[Exploration of technique for preservation of external-middle ear structure in surgery of jugular foramen paraganglioma （appended 2 case reports）].

Objective:To investigate the feasibility and effect of the modified surgery of the classic infratemporal fossa type A approach for the surgical treatment of jugular foramen paraganglioma with preservation of the external and middle ear structures. Methods:The medical data of 2 patients with jugular foraminal paraganglioma treated by sublabyrinthic-transmastoid approach were retrospectively analyzed. The clinical feature, degree of tumor resection, postoperative facial nerve function and hearing retention, and the incidence of postoperative complications were evaluated. Results:Two patients were both female, and were pathologically confirmed as paraganglioma. The tumor of case 1 was staged as C2De1, and case 2 as C1De1. Tumors were completely resected in both patients. Case 1 suffered infection after surgery, with residual tympanic membrane perforation and mixed deafness. Case 2 developed mild facial paralysis（grade Ⅱ） after surgery, and recovered after symptomatic treatment. There was no tumor residue or recurrence during half a year of follow-up. Conclusion:Surgical treatment of certain paragangliomas in the jugular foramen with a combined sublabyrinthic-transmastoid and upper neck approach might achieve both complete resection of the tumor and preserving the structure and function of the outer-middle ear. This procedure is suitable for paragangliomas restricted in the jugular foramen area, with no or limited involvement of the internal carotid artery（C1 or C2）, and with no or mild hearing loss.

CT analysis of frontal recess air cell and fluid dynamics simulation of frontal sinus in people with different frontal sinus development after Draf1-3 surgery.

OBJECTIVE: To explore the effects of Draf1-3 on frontal sinus airflow and frontal sinus irrigation in people with different frontal sinus development METHODS: The development of the frontal sinus and the distribution of the frontal recess cells were evaluated by CT scan in 150 adults (300 sides). The airflow changes into the frontal sinus and frontal recess after Draf were analyzed by Fluent software under a steady state and quiet inspiratory state. Nasal irrigation after Draf in adults with well-developed frontal sinus was simulated using 120 mL saline at a rate of 12 mL/s in a position at 45° to observe the changes in transient flow distribution. RESULTS: The moderately developed type of the frontal sinus was the most common. The airflow patterns in the frontal sinus and frontal recess in the moderate development group were laminar, while several large vortexes were formed between the frontal sinus and frontal recess in the well-development group. The Draf exerted more significant effects on the patterns, pressure, and velocity of the airflow in the frontal sinus and frontal recess in the well development group than in the moderate development group. The volume fraction of saline in the frontal sinus increased significantly from Draf1 to Draf3, and the time required for a complete infiltration of saline in the frontal sinus mucosa was significantly reduced. CONCLUSIONS: Draf1-3 has different effects on the airflow field of the frontal sinus with different developmental types; and Draf1-3 can significantly improve the postoperative flushing of the frontal sinus.

Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6.

BACKGROUND: As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs). METHODS: ApoeKO mice were utilized as a model for atherosclerosis. Endothelium-specific transgenic mice were employed to disrupt the expression level of Rnd3 in vivo. Mechanistic investigation of the impact of Rnd3 on endothelial cell pyroptosis was carried out using liquid chromatography tandem mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP) assays, and molecular docking. RESULTS: Evidence from gain-of-function and loss-of-function studies denoted a protective role for Rnd3 against ECs pyroptosis. Downregulation of Rnd3 sensitized ECs to pyroptosis under oxidized low density lipoprotein (oxLDL) challenge and exacerbated atherosclerosis, while overexpression of Rnd3 effectively prevented these effects. LC-MS/MS, Co-IP assay, and molecular docking revealed that Rnd3 negatively regulated pyroptosis signaling by direct interaction with the ring finger domain of tumor necrosis factor receptor-associated factor 6 (TRAF6). This leads to the suppression of K63-linked TRAF6 ubiquitination and the promotion of K48-linked TRAF6 ubiquitination, inhibiting the activation of NF-κB and promoting the degradation of TRAF6. Moreover, TRAF6 knockdown countered Rnd3 knockout-evoked exacerbation of EC pyroptosis in vivo and vitro. CONCLUSIONS: These findings establish a critical functional connection between Rnd3 and the TRAF6/NF-κB/NLRP3 signaling pathway in ECs, indicating the essential role of Rnd3 in preventing pyroptosis of ECs.

