Supramarginal resection of skull base chordomas: proof of concept and preliminary outcomes.

OBJECTIVE: The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. METHODS: This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. RESULTS: Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. CONCLUSIONS: In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.

PU.1 induces tumor-associated macrophages promoting glioma progression through BTK-mediated Akt/mTOR pathway activation.

Glioma, the most common primary malignant brain tumor, is characterized by infiltrating immune cells that contribute to tumor progression and therapeutic resistance. Tumor-associated macrophages (TAMs) constitute a significant proportion of these infiltrating immune cells and have been implicated in glioma progression. However, the underlying molecular mechanisms by which TAMs promote glioma progression remain elusive. In this study, we investigated the role of PU.1, a crucial transcription factor involved in myeloid cell development, in glioma-associated macrophage polarization and activation. First, bioinformatics and analysis of clinical glioma samples demonstrated a positive correlation between PU.1 expression in TAMs and disease severity. Further experiments using in vitro coculture systems revealed that the expression of PU.1 is increased in glioma cells vs. control cells. Importantly, PU.1-overexpressing macrophages exhibited a protumorigenic phenotype characterized by enhanced migration, invasion, and proliferation. Mechanistically, we found that PU.1-induced activation of the Bruton tyrosine kinase (BTK) signaling pathway led to Akt/mTOR pathway activation in macrophages, which further enhanced their protumorigenic functions. Furthermore, pharmacological inhibition of the BTK or Akt/mTOR pathway reversed the protumorigenic effects of macrophages in vitro and impaired their ability to promote glioma progression in vivo. In conclusion, our study elucidates a novel mechanism by which PU.1 induces the polarization and activation of TAMs in the glioma microenvironment. We highlight the significance of BTK-mediated Akt/mTOR pathway activation in driving the protumorigenic functions of TAMs. Targeting PU.1 and its downstream signaling pathways in TAMs may provide a promising therapeutic strategy to suppress glioma progression and improve patient outcomes.

The design of an RGD in situ sustained delivery system utilizing scallop byssal protein through genetic engineering.

Although bioactive peptides enhancing bone healing have demonstrated effectiveness in treating bone defects, in vivo instability poses a challenge to their clinical application. Currently reported peptide delivery systems do not meet the demands of bone tissue repair regarding stability and peptide release efficacy. Herein, the self-assembling recombinant chimeric protein (Sbp5-2RGD) is developed by genetic engineering with cell adhesion peptide RGD as the targeted peptide and a newly discovered scallop byssal-derived protein Sbp5-2 that can assemble into wet stable films as the structural domain. In vitro studies show that the Sbp5-2RGD film exhibits excellent extensibility and biocompatibility. In vitro and in vivo degradation experiments demonstrate that the film remains stable due to the layer-by-layer degradation mode, resulting in sustained delivery of RGD in situ for up to 4 weeks. Consequently, the film can effectively promote osteogenesis, which accelerates bone defect healing and the implants osseointegration. Cell-level studies further show that the film up-regulates the expression of genes and proteins (ALP, OCN, OSX, OPN, RUNX2, VEGF) associated with osteogenesis and angiogenesis. Overall, this novel protein film represents an intelligent platform for peptide immobilization, protection, and release through its self-assembly, dense structure, and degradation mode, providing a therapeutic strategy for bone repair.

Endoscopic endonasal pituitary sacrifice for select tumors with retrochiasmatic and/or retrosellar extension: surgical anatomy, operative technique, and case series.

