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NK cells play a role in various cancers, but their role in head and neck squamous cell carcinoma (HNSCC) still needs to be explored. All public data are obtained from the Cancer Genome Atlas Program (TCGA) database. All analysis was performed using specific packages in R software. In our study, we quantified the immune microenvironment of HNSCC through multiple algorithms. Next, we identified NK cell‐associated genes by quantifying NK cells, including SSNA1, TRIR, PAXX, DPP7, WDR34, EZR, PHLDA1 and ELOVL1. Then, we explored the single‐cell expression pattern of these genes in the HNSCC microenvironment. Univariate Cox regression analysis indicated that the EZR, PHLDA1 and ELOVL1 were related to the prognosis of HNSCC patients. Following this, we selected EZR for further analysis. Our results showed that the patients with high EZR expression might have a poor prognosis and worse clinical features. Biological enrichment analysis showed that EZR is associated with many oncogenic pathways and a higher tumour stemness index. Meanwhile, we found that EZR can remodel the immune microenvironment of HNSCC. Moreover, we noticed that EZR could affect the immunotherapy and specific drug sensitivity, making it an underlying clinical target. In summary, our results can improve the understanding of NK cell in HNSCC. Meanwhile, we identified EZR as the underlying clinical target of HNSCC. [ABSTRACT FROM AUTHOR]

Objective Growing evidence indicates that microRNAs (miRNA) play a critical role in the pathogenesis of OA, and overexpressing or silencing miRNA expression in OA models can contribute to the development of miRNA-based therapeutics. The objective of this study was to determine whether intra-articular injection of miRNA can inhibit OA progression. Methods The miRNA expression profile was determined in OA cartilage tissues and controls. Functional analysis of the miRNAs on extracellular matrix degradation was performed after miRNA mimic or inhibitor transfection. Luciferase reporter assays and western blotting were employed to determine miRNA targets. To investigate the functional mechanism of miR-21-5p in OA development, miR-21-5pfl/flCol2a1-CreER and wild-type mice were subject to surgical destabilization of the medial meniscus. Therapeutically, wild-type mice undergoing surgical destabilization of the medial meniscus were treated with intra-articular injection of agomir- and antagomir-21-5p. Results We found that expression of miR-21-5p was significantly up-regulated in OA cartilage tissues. The articular cartilage degradation of miR-21-5p conditional knockout mice was significantly alleviated compared with that of wild-type mice in spontaneous and destabilization of the medial meniscus models. Through gain-of-function and loss-of-function studies, miR-21-5p was shown to significantly affect matrix synthesis genes expression, and chondrocyte proliferation and apoptosis. Further, fibroblast growth factor 18 (FGF18) was identified as a target of miR-21-5p. Intra-articular injection of antagomir-21-5p significantly attenuated the severity of experimental OA. Clinically, FGF18 expression level was correlated with miR-21-5p expression and a modified Mankin scale. Conclusion Our findings reveal a miRNA functional pathway important for OA development, highlighting miRNA-21-5p silencing as an attractive therapeutic regimen in future clinical trials involving patients with OA. [ABSTRACT FROM AUTHOR]

Emerging evidence supports the involvement of autophagy in the pathogenesis of intervertebral disc degeneration (IDD). MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play fundamental roles in various cellular processes, including autophagy. However, it remains largely unknown as to how autophagy is regulated by miRNAs and lncRNAs in IDD. Biological functions of miR‐153‐3p and long intergenic nonprotein coding RNA 641 (LINC00641) were investigated. Luciferase reporter assays was done to validate miR‐153‐3p targets. To induce nutritional stress, nucleus pulposus (NP) cells were cultured in the normal nutritional condition and the low nutritional condition. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) was used to analyze miR‐153‐3p and LINC00641 in response to nutrient deprivation. Autophagic activity was assessed by transmission electron microscopy, western blot analysis and green fluorescent protein‐light chain 3 puncta. Pull‐down assay and RNA fluorescent in situ hybridization were performed to validate LINC00641 target and the location. MiR‐153‐3p is downregulated in NP tissues from IDD patients. Further, LINC00641 can affect collagen II and matrix metalloproteinase‐3 expressions. Upregulation of LINC00641 and downregulation of miR‐153‐3p are detected in NP cells under nutritional stress. LINC00641 can regulate autophagic cell death by targeting miR‐153‐3p and autophagy‐related gene 5 (ATG5). MiR‐153‐3p inhibits autophagy and IDD by targeting ATG5. More important, LINC00641 targets miR‐153‐3p, and thus affects ATG5 expression, autophagic cell death and IDD. These findings uncover a novel regulatory pathway that is composed of LINC00641, miR‐153‐3p, and ATG5 in IDD. This mechanism may stimulate to a more understanding of IDD pathogenesis and provide new sights for the treatment of this disorder. We demonstrated that long intergenic nonprotein coding RNA 641 (LINC00641) acts as endogenous sponge RNA and inhibits miR‐153‐3p expression and its biological function. Therefore, modulation of LINC00641 may represent a novel treatment paradigm in human IDD. These findings shed new light on the importance of the orchestrated interactions between lncRNAs, miRNAs, and autophagy in maintaining cellular homeostasis and suggest that a disturbance in these networks might lead to diseases. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis. Key messages: [ABSTRACT FROM AUTHOR]

