Ultrasonic Evaluation of the Asian Nasal Soft Tissue Envelope.

OBJECTIVE: The thickness of the nasal soft tissue envelope (STE) plays a crucial role in the final rhinoplasty results. The Asian nasal contour is typically characterized by a thicker STE and broader nasal tip, but objective data are lacking. The purpose of this study was to objectively measure nasal dermal thickness and overall STE thickness and to determine any demographic differences. METHODS: From July to September 2023, 110 patients presenting for consultation underwent ultrasound evaluation of their nasal STE. STE thickness was measured at predetermined subsites and compared with published data on white patients. RESULTS: The thickness of the STE in Asian patients was greater than that in white patients. The STE was thickest at the supratip (mean [SD]), (4.88 [0.74] mm) rather than at the nasion and thinnest at the rhinion (2.25 [0.51] mm). The nasal tip (4.07 [0.72] mm) showed comparable STE thickness with the nasion (4.13 [0.72] mm) but had a significantly thicker dermis than the nasion (2.35 ± 0.49 mm vs. 1.35 ± 0.35 mm, P < 0.05). Male sex and higher BMI tended to be correlated with a thicker nasal STE, but age did not show any relationship. A thicker nasal tip STE showed significantly greater nasal tip width and nasal alar thickness. CONCLUSION: STE thickness at different nasal subsites varies and affects external nasal contour and rhinoplasty outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Knocking Down lncRNA HOXA-AS2 Mitigates the Progression of Epilepsy via Regulation of the miR-372-3p/STAT3 Axis.

AIM: To explore the potential activity of HOXA cluster antisense RNA 2 (HOXA-AS2), a long non-coding RNA (lncRNA), in epilepsy progression, as well as the mechanisms behind its activity. MATERIAL AND METHODS: Kainic acid (KA) was used to treat rat astroglial CTX-TNA2 cells to establish a cellular model of epilepsy. Reverse transcription-quantitative PCR was conducted to examine the expression levels of HOXA-AS2, microRNA (miR)-372-3p and STAT3. Cell Counting Kit-8, flow cytometry and western blot assays were performed to analyze cell viability and apoptosis. The secretion levels of various inflammatory factors (IL-6, IL-1? and TNF-?) were identified by ELISA. To validate the functional interaction between HOXA-AS2/STAT3 and miR?372-3p, dual-luciferase reporter assay was performed. RESULTS: The HOXA-AS2 and STAT3 expression levels were notably upregulated, whereas miR?372-3p was downregulated in KAtreated CTX-TNA2 cells. Silencing HOXA-AS2 or overexpressing miR-372-3p inhibited the secretion of inflammatory factors and apoptosis in KA-treated CTX-TNA2 cells. HOXA-AS2 negatively regulated miR?372-3p, and miR?372-3p targeted STAT3 mRNA. Suppression of miR-372-3p or overexpression of STAT3 abrogated the rescue effect of small interfering HOXA-AS2 in KA-treated CTX-TNA2 cells. CONCLUSION: The current study suggested that targeting HOXA-AS2 could alleviate cellular damages in the epileptic model by regulating the miR-372-3p/STAT3 axis. Therefore, HOXA-AS2 may serve as a potential anti-epilepsy therapeutic target.

LncRNA SNHG15 mediates 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal damage through targeting miR-29c-3p/SNCA axis.

BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative disease in the elderly people. Long non-coding ribose nucleic acids (LncRNAs) can serve as molecular sponges for micro RNA (miRNA) and regulate gene expression, which is implicated in the occurrence and progression of PD. In this work, we investigated the functional role of lncRNA SNHG15 in a neuronal damage cell model and its potential mechanism. METHODS: SK-N-SH cells treated with 1-methyl-4-phenylpyridinium (MPP+) were employed as the in vitro cellular model to mimic neuronal degeneration. The expression levels of SNHG15, miR-29c-3p, and SNCA were determined by qRT-PCR. ELISA, CCK-8 proliferation assay, and flow cytometry were conducted to explore the effects of SNHG15 and miR-29c-3p on the production of inflammatory factors, cell proliferation, and apoptosis, respectively. Dual-luciferase reporter assay was utilized to validate the functional interactions among SNHG15, miR-29c-3p, and SNCA. SNCA protein levels were examined by Western blot. RESULTS: SNHG15 was highly induced in the cell model of MPP+-induced neuronal damage. SNHG15 knockdown significantly mitigated MPP+-induced damages in SK-N-SH cells. SNHG15 served as a sponge to down-regulate miR-29c-3p, thereby releasing the inhibition of miR-29c-3p on SNCA expression, which promoted neuronal damages upon MPP+ challenge. CONCLUSION: The upregulation of SNHG15 upon MPP+ challenge mediates neuronal damages in SK-N-SH cells by regulating miR-29c-3p/SNCA axis. Future work is required to validate these findings in PD patients and animal models, which could provide insights into the diagnosis and therapy of PD.

Knockdown of small nucleolar RNA host gene 10 (SNHG10) alleviates the injury of human neuroblastoma cells via the miR-1277-5p/insulin substrate receptor 2 axis.