[Clinical practice of infratemporal fossa benign tumor endoscopic transnasal/oral surgery in 36 patients].

Objective:According to the characteristics of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, we divided and named subzones of the infratemporal fossa, to explore the approaches of endoscopic transnasal and transoral surgery for infratemporal fossa tumors, and to analyze their advantages and disadvantages. Methods:We retrospectively analyzed the clinical data of 36 patients with benign tumors of infratemporal fossa successfully resected through nose or mouth under endoscope, summarized and analyzed the localization characteristics of these tumors in infratemporal fossa, and made a subzone naming rule of infratemporal fossa. We also summarized the selection principles, advantages and disadvantages of endoscopic transnasal and transoral surgical approaches. Results:The infratemporal fossa area is divided into ABC area. Area A is the fat pad area posterolateral of maxillary sinus. Area B is further divided into B1 （above the plane of maxillary sinus floor, anterior styloid process）, B2 （below the plane of maxillary sinus floor, anterior styloid process）, and B3 （posterior styloid process to anterior vertebra）; Area C is retropharyngeal and eustachian tube area. The location of the tumor in the infratemporal fossa determines the choice of transnasal and transoral approaches. All tumors were completely removed, and no tumor recurred during the follow-up. A few patients had temporary local sensory function decline, and recovered during the follow-up. Conclusion:The infratemporal fossa region naming rule according to the characteristics of endoscopic transoral and transnasal surgery approach is simple and practical, which can effectively guide the operation of the infratemporal fossa region and has clinical application value.

Sirt6-Mediated Endothelial-to-Mesenchymal Transition Contributes Toward Diabetic Cardiomyopathy via the Notch1 Signaling Pathway.

BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) is an important source of myofibroblasts that directly affects cardiac function in diabetic cardiomyopathy (DCM) via an unknown underlying mechanism. Sirt6 is a member of the Sirtuin family of NAD(+)-dependent enzymes that plays an important role in glucose and fatty acid metabolism. In this study, we investigated whether Sirt6 participates in EndMT during the development of T2DM and the possible underlying regulatory mechanisms. METHODS: Endothelium-specific Sirt6 knockout (Sirt6-KOEC) mice (C57BL/6 genetic background) were generated using the classic Cre/loxp gene recombination system. T2DM was induced in eight-week-old male mice by feeding with a high-fat diet for three weeks followed by i.p. injection with 30 mg/kg of streptozotocin. The weight, lipids profiles, insulin, food intake and water intake of experimental animals were measured on a weekly basis. Cardiac microvascular endothelial cells (CMECs) were obtained from adult male mice; the isolated cells were cultured with high glucose (HG; 33 mmol/L) and palmitic acid (PA; 500 µmol/L) in DMEM for 24 h, or with normal glucose (NG; 5 mmol/L) as the control. RESULTS: Sirt6 expression is significantly downregulated in CMECs treated with HG+PA. Additionally, Sirt6-KOEC was found to worsen DCM, as indicated by aggravated perivascular fibrosis, cardiomyocyte hypertrophy, and decreased cardiac function. In vitro, Sirt6 knockdown exacerbated the proliferation, and migration of CMECs exposed to HG+PA. Mechanistically, Sirt6 knockdown significantly enhanced Notch1 activation in CMECs treated with HG+PA, whereas Notch1 adenoviral interference significantly blunted the effects of Sirt6 knockdown on CMECs. CONCLUSION: This study is the first to demonstrate that Sirt6 participates in EndMT via the Notch1 signaling pathway in CMECs stimulated with HG+PA. Therefore, the findings of this study suggest that Sirt6 could provide a potential treatment strategy for DCM.