FTH1 indicates poor prognosis and promotes metastasis in head and neck squamous cell carcinoma.

Background: Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. Methods: Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. Results: The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. Conclusion: Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.

[Surgical issues and managements in cochlear reimplantation in 32 children].

Objective:To summarize the clinical characteristics of children undergoing surgery of cochlear reimplantation, focus on various problems and management in cochlear reimplantation, in order to avoid related problems in surgery of cochlear reimplantation and the initial implantation. Methods:A total of 32 children who underwent cochlear reimplantation in Peking University Third Hospital from July 2018 to July 2022 were retrospectively analyzed, and the duration from the initial implantation was from 1 year to 8 years. The cochlear implant mapping was performed 4 weeks after the operation, and the auditory performance was evaluated. Results:Special intraoperative issues included 32 cases with bone and soft tissue hyperplasia at various sites（2 cases with obvious bone hyperplasia in cochlear window, 1 case with obvious bone hyperplasia in subperiosteal tunnel of wire）, 5 cases with bone defects in important structures（including the posterior wall of the external auditory canal, the facial nerve canal, and the subperiosteal pocker of the receiver-stimulator）, 1 case with cholesteatoma, 4 cases with other lesions or foreign bodies, 4 cases with abnormal position of the electrodes（migration or reversal）. All operations were successfully completed without complications. Postoperative recoveries were smooth. Conclusion:In the initial cochlear implantation, attention should be paid to retain residual hearing as much as possible, fully consider the possibility of postoperative bone hyperplasia, avoid large amounts of non-absorbable adhesive materials, avoid bone defects in important structures（such as facial nerve canal or posterior wall of the external auditory canal）, pay attention to the depth and orientation of electrode implantation. The possibility of "hidden injury" mentioned above should be fully considered in surgery of cochlear reimplantation to avoid new injury or complication.

Bicarbonate transporter SLC4A7 promotes EMT and metastasis of HNSCC by activating the PI3K/AKT/mTOR signaling pathway.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Currently, therapeutic modalities such as surgery, chemotherapy, radiotherapy, and immunotherapy are being used to treat HNSCC. However, the treatment outcomes of most patients are dismal because they are already in middle or advanced stage by the time of diagnosis and poorly responsive to treatments. It is therefore of great interest to clarify mechanisms that contribute to the metastasis of cells to identify possible targets for therapy. In this study, we identified the Na+ -coupled bicarbonate transporter, SLC4A7, play essential roles in the metastasis of HNSCC. Our results showed that the relative expression of SLC4A7 messenger RNA was highly expressed in HNSCCs samples from TCGA, and compared with precancerous cells of human oral mucosa (DOK), SLC4A7 was highly expressed in HNSCC cell lines. In vitro and in vivo experiments showed that dysregulation of SLC4A7 had minor influence on the proliferation of HNSCC but impacted HNSCC's migration and invasion. Meanwhile, SLC4A7 could promote epithelial-mesenchymal transition (EMT) in HNSCC. RNA-seq, KEGG pathway enrichment analysis and Western blot further revealed that downregulation of SLC4A7 in HNSCC cells inhibited the PI3K/AKT pathway. These findings were further validated via rescue experiments using a small molecule inhibitor of PI3K/mTOR (GDC-0980). Our findings suggest that SLC4A7 promotes EMT and metastasis of HNSCC through the PI3K/AKT/mTOR signaling pathway, which may be a valuable predictive biomarker and potential therapeutic target in HNSCC.

Wnt5a-mediated autophagy promotes radiation resistance of nasopharyngeal carcinoma.

Wnt signaling pathways and autophagy play an essential role in tumor progression. Canonical Wnt signaling pathways in radiation resistance have been studied in the past, but it remains unclear whether the noncanonical Wnt signaling pathways can affect tumor radiation resistance through protective autophagy. Nasopharyngeal carcinoma, a particular subtype of head and neck squamous cell carcinoma, relies on radiation therapy. In this study, we found that radioactive rays could significantly promote the expression of Wnt noncanonical signaling pathways ligands in nasopharyngeal carcinoma, among which Wnt5A was the most markedly altered. We have demonstrated that Wnt5a can reduce the radiation sensitivity of nasopharyngeal carcinoma in vitro and in vitro experiments. Meanwhile, we found much more greater autophagosomes in overexpressed-Wnt5A nasopharyngeal carcinoma cells by electron microscopy. Further mechanism exploration revealed that Beclin1 is the main target of Wnt5A, and knocking down Beclin1 can partially reduce Wnt5a-induced radiation resistance. By studying Wnt5A-mediated protective autophagy in promoting radiation resistance in nasopharyngeal carcinoma cells, we hope that the Wnt5A and Beclin1 can become effective targets for overcoming radiation resistance in the future.

