Causal Role of Immune Cells in Chronic Obstructive Pulmonary Disease: A Two-Sample Mendelian Randomization Study.

Accumulating evidence has highlighted the importance of immune cells in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the understanding of the causal association between immunity and COPD remains incomplete due to the existence of confounding variables. In this study, we employed a two-sample Mendelian randomization (MR) analysis, utilizing the genome-wide association study database, to investigate the causal association between 731 immune-cell signatures and the susceptibility to COPD from a host genetics perspective. To validate the consistency of our findings, we utilized MR analysis results of lung function data to assess directional concordance. Furthermore, we employed MR-Egger intercept tests, Cochrane's Q test, MR-PRESSO global test, and "leave-one-out" sensitivity analyses to evaluate the presence of horizontal pleiotropy, heterogeneity, and stability, respectively. Inverse variance weighting results showed that seven immune phenotypes were associated with the risk of COPD. Analyses of heterogeneity and pleiotropy analysis confirmed the reliability of MR results. These results highlight the interactions between the immune system and the lungs. Further investigations into their mechanisms are necessary and will contribute to inform targeted prevention strategies for COPD.

Identification and immunological characteristics of anoikis-associated molecular clusters in lung adenocarcinoma.

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

Thyroid tuberculosis and cold abscess after infection with COVID-19: A case report.

There is mounting evidence that coronavirus disease 2019 (COVID-19) can cause immune dysregulation. The consequence of this immune dysregulation may contribute to susceptibility to tuberculosis (TB). Thyroid gland involvement by TB is extremely uncommon and typically the result of disseminated infection. It can be hard to diagnose because there are no identifiable symptoms. We present the case of a Chinese patient who had a fever again after COVID-19 infection that was finally diagnosed as thyroid tuberculosis with a cold abscess. Clinicians should maintain a high index of suspicion for high-risk patients from endemic regions with medical comorbidities, such as immunocompromised disease and malnutrition.

Axl as a potential therapeutic target for adamantinomatous craniopharyngiomas: Based on single nucleus RNA-seq and spatial transcriptome profiling.

Craniopharyngiomas (CPs), particularly Adamantinomatous Craniopharyngiomas (ACPs), often exhibit a heightened risk of postoperative recurrence and severe complications of the endocrine and hypothalamic function. The primary objective of this study is to investigate potential novel targeted therapies within the microenvironment of ACP tumors. Cancer-Associated Fibroblasts (CAFs) were identified in the craniopharyngioma microenvironment, notably in regions characterized by cholesterol clefts, wet keratin, ghost cells, and fibrous stroma in ACPs. CAFs, alongside ghost cells, basaloid-like epithelium cells and calcifications, were found to secrete PROS1 and GAS6, which can activate AXL receptors on the surface of tumor epithelium cells, promoting immune suppression and tumor progression in ACPs. Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

Circ_0070934 promotes MGAT3 expression and inhibits epithelial-mesenchymal transition in bronchial epithelial cells by sponging miR-199a-5p.

