Combination of MRI-based prediction and CRISPR/Cas12a-based detection for IDH genotyping in glioma.

Early identification of IDH mutation status is of great significance in clinical therapeutic decision-making in the treatment of glioma. We demonstrate a technological solution to improve the accuracy and reliability of IDH mutation detection by combining MRI-based prediction and a CRISPR-based automatic integrated gene detection system (AIGS). A model was constructed to predict the IDH mutation status using whole slices in MRI scans with a Transformer neural network, and the predictive model achieved accuracies of 0.93, 0.87, and 0.84 using the internal and two external test sets, respectively. Additionally, CRISPR/Cas12a-based AIGS was constructed, and AIGS achieved 100% diagnostic accuracy in terms of IDH detection using both frozen tissue and FFPE samples in one hour. Moreover, the feature attribution of our predictive model was assessed using GradCAM, and the highest correlations with tumor cell percentages in enhancing and IDH-wildtype gliomas were found to have GradCAM importance (0.65 and 0.5, respectively). This MRI-based predictive model could, therefore, guide biopsy for tumor-enriched, which would ensure the veracity and stability of the rapid detection results. The combination of our predictive model and AIGS improved the early determination of IDH mutation status in glioma patients. This combined system of MRI-based prediction and CRISPR/Cas12a-based detection can be used to guide biopsy, resection, and radiation for glioma patients to improve patient outcomes.

The Association Between Thymidylate Synthase Gene Polymorphisms and the Risk of Ischemic Stroke in Chinese Han Population.

Family history of hypertension, smoking, diabetes and alcohol consumption and atherosclerotic plaque were identified as common risk factors in IS. We aimed at investigating the relationship between Thymidylate Synthase (TS) gene polymorphisms and ischemic stroke (IS).This case-control research selected and genotyped three single nucleotide polymorphisms (SNPs)of TS( rs699517, rs2790, and rs151264360) with Sanger sequencing in Chinese Han population. We also adopted logistic regression analysis in genetic models for calculating odds ratios and 95% confidence intervals. Genotype-Tissue Expression(GTEx) database analyzed the tissue-specific expression and TS polymorphisms. The ischemic stroke patients showed higher low-density lipoprotein cholesterol and total homocysteine (tHcy). It was found that patients with the TT genotype of rs699517 and GG genotype of rs2790 had larger degrees of tHcy than those with CC + CT genotypes and AA + AG genotypes, respectively. The genotype distribution of the three SNPs did not deviate from Hardy-Weinberg equilibrium (HWE). Haplotype analysis showed that T-G-del was the major haplotype in IS, and C-A-ins was the major haplotype in controls. GTEx database indicated that the rs699517 and rs2790 increased the expression of TS in healthy human and associated with TS expression level in a single tissue. In conclusion: This study has shown that TS rs699517 and rs2790 were significantly related to ischemic stroke patients.

Exosomal OIP5-AS1 attenuates cerebral ischemia-reperfusion injury by negatively regulating TXNIP protein stability and inhibiting neuronal pyroptosis.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) can cause neuronal apoptosis and lead to irreversible brain injury. Numerous lncRNAs have been reported to play important roles in CIRI, but it is unclear whether these lncRNAs can function through exosomes. METHODS: In this study, we utilized the middle cerebral artery occlusion/reperfusion (MCAO/R) animal model and the oxygen-glucose deprivation/ reoxygenation (OGD/R) cell model. RNA sequencing was performed to screen for differentially expressed lncRNAs in M2 microglia-derived exosomes (M2-Exos). RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation and ubiquitination assays were used to explore the molecular mechanism of OIP5-AS1 in alleviating CIRI. RESULTS: M2-Exos could alleviate nerve injury and pyroptosis after CIRI in vitro and in vivo. OIP5-AS1 was found to be significantly up-regulated in M2-Exos and down-regulated in OGD/R neurons, MCAO/R mice and ischemic stroke patients. In MCAO/R mice, OIP5-AS1 could reduce cerebral infarct size, cerebral edema and mNSS scores, and inhibit the expression levels of pyroptosis-related proteins in brain tissue. TXNIP was confirmed to be a reliable binding protein of OIP5-AS1. OIP5-AS1 overexpression significantly attenuated MCAO/R-induced upregulation of TXNIP at the protein level, but not at the mRNA level. OIP5-AS1 promoted the TXNIP degradation process and increased the ubiquitination of TXNIP. ITCH could bind to TXNIP. ITCH overexpression or knockdown did not alter the mRNA level of TXNIP, but negatively regulated TXNIP expression at the protein level. ITCH accelerated the degradation and ubiquitination of TXNIP, which could be attenuated by OIP5-AS1 knockdown. OIP5-AS1 could improve neuronal damage and inhibit neuronal pyroptosis through TXNIP. CONCLUSIONS: M2-Exo-derived OIP5-AS1 can induce TXNIP ubiquitination and degradation by recruiting ITCH, negatively regulate TXNIP protein stability, inhibit neuronal pyroptosis, and attenuate CIRI.