Essential Oil Compositions, Antioxidant Activities, and Procollagen Synthesis Abilities of Four Lavandula angustifolia Varieties.

BACKGROUND: Lavender is an essential commercial crop with multiple varieties grown in the Ili River valley. The lavender essential oils (LEOs) produced from various vary in quality. METHODS: This study evaluated the biological activity of LEOs from the four commonly planted Lavandula angustifolia cultivars (L.Angustifolia 'Xinxun-1'-'Xinxun-4') in Ili. The chemical composition, antioxidant activity, and effect on human skin fibroblasts were analyzed. RESULTS: Gas chromatography results, coupled with flame ionization detection and mass spectrometry of the LEOs, indicated the presence of linalool, linalyl acetate, geranyl acetate, and trans-ß-ocimene as the significant components of the essential oils. All LEOs exhibited significant antioxidant activity, with Xinxun3 oil exhibiting the most vigorous activity. Xinxun2 showed the highest ferrous ion chelating activity and reducing power, displaying the most increased collagen regeneration activity. CONCLUSION: To our knowledge, this is the first report on the collagen regeneration ability of LEO from the Ili river valley and reveals Xinxun2 as a potential collagen regeneration promoter.

The efficacy of function-preservation in treating paranasal sinus and nasal cavity neoplasms.

Background: Craniofacial resection (CFR) has been regarded as the gold standard for paranasal sinus and nasal cavity (PNSNC) neoplasms. The improvement of surgical procedures has been ongoing in recent years. We analyzed the clinical curative effects of the function-preservation therapy that was mainly using nasal endoscopic surgery along with appropriate radiotherapy and chemotherapy as applicable. Methods: We performed a retrospective analysis of factors that influence the survival time of the 28 patients with PNSNC neoplasms who underwent nasal endoscopic surgery. All patients with tumor lesions underwent a complete resection in en bloc or piecemeal resection. Five cases did not undergo radiotherapy or chemotherapy; the remaining 23 patients had multimodality therapy. Results: The median follow-up time was 41.5 (range = 14-97) months. The overall 3-year survival rate was 78.57% for T3 cancer and 50% for those with T4. T classification (P = 0.031) and multimodality therapy (P = 0.038) were independent prognostic factors for postoperative 3-year survival rate of patients with PNSNC neoplasms. Conclusion: Function-preservation therapy based on the minimally invasive endoscopic resection (MIER) with appropriate adjuvant therapy not only prolonged the overall survival time but also provided an opportunity to preserve organ function at the same time, which helped to improve the patients' quality of life.

[Postoperative hearing in tympanoplasty preserving the manubrium of malleus and tensor tympani muscle tendon].

Objective:To study the effect of retaining the manubrium of malleus and tensor tympani muscle tendon （TT） on postoperative hearing reconstruction in tympanoplasty. Methods:Ninety-seven patients underwent tympanoplasty and ossiculoplasty in Peking University Third Hospital from January 2012 to December 2017, their postoperative results of audiometry were analyzed and compared with the preoperative results. The patients were divided into two groups according to retaining the manubrium of malleus and TT or not during the operation. Retention group include the cases with the manubrium of malleus and TT retained, resection group include the cases with TT resected with the manubrium retained or resected. T test was used to analyze and compare the differences of air conduction threshold air-bone gap （ABG） and the postoperative improvement between the two groups. Results:One year after operation, the air conduction thresholds and ABG were lower in retention group （n= 44） than those in resection group （n= 53） at each frequency, and there were differences with statistically significant at 0.25, 0.5 and 1.0 kHz （P<0.05）; the postoperative improvement of hearing thresholds and ABG at above frequencies in retention group was better than that in resection group. In cases with canal-wall-up operations or partial ossicular prostheses implanted, the above differences still existed between the two groups with statistical significance （P<0.05）; while in cases with canal-wall-down operations or total ossicular prostheses implanted, there were no significant differences between the two groups （P>0.05）. Conclusion:The preservation of the manubrium of malleus and TT is significant for postoperative hearing improvement in tympanoplasty, especially in the canal-wall-up operation with partial ossicular prostheses.

[Clinical analysis of 21 cases of cholesteatoma recidivism after canal-wall-up mastoidectomy with tympanoplasty].

