miR-211-3p enhances induction chemotherapy insensitivity by upregulating CSF2/CCL20/TNF signaling in hypopharyngeal squamous cell carcinoma.

PURPOSE: To investigate the potential mechanisms of miR-211-3p on induction chemotherapy (IC) sensitivity in hypopharyngeal squamous cell carcinoma (HSCC). METHODS: qRT-PCR was assessed to compare the miR-211-3p expression between IC sensitive and insensitive tumor tissues. The MTT assay was performed to analyze cell proliferation and viability to paclitaxel after alteration of miR-211-3p. Flow cytometry assay was conducted to explore cell apoptosis. Transwell assay was used to explore the effect of miR-211-3p on cell migration. Transcriptome sequencing was then performed to select differentially expressed genes (DEGs) after over-expression of miR-211-3p. GO and KEGG enrichment analyses were conducted to annotate DEGs. PPI analysis was conducted to screen candidate genes. The differential expression and survival status of candidate genes were further validated in TCGA-HNSCC data. The single sample GSEA method was used to investigate the association between downstream genes and immune cell infiltration. RESULTS: miR-211-3p was up-regulated in IC insensitive larynx-hypopharyngeal tumor tissues. Over-expression of miR-211-3p promoted cell proliferation and migration, and inhibited apoptosis. The IC50 value of miR-211-3p overexpression (OE) group was significantly higher than negative control (NC) group treated with paclitaxel, suggesting miR-211-3p enhanced IC insensitivity in HSCC. We found 778 DEG after over-expression of miR-211-3p and 11 significant genes were then identified. Finally, colony stimulating factor 2 (CSF2) and C-C motif chemokine ligand 20 (CCL20) were validated to be significantly high expressed and associated with poorer overall survival in head and neck squamous cell carcinoma, which were involved in TNF signaling pathway and then regulated immune cell infiltration. CONCLUSION: The miR-211-3p could promote HSCC progression and upregulate CSF2/CCL20/TNF signaling to promote IC insensitivity in HSCC, which may provide new ideas for HSCC therapy.

Transcriptome Analysis Identified 2 New lncRNAs Associated with the Metastasis of Papillary Thyroid Carcinoma.

INTRODUCTION: Papillary thyroid microcarcinoma (PTMC) is a specific subgroup of papillary thyroid carcinoma and defined with the dimension ≤1 cm by the WHO. Although it shows a relatively high 10-year livability, the metastasis of PTMC into other tissues and organs seriously affects the daily life of patients with relatively high mortality. Therefore, the genetic basis for the metastasis of PTMC needs to be explored for effective therapeutic targets. Here, we conducted a series of comparative analysis of the transcriptional expression profile between PTMC patients with and without lymph node metastasis. METHODS: Gene expression profile and gene function were analyzed using RNA extracted from pathological tissues of 12 patients with PTMC, and the core biomarkers closely related to its metastasis were identified. RESULTS: Our results showed that 7,507 genes and 42 RNAs showed remarkably different expression patterns. More sophisticated analysis showed that the high expression of 2 lncRNAs (T077499 and T004533) resulted in the metastasis of PTMC, which suggests that the expression pattern of the 2 lncRNAs may act as a potential biomarker for pathogenesis and prognosis of PTMC metastasis. CONCLUSION: Our findings preliminarily reveal the molecular mechanisms for PTMC metastasis, which will provide vital reference for subsequent studies about the genetic basis and molecular targeted therapy for PTMC metastasis.

Induction chemotherapy for the individualised treatment of hypopharyngeal carcinoma with cervical oesophageal invasion: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the potential of induction chemotherapy as an indicator of the management of advanced hypopharyngeal carcinoma with cervical oesophageal invasion. METHODS: Sixty-eight patients admitted to our hospital between February 2003 and November 2016 with stage IVB hypopharyngeal carcinoma with cervical oesophageal invasion were retrospectively analysed. Patients were divided into two groups according to the treatment they selected following an explanation of the different treatments available. Patients in group A received induction chemotherapy and had (1) complete/partial remission following chemotherapy and radiotherapy/concurrent chemoradiotherapy or (2) stable disease following chemotherapy and surgery. Patients in group B underwent surgery followed by adjuvant radiotherapy/concurrent chemoradiotherapy. Survival analyses were performed using the Kaplan-Meier method, and differences between the groups were evaluated using the log-rank test. Laryngeal and oesophageal retention rates were compared using the cross-tabulation test. RESULTS: The 3- and 5-year overall survival rates were 22.86% and 11.43% in group A and 24.25% and 6.06% in group B, respectively (all P > 0.05). The laryngeal and oesophageal retention rates were 40.0% and 74.3% in group A and 0.0% and 27.3% in group B, respectively (all P < 0.01). There was no statistically significant difference in the incidence of post-operative complications between the two groups (group A 8.6%, group B 12.1%; P > 0.05). CONCLUSIONS: Induction chemotherapy may be an appropriate first choice to ensure laryngeal and oesophageal preservation in the individualised treatment of advanced hypopharyngeal carcinoma with cervical oesophageal invasion.