BACKGROUND: Circular RNA (circRNA) has the potential to serve as a crucial regulator in the progression of bronchial asthma. The objective of this investigation was to elucidate the functional dynamics of the circ_0070934/miR-199a-5p/Mannoside acetylglucosaminyltransferase 3 (MGAT3) axis in the development of asthma. METHODS: Circ_0070934, miR-199a-5p and MGAT3 in peripheral venous blood of 38 asthmatic patients and 43 healthy controls were detected by qRT-PCR, and the expression of MGAT3 protein was examined by ELISA. The GSE148000 dataset was analyzed for differences in MGAT3. The BEAS-2B cells were transfected with circ_0070934 plasmid and small interfering RNA, miR-199a-5p mimics and inhibitors. The apoptosis level was detected by flow cytometry and MGAT3 was detected by qRT-PCR and Western blot. The expression of E-cadherin, N-cadherin, Vimentin was examined by Western blot. Interleukin-4 (IL-4) and IL-13 were used to co-stimulate BEAS-2B cells as an asthmatic airway epithelial cell model. BEAS-2B cells exposed to type 2 cytokines (IL-4 and IL-13) were treated with circ_0070934 plasmid, and the expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The binding relationships were verified using dual-luciferase reporter assay and miRNA pull-down assay. RESULTS: The expression of circ_0070934 and MGAT3 in peripheral venous blood of asthmatic patients was down-regulated, and the expression of miR-199a-5p was up-regulated. And the expression of MGAT3 was reduced in sputum of asthma patients. Down-regulating the expression of circ_0070934 could promote apoptosis of BEAS-2B cells and increase epithelial-mesenchymal transition (EMT), and this effect can be partially reversed by down-regulating miR-199a-5p. Circ_0070934 could inhibit the process of epithelial mesenchymal transition induced by IL-4 and IL-13 in BEAS-2B cells. In addition, miR-199a-5p could respectively bind to circ_0070934 and MGAT3. CONCLUSION: The findings of this study indicate that circ_0070934 may function as a competitive endogenous RNA (ceRNA) of miR-199a-5p, thereby modulating the expression of MGAT3 and impacting the process of EMT in bronchial epithelial cells. These results contribute to the establishment of a theoretical framework for advancing the prevention and treatment strategies for asthma.

IDH1 mutation predicts seizure occurrence and prognosis in lower-grade glioma adults.

Epileptic seizures are frequently the first symptom in glioma patients. However, the causal relationship between glioma and epilepsy is not yet fully understood, as it cannot be explained solely by tumor mass effect or peritumoral factors. In this study, we retrospectively enrolled 320 patients with grade 2-4 glioma who received treatment between January 2019 and July 2022, and explored the biomarkers of seizure occurrence and seizure outcome prediction using univariate and multivariate logistic regression analyses. Our results showed that IDH1 R132H mutation was an independent risk factor for seizure occurrence in lower-grade glioma (LGG) patients (OR = 4.915, 95%CI = 1.713 - 14.103, P = 0.003). Additionally, IDH1 R132H mutation predicted higher seizure-free ratios in LGG patients with intact ATRX expression (OR = 6.793, 95%CI = 1.217 - 37.923, P = 0.029) one year after diagnosis. Therefore, our findings suggest that IDH1 mutation can predict seizure occurrence and control in LGG patients, providing further insights into the relationship between glioma and epilepsy.

The Evolution of Anterior Transpetrosal Approach for the Treatment of Petroclival Meningiomas: A Single-Center 128-Case Experience.

BACKGROUND: The profound understanding of anterior transpetrosal approach (ATPA) is increasingly used to treat petroclival meningiomas (PCMs). We introduce the evolution of ATPA and the outcomes of PCMs treatment. METHODS: Between January 2013 and December 2019, 128 patients with PCMs underwent surgery. According to tumor extension, we classified the 128 patients into 5 types (I-V), introduced key technologies of ATPA into different types for the first time, and achieved a supreme surgical technology. Clinical data, radiological findings, surgical treatments, complications, and patient outcomes were retrospectively analyzed. RESULTS: A total of 22 (17.2%), 44 (34.4%), 25 (19.5%), 29 (22.7%), and 8 (6.3%) patients had type I, II, III, IV, and V disease, respectively. Tumors were gross totally removed (Simpson I and II) in 100 patients (78.1%), subtotally removed (Simpson III) in 20 patients (15.6%), and partially removed (Simpson IV) in 8 patients (6.3%). The progression or recurrence rates were 5% (5/100) for gross totally removed, 22.3% (6/20) for subtotally removed, and 62.5% (5/8; 1 died) for partially removed. According to the Karnofsky Performance Scale and Glasgow Outcome Scale, 108 patients had good recovery (84.4%, 108/128) and 115 were independent (89.8%, 115/128) at the end of follow-up. CONCLUSIONS: Because some key technologies were used in ATPA, the application of ATPA was extended, and greater tumor resection and nerve function protection could be achieved in the treatment of PCMs.

