parameters and the total survival rate, and correlation between the protein expression levels of the most significant key genes and prognosis was analyzed. RESULTS: In total, 668 genes were upregulated and 869 genes were downregulated in SNMM (fold change ⩾ 2, adjusted p value < 0.01). Both mRNA and protein expression levels of the key genes in SNMM tumor tissues were higher than those in the normal control nasal mucosal tissues. The expression rates of TYRP1, ABCB5, and MMP17 in 31 primary SNMM cases were 90.32%, 80.65%, and 64.52%, respectively. In addition, age, typical symptoms, and AJCC stage were related to overall survival rate of patients with SNMM (p< 0.05). Furthermore, the expression of ABCB5 was age-related (p= 0.002). Compared with individuals with negative ABCB5 expression, those with positive expression exhibited significantly poor overall survival (p= 0.02). CONCLUSION: The expression levels of TYRP1, ABCB5, and MMP17 were significantly upregulated in SNMM tissues, and the expression of ABCB5 was related to poor prognosis in SNMM. Thus, ABCB5 may serve as a progression marker and can predict unfavorable prognosis in patients with SNMM.

Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib.

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end. Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo. Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis. Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.

Early Efficacy Analysis of Cluster and Conventional Immunotherapy in Patients With Allergic Rhinitis.

BACKGROUND: Specific immunotherapy is an important immune-modifying treatment for patients with allergic rhinitis (AR). We compared the early efficacy and safety of cluster and conventional immunotherapies for patients with AR. METHODS: One hundred forty-nine patients with persistent AR were enrolled in a randomized and open-label trial and were divided into the following 4 groups: 60 children treated conventionally, 33 children treated using the cluster schedule, 23 adults treated conventionally, and 33 adults treated using the cluster schedule. Patients in the cluster groups reached the maintenance dose within 6 weeks, while those receiving conventional therapy reached the maintenance dose within 14 weeks. Symptom scores and skin prick test scores (SPTs) were used to evaluate clinical efficacy and adverse reactions. RESULTS: After buildup phase of treatment, symptom scores, and SPTs were significantly lower than those prior to treatment in each group (P < .05). No significant differences were found in the efficacy of nasal symptoms scores among four groups (P > .05).However, the efficacy of SPTs using conventional schedule was higher than cluster schedule in children groups (group A and B, 57.7 vs 30.2%, P = .001). Besides, the efficacy of SPTs in adults was higher than children when using the cluster treatment (group D and B, 53.0 vs 30.2%, P = .008). No severe adverse reaction occurred. CONCLUSIONS: Conventional and cluster immunotherapy schedules have similar efficacies, which do not vary with age; both schedules are safe and reliable. Also, SPT facilitate evaluation of clinical efficacy.

Gene Expression Profiles of Circular RNAs and MicroRNAs in Chronic Rhinosinusitis With Nasal Polyps.

