A Safe Technique for Excising the Perpendicular Plate of the Ethmoid Bone in Patients with Crooked Nose: A Finite Element Analysis.

BACKGROUND: Correction of the crooked nose, especially the perpendicular plate of the ethmoid bone, has the potential to cause skull base injury. At present, the safe and effective method for perpendicular plate resection has not been clearly defined through biomechanics. METHOD: CT scan data of 48 patients with crooked nose and deviated nasal septum were divided into C-type, angular deformity-type, and S-type based on the morphology of the 3D model. Different types of finite element models of the nasal bony septum and skull base were established. The osteotomy depth, angle, and force mode of the PPE resection were simulated by assembling different working conditions for the models. The von Mises stress of the anterior cranial fossa was observed. RESULTS: When the osteotomy line length was 0.5 cm, the angle was at 30° to the Frankfurt plane, and 50 N·mm torque was applied, the von Mises stress of the skull base was minimal in the four models, showing 0.049 MPa (C-type), 0.082 MPa (S-type), 0.128 MPa (angular deformity-type), and 0.021 MPa (control model). The maximum von Mises stress values were found at the skull base when the osteotomy line was 1.5 cm, the angle was 50°, and the force was 10 N along the X-axis, showing 0.349 MPa (C-type), 0.698 MPa (S-type), 0.451 MPa (angular deformity-type), and 0.149 MPa (control model). CONCLUSION: The use of smaller resection angle with the Frankfurt plane, conservative resection depth, and torsion force can better reduce the stress value at the skull base and reduce the risk of basicranial fracture. It is a safe and effective technique for perpendicular plate resection of the ethmoid bone in the correction of crooked nose. 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 .

The Morphological and Functional Effects of the Endoscope-Assisted One-Stage Approach for Crooked Nose.

BACKGROUND: A crooked nose is an external nose deformity predominantly caused by congenital aplasia or acquired secondary to trauma or surgery, often accompanied by a deviated nasal septum. Patients with crooked nose have dual needs to improve both esthetic and functional problems. METHODS: The clinical and photographic information of 48 patients diagnosed with a crooked nose and nasal septum deviation treated from January 2018 to January 2022 was acquired. The morphology and functional effects were investigated by evaluating the general condition of the operation, measuring the esthetic indexes of the nose, and subjectively scoring. RESULTS: For both morphology and function, endoscopy-assisted one-stage correction showed positive results in this study. The external nose deviation distance postoperatively measured 1.28 (0.85, 1.97) mm, which significantly decreased from the preoperative value of 3.96 (3.31, 5.29) mm. The scores of doctors and irrelevant medical students on nose morphology increased significantly from 4.75±1.88 and 3.84±0.76 to 6.48±1.21 and 7.21±0.67, respectively. The rhinoplasty outcome evaluation score and the "nasal obstruction symptom evaluation "score of patients were both significantly improved ( t = -7.508 and t =6.310, respectively, P < 0.001). CONCLUSION: Endoscope-assisted one-stage correction of the crooked nose can restore nasal morphology, improve the symptoms of nasal obstruction, and achieve patient satisfaction. It is a minimally invasive, safe, effective, and fast recovery approach for patients who need to solve both esthetic and functional problems.

Successful replantation of amputated facial tissues by supermicrosurgery.

BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.

Modulation of Immune Reaction in Hydrodynamic Gene Therapy for Hemophilia A.

Hemophilia A (HA) is a monogenic disease characterized by plasma clotting factor 8 (F8) deficiency due to F8 mutation. We have been attempting to cure HA permanently using a CRISPR-Cas9 gene-editing strategy. In this study, we induced targeted integration of BDDF8 (B-domain-deleted F8) gene into the albumin locus of HA mice by hydrodynamic tail vein injection of editing plasmid vectors. One week after treatment, a high F8 activity ranging from 70% to 280% of normal serum levels was observed in all treated HA mice but dropped to background levels 3-5 weeks later. We found that the humoral immune reaction targeting F8 is the predominant cause of the decreased F8 activity. We hypothesized that hydrodynamic injection-induced liver damage triggered the release of large quantities of inflammatory cytokines. However, coinjection of plasmids expressing a dozen immunomodulatory factors failed to curtail the immune reaction and stabilize F8 activity effectively. The spCas9 plasmid carrying a miR-142-3p target sequence alleviated the cellular immune response but could not deliver therapeutic efficacy. Strikingly, immunosuppressant cyclophosphamide virtually abolished the immune response, leading to a year-long stable F8 level. Our findings should have important implications in developing therapies in mouse models using the hydrodynamic gene delivery approach, highlighting the necessity of modulating the innate immune response triggered by liver damage.

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia.

Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25% to 30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, they cannot eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel effective treatment strategies. Here, we demonstrate that FLT3 inhibition induces histone deacetylase 8 (HDAC8) upregulation through FOXO1- and FOXO3-mediated transactivation in FLT3-ITD+ AML cells. Upregulated HDAC8 deacetylates and inactivates p53, leading to leukemia maintenance and drug resistance upon TKI treatment. Genetic or pharmacological inhibition of HDAC8 reactivates p53, abrogates leukemia maintenance, and significantly enhances TKI-mediated elimination of FLT3-ITD+ AML cells. Importantly, in FLT3-ITD+ AML patient-derived xenograft models, the combination of FLT3 TKI (AC220) and an HDAC8 inhibitor (22d) significantly inhibits leukemia progression and effectively reduces primitive FLT3-ITD+ AML cells. Moreover, we extend these findings to an AML subtype harboring another tyrosine kinase-activating mutation. In conclusion, our study demonstrates that HDAC8 upregulation is an important mechanism to resist TKIs and promote leukemia maintenance and suggests that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias.

Modified Anterior Tibial Artery Perforator-Pedicled Propeller Flap for Soft-Tissue Coverage of the Ankle and Heel.

BACKGROUND: The ankle and heel are challenging regions to reconstruct functionally. Here, we explored the feasibility and clinical outcomes of a modified anterior tibial artery perforator-pedicled propeller flap for the repair of soft-tissue defects of the ankle and heel. PATIENTS AND METHODS: Between January 2013 and December 2015, 12 patients with soft-tissue defects of the ankle and/or heel underwent reconstructive surgery that included our flap technique. The flaps measured 20 × 8 cm to 7 × 4 cm. A hand-held Doppler was used to identify a proper constant perforator in the distal ankle. In each case, the base of the flap was well preserved. The flap was transposed (180° rotation) to reach and cover the defect. RESULTS: The average follow-up time was 13 months (10-28 months). We observed good texture matches and contour in all of the flaps. All patients could walk and wear normal footwear. All but one flap survived completely without complications. Partial loss was observed in one patient, and the necrotic region was healed with secondary intention. CONCLUSION: Our modified anterior tibial artery free-style perforator-pedicled propeller flap provides a novel option for functional ankle and heel reconstruction. LEVEL OF EVIDENCE: Level IV.

Interlaced Pd-Ag nanowires rich in grain boundary defects for boosting oxygen reduction electrocatalysis.

Given the high cost and poisoning issues of Pt, developing Pd-based catalysts as substitutes is highly essential. Although substantial progress has been made, the synthesis of Pd-based electrocatalysts with both high activity and stability in the oxygen reduction reaction (ORR) remains a challenge. In this work, we prepared Pd-Ag nanowires with up to micro-sized length and a diameter of ∼17 nm via a facile modified polyol method. The obtained Pd-Ag nanowires (NWs) exhibit interlaced features and are rich in grain boundary defects. Due to the continuous grain boundaries in the one-dimensional (1D) structure and the optimized composition, the synthesized Pd1Ag1 NWs show half-wave potential of 0.897 V and mass activity of 0.103 A mg-1 in alkaline media toward ORR, higher than those of both state-of-the-art Pt/C and other Pd-Ag counterparts. Significantly, after stability tests over 5000 cycles, Pd1Ag1 NWs shows a 2 mV positive shift, much better than that of Pt/C, exhibiting striking stability for ORR. This work may provide an avenue to construct advanced catalysts by surface defect engineering.

Effect of exosomes from adipose-derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury.

AIMS: Recovery after peripheral nerve injury (PNI) is often difficult, and there is no optimal treatment. Schwann cells (SCs) are important for peripheral nerve regeneration, so SC-targeting treatments have gained importance. Adipose-derived stem cells (ADSCs) and their exosomes can promote peripheral nerve repair, but their interactions with SCs are unclear. METHODS: Purified SCs from sciatic nerve injury sites were harvested, and apoptosis and proliferation of SCs at post-PNI 24 hours were analyzed. The effects of coculture with ADSCs and different concentrations of ADSC-derived exosomes (ADSC-Exo) were studied through in vitro experiments by flow cytometry, CCK8 assay, immunofluorescence staining, and histological analysis. The expression of the apoptosis-related genes Bcl-2 and Bax was also analyzed by qRT-PCR. RESULTS: ADSC-Exo reduced the apoptosis of SCs after PNI by upregulating the anti-apoptotic Bcl-2 mRNA expression and downregulating the pro-apoptotic Bax mRNA expression. Further, it also improved the proliferation rate of SCs. This effect was confirmed by the morphological and histological findings in PNI model rats. CONCLUSION: Our results present a novel exosome-mediated mechanism for ADSC-SC cross talk that reduces the apoptosis and promotes the proliferation of SCs and may have therapeutic potential in the future.

[The analysis of natural and synthetic ruby by Raman spectra].

The differentiation of natural and synthetic gems is still a difficult problem in gems identification. The full width at half maximum (FWHM) of Raman spectrum, that is the life-span of phonon, can provide valuable information about. natural or synthetic gem. Analysis of the natural and synthetic ruby was performed by BTR111--785 mini-Raman spectroscopy, and it was found that the FWHM of natural ruby is more than 10 cm(-1), withal the FWHM of synthetic ruby is less than 10 cm(-1).