Exploring the association of glioma tumor residuals from incongruent [18F]FET PET/MR imaging with tumor proliferation using a multiparametric MRI radiomics nomogram.

PURPOSE: The study aimed to using multiparametric MRI radiomics to predict glioma tumor residuals (TRFET over MR) derived from incongruent [18F]fluoroethyl-L-tyrosine ([18F]FET) PET/MR imaging. METHODS: One hundred ten patients with gliomas who underwent [18F]FET PET/MR scanning were retrospectively analyzed. The TRFET over MR was identified by the discrepancy-PET that the extent of resection (EOR) based on MRI subtracted the biological tumor volume on PET images. The MRI parameters and radiomics features were extracted based on EOR and selected by the least absolute shrinkage and selection operator to construct radiomics score (Rad-score). The correlation network analysis of all features was analyzed by Spearman's correlation tests. The methods for evaluating the clinical usefulness consisted of the receiver operating characteristic curve, the calibration curve, and decision curve analysis. RESULTS: The Rad-score of the patients with the TRFET over MR was significantly higher than those with the non TRFET over MR (p < 0.001). The Rad-score was significantly correlated with the discrepancy-PET (r = 0.72, p < 0.001), Ki-67 level (r = 0.76, p < 0.001), and epidermal growth factor receptor (EGFR) of gliomas (r = 0.75, p < 0.001), respectively. Moreover, there was a difference of the correlation network analysis between the TRPET over MR group and non TRFET over MR group. The nomogram combing Rad-score and clinical features had the greatest performance in predicting TRFET over MR (AUC = 0.90/0.87, training/testing). There was a significant difference in prognosis (median OS, 17 m vs. 43 m) between patients with TRFET over MR and non TRFET over MR based on nomogram prediction (p < 0.001). CONCLUSION: The nomogram based on MRI radiomics would predict gliomas tumor residuals caused by the absence of 18F-PET PET examination and adjust EOR to improve prognosis.

Application of metagenomic next-generation sequencing (mNGS) in diagnosing pneumonia of adults.

INTRODUCTION: Accurate identification of pathogens that cause pulmonary infections is essential for effective treatment and hastening recovery in adults diagnosed with pneumonia. At present, despite metagenomic next-generation sequencing (mNGS) technology has been widely used in clinical practice for pathogen identification, the clinical significance and necessity of detecting pathogen in bronchoalveolar lavage fluid (BALF) for pneumonia-stricken adults remain ambiguous. METHODOLOGY: In this study, 80 patients suffering from pulmonary infection were enrolled, who were admitted to the Affiliated Changzhou Second People's Hospital of Nanjing Medical University between January 2020 and September 2022. The diagnostic performances of mNGS and conventional methods (CM) were systematically analyzed based on BALF samples, and we further investigated the influence of mNGS and CM in diagnosis modification and treatment. RESULTS: We found a significantly higher positive rate for the mNGS method in contrast to CM. Bacteria were the most common pathogens, and Streptococcus pneumoniae was the most commonly identified pathogen. Candida albicans and Epstein-Barr virus were the most frequently identified fungus and virus. Atypical pathogens such as Mycobacterium tuberculosis, virus Nontuberculous mycobacteria, and Chlamydia psittaci were also identified. A total of 77 patients were identified with mixed infections by mNGS. As the disease progressed and recurrent antibiotic treatment persisted, significant dynamic changes in the clinical manifestation from the BALF samples could be found by mNGS. CONCLUSIONS: This study underscores the efficacy of mNGS in detecting pathogens in BALF samples from patients suffering pulmonary infections. Compared with the CM, mNGS significantly enhanced the positive diagnosis ratio, particularly in diagnosing Mycobacterium tuberculosis, atypical pathogens, and viral or fungal infections.

Anatomic Study of Petrous Bone and Its Surrounding Structures in the Extended Anterior Transpetrosal Approach.