Introduction: Chronic rhinosinusitis (CRS) is often classified primarily on the basis of the absence or presence of nasal polyps (NPs), that is, as CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). Additionally, according to the percentage of eosinophils, CRSwNP can be further divided into eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP. CRSwNP is a significant public health problem with a considerable socioeconomic burden. Previous research reported that the pathophysiology of CRSwNP is a complex, multifactorial disease. There have been many studies on its etiology, but its pathogenesis remains unclear. Dysregulated expression of microRNAs (miRNAs) has been shown in psoriasis, rheumatoid arthritis, pulmonary fibrosis, and allergic asthma. Circular RNAs (circRNAs) are also involved in inflammatory diseases such as rheumatoid arthritis, septic acute kidney injury, myocardial ischemia/reperfusion injury, and sepsis-induced liver damage. The function of miRNAs in various diseases, including CRSwNP, is a research hotspot. In contrast, there have been no studies on circRNAs in CRSwNP. Overall, little is known about the functions of circRNAs and miRNAs in CRSwNP. This study aimed to investigate the expression of circRNAs and miRNAs in a CRSwNP group and a control group to determine whether these molecules are related to the occurrence and development of CRSwNP. Methods: Nine nasal mucosa samples were collected, namely, three ECRSwNP samples, three non-ECRSwNP samples, and three control samples, for genomic microarray analysis of circRNA and microRNA expression. All of the tissue samples were from patients who were undergoing functional endoscopic sinus surgery in our department. Then we selected some differentially expressed miRNAs and circRNAs for qPCR verification. Meanwhile, GO enrichment analysis and KEGG pathway analysis were applied to predict the biological functions of aberrantly expressed circRNAs and miRNAs based on the GO and KEGG databases. Receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) were performed to confirm these molecules are involved in the occurrence and development of CRSwNP. Results: In total, 2,875 circRNAs showed significant differential expression in the CRSwNP group. Specifically, 1794 circRNAs were downregulated and 1,081 circRNAs were upregulated. In the CRSwNP group, the expression of 192 miRNAs was significantly downregulated, and none of the miRNAs were significantly upregulated. GO and KEGG analysis showed differential circRNAs and miRNAs were enriched in "amoebiasis," "salivary secretion," "pathways in cancer," and "endocytosis." Through qRT-PCR verification, the expression profiles of hsa-circ-0031593, hsa-circ-0031594, hsa-miR-132-3p, hsa-miR-145-5p, hsa-miR-146a-5p, and hsa-miR-27b-3p were shown to have statistical differences. In addition, ROC curve analysis showed that the molecules with the two highest AUCs were hsa-circ-0031593 with AUC 0.8353 and hsa-miR-145-5p with AUC 0.8690. Through PCA with the six ncRNAs, the first principal component explained variance ratio was 98.87%. The AUC of the six ncRNAs was 0.8657. Conclusion: In our study, the expression profiles of ECRSwNP and non-ECRSwNP had no statistical differences. The differentially expressed circRNAs and miRNAs between CRSwNP and control may play important roles in the pathogenesis of CRSwNP. Altered expression of hsa-circ-0031593 and hsa-miR-145-5p have the strongest evidence for involvement in the occurrence and development of CRSwNP because their AUCs are higher than the other molecules tested in this study.

Interactions between gastric microbiota and metabolites in gastric cancer.

The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.

Clinical Treatment Efficacy of Total Thyroidectomy Combined with Radioactive Iodine on Treatment of Thyroid Cancer and Its Effect on the Quality of Life of Patients.

BACKGROUND: To investigate the treatment efficacy of radioactive iodine therapy on patients after total thyroidectomy and its effect on the quality of life. METHODS: A retrospective analysis of clinical data of 120 thyroid cancer patients admitted to Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China from February 2014 to February 2017 was performed. According to different treatment methods, they were divided into observation group of 62 cases and control group of 58 cases. Both groups were treated with total thyroidectomy. The control group was treated with anti-infection and prevention of complications after operation, the observation group with radioactive iodine therapy. Treatment efficacy, quality of life score, recurrent laryngeal nerve injury and postoperative survival rate were compared between the two groups. RESULTS: The total effective rate of treatment in the test group was 98.39%, significantly higher than 72.41% in the control group, with a statistically significant difference (P<0.05). Compared with the control group, the fatigue score of the test group was lower, but the score in the area of emotion function and the overall health status score were higher, with a statistically significant difference (P<0.05). There was no significant difference in the recurrent laryngeal nerve injury between the two groups of patients. The postoperative survival rate of the test group of patients was 96.77%, significantly higher than 86.21% of the control group. CONCLUSION: The effect of radioactive iodine therapy after total thyroidectomy is remarkable, which can significantly improve the clinical treatment efficacy and postoperative quality of life of patients, worthy of clinical application.

Novel Bougie for the Management of Esophageal Coins in Children: An Observational Study.

