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A multifunction processor for a broadband signal based on the active mode-locking optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The central frequency down-conversion and frequency spectrum convolution of the target broadband signal (TBS) are realized by just tuning the wavelength of the optical carrier or by the time domain product, respectively. To achieve the central frequency down-conversion of the TBS, an optical tunable delay line (OTDL) is adopted to match the delay time of the OEO loop with the repetition period of the TBS. Then the spectrum convolution of the TBS is produced by just injecting a lower frequency signal consistent with the free spectral range (FSR) of the OEO loop. Moreover, the frequency convolution repetition is also greatly increased by harmonic mode-locking injection. The equivalent bandwidth of the TBS is enlarged by â¼50 times, benefiting from the frequency convolution. The central frequency conversion flexibility and the bandwidth compatibility are also discussed in detail. This work provides a multifunction processor system and may have potential usage in multifunctional integrated radar systems.
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OBJECTIVES: This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. METHODS: Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. RESULTS: Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. CONCLUSION: Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.
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BACKGROUND: Skull base reconstruction is a key technique in patients undergoing endoscopic transnasal skull base surgery. Although a pedicled nasoseptal flap (PNSF) is often used to repair large skull base defects with high-flow cerebrospinal fluid leakage, bone exposure of the donor site of the PNSF can result in long-term crusting. OBJECTIVE: To design a novel and versatile mini posterior nasoseptal graft for the reconstruction of defects in the sellar floor or PNSF or pedicled nasoseptal rescue flap (PNSRF) donor site in patients undergoing pituitary adenoma surgery. METHODS: Patients who underwent pituitary adenoma removal through an endoscopic endonasal approach and repair of a sellar defect or PNSF/PNSRF donor site using the mini posterior nasoseptal graft technique from January 2019 to January 2020 were retrospectively evaluated. Pituitary adenomas were removed using a binostril 4-hand technique through a transnasal transsphenoidal transsellar approach or an expanded transsellar approach. RESULTS: Mini posterior nasoseptal grafts were successfully used in 70 patients who underwent pituitary adenoma removal through an endoscopic transsphenoidal sellar approach. Mini posterior nasoseptal grafts repaired sellar defects in 40 patients and donor site defects of the contralateral PNSF/PNSRF in 30 patients. None of these patients experienced cerebrospinal fluid leakage or major complications. CONCLUSIONS: A mini posterior nasoseptal graft is a safe and effective technique for repairing sellar defects after endoscopic transnasal pituitary adenoma surgery. This technique can also be used to repair defects in PNSF/PNSRF donor sites.
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Adenoma , Neoplasias Hipofisárias , Procedimentos de Cirurgia Plástica , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Estudos Retrospectivos , Septo Nasal/transplante , Endoscopia/métodos , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Base do Crânio/cirurgia , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/complicaçõesRESUMO
Nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) was a member of the NOD-like receptor family and played an important role in the innate immune response. Dysregulated NOD2 had been reported to contribute to tumorigenesis and progression. Here, we investigated that decreased NOD2 expressions could affect the phenotypic polarization of tumour-associated macrophages and thus lead to the poor prognosis of lung adenocarcinoma patients. We clustered the patients by the single-sample gene set enrichment analysis of tumour microenvironment and 13 prognostic differentially expressed immune-related genes (PDEIRGs) were obtained based on prognostic analyses. After multiple assessments on the 13 PDEIRGs, NOD2 was considered to be the central immune gene and had a strong effect on suppressing tumour progression. Decreased NOD2 expression could be induced by cancer cells and lead to the phenotypic polarization of macrophages from protective M1 phenotype to pro-tumorigenic M2 subtype which might be attributed to the down-regulating of NF-κB signalling pathway. This study draw attention to the role of inhibited innate immune function mediated by depletion of NOD2 in the TME. Our work also points to a potential strategy of NOD2-mediated TAM-targeted immunotherapy.