Objective:To discuss the possible reasons for cholesteatoma recidivism after canal-wall-up mastoidectomy with tympanoplasty by analyzing clinical characteristics of patients. Methods:Data of 21 cases who suffered from cholesteatoma recidivism after canal-wall-up surgery were retrospectively reviewed, including preoperative examination, high resolution temporal bone CT, and intraoperative findings. Results:90.5%（19/21） cases had recurrent cholesteatoma with retraction pockets. Among 12 cases with previous operative notes, 66.7%（8/12） had extensive cholesteatoma which was not limited to attic in the original surgery. The intraoperative features of revision surgery in 21 patients including the destruction of reconstructive lateral attic wall and scutumwere found in 19.0%（4/21） cases, the head of malleus left in 19.0%（4/21） cases, the cholesteatoma found in hidden part in 14.3%（3/21） cases, the hadeustachian tube dysfunction in 38.1%（8/21）cases. the sclerotic mastoid in 42.9%（9/21） cases. hadanatomic variations of the temporal bone in 14.3%（3/21） cases and atresia of external auditory canal in 4.8%（1/21） cases. Conclusion:In this group of recidivism cases, most patients had extensive cholesteatoma, which may lead to excessive mucosa loss during lesion clearance, poor ventilation of tympanic isthmus after surgery, and promote the formation of retraction pocket. In addition, some cases had eustachian tube dysfunction, unstable reconstruction of attic lateral wall, and improper selection of the indications, which may also increase the risk of recurrence. Therefore, in order to reduce cholesteatoma recidivism after canal-wall-up surgery, attention should be paid to the striction of surgical indications, comprehensive preoperative evaluation, thorough clearance of lesions and firm reconstruction.

Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma.

Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown. Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC's pathogenesis. Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC. Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.

Prognostic Value of a Ten-Gene Signature in HNSCC Patients Based on Tumor-Associated Macrophages Expression Profiling.

Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC), which plays an essential role in immunosuppression and tumorigenesis. In the TCGA HNSCC cohort, 500 patients with clinical-pathological information and RNA sequence expression were randomly assigned to training for lasso regression and validation for verification, respectively. A TAM-based ten-gene signature (TBGs) was constructed, which divided the patients into high-risk and low-risk groups, could predict overall survival (OS) of HNSCC patients in the training dataset (p = 3.527e-05) and validation dataset (p = 3.785e-02). The result of Cox univariate and multivariate regression analyses showed that the risk score of TBGs could be an independent prognostic factor in HNSCC. ROC curve confirmed that the risk score of TBGs has good sensitivity and specificity for prognosis prediction (AUC = 0.659) and was also verified by the validation dataset (AUC = 0.621). We obtained key risk transcription factors (TFs)-EHF and SNAI2-by correlation analysis with TBGs. Moreover, we ran a gene set enrichment analysis (GSEA) to speculate that TBGs act on interstitial remodeling, tumor killing, metabolic reprogramming, and tumor immune-related pathways. Finally, we combined clinical-pathological features and risk score of TBGs to establish clinical nomograms, and calibration curves verified the accuracy of long-term clinical prognosis in the two datasets (C-index of 5-year OS = 0.721 and 0.716). In general, the TBGs we obtained may accurately predict the prognosis of HNSCC patients to provide personalized treatment.

miR-30e-5p represses angiogenesis and metastasis by directly targeting AEG-1 in squamous cell carcinoma of the head and neck.

Metastasis is a critical determinant for the treatment strategy and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). However, the mechanisms underlying SCCHN metastasis are poorly understood. Our study sought to determine the key microRNA and their functional mechanisms involved in SCCHN metastasis. For The Cancer Genome Atlas (TCGA) data analysis, quantitative PCR was used to quantify the level of miR-30e-5p in SCCHN and its clinical significance was further analyzed. A series of in vitro and in vivo experiments were applied to determine the effects of miR-30e-5p and its target AEG-1 on SCCHN metastasis. A mechanism investigation further revealed that AEG-1 was implicated in the angiogenesis and metastasis mediated by miR-30e-5p. Overall, our study confirms that miR-30e-5p is a valuable predictive biomarker and potential therapeutic target in SCCHN metastasis.

Increased miRNA-518b inhibits trophoblast migration and angiogenesis by targeting EGR1 in early embryonic arrest†.

Evidence indicates that microRNAs (miRNAs) play essential roles in early embryonic development. The miRNA-518 family is a special biomarker of the placenta, and miRNA-518b is abnormally expressed in placental tissue in preeclampsia. Early growth response protein 1 (EGR1), a zinc finger transcriptional factor, plays an essential role in regulating cell differentiation, angiogenesis, and migration. Moreover, earlier studies have shown that EGR1 protein plays a key role in implantation. However, little is known about the role of miR-518b and EGR1 on early embryonic arrest (EEA) in humans. In our study, increased miR-518b along with decreased EGR1 was found in human villus tissues with EEA. Furthermore, we demonstrated by luciferase assay that miR-518b is a direct regulator of EGR1. After comparing the effect of silencing EGR1, vascular endothelial growth factor (VEGF) individually, and EGR1/VEGF in combination, we found that EGR1 can inhibit migration and angiogenesis of HTR-8 SVneo cells by decreasing the VEGF expression. Hypoxia plays an initial role in early embryonic development, and we found that hypoxia reduces the expression of miR-518b and increases the expression of EGR1 and VEGF to facilitate migration and angiogenesis in a hypoxic model of HTR-8/SVneo cell line. Our findings provide new insights into the role of miR-518b in EEA and implicate the potential application of miR-518b in the diagnosis and development of intervention for EEA.