Extended anterior transpetrosal approach (ATPA) includes drilling the petrous bone to achieve maximal exposure of the petroclival region. Injuring of surrounding neurovascular structures, such as the internal carotid artery (ICA), during the procedure may result in severe complications. In this study, we aimed to use computer topographic images to provide comprehensive anatomic information on the petrous bone and surrounding structures to help surgeons during the extended ATPA. Computer topographic angiography images of 110 individuals were reviewed, and measurements were performed on coronal, sagittal, and axial planes following multiplanar reformation. The petrous apex and sagittal midline were used to locate the anterior, middle, and posterior parts of the petrous bone and petrosal segment of the ICA during the ATPA. The thicknesses of the petrous bone were 3.28±0.71, 3.53±0.88, and 7.02±1.11 mm at the petrous apex, trigeminal impression, and internal opening of internal auditory canal (IAC) positions, respectively. The distances between the petrous apex to the trigeminal impression, internal opening of the IAC, auris interna, and labyrinth were 7.39±1.62, 15.95±2.48, 17.39±2.39, and 29.00±3.18 mm, respectively. Furthermore, the petrosal segment of the ICA was located at the above landmarks on the petrous bone. Our findings provide anatomic information on the petrous bone and surrounding structures during the extended ATPA procedure based on fixed anatomic landmarks so as to achieve maximal exposure and reduce the number of complications.

A2M Serves as Promising Biomarker for Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) often associated with cigarette smoking. However, increasing evidence suggests that non-smoking COPD is much higher than previously thought. This study aims to identify a nonsmoking COPD biomarker and examined its value in diagnosis and prediction of acute exacerbation. Methods: A total of 35 stable COPD patients, 70 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients and 35 healthy control subjects were included. Plasma α 2 macroglobulin (A2M) and matrix metalloproteinase-9 (MMP-9) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method on all participants. Their association with clinical characteristics and lung function parameters were determined by regression analysis. Receiver operating characteristic (ROC) curve was used to determine the diagnostic sensitivity and specificity. Correlation coefficients were evaluated using Pearson's correlation. Results: Plasma A2M concentration was decreased and MMP-9 concentration, MMP-9/A2M ratio were elevated in stable COPD patients compared with control groups. And MMP-9 expression was significantly higher in AECOPD patients. A2M level was increased in AECOPD patients with infection compared with those without. In addition, there was no statistical difference in A2M levels between smokers and nonsmokers COPD or healthy control subjects. Furthermore, A2M, MMP-9 and MMP-9/A2M were correlated with forced expiratory volume in one second (FEV1)%, FEV1/ forced vital capacity (FVC), CAT and mMRC score in COPD patients, but had no correlation with fraction of exhaled nitric oxide (FeNO) and concentration of alveolar nitric oxide (CaNO). Conclusion: A2M is altered in peripheral blood of COPD patients and correlated with severity and infection. Moreover, there was no significant correlation between the change in A2M and smoking, FeNO and CaNO, suggesting A2M may reflect the overall rather than local inflammation in COPD patients and serve as a potential biomarker for nonsmoking COPD patients.

LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter.

Long non-coding RNAs (lncRNAs) have been reported as key regulators of chronic obstructive pulmonary disease (COPD). This study aimed to figure out the regulatory mechanism as well as the effects of lncRNA00612 (LINC00612) in lipopolysaccharide (LPS)-induced inflammation and apoptosis in BEAS-2B cells. LINC00612 and its co-expressed gene alpha-2-macroglobulin (A2M) were strikingly downregulated in the peripheral venous blood of COPD patients. Overexpressed LINC00612 enhances BEAS-2B cells against apoptosis and inflammatory reactions mediated by LPS, however, an A2M knockdown can attenuate the degree of the enhancement. Bioinformatics analysis revealed putative binding sites between LINC00612, signal transducer and activator of transcription 3 (STAT3) and the A2M promoter, while RNA antisense purification and Chromatin immunoprecipitation were performed to confirm the prediction. Knockdown of LINC00612 impaired the binding of p-STAT3 to the promoter of A2M, which meant that LINC00612 was critical for the binding of STAT3 with the A2M promoter. Therefore, it can be concluded that LINC00612 ameliorates LPS-induced cell apoptosis and inflammation via recruiting STAT3 to bind to A2M. This conclusion will serve as a theoretical foundation for the treatment of COPD.