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Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Proteína Adaptadora de Sinalização NOD2/genética , Macrófagos Associados a Tumor/metabolismo , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteína Adaptadora de Sinalização NOD2/deficiência , Proteína Adaptadora de Sinalização NOD2/metabolismo , Fenótipo , Células THP-1 , Microambiente Tumoral , Macrófagos Associados a Tumor/patologiaRESUMO
Cancer immunotherapy is a promising method for cancer therapy. Imiquimod (R837) is a molecule that could activate immune systems for cancer immunotherapy, but an easily manufactured biocompatible carrier to deliver R837 may be needed to overcome the disadvantages of R837. Micelles formed by biocompatible copolymers have been widely used to deliver chemotherapeutic drugs but not immunotherapeutic drugs. In this study, R837 was linked to an amphiphilic biodegradable copolymer mPEG-b-PLA via acid-sensitive Schiff bases. The molecular structures were investigated by 1 H nuclear magnetic resonance, gel permeation chromatography and Fourier transform infrared spectroscopy. The product could be self-assembled into micelles with R837 content as high as 22.4%. Owing to acid-cleavable Schiff bases, the release of R837 from micelles was markedly accelerated under acidic media. Consequently, the micelles linked with R837 stimulated the expression of major histocompatibility complex II-stimulating molecules on the surface of RAW 264.7 macrophages at pH 6.5 but not pH 7.4. By using human umbilical vein endothelial cells as the in vitro model, it was shown that the polymer carriers and R837-linked micelles were minimally cytotoxic and did not induce the activation of endothelial cells under physiological pH, which suggested the relatively high biocompatibility. In conclusion, this study successfully developed pH-responsive immunotherapeutic drug-loaded micelles that could activate macrophages at acidic pH in vitro. The high biocompatibility of the micelles to endothelial cells also indicated the potential uses under in vivo conditions.
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Portadores de Fármacos , Agentes de Imunomodulação/farmacologia , Micelas , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Poliésteres , Polietilenoglicóis , PolímerosRESUMO
This paper developed and evaluated a quantitative image analysis method to measure the concentration of the nanoparticles on which alkaline phosphatase (AP) was immobilized. These AP-labeled nanoparticles are widely used as signal markers for tagging biomolecules at nanometer and sub-nanometer scales. The AP-labeled nanoparticle concentration measurement can then be directly used to quantitatively analyze the biomolecular concentration. Micro-droplets are mono-dispersed micro-reactors that can be used to encapsulate and detect AP-labeled nanoparticles. Micro-droplets include both empty micro-droplets and fluorescent micro-droplets, while fluorescent micro-droplets are generated from the fluorescence reaction between the APs adhering to a single nanoparticle and corresponding fluorogenic substrates within droplets. By detecting micro-droplets and calculating the proportion of fluorescent micro-droplets to the overall micro-droplets, we can calculate the AP-labeled nanoparticle concentration. The proposed micro-droplet detection method includes the following steps: (1) Gaussian filtering to remove the noise of overall fluorescent targets, (2) a contrast-limited, adaptive histogram equalization processing to enhance the contrast of weakly luminescent micro-droplets, (3) an red maximizing inter-class variance thresholding method (OTSU) to segment the enhanced image for getting the binary map of the overall micro-droplets, (4) a circular Hough transform (CHT) method to detect overall micro-droplets and (5) an intensity-mean-based thresholding segmentation method to extract the fluorescent micro-droplets. The experimental results of fluorescent micro-droplet images show that the average accuracy of our micro-droplet detection method is 0.9586; the average true positive rate is 0.9502; and the average false positive rate is 0.0073. The detection method can be successfully applied to measure AP-labeled nanoparticle concentration in fluorescence microscopy.
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Nanopartículas , Fosfatase Alcalina , Corantes Fluorescentes , Humanos , Microscopia de FluorescênciaRESUMO
OBJECTIVE: To retrospectively analyze the auditory and speech development of young children with bilateral congenital aural atresia after using bone-anchored hearing aid (BAHA) softband. METHODS: From August 2010 to January 2013, a total of 12 patients aged at a range of 3 months to 6 years with bilateral aural atresia using BAHA softband were divided into under 4-year-old group (n = 7, an average age of 14 months) and over 4-year-old group (n = 5, an average age of 77 months). The air and bone auditory thresholds of the under 4-year-old group were assessed by auditory brainstem response (ABR). The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was used to evaluate early auditory development.Soundfield pure tone audiometry (PTA) was applied in the over 4-year-old group. The Standard Chinese lexical neighborhood test (LNT) was conducted to evaluate the speech discrimination scores unaided and aided for 6, 12 and 24 months. RESULTS: For the under 4-year-old group, the unaided air and bone conduction hearing thresholds were 70-90(73 ± 12) and 15-25(21 ± 4) dB nHL respectively.IT-MAIS score improved significantly after using softband for 6 months in comparisons with unaided situations. The average hearing threshold of patients in the over 4-year-old group was (63 ± 6) dB HL unaided versus (31 ± 4)dB HL aided. The average decline in pure-tone threshold was (32 ± 3)dB HL with BAHA softbands and LNT demonstrated improvements in the speech discrimination score. The differences of paired comparison were significant (all P < 0.05). CONCLUSIONS: The hearing ability of children with bilateral congenital aural atresia improves significantly after using BAHA softband. And its application at a young age can guarantee a relatively normal hearing development and avoid oral communication impairment.
