Clinical efficacy and safety study of Loratadine combined with glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis.

OBJECTIVE: To investigate the clinical efficacy and safety of Loratadine combined with Glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. METHODS: A total of 100 pediatric patients with moderate to severe bronchial asthma and seasonal allergic rhinitis admitted to our hospital between January 2020 and January 2023 were included in this study. All patients met the complete inclusion and exclusion criteria. Based on different treatment interventions, they were divided into the control group (n = 50) and the observation group (n = 50). Patients in the control group received treatment with glucocorticoid nasal spray, while patients in the observation group received combined intervention with Loratadine in addition to the treatment received by the control group. The clinical treatment outcomes, incidence of adverse reactions, as well as the scores of nasal symptoms, asthma control, and peak expiratory flow rates at different treatment time points (baseline, T1: 30 days after treatment, T2: 60 days after treatment, T3: 90 days after treatment) were compared between the two groups. The combined treatment of Loratadine with Glucocorticoid nasal spray demonstrates significant clinical efficacy in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. It further promotes the recovery of peak expiratory flow rates, improves symptoms of rhinitis and asthma in pediatric patients. Importantly, the application of this combined treatment does not increase the risk of adverse reactions in pediatric patients, indicating its high safety profile. This treatment approach is worthy of clinical application and further promotion.

[Retracted] MicroRNA­379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52.

[This retracts the article DOI: 10.3892/etm.2018.6302.].

Identification and Characterization of a Cryptic Genomic Deletion-Insertion in EYA1 Associated with Branchio-Otic Syndrome.

Branchio-oto-renal spectrum disorder (BORSD) is characterized by hearing loss accompanied by ear malformations, branchial cysts, and fistulae, with (branchio-oto-renal syndrome (BORS)) or without renal abnormalities (BOS (branchio-otic syndrome)). As the most common causative gene for BORSD, dominant mutations in EYA1 are responsible for approximately 40% of the cases. In a sporadic deaf patient diagnosed as BOS, we identified an apparent heterozygous genomic deletion spanning the first four coding exons and one 5' noncoding exon of EYA1 by targeted next-generation sequencing of 406 known deafness genes. Real-time PCR at multiple regions of EYA1 confirmed the existence of this genomic deletion and extended its 5' boundary beyond the 5'-UTR. Whole genome sequencing subsequently located the 5' and 3' breakpoints to 19268 bp upstream to the ATG initiation codon and 3180 bp downstream to exon 5. PCR amplification across the breakpoints in both the patient and his parents showed that the genomic alteration occurred de novo. Sanger sequencing of this PCR product revealed that it is in fact a GRCh38/hg38:chr8:g.71318554_71374171delinsTGCC genomic deletion-insertion. Our results showed that the genomic variant is responsible for the hearing loss associated with BOS and provided an example for deciphering such cryptic genomic alterations following pipelines of comprehensive exome/genome sequencing and designed verification.

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4.

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma.

BACKGROUND: Berbamine (BBM), one of the bis-benzylisoquinoline products isolated from Berberis amurensis, has been demonstrated for its anticancer effect against leukemia, breast cancer, liver cancer, etc. There are some studies focusing on the chemosensitization effect of BBM. However, there is no report about whether BBM could enhance the anticancer effect of radiation, which made us to explore the possible radiosensitization effect of BBM. MATERIALS AND METHODS: Here, in vitro cytotoxicity of BBM was evaluated on two kinds of head and neck squamous cancer cell lines. Clonogenic assay was performed to study the radiosensitization effect of BBM. Western blot was utilized to elucidate the possible mechanism underlying the radiosensitization effect. RESULTS: BBM effectively inhibited the growth of two kinds of cancer cells in a time- and dose-dependent manner. Radiation plus BBM led to significantly more reduction of the colony-forming ability of cancer cells when compared with radiation alone. BBM plus radiation led to the most reduction of STAT3 phosphorylation, followed by the significant decrease of the ratio of Bax/Bcl-2. In vivo study demonstrated that the combinational administration of BBM and radiation generated the most significant tumor-delaying effect among all of the treatment regimens. CONCLUSION: We reported, in the current study, the potential role of BBM in not only treating cancer by itself but also offering a promising way to improve the efficacy of radiotherapy by inhibiting the activation of STAT3 and subsequently inducing the apoptosis of cancer.

MicroRNA-379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52.

