Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Effects of SENP1-induced deSUMOylation of STAT1 on proliferation and invasion in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is the most common nasopharyngeal squamous cell carcinoma, and recurrence and metastasis are still difficult problems in its current treatment. This study aimed to investigate the effect of SUMO modification of STAT1 protein on the proliferation and invasion of NPC, and to reveal the underlying mechanism. Two gene expression profiles (GSE12452 and GSE53819) of 49 nasopharyngeal carcinomas and 28 normal controls were analyzed to identify differentially expressed genes. In total, 448 up-regulated genes and 622 down-regulated genes were identified. In addition, 16 SUMO-related molecules in the NPC dataset GSE102349 with survival data were analyzed, and it was found that the high expression of SENP1 and SENP2 was closely related to the poor prognosis of NPC. GO and GSEA analysis suggested that immune-related biological processes, IFN-γ-STAT signaling pathway and protein modification-related molecules were significantly enriched in NPC, resulting in poor survival prognosis. In order to verify the results of bioinformatics analysis and explore its underlying molecular mechanisms, western blot, Immunofluorescence, Immunoprecipitation and Immunohistochemistry are conducted in NPC cells, animals and clinical samples. SENP1 and STAT protein levels were increased in NPC tissues. SENP1 inhibited SUMOylation of STAT1, thereby promoting the protein level of STAT1 and the nuclear translocation. SENP1 promoted the proliferation and invasion of NPC by inducing STAT1. Overall, SENP1-induced deSUMOylation of STAT1, resulting in an increased proliferation and invasion of nasopharyngeal carcinoma.

LINC00669 insulates the JAK/STAT suppressor SOCS1 to promote nasopharyngeal cancer cell proliferation and invasion.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer emerging from the lining of nasopharyngeal mucosa, with extremely frequent occurrence in east and southeast Asia. For the purpose of exploring roles of the dysregulated long non-coding RNA (lncRNA) in NPC, we identified a novel lncRNA LINC00669 with an apparent negative correlation to the overall survival from human NPC mRNA expression profiling databases. We further performed RNA pulldown coupled with mass spectrum to find out its target protein, and applied a series of in vitro and in vivo loss-and-gain-of function assays to investigate its oncogenic roles in NPC tumor development and progression. Our results demonstrated that LINC00669 competitively binds to the key JAK/STAT signaling pathway suppressor SOCS1, and insulates it from imposing ubiquitination modification on the pathway component of STAT1, which leads to its abnormal stabilization and activation. The activated STAT1 is then transferred into the nucleus and initiates the transcription of genes related to proliferation and invasion. In summary, our study reveals that the cytoplasmic resident lncRNA LINC00669 confers malignant properties on NPC cancer cells by facilitating a persistent activation of the JAK/STAT signaling pathway. Findings in the current study shed lights on prospects for treating NPC using strategies targeting the novel regulator of the JAK/STAT signaling.

[Therapeutic effect of vadian neurectomy under the nasal endoscope on the vasomotor rhinitis].

OBJECTIVE: To explore the therapeutic effect of vadian neurectomy under the nasal endoscope on the vasomotor rhinitis. METHODS: Anatomic measurements of vadian canal in 14 cadavers were carried out, and vadian neurectomy under the nasal endoscope was performed on 51 patients with vasomotor rhinitis. RESULTS: Anatomic measurements showed vadian canal was located behind the sphenoid-palatine hole, and its external orifice was shaped as infundibular. The vertical diameter was (3.5+/-0.9) mm and the horizontal diameter was (2.9+/-0.5) mm. The distance to the rotundum foramen and nasal septum was (6.1+/-1.2) mm and (10.5+/-5.9) mm. Longitudinal axes of the vadian canal was (27.0+/-9.6) degrees with the horizontal plane, and (7.8+/-2.5) degree with the sagittal plane. Among the 51 patients, 41(80.4%) patients showed complete response and 3(5.9%) partial response at the 5-year follow-up. CONCLUSION: Vadian neurectomy under nasal endoscope is an effective technique for vasomotor rhinitis.