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Condução Óssea , Anormalidades Congênitas/reabilitação , Meato Acústico Externo/anormalidades , Orelha/anormalidades , Auxiliares de Audição , Limiar Auditivo , Criança , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Testes de Discriminação da FalaRESUMO
NUT Carcinomaï¼NCï¼ is a rare malignant tumor of unknown origin, which is highly aggressive. It is characterized by chromosome rearrangement accompanied by NUTM1 gene. The pathological manifestations were sudden and focal squamous in poorly differentiated or undifferentiated carcinoma. NUTM1gene rearrangement can be used to diagnose NC. The prognosis of NUT cancer is poor. Clinically, there is no established treatment plan. treatment options mainly comprise surgery, radiotherapy and chemotherapy. A 74-year-old patient with NC of the nasal cavity and sinuses was reported. Her clinical presentation was right nasal congestion with facial swelling. Sinus CT and MRI showed soft tissue density in the right nasal cavity and maxillary sinus with bone destruction. After admission, the patient underwent nasal endoscopic biopsy, and the postoperative pathological FISH staining showed BRD4/NUT fusion tï¼15, 19ï¼. The tumor was significantly reduced after two courses of sequential chemoradiotherapy. Two months later, the patient underwent a partial maxillary resection due to the rapid regrowth of sinusoidal mass, invading the hard palate. The patient died 2 months after surgery due to multiple organ failure resulted from tumor metastasis, with a survival time of 11 months. The clinical characteristics, diagnosis and treatment of this case were reported and related literature was reviewed.
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Cavidade Nasal , Neoplasias Nasais , Humanos , Idoso , Feminino , Cavidade Nasal/patologia , Neoplasias Nasais/terapia , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Evolução Fatal , CarcinomaRESUMO
BACKGROUND: The study was designed to identify new landmarks in the parapharyngeal segment of the internal carotid artery (ICA) for nasopharyngectomy and describe a surgical procedure of endoscopic endonasal transpterygoid nasopharyngectomy (EETPN). METHODS: Four cadaveric specimens were injected with colored silicone and subjected to CT scanning before dissection. The nasopharyngeal skull base was exposed using the endoscopic endonasal transpterygoid approach. The clinical data of four patients with nasopharyngeal malignances who underwent EETPN were reviewed. RESULTS: The lateral edge of the longus capitis muscle medially; the foramen lacerum, petrous apex spine and the stump of the levator veli palatini muscle superior laterally; and the upper parapharyngeal ICA laterally constitute the ICA-longus capitis muscle-petrous apex spine triangle which was a novel landmark for the upper parapharyngeal segment of the ICA. CONCLUSION: The ICA-longus capitis muscle-petrous apex spine triangle are important landmarks of the upper parapharyngeal segment of the ICA.
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Procedimentos Cirúrgicos Nasais , Nariz , Humanos , Endoscopia/métodos , Base do Crânio/cirurgia , Osso Petroso/irrigação sanguínea , Osso Petroso/cirurgia , Cadáver , Artéria Carótida InternaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear. AIM OF THE STUDY: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD). MATERIALS AND METHODS: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR. RESULTS: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism. CONCLUSIONS: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia.
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Hipercolesterolemia , Hiperlipidemias , Ratos , Animais , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Colesterol , Fígado , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Colesterol 7-alfa-Hidroxilase/metabolismo , Inflamação/patologia , Ácidos e Sais Biliares/metabolismo , Dieta HiperlipídicaRESUMO
Hemifacial microsomia (HFM), a rare disorder of first- and second-pharyngeal arch development, has been linked to a point mutation in VWA1 (von Willebrand factor A domain containing 1), encoding the protein WARP in a five-generation pedigree. However, how the VWA1 mutation relates to the pathogenesis of HFM is largely unknown. Here, we sought to elucidate the effects of the VWA1 mutation at the molecular level by generating a vwa1-knockout zebrafish line using CRISPR/Cas9. Mutants and crispants showed cartilage dysmorphologies, including hypoplastic Meckel's cartilage and palatoquadrate cartilage, malformed ceratohyal with widened angle, and deformed or absent ceratobranchial cartilages. Chondrocytes exhibited a smaller size and aspect ratio and were aligned irregularly. In situ hybridization and RT-qPCR showed a decrease in barx1 and col2a1a expression, indicating abnormal cranial neural crest cell (CNCC) condensation and differentiation. CNCC proliferation and survival were also impaired in the mutants. Expression of FGF pathway components, including fgf8a, fgfr1, fgfr2, fgfr3, fgfr4, and runx2a, was decreased, implying a role for VWA1 in regulating FGF signaling. Our results demonstrate that VWA1 is essential for zebrafish chondrogenesis through effects on condensation, differentiation, proliferation, and apoptosis of CNCCs, and likely impacts chondrogenesis through regulation of the FGF pathway.