OBJECTIVE: Tumors located in the retrochiasmatic region with extension to the third ventricle might be difficult to access when the pituitary-chiasmatic corridor is narrow. Similarly, tumor extension into the interpeduncular and retrosellar space poses a major surgical challenge. Pituitary transposition techniques have been developed to gain additional access. However, when preoperative pituitary function is already impaired or the risk of postoperative panhypopituitarism (PH) is considered to be particularly high, removal of the pituitary gland (PG) might be the preferred option to increase the working corridor. The aim of this study was to describe the relevant surgical anatomy, operative steps, and clinical experience with the endoscopic endonasal pituitary sacrifice (EEPS) and transsellar approach. METHODS: This study comprised anatomical dissections to highlight the relevant surgical steps and a retrospective case series reporting clinical characteristics, indications, and outcomes of patients who underwent EEPS. The surgical technique is as follows: both lateral opticocarotid recesses are exposed laterally, the limbus sphenoidale superiorly, and the sellar floor inferiorly. After opening the dura, the PG is detached circumferentially and mobilized off the medial walls of the cavernous sinuses. The descending branches of the superior hypophyseal artery are coagulated, and the stalk is transected. After removal of the PG, drilling of the dorsum sellae and bilateral posterior clinoidectomies are performed to gain access to the hypothalamic region, interpeduncular, and prepontine cisterns. RESULTS: From 2018 to 2023, 11 patients underwent EEPS. The cohort comprised mostly tuberoinfundibular craniopharyngiomas (n = 8, 73%). Seven (64%) patients had partial or complete anterior PG dysfunction preoperatively, while 4 (36%) had preoperative diabetes insipidus. Because of the specific tumor configuration, the chance of preserving endocrine function was estimated to be very low in patients with intact function. The main reasons for pituitary sacrifice were impaired visibility and surgical accessibility to the retrochiasmatic and retrosellar spaces. Gross-total tumor resection was achieved in 10 (91%) patients and near-total resection in 1 (9%) patient. Two (18%) patients experienced a postoperative CSF leak, requiring surgical revision. CONCLUSIONS: When preoperative pituitary function is already impaired or the risk for postoperative PH is considered particularly high, the EEPS and transsellar approach appears to be a feasible surgical option to improve visibility and accessibility to the retrochiasmatic hypothalamic and retrosellar spaces, thus increasing tumor resectability.

Can concentrated growth factor prevent postoperative complications of impacted third molar surgery? A split-mouth randomized double-blind trial.

OBJECTIVES: The purpose of the present study was to evaluate the effect of concentrated growth factor (CGF) on prevention of postoperative complications in the impacted third molar extraction. MATERIALS AND METHODS: A total of 25 healthy patients with symmetrical bilaterally impacted third molars (50 extraction sites) were enrolled in this split-mouth, randomized, double-blind clinical trial. Third molar extractions were performed in both sites of the mandible at the same appointment. Randomization was performed using a coin toss to choose the test and control sites. CGF was placed in the extraction socket and the socket was sutured (test group), while the contralateral socket was only sutured (control group). Each patient acted as their own control. The primary outcome were pain assessed by visual analog scale (VAS) and facial swelling on the1st, 3rd and 7th postoperative days. The secondary outcomes were bone healing in extraction sockets through alveolar bone height (ABH) and alveolar bone density (ABD) evaluated by cone beam computed tomography (CBCT) immediately after extraction and in the 3rd and 6th months. RESULTS: Twenty-five patients (12 female, 13 male; mean age 29.17) with bilateral impacted third molars participated in the study. A statistically significant reduction in pain was determined on the 3rd and 7th postoperative days in the CGF sites compared to the control sites while no statistically significant difference was found between the groups on the 1st postoperative day (3rd day, p = 0.009; 7th day, p = 0.039). There were no statistically significant differences in facial swelling and bone healing between the test and control groups at different time intervals, although the data obtained were slightly favoring the CGF group (p > 0.05). There were no serious adverse effects such as infection, alveolitis, paraesthesia, fracture through the follow-up period in all of the cases. CONCLUSION: The study has demonstrated the effect of CGF on relieving the severity of pain after the third molar extraction. CLINICAL RELEVANCE: Placement of CGF in the extraction socket could relieve postoperative pain and reduce patient discomfort after the third molar extraction. CGF is recommended during the third molar extraction due to its good biological effects, low cost and simple preparation procedures. TRIAL REGISTRATION NUMBER: ChiCTR2300077819.

[Thinking from Horqin Grassland to Horqin Sandy Land]. / 从科尔沁草原到科尔沁沙地的思考.

We systematically elaborated and compared the spatial scope and landscape changes of Horqin Grassland and Horqin Sand Land from their definitions and ranges. Horqin Grassland is an area with geographical units named after Mongolian tribes, but the boundary is unclear. Horqin Sand Land is also an area that borrows tribal names, but has independent topographic and geomorphic units, and clear boundaries. Horqin Grassland and Horqin Sand Land belong to two spatial regions that are both cross and different. The area and range of Horqin Grassland are larger than that of Horqin Sand Land which has obvious regional characteristics, and is a typical and research object area to study the development and restoration of aeolian desertification. Based on those cognition, we summarized the technologies and example models of comprehensive land management and desertification controlling over the years, and finally sorted out what should be focused on in the future to serve the annihilation war against desertification for Horqin Sand Land.

Real-world impact of chemotherapy on overall survival in craniomaxillofacial osteosarcoma.