[Genomic instability in nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the effect of genomic instability on prognostics in nasopharyngeal carcinoma. METHODS: Genomic instability was assessed by inter-simple sequence repeats polymerase chain reaction (inter-SSR PCR) in 38 patients with nasopharyngeal carcinoma. Characterization and verification of band alterations shared in different tumors were carried out by sequencing and nest PCR. RESULTS: Thirty-one (81.6%) of the 38 patients showed genomic altercations, and genomic instability index ranged 0 to 16.2 percent. A gain-based genomic damage shared in 6 tumors was identified on chromosome 6q27. Genomic alteration was significantly more in patients less than 5-year survival than those with more than 5-year survival (P<0.05). CONCLUSION: Genomic instability can be an early event marker in carcinogenesis of nasopharyngeal carcinoma. Aggravation of genomic alterations is a poor prognosis for cancer recovery.

[Therapeutic effect of endoscopic vidian neurectomy on moderate-severe persistent allergic rhinitis].

OBJECTIVE: To evaluate the efficacy of endoscopic vidian neurectomy in the management of moderate-severe persistent allergic rhinitis, and to explore its possible mechanism. METHODS: One hundred and ninety-one patients with moderate-severe persistent allergic rhinitis were divided into three groups: endoscopic vidian neurectomy was carried out in 71 patients (group A), partial inferior turbinectomy and/or septal-plasty in 39 patients (group B), and 81 patients were as control (group C). The life quality was assessed at 6 month, 1 year and 3 years after operation using rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS). RESULTS: Among 191 cases, one hundred and forty-five cases had complete follow-up documents. The average score of RQLQ and VAS score (x(-) ± s) were significantly decreased at the time of 6 months (0.84 ± 0.41, 2.55 ± 1.57), 1 year (0.91 ± 0.43, 2.63 ± 1.71) and 3 years (1.03 ± 0.46, 2.81 ± 1.75) after endoscopic vidian neurectomy than scores before operation (2.25 ± 0.49, 7.34 ± 1.11), F = 115.45, 133.09, respectively, P < 0.001, and also significantly lower than scores in patients in group B or control group at the same period after treatment. By patient's self-evaluation, the ratio of greatly-improved, improved and not-improved was respectively, 65.5% (38 cases), 24.1% (14 cases), 10.4% (6 cases), and significantly higher in patients in group A than in patients in group B (U = 237.0, P < 0.001) and group C (U = 246.0, P < 0.001). There was no severe complication in all patients observed. CONCLUSION: Endoscopic vidian neurectomy is an effective and safe technique in the management of moderate-severe persistent allergic rhinitis.

[Role of folate receptor 1 in paclitaxel-resistance of nasopharyngeal carcinoma cells].

OBJECTIVE: To provide experimental evidence for the folate receptor 1 (FOLR1) mediated targeted cancer therapy and resistance reversal, the FOLR1 expression differences in nasopharyngeal carcinoma cells (CNE-1) and immortalized normal nasopharyngeal cells (NP69) and the correlation between FOLR1 expression and paclitaxel resistance index in nasopharyngeal carcinoma were investigated. METHODS: The expressions of FOLR1 in CNE-1, CNE-1/Taxol (paclitaxel-resistance cells) and NP69 was detected by cDNA microarray, reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry. Proliferation inhibition rates of CNE-1 and CNE-1/Taxol cells were measured by colony formation assay after treated by short interfering RNA (siRNA) of FOLR1. RESULTS: The expressions of FOLR1 gene in CNE-1/Taxol cells and CNE-1 cells were 2636.0 and 176.0, respectively. The expression of FOLR1 was not detected in the NP69 by semi-quantative RT-PCR and Western blot. The high expression of FOLR1 in CNE-1/Taxol was verified by semi-quantative RT-PCR, and its expression level was positively correlated to the degree of drug-resistance (r(2) = 0.8719). The results were also validated by Western blot and immunocytochemistry. The sensitivity of CNE-1/Taxol to paclitaxel significantly increased after inhibition of FOLR1 gene expression by siRNA, and its IC(50) value was decreased by 59.6% (t = 6.92, P < 0.01). CONCLUSIONS: The expression of FOLR1 is closely related to the occurrence of NPC and Taxol resistance. FOLR1 gene may be one of the important target molecules in NPC treatment and reversion of the paclitaxel-resistance in NPC.