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Condrogênese , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Condrogênese/genética , Cartilagem/metabolismo , Condrócitos/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
BACKGROUND: Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. METHODS: We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MßCD, respectively. RESULTS: Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. CONCLUSIONS: Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Proliferação de Células , Neoplasias Pulmonares/genética , Prognóstico , Estudos Retrospectivos , TranscriptomaRESUMO
Neuroendocrine regulatory polypeptide VGF (nerve growth factor inducible) was firstly found in the rapid induction of nerve growth factor on PC12 cells. It was selectively distributed in neurons and many neuroendocrine tissues. This paper reviewed the latest literatures on the gene structure, transcriptional regulation, protein processing, distribution and potential receptors of VGF. The neuroendocrine roles of VGF and its derived polypeptides in regulating energy, water electrolyte balance, circadian rhythm and reproductive activities were also summarized. Furthermore, based on the experimental evidence in vivo and in vitro, dysregulation of VGF in different neuroendocrine diseases and the possible mechanism mediated by VGF polypeptides were discussed. We next discussed the potential as the clinical diagnosis and therapy for VGF related diseases in the future.
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Doenças do Sistema Nervoso , Neuropeptídeos , Animais , Biomarcadores/metabolismo , Fatores de Crescimento Neural/metabolismo , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/uso terapêutico , Sistemas Neurossecretores , Estudos Prospectivos , RatosRESUMO
Superficial myofibroblastoma (SMF) of the lower female genital tract is a relatively rare benign mesenchymal tumor. The diagnosis is usually challenging as it shares several similar clinicopathological features with other tumors. Herein, we present a case of a 71-year-old Chinese female patient with postmenopausal vaginal bleeding. Colposcopy imaging revealed a well-circumscribed mass in the vagina with a wide pedicle, resembling a mushroom. The patient underwent surgery, and the tumor was histologically diagnosed as SMF. To the best of our knowledge, this is the first report of colposcopic imaging of a superficial vaginal myofibroblastoma. In this case study, we review the clinicopathological features of SMF of the lower female genital tract reported in the literature to improve the understanding of the disease.
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Background: In a previous study, a total of 568 differentially expressed proteins including the signal peptidase SPC21 were identified from lung adenocarcinoma (LUAD) and paired normal lung tissues. In this study, the role of SPC21 in LUAD progression was investigated. Methods: The relationships and protein-protein interaction network of proteins differentially expressed between paired LUAD samples and adjacent normal tissues samples were identified via the String and Pajek software, respectively. The expression levels of the hub protein SPC21 were analyzed in 84 LUAD-normal paired tissues via immunohistochemistry. The prognostic value of SPC21 mRNA was investigated in 478 LUAD patients from TCGA and GTEx datasets. siRNAs were used in A549 and NCI-H1299 cells to knockdown SPC21. The SPC21 biological function was evaluated using the CCK-8, EdU, plate colony formation, transwell, wound healing, and adhesion assays. Results: Patients with lower SPC21 mRNA levels tended to have worse prognosis (overall survival) than those with higher mRNA levels. SPC21 expression was significantly downregulated in LUAD tumor tissues compared with that in paired normal tissues (P < 0.001). Functionally, SPC21 knockdown promoted cell growth, migration, and invasion. Further analyses showed that SPC21 inactivated Akt signaling, and the Akt inhibitor MK-2206 blocked the tumor-promoting effects of SPC21 knockdown. Conclusions: SPC21 plays a tumor suppressor role in LUAD cells by targeting the PTEN-PI3K/Akt axis and might be used as a prognostic indicator and therapeutic target in LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/genética , Movimento Celular/genética , Adenocarcinoma de Pulmão/genética , Transdução de Sinais/genética , Processos Neoplásicos , Proliferação de Células/genética , RNA Mensageiro , PTEN Fosfo-Hidrolase/genéticaRESUMO