MicroRNAs (miRs) have been demonstrated to be important regulators of malignant behavior in nasopharyngeal carcinoma (NPC) tumorigenesis. The present study aimed to investigate the biological roles and underlying mechanisms of miR-379 in NPC. The study initially observed that miR-379 was significantly downregulated in NPC clinical tissues and cell lines using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Next, gain-of-function assays were performed on human the NPC cell lines, C666-1 and 5-8F, including MTT, colony formation and transwell migration assays. The results indicated that ectopic expression of miR-379 suppressed the NPC cell proliferation, colony formation, migration and invasion in vitro. In addition, tumor protein D52 (TPD52) was identified as a direct target of miR-379 by a dual-luciferase reporter assay, while overexpression of miR-379 markedly reduced TPD52 expression at the mRNA and protein levels, as determined by RT-qPCR and western blot analysis, respectively. Furthermore, silencing of TPD52 significantly inhibited the C666-1 cell proliferation, migration and invasion. These findings suggest that miR-379 negatively regulates the growth and migration of NPC cells by downregulating TPD52 expression, while modulation of miR-379 expression may be a therapeutic strategy for NPC.

IL-17A promotes the proliferation of human nasopharyngeal carcinoma cells through p300-mediated Akt1 acetylation.

Interleukin (IL)-17A is a T helper (Th)17 cell-secreted cytokine that is able to induce various inflammatory responses. There is emerging evidence that IL-17A is generated in the cancer microenvironment of human nasopharyngeal carcinoma (NPC). However, the role of IL-17A in NPC remains unclear. Thus, the present study aimed to examine the direct influence of IL-17A stimulation on the proliferation of human NPC cells and identify the underlying molecular mechanisms. Furthermore, E1A binding protein p300 (p300)-mediated AKT serine/threonine kinase 1 (Akt1) acetylation and its role in regulating the proliferation of NPC cells was investigated. The results of the current study demonstrated that IL-17A stimulation in vitro increased the proliferation of human NPC cells. Furthermore, Akt1 acetylation was identified to be enhanced in human NPC cells induced by IL-17A. Additionally, p300 induction was demonstrated to be required for Akt1 acetylation in human NPC cells following exposure to IL-17A. Functionally, p300-mediated Akt1 acetylation contributed to the proliferation of human NPC cells stimulated by IL-17A. In conclusion, the results of the present demonstrate a novel activity of IL-17A that promotes human NPC cell proliferation via p300-mediated Akt1 acetylation. This may provide a potential strategy for the treatment of patients with NPC through the inhibition of IL-17A or its receptors.

A 80-gene set potentially predicts the relapse in laryngeal carcinoma optimized by support vector machine.

OBJECTIVE: The present study was performed to identify a gene set for predicting the relapse in laryngeal carcinoma using large data analysis methods. METHODS: Two gene expression profile data of laryngeal carcinoma (GSE27020 and GSE25727) were downloaded from public database. Genes associated with tumor relapse, namely informative genes, were identified by Cox regression analysis. Then the protein-protein interaction (PPI) network consisting of informative genes was constructed. Afterwards, the optimized support vector machine (SVM) classifier was constructed to classify the relapsed laryngeal carcinoma samples based on genes in specific PPI network. Furthermore, the efficiency of the SVM classifier was verified by other two independent datasets. RESULTS: A total of 331 informative genes were obtained from GSE27020 and GSE25757 datasets. A PPI network specific to laryngeal carcinoma relapse was constructed which contained informative genes and critical non-informative genes. The top 10 genes in specific PPI network were APP, NTRK1, TP53, PTEN, FN1, ELAVL1, HSP90AA1, XPO1, LDHA and CDK2 ranked by BC (betweenness centrality) value. The optimized SVM classifier including top 80 genes showed accuracy of 100% to classify the relapsed cases from laryngeal carcinoma samples. Next, the efficiency of the SVM classifier to predict relapse samples was verified in another independent datasets, which showed accuracy of 97.47%. The informative genes in the optimized SVM classifier were enriched in several pathways associated with tumor progression. CONCLUSION: A 80-gene set was identified as biomarker to predict the relapse of laryngeal carcinoma, which would be potentially applied in decision of different treatments for patients with different relapse risks.

Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met.

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively modulate gene expression at the post-transcriptional level. A growing number of studies has shown that more and more miRNAs are aberrantly expressed and involved in the pathogenesis of several types of cancers. Here, we report that the down-regulated hsa-miR-34c was also involved in oncogenesis of laryngeal carcinoma. Our studies indicated that hsa-miR-34c functioned as a tumor suppressor which inhibited growth and invasion of human laryngeal carcinoma cells. Furthermore, in our study, an inverse relationship between the expression of hsa-miR-34c and c-Met was identified in 10 paired fresh samples from tumor tissues and adjacent normal tissues. Infection of hsa-miR-34c mediated by lentivirus suppressed the expression of c-Met directly. In addition, introduction of c-Met cDNA lacking 3'-UTR largely abrogated hsa-miR-34c-induced cell growth and invasion inhibition. These findings suggest aberrantly down-regulated hsa-miR-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-Met.