Abstract Patients with distant metastasis of head and neck squamous cell carcinoma (HNSCC) often have a poor prognosis. However, early diagnosis of distant metastasis is challenging in clinical practice, and distant metastasis is often only detected in the late stages of tumor metastasis through imaging techniques. In this study, we utilized data from HNSCC patients collected from the TCGA database. Patients were divided into distant metastasis and nonmetastasis groups based on the tumor–node–metastasis (TNM) stage. We analyzed the differentially expressed genes between the two groups (DM/non-M DEGs) and their associated lncRNAs and generated a predictive model based on 23 lncRNAs that were significantly associated with the occurrence of distant metastasis in HNSCC patients. On this basis, we built a nomogram to predict the distant metastasis of HNSCC patients. Moreover, through WGCNA and Cytoscape software analysis of DM/non-M DEGs, we identified the gene most closely related to HNSCC distant metastasis: EIF5A. Our findings were validated using GEO data; EIF5A expression was significantly increased in the tumor tissues of HNSCC patients with distant metastasis. We then predicted miRNAs that can directly bind to EIF5A via the TargetScan and miRWalk websites, intersected them with differentially expressed miRNAs in the two groups from the TCGA cohort, and identified the only overlapping miRNA, miR-424; we predicted the direct binding site of EIF5A and miR-424 via the miRWalk website. Immunohistochemistry further revealed high expression of EIF5A in the primary tumor tissue of HNSCC patients with distant metastasis. These results provide a new perspective for the early diagnosis of distant metastasis in HNSCC patients and the study of the mechanisms underlying HNSCC distant metastasis.
To explore the clinical advantages of 3D-Slicer + 3D printing guide combined with transcranial neuroendoscopic in minimally invasive neurosurgery. By collecting the datum of patients who underwent craniotomy under 3D-Slicer + 3D printing guide plate positioning combined with transcranial neuroendoscopic in our hospital from October 2021 to February 2022, this paper introduces the accurate planning and positioning lesions of patients before operation and the minimally invasive operation of intraoperative neuroendoscopic and analyses clinical data such as lesion size and surgical bone window size. We collected the case datum of 16 patients who underwent craniocerebral surgery with 3D-Slicer + 3D printing guide combined with transcranial neuroendoscopic, including 5 males and 11 females, aged 46-76 years, including 6 brain tumors (3 meningiomas, 1 glioblastoma, 2 lung cancer brain metastases), 2 cavernous hemangioma, 7 hydrocephalus and 1 chronic subdural hematoma. The lesions of the 16 patients were located accurately before operation and the target areas were reached quickly during operation. Postoperative imaging datum confirmed that the lesions was removed fully, and the ventricular end of shunt tube was in good position. The technology of 3D-Slicer + 3D printing guide plate combined with transcranial neuroendoscopic is not difficult, which has many advantages such as inexpensive equipment, simple operation, easy learning, accurate positioning, and minimally invasive surgery. It is considered to be a practical technology that is feasible, reliable, convenient for diagnosis, preoperative planning and minimally invasive surgery. It is suitable for promotion in neurosurgery and other surgical departments of all medical institutions.
Abstract Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.
Backgrounds Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway. Methods Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + Ly294002 (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β. Results HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, Ly294002, suppressed the beneficial effects of HS. Conclusions HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.
Neurogenic pulmonary edema (NPE) is an acute and serious complication after subarachnoid hemorrhage (SAH) with high mortality. The present study aimed to test the therapeutic potential of brilliant blue G (BBG), a selective P2X purinoceptor 7 (P2X7R) antagonist, on NPE in a rat SAH model.SAH was induced by endovascular perforation. 86 Sprague-Dawley rats were randomly divided into sham, vehicle-, or BBG-treatment groups. Mortality, body weight, SAH grading, neurological deficits, NPE clinical symptoms, and pulmonary index were measured at 24 hours following SAH. Western blot, gelatin zymography, lung histopathology, and immunofluorescence staining were performed in the left lung lobe to explore the underlying mechanisms at 24 hours post-surgery.The incidence of clinical symptoms was correlated with pulmonary index. P2X7R and the marker of alveolar type I epithelial cells (the mucin-type glycoprotein T1-α) immunoreactivities were generally co-localized. BBG administration decreased mature interleukin-1β, myeloperoxidase, and matrix metallopeptidase-9 activation, but increased tight junction proteins, such as ZO-1 and occludin, which ameliorated pulmonary edema via anti-inflammation and improved neurological deficits.P2X7R inhibition prevented NPE after SAH by attenuating inflammation. Thus, BBG is a potential therapeutic application for NPE after SAH and warrants further research.
Abstract Past studies revealed the prognosis differed between aneurysmal subarachnoid hemorrhage (aSAH) patients with surgical clipping and endovascular coiling. We retrospectively reviewed aSAH patients in our institution to investigate the effectiveness of grading scores between two groups. In the surgical clipping group (n = 349), VASOGRADE had a favorable performance for predicting delayed cerebral ischemia (DCI) (area under curve (AUC) > 0.750), and had better results than clinical (World Federation of Neurosurgical Societies (WFNS), Hunt & Hess (HH) and radiological scores (modified Fisher Scale (mFS), Subarachnoid Hemorrhage Early Brain Edema Score) ( P < 0.05). Clinical and combined scores (VASOGRADE, HAIR) had favorable performance for predicting poor outcome (AUC > 0.750), and had better results than radiological scores ( P < 0.05). In the coiling group (n = 320), none of the grading scores demonstrated favorable predictive accuracy for DCI (AUC < 0.750). Only WFNS and VASOGRADE had AUC > 0.700, with better performance than mFS ( P < 0.05). The clinical and combined scores showed favorable performance for predicting a poor outcome (AUC > 0.750), and were better than the radiological scores ( P < 0.05). Radiological scores appeared inferior to the clinical and combined scores in clipping and coiling groups. VASOGRADE can be an effective grading score in patients with clipping or coiling for predicting DCI and poor outcome.
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