Background: Contrast-induced nephropathy (CIN) is increasingly seen in patients receiving contrast medium. Abelmoschus manihot (L.) Medik. (Malvaceae) and its preparations are widely used and effective in the treatment of various chronic kidney diseases and CIN in China. It is supposed to be an important adjuvant therapy for CIN. Methods: PubMed and CNKI were searched for the main compounds of A. manihot L. The Swiss target prediction platform, OMIM, GeneCards, DisGeNET, and DrugBank databases were mined for information relevant to the prediction of targets that A. manihot L. in the treatment of CIN. Subsequently, STRING database was applied for the construction of the PPI protein interaction network, meanwhile, the core targets were screened. DAVID database was used to perform the GO function and Kegg signal pathway enrichment analysis. AutoDockTools and PYMOAL were used for molecular docking. Vitro experiments were used to verify the effect of TFA, the main active component of A. manihot L., in the intervention of iopromide-induced cells injury. Results: A total of 17 chemical components and 133 potential targets in A. manihot L. were obtained. The top 15 proteins with higher degree value were selected from the PPI network model, AKT1, PIK3R1, EGFR, SRC,AR, APP, TNF, GAPDH, MMP9, and PTPN1, etc. may be core targets. The enrichment analysis indicated that A. manihot L. was involved in the regulation of PI3K/AKT signaling pathway, FoxO signaling pathway, VEGF signaling pathway, HIF-1, TNF signaling pathway, melanoma, hepatitis B, and other signaling pathways which were mainly associated with the regulation of transcription and apoptosis, protein phosphorylation, inflammatory response, aging, and cell proliferation. Molecular docking indicated that the key components and core targets had a good binding ability. The vitro experiments illustrated that TFA reduces iopromide induced renal tubular cell injury and apoptosis, which may be related to regulating the phosphorylation of AKT. Conclusion: The study preliminarily revealed the multi-component, multi-target, and multi-pathway synergistic effects of A. manihot L. on CIN, which provide theoretical reference and basis for the study of the pharmacological mechanism of A. manihot L. in the treatment of CIN.
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Microtia-atresia is a congenital malformation of the external ear, often affecting one side and being associated with severe-to-profound unilateral conductive hearing loss (UCHL). Although the impact of unilateral hearing loss (UHL) on speech recognition, sound localization and brain plasticity has been intensively investigated, less is known about the subjects with unilateral microtia-atresia (UMA). Considering these UMA subjects have hearing loss from birth, we hypothesize it has a great effect on brain organization. A questionnaire on speech recognition and spatial listening ability was administered to 40 subjects with UMA and 40 age- and sex-matched controls. UMA subjects showed poorer speech recognition in laboratory and poorer spatial listening ability. However, cognitive scores determined by the Montreal Cognitive Assessment (MoCA) and Wechsler Intelligence Scale for Children (WISC-IV) did not differ significantly in these two groups. The impact of hearing loss in UMA on brain functional organization was examined by comparing resting-state fMRIs (rs-fMRI) in 27 subjects with right-sided UMA and 27 matched controls. UMA subjects had increased nodal betweenness in visual networks and DMN but decreases in auditory and attention networks. These results indicate that UCHL in UMA causes significant abnormalities in brain organization. The impact of UCHL on cognition should be further examined with a battery of tests that are more challenging and better focused on the cognitive networks identified.
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Microtia Congênita , Localização de Som , Percepção da Fala , Encéfalo/diagnóstico por imagem , Criança , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Background: The endoscopic modified Lothrop procedure (EMLP) is an important procedure used to address frontal and anterior skull-base lesions. Two techniques were established, namely, the inside-out approach and the outside-in approach. The former technique take the frontal recess and the first olfactory filament (FOF) as key landmarks while the latter use the FOF as posterior boundary. In some cases, however, these two landmarks are not available. Therefore, we supplement the outside-in approach and named it trans-nasion-complex approach (TNCA) for EMLP that can be performed without locating these two landmarks. Methods: Two dry human skulls were used to observe the bony nasion complex. Then, five colored silicon-injected human head specimens were dissected via TNCA for EMLP. Finally, the outcomes of patients who underwent TNCA were reviewed. Results: The nasion complex is an osseous complex that consists of the nasion and its adjacent structures, including the bilateral root of nasal bones, nasal process of frontal bones, anterior portion of the perpendicular plate of the ethmoid bone that connects with the inferior aspect of the nasal bones, and portions of the bilateral frontal process of the maxillary bones. Surgical landmarks for TNCA include the anterior superior portion of the nasal septum, anterior margin and axilla of the middle turbinate, frontal process of the maxilla bone, nasal process of the frontal bone and upper part of the nasal bone. These structures form a "mushroom sign" during cadaveric dissection and surgery. Twenty-one patients underwent TNCA, of whom 9 had tumors and 12 had chronic rhinosinusitis with nasal polyps (CRSwNP). None of them had major complications. Conclusion: TNCA is expected to be a safe, and direct route for EMLP. Adequate understanding of the nasion complex and "mushroom sign" will be helpful to complete TNCA.