OBJECTIVES: The goal of this study was to identify the survival benefit of chemotherapy in craniomaxillofacial osteosarcoma (CMFO) patients based on a US population. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients with CMFO from 1988 to 2016. Age and tumor size were grouped by X-tail. Cox analysis were used to estimate hazards ratios (HR) among patients. All of patients were divided into two cohorts by using Propensity Score Matching (PSM) method to evaluate the effect of chemotherapy. All prognostic factors were included in the nomograms which predict the median survival time. RESULTS: 410 patients were included in our study. The results of survival rate, Kaplan-Meier and Cox regression were showed no significant difference between the group of chemotherapy performed and the group without chemotherapy. PSM analysis also demonstrated the limited survival advantage of chemotherapy. Moreover, all factors were further incorporated to construct the novel nomograms and its concordance indices (C-index) for internal validation of OS prediction were 0.749 (95 %CI:0.731-0.767). CONCLUSIONS: Our study did not show the advantage of chemotherapy on the overall survival outcome of CMFO. Although neoadjuvant chemotherapy was currently recommended in clinical treatment, more rigorous randomized controlled trials are still needed. Nomograms would assist clinicians in making more accurate survival evaluation and choosing the optimal medical treatment.

The Temporoparietal Fascia Flap Transposition Technique for Ventral Skull Base Reconstruction: Anatomic Analysis and Surgical Application.

BACKGROUND AND OBJECTIVES: The temporoparietal fascia (TPF) flap is an alternative for revision endoscopic skull base reconstruction in the absence of the nasoseptal flap, and we aimed to investigate the anatomy and surgical application of TPF flap transposition in endoscopic endonasal surgery. METHODS: Six lightly embalmed postmortem human heads and 30 computed tomography angiography imaging scans were used to analyze the anatomic features of the TPF flap transposition technique. Three cases selected from a 512 endoscopic endonasal cases database were presented for the clinical application of the TPF flap. RESULTS: The TPF flap, composed by the deepest 3 scalp layers (galea aponeurotica, loose areolar connective tissue, and pericranium), can be harvested and then transposed through the infratemporal-maxillary-pterygoid tunnel to the ventral skull base. The superficial temporal artery as its feeding artery, gives frontal and parietal branches with similar diameter (1.5 ± 0.3 mm) at its bifurcation. The typical bifurcation was present in 50 sides (83.3%), with single (frontal) branch in 5 sides (8.3%), single (parietal) branch in 2 sides (3.3%), and multiple branches (>2) in 3 sides (5%). The transposed TPF flap was divided into 3 parts according to its anatomic location: (1) infratemporal part with an area of 19.5 ± 2.5 cm2, (2) maxillary part with an area of 23.7 ± 2.8 cm2, and (3) skull base part with an area of 44.2 ± 4 cm2. Compared with the nasoseptal flap, nasal floor flap, inferior turbinate flap, and extended septal flap, the coverage area of the skull base part of the TPF flap was significantly larger than any of them (P < .0001). CONCLUSION: The TPF flap technique is an effective alternative for endoscopic endonasal skull base reconstruction. The TPF flap could successfully cover large skull base defects through the infratemporal-maxillary-pterygoid tunnel.

Porphyromonas gingivalis as a promotor in the development of the alcoholic liver disease via ferroptosis.

Alcoholic liver disease (ALD) is a liver disease caused by heavy drinking. Porphyromonas gingivalis (P.g), a major cause of periodontitis, whose antibodies are elevated in severe ALD patients in the plasma. The purpose of this study is to further study the role and the molecular mechanism of P.g in the progress of ALD. In this study, saliva of patients with ALD was collected. Then, an animal model of ALD with oral P.g administration was established, pathology of liver and spleen, intestinal microorganisms and metabolites were analyzed. The molecular mechanism of P.g on ALD was analyzed in vitro. ALD and intestinal microflora and metabolite changes were observed more serious in the alcohol and P.g groups than the alcohol group. Moreover, ferroptosis was aggravated by P.g in the liver. Meanwhile, P.g promoted ferroptosis accomplication with alcohol in vitro, which can be reversed by ferroptosis inhibitors. In conclusion, P.g aggravates ALD through exacerbation gut microbial metabolic disorder in mice with alcohol, which maybe depend on ferroptosis activation in hepatocytes. The study provides a new strategy for prevention and treatment of ALD by improving the oral micro-environment.

Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22-CCR4-ATF6-GRP78 axis.

Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.

Asymmetric pre-growing season warming may jeopardize seed reproduction of the sand-stabilizing shrub Caragana microphylla.