Objective To discuss the preliminary experience and clinical effects of stent in assisting coiling embolization for intracranial wide-necked aneurysms. Methods Stent-assisted coil embolization was carried out in 26 with 28 intracranial wide- necked aneurysm .The clinical data, treatment methods, results and follow-up results were retrospectively analyzed. The aneurymsms were located at the anterior communicating artery (n=3), at the posterior communicating segment of internal carotid artery (n = 15), at the ophthalmic segment of internal carotid artery (n =6), at the middle cerebral artery (n =4) . Results A total of 28 stents were used to assist coil embolization management of 28 intracranial wide-necked aneurysms, and the technical success rate was 100%. Procedure-related complications occur in three cases, and one of them died. According to Raymond grading for the immediate occlusion result of aneurysm, grade I was obtained in 18 lesions, grade II in 6 and grade III in 4 . Twenty five patients were followed up for 6-51 months (mean 15 months), and no newly-developed neurological dysfunction or re-bleeding was observed during the follow-up period. At three months after the procedure, the level of mRS score was 0-1 in 22 patients and 1-2 in 3 patients. Conclusions Stent-assisted detachable coil embolization is safe and effective in the treatment of intracranial wide-necked aneurymsms. The stent serves as a mechanical scaffold for the placement of aneurysm coils, prevents coil protrusion into the parent artery and may allow safe packing of the aneurysm with a denser coil mesh. [ABSTRACT FROM AUTHOR]

Objective To explore the efficacy of long- and short-acting triptorelin on pituitary down-regulation in long protocol and the pregnancy outcome in vitro fertilization and embryo transfer (IVF-ET) . Methods Three hundred and seventeen patients for IVF-ET were enrolled as study and randomized them into two groups. In group A (n = 145), patients received single dose subcutaneous injection of 1.25 mg long-acting diphereline in mid-luteal phase. In group B (n = 172), patients received 0.1 mg/d subcutaneous injection of short-acting diphereline in mid-luteal phase for 14-18 days until pituitary suppression were got, and then reduced to 0.05 mg/d until the injection of HCG. Results The dose and the days of gonadotropin administration in group A were bigger and longer than those in group B (P < 0.05) . There were no significant differences in the number of retrieved oocytes, fertilization rate, high quality embryos, implantation rate and clinical pregnancy rate between the two groups (all P > 0.05). But clinical pregnancy rate of group B had increasing trend. Conclusion Administration of short-acting diphereline has the similar effect with that of long-acting diphereline on pituitary down-regulation in long protocol. Short-acting diphereline requires lower amount of gonadotropin and is more flexible, so it should be recommended. [ABSTRACT FROM AUTHOR]

Background: The posterior and anterior circumflex humeral artery (PCHA and ACHA) are crucial for the blood supply of humeral head. We aimed to identify simple landmarks for guiding the quick access to PCHA and ACHA, which might help to protect the arteries during the surgical management of proximal humeral fractures.Methods: Twenty fresh cadavers were dissected to measure the distances from the origins of PCHA and ACHA to the landmarks (the acromion, the coracoid, the infraglenoid tubercle, the midclavicular line) using Vernier calipers.Results: The mean distances from the origin of PCHA to the infraglenoid tubercle, the coracoid, the acromion and the midclavicular line were 27.7 mm, 50.2 mm, 68.4 mm and 75.8 mm. The mean distances from the origin of ACHA to the above landmarks were 26.9 mm, 49.2 mm, 67.0 mm and 74.9 mm.Conclusion: Our study provided a practical method for the intraoperative identification as well as quick access of PCHA and ACHA based on a series of anatomical measurements. [ABSTRACT FROM AUTHOR]

Background: The ulnar styloid is an important supportive structure for the triangular fibrocartilage complex. However, it remains inconclusive whether or not a fractured ulnar styloid should be fixed in an unstable distal radius fracture (DRF) with a stable distal radioulnar joint (DRUJ). The purpose of this study is to evaluate the effect of an untreated ulnar styloid fracture on the outcome of unstable DRF treated with transarticular external fixation when the DRUJ is stable.Methods: 106 patients with an unstable DRF and a stable DRUJ were included in this study following external fixation. The patients were divided into the non-fracture, the tip-fracture and the base-fracture groups according to the location of the ulnar styloid fracture at the time of injury. Postoperative evaluation included the range of wrist motion, the radiological index, the grip strength, the PRWE-HK scores, the wrist pain scores, and the instability of DRUJ at the external fixator removal time, three months postoperatively and the final follow-up visit.Results: The patients were followed for 12 to 24 months (15 months in average). Sixty-two of 106 patients (58%) had ulnar styloid fracture and 16 patients (26%) showed radiographic evidence of union of ulnar styloid fractures at the final follow-up visit. No significant difference in the radiological findings, the range of wrist motion, the grip strength, the PRWE-HK scores, and the wrist pain scores among three patient groups was detected at the external fixator removal time, three months postoperatively, or the final follow-up visit. Six of the 106 patients (5.7%) complained of persistent ulnar-side wrist pain during daily activities. One patient (0.9%) showed a positive sign in a stress-test, three patients (2.8%) showed a positive sign in a provocative-test, and five patients (4.7%) showed a positive sign in a press-test. There was no significant difference in the percentages of patients who complained of persistent ulnar-side wrist pain or showed a positive sign in the physical examination of the distal radioulnar joint among the three groups at the final follow-up time points.Conclusion: When the DRUJ is stable, an untreated ulnar styloid fracture does not affect the wrist outcome of the patient with an unstable DRF treated with external fixation. [ABSTRACT FROM AUTHOR]