A case report of jejunum transplantation in the treatment of severe cervical esophageal stricture in patients with dystrophic epidermolysis bullosa.

Epidermolysis bullosa (EB) is a rare disorder caused by autosomal genetic variation. Its main clinical features include skin and mucous membrane blisters, erosion, repeated ulcers and scar formation. The lesions mostly involve the skin, oral cavity, digestive system and urinary system. Epidermolysis bullosa complicated with esophageal stenosis is a common gastrointestinal manifestation of this disorder. Currently, there is no cure for EB, and thus symptomatic treatment is usually applied. Here we describe the case of a patient with recessive dystrophic EB complicated with severe esophageal stenosis. The narrow segment of esophagus was removed and the free part of jejunum was transplanted into the esophageal defect to reconstruct the esophagus and restore the patient's normal swallowing. For patients with EB complicated with severe esophageal stenosis, surgical resection of the diseased esophagus and jejunal transplantation can be used to repair the esophageal and restore normal swallowing pathway, providing an effective treatment for this condition.

[The bacteriological characteristics and drug resistance of the nasopharyngeal region in 311 cases of adenoid hypertrophy with secretory otitis media].

Objective:To analyze the bacteriological distribution and drug resistance of nasopharynx in patients with adenoid hypertrophy complicated with secretory otitis media, and to clarify the distribution of pathogenic bacteria, so as to provide guidance and basis for antibiotic use in clinical treatment. Methods:A retrospective analysis was performed on 311 patients with adenoid hypertrophy and secretory otitis media who underwent surgical treatment in the department of otolaryngology head and neck surgery, Affiliated Hospital of Qingdao University from February 2013 to January 2020. They were divided into 3 groups by age: Group A（0-5 years old）, Group B（6-10 years old）, and Group C（11-16 years old）. The secretions from deep adenoid near the eustachian tube of the affected ear were collected during the surgery for bacterial culture and drug resistance analysis. Results:One hundred and forty-two strains of pathogenic bacteria were isolated and cultured, with a detection rate of 45.66%. Staphylococcus aureus （63 strains）, streptococcus pneumoniae （15 strains） ,streptococcus pyogenes （13 strains） and moraxella cachinella（28 strains）was the main strain.Staphylococcus aureus had high drug resistance rate to penicillin, erythromycin and clindamycin.Streptococcus pneumoniae and Streptococcus pyogenic had high resistance rates to erythromycin,clindamycin and tetracycline. The resistance rate of Moraxella catarrhalis to ampicillin and co-trimoxazole was higher. Conclusion:The main pathogens detected in patients with adenoid hypertrophy complicated with secretory otitis media are staphylococcus aureus, streptococcus pneumoniae, streptococcus pyogenes and moraxella catarrhalis. Drug resistance of different pathogens is quite different. So it is recommended to carry out extensive bacteriological detection, and select antibiotics according to the principle of rational drug use and the results of drug resistance test, so as to achieve good therapeutic effect.

Uncovering the interplay between pH receptors and immune cells: Potential drug targets (Review).

Extracellular acidosis is associated with various immunopathological states. The microenvironment of numerous solid tumours and inflammatory responses during acute or chronic infection are all related to a pH range of 5.5­7.0. The relationship between inflammation and immune escape, cancer metabolism, and immunologic suppression drives researchers to focus on the effects of low pH on diverse components of disease immune monitoring. The potential effect of low extracellular pH on the immune function reveals the importance of pH in inflammatory and immunoreactive processes. In this review, the mechanism of how pH receptors, including monocarboxylate transporters (MCTs), Na+/H+ exchanger 1, carbonic anhydrases (CAs), vacuolar­ATPase, and proton­sensing G­protein coupled receptors (GPCRs), modulate the immune system in disease, especially in cancer, were studied. Their role in immunocyte growth and signal transduction as part of the immune response, as well as cytokine production, have been documented in great detail. Currently, immunotherapy strategies have positive therapeutic effects for patients. However, the acidic microenvironment may block the effect of immunotherapy through compensatory feedback mechanisms, leading to drug resistance. Therefore, we highlight promising therapeutic developments regarding pH manipulation and provide a framework for future research.