Microsurgery for vestibular schwannoma: analysis of short-term clinical outcome.

BACKGROUND: Total removal of the vestibular schwannoma when preserving the function of the facial nerve is difficult. The objective of the current study was to investigate the short-term clinical outcome of vestibular schwannoma removal via retro-sigmoid approach. METHODS: One-hundred consecutive patients diagnosed with vestibular schwannoma were surgically treated between December 2018 and August 2019 in Xuanwu Hospital, Capital Medical University. The clinical classification, surgical position, gross total removal rate, the anatomical and functional preservation rates of facial nerve, and the postoperative complications were retrospectively analyzed. RESULTS: All 100 patients including 34 males and 66 females were operated on via retro-sigmoid approach. According to Koos vestibular schwannoma grading system, 18 cases were grade 2, 34 cases were grade 3, and 48 cases were grade 4. According to Hannover vestibular schwannoma grading system, 5 cases were T2, 6 cases were T3a, 8 cases were T3b, 30 cases were T4a, and 51 cases were T4b. Seventy-three surgeries were performed under lateral position, and 27 cases were operated under semi-sitting position. The gross total removal rate was 90.0%; the anatomic reservation rate of the facial nerve was 96.0%. According to the House-Brackman system, the facial nerve function was grades 1-2 in 78.0% cases, grade 3 in 7.0% cases, and grades 4-5 in 15% cases. For patients with effective hearing before operation, the hearing reservation rate was 19.0%. Two patients (2.0%) developed intracranial hematoma after operation. CONCLUSION: Most vestibular schwannoma could be completely removed with good postoperative facial nerve function. If total removal of tumor is difficult, we should give priority to the functional preservation of the nerve function.

MicroRNA-21 promotes epithelial-mesenchymal transition and migration of human bronchial epithelial cells by targeting poly (ADP-ribose) polymerase-1 and activating PI3K/AKT signaling.

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

The effects of different surgical positions (semi-sitting and lateral position) on the surgical outcomes of large vestibular schwannoma: study protocol for a randomized controlled trial.

BACKGROUND: There is an ongoing discussion about the advantages and disadvantages of different surgical positions (semi-sitting and lateral position) for vestibular schwannoma surgery. Each position has its advantages, disadvantages, challenges, and risk profiles. The objectives of this study are to compare the effects of different surgical positions (semi-sitting and lateral position) on the outcomes of large vestibular schwannoma, primarily including effectiveness and safety. METHODS: In this single-centre, open, randomized controlled trial, we will recruit a total of 116 participants according to the inclusion and exclusion criteria who will be randomized to an experimental group or control group. Patients will undergo operations in semi-sitting and lateral positions. The primary endpoint will be the percentage of gross total resection. The secondary endpoints will include the facial nerve function, hearing preservation, surgical position placement time, time of operation (skin-to-skin surgical time), hospital stay, total hospitalization fee, and complications. The follow-up period will be at least 12 months, during which time patients will be evaluated both clinically and radiologically. DISCUSSION: This issue is still debated after 30 years since the first large comparative study was published in 1989, so the study will be useful. Therefore, more high-quality studies are required to compare clinical outcomes, complications, and other factors associated with these two positions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027550 . Registered on 17 November 2019.

Surgical resection of petroclival meningiomas of the cerebellopontine angle and/or diaphragma sellae extension via an extended intradural anterior transpetrous approach.