Parkinson's disease is a common neurodegenerative disease with a complex physio-pathology. So far, there is no effective medical strategies to prevent the progression of Parkinson's disease. Understanding the mechanisms underlying the progression of Parkinson's disease could provide insights into the formulation of novel preventative or treatment strategies. Small nucleolar RNA host gene 10 (SNHG10) is a lncRNA which has been implicated in the development of many cancers. However, its potential role in Parkinson's disease remains unknown. In this study, we found that SNHG10 was upregulated while miR-1277-5p was downregulated in the Parkinson's disease cell model of 1-Methyl-4-phenyl-pyridine ion (MPP+) induced SH-SY5Y cells. We further revealed that SNHG10 sponged miR-1277-5p to negatively regulate its expression, and miR-1277-5p could bind to the 3'UTR of insulin substrate receptor 2 (IRS2) mRNA to suppress its expression. These data suggest that SNHG10 regulates IRS2 through interacting with miR-1277-5p in the cell model of Parkinson's disease. Through a series of molecular experiments and functional assays, we demonstrated that downregulating SNHG10 in the cell model of Parkinson's disease attenuated the cell injury by reducing the expression of IRS2. Meanwhile, inhibiting miR-1277-5p or overexpressing IRS2 could partially reverse the effect of SNHG10 knockdown. In summary, our data indicate that knockdown of SNHG10 mitigates MPP+ induced damage in SH-SY5Y cells via the miR-1277-5p/IRS2 axis.

Upregulation of CPNE7 in mesenchymal stromal cells promotes oral squamous cell carcinoma metastasis through the NF-κB pathway.

A remarkable shift in Mesenchymal stromal cells (MSCs) plays an important role in cancer metastasis, but the molecular mechanism is still unclear. CPNE7, a calcium-dependent phospholipid-binding protein, mediates signal transduction and metastasis in many tumours. Here, we demonstrated that MSCs derived from OSCC (OSCC-MSCs) promoted the metastasis of OSCC cells by transwell assay and animal models through epithelial to mesenchymal transition (EMT) (p < 0.05). RNA-sequencing, ELISA, neutralizing antibody and CXCR2 inhibitor assay confirmed that CXCL8 secreted by OSCC-MSCs was associated with the upregulated expression of CPNE7 by immunohistochemical and western blotting (p < 0.05). This is mechanistically linked to the activation of CPNE7 to NF-κB pathway-induced metastasis, including phosphorylated p65 and IκBa. CPNE7 silencing inhibited metastatic abilities and the expression of CXCL8, phosphorylated p65, IκBa, and p65 nuclear translocation by western blotting and immunofluorescence, while CPNE7 overexpression markedly promoted these events (p < 0.05). We also identified that Nucleolin could be bind CPNE7 and IκBa by co-immunoprecipitation. Together, our results suggest that upregulation of CPNE7 in MSCs interacted with surface receptor -Nucleolin and then combined with IκBa to promoted phosphorylated IκBa and p65 nuclear translocation to active NF-κB pathway, and then regulates CXCL8 secretion to promote the metastasis of OSCC cells. Therefore, CPNE7 in MSCs could be promising therapeutic targets in OSCC.

Effectiveness and safety of high dose clopidogrel plus aspirin in ischemic stroke patients with the single CYP2C19 loss-of-function allele: a randomized trial.

BACKGROUND: Dual antiplatelet aggregation therapy leads to better outcomes in patients with carotid artery stenosis, intracranial artery stenosis, minor strokes, or transient ischaemic attacks. However, carriers of the CYP2C19 loss-of-function allele may not experience the desired effects. We attempted to increase the clopidogrel dose to determine whether it would improve the outcomes of stroke patients who carry a single loss-of-function allele. METHODS: We recruited 131 patients with minor ischaemic stroke, within less than 7 days of stroke onset and a CYP2C19 loss-of-function allele, who had moderate-to-severe cerebral artery stenosis. Patients were divided into the high dose group (clopidogrel 150 mg per day + aspirin 100 mg per day over 21 days.) and a normal dose group (clopidogrel 75 mg per day + aspirin 100 mg per day over 21 days). The reported outcomes included any vascular or major bleeding events as the primary and safety endpoints, respectively. RESULTS: One and six vascular events occurred in the high dose and normal dose groups during the 3-months follow-up period, respectively. However, no significant difference was found between the two groups when adjusted for history of diabetes (hazard ratio, 5482; 95% confidence interval, 0.660 to 45.543; P = 0.115). No major bleeding events occurred. CONCLUSIONS: In patients with ischaemic stroke who had a single CYP2C19 loss-of-function allele and moderate to severe cerebral stenosis, fewer vascular events occurred within 3 months with high dose of clopidogrel and aspirin than with normal dose of clopidogrel and aspirin. However, the difference between the two groups was not significant. TRIAL REGISTRATION: Clinical study of clopidogrel in the treatment of patients with symptomatic moderate to severe cerebral artery stenosis with intermediate metabolites of CYP2C19, URL: http://www.chictr.org.cn/ . Unique identifier: ChiCTR1800017411 , 07/28/2018.

A two-dimensional coupled flow-mass transport model based on an improved unstructured finite volume algorithm.

A two-dimensional coupled water quality model is developed for modeling the flow-mass transport in shallow water. To simulate shallow flows on complex topography with wetting and drying, an unstructured grid, well-balanced, finite volume algorithm is proposed for numerical resolution of a modified formulation of two-dimensional shallow water equations. The slope-limited linear reconstruction method is used to achieve second-order accuracy in space. The algorithm adopts a HLLC-based integrated solver to compute the flow and mass transport fluxes simultaneously, and uses Hancock's predictor-corrector scheme for efficient time stepping as well as second-order temporal accuracy. The continuity and momentum equations are updated in both wet and dry cells. A new hybrid method, which can preserve the well-balanced property of the algorithm for simulations involving flooding and recession, is proposed for bed slope terms approximation. The effectiveness and robustness of the proposed algorithm are validated by the reasonable good agreement between numerical and reference results of several benchmark test cases. Results show that the proposed coupled flow-mass transport model can simulate complex flows and mass transport in shallow water.