Down-conversion and frequency spectrum convolution of the broadband signal based on active mode-locking technology.

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 ∼50 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.

Endoscopic endonasal transpterygoid nasopharyngectomy: Anatomical considerations and technical note.

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.

Polymethoxyflavones in citrus extract has a beneficial effect on hypercholesterolemia rats by promoting liver cholesterol metabolism.

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.

Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma.

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.

Application of a Novel Versatile Mini Posterior Nasoseptal Graft in Endoscopic Transsphenoidal Pituitary Adenoma Surgery.

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.

vwa1 Knockout in Zebrafish Causes Abnormal Craniofacial Chondrogenesis by Regulating FGF Pathway.

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.

Superficial vaginal myofibroblastoma with mushroom-like appearance: A case report with colposcopic findings and literature review.

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.

Signal peptidase 21 suppresses cell proliferation, migration, and invasion via the PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma.

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.

Trans-Nasion-Complex Approach for Endoscopic Modified Lothrop Procedure: Conception, Anatomy, and Technique.

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.

VGF: A prospective biomarker and therapeutic target for neuroendocrine and nervous system disorders.

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.

Medial Buttress Plate and Allograft Bone-Assisted Cannulated Screw Fixation for Unstable Femoral Neck Fracture with Posteromedial Comminution: A Retrospective Controlled Study.

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.

Mechanism of Abelmoschus manihot L. in the Treatment of Contrast-Induced Nephropathy on the Basis of Network Pharmacology Analysis.

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.

Poor speech recognition, sound localization and reorganization of brain activity in children with unilateral microtia-atresia.

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.

NOD2 deficiency confers a pro-tumorigenic macrophage phenotype to promote lung adenocarcinoma progression.

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.

Probing cell metabolism on insulin like growth factor(IGF)-1/tumor necrosis factor(TNF)-α and chargeable polymers co-immobilized conjugates.

Cell culturing on different synthetic biomaterials would reprogram cell metabolism for adaption to their living conditions because such alterations in cell metabolism were necessary for cellular functions on them. Here we used metabolomics to uncover metabolic changes when liver cells were cultured on insulin-like growth factor (IGF)/tumor necrosis factor-α (TNF-α) and chargeable polymers co-modified biomaterials with the aim to explain their modulating effects on cell metabolism. The results showed that cell metabolism on IGF-1/TNF-α co-immobilized conjugates was significantly regulated according to their scatterings on the score plot of principal component analysis. Specifically, cell metabolisms were reprogrammed to the higher level of pyrimidine metabolism, ß-alanine metabolism, and pantothenate and CoA biosynthesis, and the lower level of methionine salvage pathway in order to promote cell growth on IGF/TNF-α co-modified surface. Furthermore, cell senescence on PSt-PAAm-IGF/TNF-α surface was delayed through the regulation of branch amino acid metabolism and AMPK signal pathway. The research showed that metabolomics had great potential to uncover the molecular interaction between biomaterials and seeded cells, and provide the insights about cell metabolic reprogramming on IGF/TNF-α co-modified conjugates for cell growth.

Simultaneous Endoscopic Endonasal Decompression of the Optic Canal, Superior Orbital Fissure, and Proper Orbital Apex for Traumatic Orbital Apex Syndrome: Surgical Anatomy and Technical Note.

OBJECTIVES: Traumatic orbital apex syndrome (TOAS) is an uncommon but severe ocular complication of craniomaxillofacial fracture. The optimal surgical strategy for TOAS has not been determined. To investigate the endoscopic anatomy of the orbital apex region, propose a protocol for simultaneous endoscopic endonasal decompression of the optic canal, superior orbital fissure, and proper orbital apex (EEDCFA) for TOAS and report its use in two patients. METHODS: An endoscopic endonasal approach was utilized to dissect the orbital apex region in two silicon-injected adult cadaveric heads. The details of the procedure used for decompression of the orbital apex were determined. The effects of this procedure were determined in two patients with TOAS who underwent simultaneous decompression of the optic canal, superior orbital fissure, and proper orbital apex. RESULTS: The orbital apex consisted of three portions, the contents of the optic canal superomedially; the contents of the superior orbital fissure inferolaterally; and the converging portion, or proper orbital apex, anteriorly. From an endoscopic endonasal approach, the optic nerve, superior orbital fissure, and orbital apex convergence prominences were found to form a π-shaped configuration. This π-shaped configuration was indicative of the orbital apex and was an important landmark for decompression of the orbital apex. Endonasal decompression of the orbital apex in the two patients resulted in the satisfactory recovery of extraocular mobility, with no surgical complications. CONCLUSIONS: EEDCFA is feasible, effective, and safe for patients with TOAS caused by direct compression of displaced fracture segments. The π-shaped configuration is a valuable landmark for EEDCFA.

A pH-responsive polymer linked with immunomodulatory drugs: synthesis, characteristics and in vitro biocompatibility.

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.

A novel surgical treatment for long lasting unilateral peripheral parosmia: Olfactory cleft blocking technique.

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.

A Mutation in VWA1, Encoding von Willebrand Factor A Domain-Containing Protein 1, Is Associated With Hemifacial Microsomia.

BACKGROUND: Hemifacial microsomia (HFM) is a type of rare congenital syndrome caused by developmental disorders of the first and second pharyngeal arches that occurs in one out of 5,600 live births. There are significant gaps in our knowledge of the pathogenic genes underlying this syndrome. METHODS: Whole exome sequencing (WES) was performed on five patients, one asymptomatic carrier, and two marry-in members of a five-generation pedigree. Structure of WARP (product of VWA1) was predicted using the Phyre2 web portal. In situ hybridization and vwa1-knockdown/knockout studies in zebrafish using morpholino and CRISPR/Cas9 techniques were performed. Cartilage staining and immunofluorescence were carried out. RESULTS: Through WES and a set of filtration, we identified a c.G905A:p.R302Q point mutation in a novel candidate pathogenic gene, VWA1. The Phyre2 web portal predicted alterations in secondary and tertiary structures of WARP, indicating changes in its function as well. Predictions of protein-to-protein interactions in five pathways related to craniofacial development revealed possible interactions with four proteins in the FGF pathway. Knockdown/knockout studies of the zebrafish revealed deformities of pharyngeal cartilage. A decrease of the proliferation of cranial neural crest cells (CNCCs) and alteration of the structure of pharyngeal chondrocytes were observed in the morphants as well. CONCLUSION: Our data suggest that a mutation in VWA1 is functionally linked to HFM through suppression of CNCC proliferation and disruption of the organization of pharyngeal chondrocytes.