Our current understanding of the processes and mechanisms by which seasonal asymmetric warming affects seed reproduction in semiarid regions, which are essential in preserving the stability of both vegetation ecosystem structure and function, remains poorly understood. Here, we conducted a field warming experiment, including pre-growing season warming (W1), in-growing season warming (W2), and combined pre- and in-growing season warming (W3) treatments, to investigate the seed reproductive strategy of Caragana microphylla, an important sand-stabilizing shrub, from the perspective of reproductive phenology, reproductive effort, and reproductive success. Results show that the warming treatments advanced the initial stages of reproductive phenology, prolonged its duration, and decreased its synchrony (magnitude = W3 > W2 > W1). Additionally, flowering phenology was more sensitive to warming than podding phenology. The W1 treatment inclined seed reproduction towards the conservative strategy with low reproductive effort and success. The W3 treatment tended to increase seed reproductive effort and success. While the W2 treatment did not affect reproductive success, it did increase reproductive effort. Changes in reproductive phenology explained 20 % of the variation in reproductive effort and 38 % of the variation in reproductive success. However, these changes also directly hindered reproductive success (direct effect = -0.57) while indirectly promoting reproductive success (indirect effect = 0.27) by increasing reproductive efforts. Our results reveal that the seasonal asymmetry of warming altered the seed reproduction strategy of sand-stabilizing shrubs, with warmer winters and springs before the growing season decreasing seed fecundity.

Resection of corticotroph microadenomas invading the medial wall of the cavernous sinus in two cases of a primary and recurrent case of Cushing's disease.

Emerging evidence from multiple highly specialized groups continues to support a role for resection of the medial wall of the cavernous sinus when it is invaded by functional pituitary adenomas, to offer durable biochemical remission. The authors present two cases of Cushing's disease that underscore the power of this surgical technique in achieving remission in microadenomas that ectopically present in the cavernous sinus or have invaded the medial wall of the sinus. This video demonstrates key steps in the safe removal of the medial wall of the cavernous sinus and successful resection of tumor burden in the cavernous sinus for sustained postoperative remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2323.

Oxidative stress in pituitary neuroendocrine tumors: Affecting the tumor microenvironment and becoming a new target for pituitary neuroendocrine tumor therapy.

Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress-regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy.

The Pterygosphenoidal Triangle: Surgical Anatomy and Case Series in Endoscopic Endonasal Skull Base Surgery.

BACKGROUND: Safe exposure of the lacerum segment of the carotid artery remains a challenge in endoscopic endonasal surgery. OBJECTIVE: To introduce the pterygosphenoidal triangle as a novel and reliable landmark for facilitating access to the foramen lacerum. METHODS: Fifteen colored silicone-injected anatomic specimens were dissected using an endoscopic endonasal approach to the foramen lacerum region in a stepwise manner. Twelve dried skulls were studied and 30 high-resolution computed tomography scans were analyzed to measure the borders and angles of the pterygosphenoidal triangle. Surgical cases incorporating the foramen lacerum exposure between July 2018 and December 2021 were reviewed to provide surgical outcomes of the proposed surgical technique. RESULTS: The pterygosphenoidal triangle is delineated by the pterygosphenoidal fissure medially and the vidian nerve laterally. The palatovaginal artery is located at the base of the triangle anteriorly, while the apex is formed by the pterygoid tubercle posteriorly, which leads to the anterior wall of the foramen lacerum and lacerum internal carotid artery. In the reviewed surgical cases, 39 patients underwent 46 foramen lacerum approaches for resection of pituitary adenoma (12 patients), meningioma (6 patients), chondrosarcoma (5 patients), chordoma (5 patients), or other lesions (11 patients). There were no carotid injuries or ischemic events. Near-total resection was achieved in 33 (85%) of 39 patients (gross-total in 20 [51%]). CONCLUSION: This study details the pterygosphenoidal triangle as a novel and practical anatomic surgical landmark for safe and effective exposure of the foramen lacerum in endoscopic endonasal surgery.

Reappraisal of the anatomy of the frontotemporal branches of the facial nerve.