OBJECTIVE: This study aimed to describe the extended intradural anterior transpetrous approach (ATPA) and its usefulness for the surgical resection of petroclival meningiomas (PCMs) of the cerebellopontine angle (CPA) and/or diaphragma sellae (DS) extension. METHODS: Between January 2017 and December 2019, a total of 22 patients with PCMs extending to the CPA/or DS underwent surgery via extended intradural ATPA by the senior author (Xr.X.). We retrospectively analysed the clinical data, radiological findings, surgical treatment, complications, and outcomes of patients and discussed the operative technique. RESULTS: In 22 patients, the tumours were gross totally removed (Simpson I and II) in 18 patients (81.8%), subtotally (Simpson III) in 3 patients (13.6%), and partially (Simpson IV) in 1 patient (4.5%). One patient died 48 days after the operation, and no recurrence was found in 21 patients during a median follow-up of 26 months. Postoperative complications included in abducens nerve palsy in 12 patients with recovery in 10 patients, facial numbness in 4 patients with recovery in 3 patients, and hemiplegia and oculomotor nerve palsy in 1 patient each with recovery in all patients. The postoperative MRI showed temporal lobe oedema but no clinical symptoms in 3 patients. CONCLUSION: Extended intradural ATPA is an alternative approach for PCMs of the CPA and/or DS extension. The single approach can expose both the sellar region and the posterolateral area of the IAC, which is advantageous for extended intradural ATPA.

MiR-21 modulates proliferation and apoptosis of human airway smooth muscle cells by regulating autophagy via PARP-1/AMPK/mTOR signalling pathway.

Superfluous human airway smooth muscle (HASM) cell proliferation is an important pathological feature of airway remodelling in asthma. This study aimed to determine whether miR-21 is involved in the regulation of HASM cell survival. Overexpressed miR-21 inhibited HASM cell apoptosis and autophagy and promoted proliferation, whereas a miR-21 inhibitor exerted the opposite effects (P < 0.05). Overexpressed poly (ADP-ribose) polymerase-1 (PARP-1) promoted apoptosis and inhibited proliferation of HASM cells (P < 0.05). Dual-luciferase assays confirmed that miR-21 directly targeted poly (ADP-ribose) polymerase-1 (PARP-1) mRNA (P < 0.05). Silencing PARP-1 based on miR-21 downregulation mimicked the role of 3-methyladenine (3-MA), an autophagy inhibitor (P < 0.05). Overexpressed PARP-1 reversed the effects of miR-21 on HASM cells, somewhat dependently on PARP-1-induced enhanced autophagy, which we elucidated by 3-MA block (P < 0.05). MicroRNA-21 mimics reduced AMPK and increased mTOR signalling by downregulating PARP-1, and a miR-21 inhibitor exerted the opposite effects (P < 0.05). Collectively, miR-21 inhibitor could upregulate PARP-1 in HASM cells to promote autophagy and thus inhibit proliferation and promote apoptosis that might be mediated by the AMPK/mTOR signalling pathway.

Drilling off the Petrosal Apex and Opening the Upper Wall of Meckel's Cave Are the Key Elements of Good Outcomes in the Treatment of Trigeminal Neuralgia Secondary to Petrous Apex Meningioma.

OBJECTIVE: The surgical management of trigeminal neuralgia (TN) caused by petrous apex meningioma (PAM) is still a challenge because of the lesion's deep location and the surrounding complex structures. The authors describe the intradural anterior transpetrosal approach (ATPA) and its effect on the treatment of TN secondary to PAM. METHODS: A retrospective analysis of 15 patients with TN secondary to PAM who underwent surgery via the intradural ATPA was conducted. The key techniques, which included drilling off the petrosal apex (PA) and opening the upper wall of Meckel's cave (MC), are described in detail. RESULTS: Total removal of the tumor and complete pain relief (Barrow Neurological Institute I) were achieved in all 15 patients without significant morbidity. Five patients developed new facial numbness postoperatively, which disappeared within three months after surgery. The postoperative magnetic resonance imaging showed temporal lobe swelling in three patients, but no clinical symptoms. One patient had cerebrospinal fluid leakage and was managed with bed rest and temporary lumbar drainage. One patient had an intracranial infection and was treated with antibiotics. By the last follow up, no patients had pain relapse or/and tumor recurrence. It is worth noting that the vascular compression at the root of the trigeminal nerve was found in one patient during the operation. CONCLUSION: Our experience suggests that drilling off the PA and opening the upper wall of the MC are key elements for a good outcome of the treatment of TN secondary to PAM. The intradural ATPA has the advantages for both tumor resection and pain relief.