Autophagy regulation by microRNAs in chemotherapy resistance (Review).

Chemotherapy, as an adjuvant therapy, utilizes drugs to treat cancer, and resistance to therapeutic drugs limits the efficacy of chemotherapy treatments. Several mechanisms have been proposed to improve the effect of tumor chemotherapy in order to overcome drug resistance. Among these, autophagy mediated by microRNAs (miRNAs) is one of the primary mechanisms. A large number of molecules targeted by miRNAs are involved in each step of the autophagic pathway. Recent advancement in chemotherapy research has revealed that miRNAs involved in the autophagy process target some of these molecules, thereby influencing the therapeutic effect of chemotherapy drugs. Thus, miRNAs appear to be potential tools or targets with which to suppress tumor growth and should be studied in further details for their clinical application against drug resistance.

MUC1 confers radioresistance in head and neck squamous cell carcinoma (HNSCC) cells.

Mucin 1 (MUC1), a transmembrane glycoprotein, has shown to be as the possible prognostic marker to predict the risk of aggressive head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the effect of MUC1 in HNSCC cells and the response to X-ray irradiation (IR). Here, we examined the impact of MUC1 overexpression or downexpression on clonogenic survival and apoptosis in response to X-ray irradiation (IR). Radioresistance and radiosensitivity were also observed in HNSCC cells that are MUC1 overexpression and MUC1 downexpression. This enhanced resistance to IR in MUC1-overexpressing cells is primarily due to increased the number of radiation-induced γH2AX/53BP1-positive foci and DNA double-strand break (DSB) repair kinetics. MUC1 overexpression repaired more than 90% of DSBs after 2 Gy radiation by 24 h compared to the empty vector overexpressing cells with less than 50% of DSB repair. However, MUC1 downexpression repaired less than 20% of DSBs compared to the empty vector-overexpresing cells. MUC1 overexpression inhibited proapoptotic protein expression, such as caspase-3, caspase-8, and caspase-9, and induced antiapoptotic protein Bcl-2, followed by resistance to IR-induced apoptosis. Our results showed that targeting MUC1 may be as a promising strategy to counteract radiation resistance of HNSCC cells.

Endoscopic surgery of a sinonasal inverted papilloma: Surgical strategy, follow-up, and recurrence rate.

BACKGROUND: Sinonasal inverted papilloma (SNIP) is noted for its high rate of recurrence and malignant transformation. Although many clinical studies have demonstrated the effectiveness of the endoscopic approach for SNIP, the surgical strategy has been the subject of much debate. OBJECTIVE: To evaluate the effectiveness of the endoscopic endonasal approach in SNIP. METHODS: A systematic review of patients with a diagnosis of SNIP and who had surgery at our institution from June 2005 to March 2013 was performed. All the patients who had postoperative follow-up for >2 years were enrolled. Each case was categorized into one of four stages as reported by Krouse. Demographic and tumor date, operative approach, complications, and recurrence rates were collected. RESULTS: A total of 125 patients were included in this study. There were 17 patients in stage 1, 40 in stage 2, 57 in stage 3, and 11 in stage 4. The overall recurrence rate was 8.0%. There was no significant difference in recurrence among the stages (all p > 0.05). Recurrence after endoscopic endonasal approach (8.4%) and a combined endoscopic and open exposure procedure (5.6%) were not significantly different (p > 0.05). The recurrence rate was significantly (p < 0.05) higher in patients with revision (15.6%) than in patients in the primary cases (3.8%). A common site of tumor origin was recorded to be from the maxillary sinus (40.2%). Twenty percent of recurrences were observed up to 5 years after surgery. CONCLUSION: Endoscopic surgery may be preferred for treating SNIP. The elevated recurrence rate after revision emphasized the significance of the first surgery. We encourage a follow-up period of at least 5 years.