OBJECTIVE: The anatomy of the temporal branches of the facial nerve (FN) has been widely described in the neurosurgical literature because of its relevance in anterolateral approaches to the skull base and implication in frontalis palsies from these approaches. In this study, the authors attempted to describe the anatomy of the temporal branches of the FN and identify whether there are any FN branches that cross the interfascial space of the superficial and deep leaflets of the temporalis fascia. METHODS: The surgical anatomy of the temporal branches of the FN was studied bilaterally in 5 embalmed heads (n = 10 extracranial FNs). Exquisite dissections were performed to preserve the relationships of the branches of the FN and their relationship to the surrounding fascia of the temporalis muscle, the interfascial fat pad, the surrounding nerve branches, and their final terminal endpoints near the frontalis and temporalis muscles. The authors correlated their findings intraoperatively with 6 consecutive patients with interfascial dissection in which neuromonitoring was performed to stimulate the FN and associated twigs that were observed to be interfascial in 2 of them. RESULTS: The temporal branches of the FN stay predominantly superficial to the superficial leaflet of the temporal fascia in the loose areolar tissue near the superficial fat pad. As they course over the frontotemporal region, they give off a twig that anastomoses with the zygomaticotemporal branch of the trigeminal nerve, which crosses the superficial layer of the temporalis muscle, spanning the interfascial fat pad, and then pierces the deep temporalis fascial layer. This anatomy was observed in 10 of the 10 FNs dissected. Intraoperatively, stimulation of this interfascial segment yielded no facial muscle response up to 1 mA in any of the patients. CONCLUSIONS: The temporal branch of the FN gives off a twig that anastomoses with the zygomaticotemporal nerve, which crosses the superficial and deep leaflets of the temporal fascia. Interfascial surgical techniques aimed at protecting the frontalis branch of the FN are safe in their efforts to protect against frontalis palsy with no clinical sequelae when executed properly.

A YAP/TAZ-CD54 axis is required for CXCR2-CD44- tumor-specific neutrophils to suppress gastric cancer.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.

Periodontitis exacerbates atherosclerosis through Fusobacterium nucleatum-promoted hepatic glycolysis and lipogenesis.

AIMS: Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. METHODS AND RESULTS: A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE-/- mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. CONCLUSIONS: PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.

Refining the Anatomy of Percutaneous Trigeminal Rhizotomy: A Cadaveric, Radiological, and Surgical Study.

BACKGROUND: Percutaneous trigeminal rhizotomy (PTR) is a widely used procedure for trigeminal neuralgia. However, comprehensive analyses that combine anatomic, radiological, and surgical considerations are rare. OBJECTIVE: To present high-quality anatomic dissections and radiological studies that highlight the technical nuances of this procedure. METHODS: Six silicon-injected postmortem heads underwent PTR. The surgical corridors were dissected, and the neurovascular relationships were studied. In addition, 20 dried human skulls and 50 computed tomography angiography and MRI scans were collected to study the anatomic relationships for a customized puncture corridor. RESULTS: The PTR corridor was divided into 3 segments: the buccal segment (length, 34.76 ± 7.20 mm), the inferior temporal fossa segment (length, 42.06 ± 6.92 mm), and the Meckel cave segment (length, 24.75 ± 3.34 mm). The puncture sagittal (α) and axial (ß) angles measured in this study were 38.32° ± 4.62° and 19.13° ± 2.82°, respectively. The precondylar reference line coincided with the foramen ovale in 75% of the computed tomography angiography scans, and the postcondylar line coincided with the carotid canal in 70% of the computed tomography angiography scans; these lines serve as the intraoperative landmarks for PTR. The ovale-carotid-pterygoid triangle, delineated by drawing a line from the foramen ovale to the carotid canal and the lateral pterygoid plate, is a distinguished landmark to use for avoiding neurovascular injury during fluoroscopy. CONCLUSION: Knowledge of the anatomic and radiological features of PTR is essential for a successful surgery, and a customized technical flow is a safe and effective way to access the foramen ovale.

Interaction of rod decussation and crack growth in enamel.

Enamel possesses ingenious hierarchical structure that gives rise to superior fracture resistance. Despite considerable efforts devoted to characterization of fracture behavior of enamel, the role of rod decussation in fracture of enamel is largely unknown. In this study, the features of rod decussation in the inner enamel are experimentally identified, and analyses of crack growth in enamel are carried out using a micromechanical model of enamel, in which the structural features of the outer enamel and rod decussation of the inner enamel are incorporated. We carry out calculations within a framework based on the extended finite element method, and the crack growth and crack path selection are natural outcomes of imposed loading. We show that crack deflection in enamel is controlled by rod decussation. For crack growth in the parazone, the crack path is oriented along the axis of enamel rods, leading to gross crack deflection. The microstructure of inner enamel with intermediate inclination angle enables multiple crack deflections, giving rise to enhanced toughness. For crack growth in the diazone, the transition in orientation of crack deflection occurs as inclination angle increases. The relatively straight crack path emerges in the case of the microstructure of enamel with intermediate inclination angle, leading to weak fracture resistance. It is further found that compared with the diazone, the gross crack deflection in the parazone provides greater contribution to fracture resistance of enamel. The findings of this study provide a good mechanistic understanding of the role of rod decussation in enamel.