High-throughput transcriptome-Seq and small RNA-Seq reveal novel functional genes and microRNAs for early embryonic arrest in humans.

Early Embryonic Arrest (EEA) is one of the major causes of female infertility. Genetic factors including specific genes and miRNAs may play pivotal roles on EEA. However, it is not well defined what genes and micro RNAs participate the pathophysiological alterations of EEA. In this work, we compared the Transcriptome -Seq and microRNA profiles from three pairs of villi (three EEA patients and three normal pregnancy, NP). We first confirmed the array data by qPCR with ten randomly selected differentially expressed genes and ten differentially expressed miRNAs in villi from 20 EEA and 20 NP controls. We next applied Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis and found that these differentially expressed genes enriched in the PI3K-Akt signaling pathway, Jak-STAT signaling pathway, MAPK signaling pathway, Complement and coagulation cascades, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM). Interestingly, hsa-miR-6515-5p and its target genes NLRP3, UGP2 may regulate the Immune system and carbohydrate metabolism. Hsa-miRNA 518 and its target gene EGR1 may regulate cell proliferation, angiogenesis, and cell apoptosis to impact early embryonic development. Moreover, novel-m0045-5p and its target gene RMDN3 may regulate microtubule formation on the development of EEA. Our research provides novel biomarkers for EEA and establishes a foundation for further study of the mechanism of EEA.

Modification of 6SV to remove skylight reflected at the air-water interface: Application to atmospheric correction of Landsat 8 OLI imagery in inland waters.

During the atmospheric correction of remote sensing data in inland waters, the original Second Simulation of the Satellite Signal in the Solar Spectrum-Vector version (6SV) model does not eliminate the specular reflection of downward skylight radiance at the air-water interface. Thus, we propose a modified version of the 6SV model (M6SV) that does remove reflected skylight at the air-water interface. We apply the new model to the atmospheric correction of a Landsat 8 Operational Land Imager (OLI) image over Taihu Lake, China, where the aerosol optical depth is known. In situ reflectance measurements acquired concurrently with the L8/OLI image are used to validate the performance of the new M6SV algorithm. To further analyze the merits and demerits of M6SV, the model is compared with two short-wave infrared (SWIR)-based atmospheric correction models: the Sea-Viewing Wide Field-of-View Sensor Data Analysis System short-wave infrared (SD-SWIR) model and the Vanhellemont & Ruddick short-wave infrared with a per scene fixed aerosol type (VR-SWIR-F) model. Comparisons of results from all three L8/OLI image atmospheric corrections with the in situ remote sensing reflectance data show that M6SV produces reliable atmospheric corrections in the green and red spectral bands and is an effective alternative for Landsat 8 OLI atmospheric correction in inland waters.

MicroRNA-139-5p affects cisplatin sensitivity in human nasopharyngeal carcinoma cells by regulating the epithelial-to-mesenchymal transition.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer associated with poor prognosis. Many studies have shown that the epithelial-to-mesenchymal transition (EMT) is important in cancer progression, metastasis, and chemotherapy resistance and that microRNAs (miRNAs) play a key role in chemotherapy resistance associated with EMT. The miRNA miR-139-5p is downregulated in many human cancers and is closely related to tumor progression. The aim of this study was to investigate the ability of miR-139-5p to influence the cisplatin resistance, apoptosis, invasion and migration in NPC cells through the regulation of the EMT. We investigated these processes in parental HNE1 and cisplatin-resistant HNE1/DDP cells transfected with miR-139-5p inhibitors and mimics, respectively. Our results suggest that the upregulation of miR-139-5p expression inhibits proliferation, invasion, migration and EMT in human NPC cells. In addition, we found that miR-139-5p expression levels and DDP-induced apoptosis positively correlate in NPC cells. In conclusion, our results demonstrate that miR-139-5p can regulate the migration, invasion and DDP resistance in human NPC by modulating the EMT. The regulation of miR-139-5p levels might be a new approach to reverse EMT and DDP resistance and counteract metastasis and chemotherapy resistance in human NPC.