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OBJECTIVE: To investigate the outcomes of open reduction and internal fixation combined with medial buttress plate (MBP) and allograft bone-assisted cannulated screw (CS) fixation for patients with unstable femoral neck fracture with comminuted posteromedial cortex. METHODS: In a retrospective study of patients operated on for unstable femoral neck fractures with comminuted posteromedial cortex from March 2016 to August 2020, the clinical and radiographic outcomes of 48 patients treated with CS + MBP were compared with the outcomes of 54 patients treated with CS only. All patients in the CS + MBP group were fixed by three CS and MBP (one-third tubular plates or reconstructive plates) with bone allografts. The surgery-related outcomes and complications were evaluated, including operative time, blood loss, union time, femoral head necrosis, femoral neck shortening, and other complications after the operation. The Harris score was evaluated at 12 months after the operation. RESULTS: All patients were followed up for 12-40 months. The average age of patients in the CS-only group (54 cases, 22 females) and CS + MBP group (48 cases, 20 females) was 48.46 ± 7.26 and 48.73 ± 6.38 years, respectively. More intraoperative blood loss was observed in the CS + MBP group than that of patients in CS-only group (153.45 ± 64.27 vs 21.86 ± 18.19 ml, t = 4.058, P = 0.015). The average operative time for patients in the CS + MBP group (75.35 ± 27.67 min) was almost double than that of patients in the CS-only group (36.87 ± 15.39 min) (t = 2.455, P < 0.001). The Garden alignment index of patients treated by CS + MBP from type I to type IV was 79%, 19%, 2%, and 0%, respectively. On the contrary, they were 31%, 43%, 24% and 2% for those in the CS-only group, respectively. The average healing times for the CS-only and CS + MBP groups were 4.34 ± 1.46 and 3.65 ± 1.85 months (t = 1.650, P = 0.102), respectively. Femoral neck shortening was better in the CS + MBP group (1.40 ± 1.73 mm, 9/19) than that in the CS-only group (4.33 ± 3.32 mm, 24/44). Significantly higher hip function was found in the CS + MBP group (85.60 ± 4.36 vs 82.47 ± 6.33, t = 1.899, P = 0.06). There was no statistical difference between femoral head necrosis (4% vs 11%, χ2 = 1.695, P = 0.193) and nonunion (6% vs 9%, χ2 = 0.318, P = 0.719). CONCLUSION: For unstable femoral neck fractures with comminuted posteromedial cortex, additional MBP combined with bone allografts showed better reduction quality and neck length control than CS fixation only, with longer operative time and more blood loss.
Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Fraturas Cominutivas , Adulto , Aloenxertos , Parafusos Ósseos , Feminino , Fraturas do Colo Femoral/etiologia , Fraturas do Colo Femoral/cirurgia , Necrose da Cabeça do Fêmur/etiologia , Fixação Interna de Fraturas/efeitos adversos , Fraturas Cominutivas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The treatment of qualitative olfactory disease is challenging. We aimed to treat parosmia using a new minimally invasive surgical technique-the olfactory cleft blocking technique- by preventing odorants from reaching the olfactory epithelium. A novel surgical procedure for blocking the anterior and inferior openings of the olfactory cleft was accomplished in a patient with unilateral persistent peripheral parosmia. The HRCT and endoscopy were performed preoperatively and postoperatively to evaluate the anatomical structure of the olfactory cleft. The T&T olfactometer was used to assess the preoperative and postoperative olfactory function. After surgery, the patient's parosmia disappeared. Endoscopic examination and CT scan showed complete obstruction of the anterior and inferior portions of the olfactory cleft. No recurrence was reported during a 2-year follow-up. No surgical complications were reported except olfactory loss in the operative nostril. For patients with long-term unilateral peripheral olfactory dysfunction, the olfactory cleft blocking technique seems a novel, simple, safe and effective treatment. Further studies are required with a larger number of patients in order to access success rate.