Anatomical Study of Ethmoidal Foramina and Optic Canal in Endoscopic Trans-Nasal Approach to Anterior Skull Base.

BACKGROUND: Surgery to anterior skull base is challenging since complex structures are involved. Injury of olfactory fila and optic nerve may result in postoperative complications. In our study, the authors aim to use computer topographic image to provide a comprehensive anatomical information of anterior skull base and set up a new classification of optic canal (OC) in ethmoid sinus by the degree of bony defect, so as to help surgeons in endoscopic transnasal approach to anterior skull base. METHOD: Computer topographic angiography images of 112 individuals were reviewed, the measurement was performed on coronal, sagittal, and axis planes after the multiplanar reformation. Nostril and mid-sagittal lines were used to locate the anterior, middle, and posterior part of ethmoidal foramina and orbital opening of OC. Further, the authors classified OC in ethmoidal sinus into 4 types by the degree of the bony defect. RESULT: Distance between nostril to anterior, middle, and posterior part of ethmoidal foramina and OC are 6.23 ± 0.21, 6.62 ±â€Š0.26, 7.29 ±â€Š0.25, and 7.76 ±â€Š0.41 mm, respectively. Angle between line from nostril to ethmoidal foramina and horizontal plane are 47.50°â€Š±â€Š1.03°, 41.67°â€Š±â€Š1.33°, 37.20°â€Š±â€Š1.34°, respectively. For the 4 types of OC, the percentage is 15.6%, 11.6%, 31.3%, and 41.5%, respectively. CONCLUSIONS: Our findings provide anatomical information of ethmoidal foramina and OC during endoscopic transnasal approach to anterior skull base, on the basis of some fixed anatomical landmarks. So as to enhance the surgical safety of this procedure and aid in the choice of the appropriate endoscopic equipment for the procedure.

Glioma Imaging by O-(2-18F-Fluoroethyl)-L-Tyrosine PET and Diffusion-Weighted MRI and Correlation With Molecular Phenotypes, Validated by PET/MR-Guided Biopsies.

Gliomas exhibit high intra-tumoral histological and molecular heterogeneity. Introducing stereotactic biopsy, we achieved a superior molecular analysis of glioma using O-(2-18F-fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI). Patients underwent simultaneous DWI and FET-PET scans. Correlations between biopsy-derived tumor tissue values, such as the tumor-to-background ratio (TBR) and apparent diffusion coefficient (ADC)/exponential ADC (eADC) and histopathological diagnoses and those between relevant genes and TBR and ADC values were determined. Tumor regions with human telomerase reverse transcriptase (hTERT) mutation had higher TBR and lower ADC values. Tumor protein P53 mutation correlated with lower TBR and higher ADC values. α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX) correlated with higher ADC values. 1p/19q codeletion and epidermal growth factor receptor (EGFR) mutations correlated with lower ADC values. Isocitrate dehydrogenase 1 (IDH1) mutations correlated with higher TBRmean values. No correlation existed between TBRmax/TBRmean/ADC/eADC values and phosphatase and tensin homolog mutations (PTEN) or O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Furthermore, TBR/ADC combination had a higher diagnostic accuracy than each single imaging method for high-grade and IDH1-, hTERT-, and EGFR-mutated gliomas. This is the first study establishing the accurate diagnostic criteria for glioma based on FET-PET and DWI.