OBJECTIVES: To determine the efficacy and safety of a novel bougie for the removal of esophageal coins lodged in the proximal esophagus. SUBJECTS AND METHODS: This was an observational study. Medical records were reviewed of patients who were confirmed with esophageal coins between July 2015 and October 2016 in our department. Sixty-three patients, upper esophageal coins were confirmed by radiographs, were treated by using this novel bougie to remove esophageal coins. RESULTS: A total of 63 children were enrolled in this study. Sixty coins (95%) were removed successfully. The coin was extracted on the first attempt in 56 cases (89%), the second attempt in 3 cases (5%), and the third attempt in 1 case (2%). Two coins retained in the esophagus underwent endoscopy. In the remaining patient, the coin passed into the stomach and was confirmed to be passed in the stool within 48 hours. No serious complications occurred in any subject. CONCLUSIONS: Our novel bougie procedure is likely a safe, highly efficient approach to managing esophageal coins given that no serious complications of the 63 patients were reported. This simple technique may provide another valuable option to physicians.

Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.

BACKGROUND: Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized. METHODS: Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference. Invasion potential was determined by Matrigel and three-dimensional invasion. The secretion of matrix metalloproteinase 2 (MMP2) and MMP9 were measured by ELISA. Protein levels were assessed by Western blotting and immunohistochemistry. Protein-protein interactions were determined by immunoprecipitation. An experimental mouse model was generated to investigate the gene regulation in tumor growth and metastasis. RESULTS: Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. Overexpression of NAP1 in lowly invasive NSCLC cells enhances MMP9 secretion and invasion potential, whereas NAP1 silencing in highly invasive NSCLC cells produces opposing effects in comparison. Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells. CONCLUSIONS: Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis.

RNAi Knockdown of Ape1 Gene in the Differentiation of Mouse Embryonic Stem Cells.

Murine embryonic stem cells (ES) are pluripotent cells and have the potential to become a wide variety of specialized cell types. Mouse ES cell differentiation can be regarded as a valuable biological tool that has led to major advances in our understanding of cell and developmental biology. In vitro differentiation of mouse ES cells can be directed to a specific lineage formation, such as hematopoietic lineage, by appropriate cytokine and/or growth factor stimulation. To study specific gene function in early developmental events, gene knockout approaches have been traditionally used, however, this is a time-consuming and expensive approach. Recently, we have shown that siRNA is an effective strategy to knock down target gene expression, such as Ape1, during ES cell differentiation, and consequently, one can alter cell fates in ES-derived differentiated cells. This approach will be applicable to test the function of a wide variety of gene products using the ES cell differentiation system.

[Clinical observation of the adverse effects of standardized dust mite allergen preparation in the treatment of allergic rhinitis].

OBJECTIVE: To observe the adverse effects of specific immunotherapy (SIT) with standardized dust mite allergen preparation in the treatment of allergic rhinitis. METHOD: Three hundred and eighty-six patients with allergic rhinitis who received subcutaneous SIT with a standardized dust mite allergen preparation were enrolled in this study. The patients were treated for at least 15 weeks,adverse effects after each injection from dosing phase to maintenance phase were recorded and incidence of adverse effects were analyzed. RESULT: Of all the patients,adverse reactions occurred in 42 patients (10. 9%),10 local reactions (2. 6%) and 36 systemic side effects (9. 3%) which included 34 mild ,1 moderate and 1 severe side effects (no fatal) were reported respectively. None had anaphylactic shock. Among three treatment options, incidence of routine program was the highest (21.1%),followed by adult cluster program (11. 9%), adverse effects of children cluster program was the least (1. 5%). The adverse effects often happened in the middle and late phase of does addition period and early phase of maintenance period. CONCLUSION: SIT with standardized dust mite allergen preparation in the treatment of allergic rhinitis is a safe and effective treatment by complying with the guidelines and taking specific interventions.