Clinical efficacy of minimally invasive puncture and drainage versus trepanation and drainage for chronic subdural hematoma: Systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the clinical efficacy of minimally invasive puncture and drainage (MIPD) versus trepanation and drainage in the treatment of chronic subdural hematoma (CSDH). METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched for studies on the treatment of CSDH by MIPD and trepanation and drainage. By reading the title, abstract and full text, and screening according to the inclusion and exclusion criteria, the qualified articles were confirmed. Subsequently, the literature quality was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions, and the data of the research subjects and the primary outcome measures were extracted for meta-analysis with RevMan 5.1 software. RESULTS: Ten articles were included, with a total of 1000 patients. According to the meta-analysis, the 2 groups showed no statistical difference in CSDH recurrence rate (P > .05). The operation time, intraoperative blood loss, and incidence of postoperative adverse reactions were lower and the cure rate was higher in the MIPD group compared with trepanation and drainage group (all P < .05). By drawing the funnel plot of the outcome measures with heterogeneity, it can be seen that the distribution on both sides of the funnel was basically symmetrical, suggesting a low deviation possibility of the analysis results and reliable reference significance of our findings. CONCLUSION: Compared with trepanation and drainage, MIPD has better clinical effects and higher safety in treating CSDH and can effectively reduce surgery-induced damage, which is worth popularizing in clinical practice.

Rare incidence of a diffuse brain metastatic carcinoma: A case report.

Brain metastases generally present in the parenchyma of the brain. In the current report, a very rare case of brain metastasis, which simultaneously invaded the subgaleal region, the skull, and the dural and cavernous sinuses is presented. The patient, a 54-year-old female, complained of a progressive headache and exhibited the symptoms of intracranial hypertension. Coronal contrast-enhanced T1-weighted magnetic resonance imaging (MRI) showed high intensity signals in the subgaleal tissue of the left frontoparietal area, as well as in the dural and the cavernous sinuses. The patient was initially diagnosed with an intracranial infection, however, the administered treatment was ineffective. The patient subsequently underwent a biopsy and the pathological diagnosis was determined as a metastatic adenocarcinoma; a primary tumor was not identified during the examinations. Surgical removal of certain metastases and a decompressive craniectomy were performed to relieve the intracranial hypertension. However, the prognosis was unsatisfactory. The patient's neurological condition progressively worsened and an axial computed tomography scan with a bone window demonstrated a bulging growth in the brain tissue. The patient succumbed after one month due to the widespread metastasis. Thus, this case presents the unusual clinical development of this type of metastatic adenocarcinoma. In addition, due to the intracranial hypertension, the unusual sites of the high intensity signals in the MRI and the lack of a primary tumor, the patient was misdiagnosed with an intracranial infection. Furthermore, this case highlights the necessity for conducting a biopsy as soon as possible and demonstrates the poor prognosis associated with this type of patient.

[Application of high-field intraoperative magnetic resonance imaging in stereotactic aspiration and drainage of hypertensive hematomas].

OBJECTIVE: To explore the application values of high-field intraoperative magnetic resonance imaging (MRI) in stereotactic aspiration and drainage of hypertensive hematomas. METHODS: During a period of August 2011 to January 2012, 11 patients with hypertensive hemorrhage were examined preoperatively by conventional MRI and diffusion tensor imaging (DTI) with 1.5T intraoperative MRI system (Signa HDi, GE, USA) at Tianjin Medical University General Hospital. The anatomic relationship of corticospinal tract (CST) and hematoma was used for the operative planning with the neuronavigation planning workstation (iPlan Cranial 3.0 software, BrainLab, Germany) for 3D reconstruction. During stereotactic surgery, intraoperative MRI scan was performed. According to the clearance rate of hematomas, the operators decided to finish the operation or update the operative planning to continue hematoma removal. All patients were reexamined by conventional MRI and DTI at Week 3 postoperation. Then comparative analysis was performed for the preoperative and postoperative integrity of CST. RESULTS: No death or severe complications occurred. All patients showed improvement of motor function and the postoperative integrity of CST. CONCLUSION: The intracranial condition may be monitored effectively by intraoperative MRI throughout surgery so as to increase the rate of hematoma removal and reduce the postoperative complications.

MR imaging of the cisternal segment of the posterior group of cranial nerves: neurovascular relationships and abnormal changes.

OBJECTIVE: To evaluate the detailed anatomic features, neurovascular relationships of the cisternal segment of the posterior group of cranial nerves (PGCN: IX, X, XI, XII); to evaluate the utility of magnetic resonance (MR) in demonstrating the PGCN with disorders caused by abnormal compression related to artery or tumor. METHODS: A total of 59 volunteers, 12 patients with abnormal symptom in the PGCN underwent three-dimensional (3D) Fourier transformation constructive interference in steady-state (CISS) MR imaging, and 22 of these volunteers and 12 patients also underwent MR angiography in which a time-of-flight (TOF) sequence was used to further distinguish the PGCN from the adjacent blood vessels. Anatomical features, neurovascular relationships of the PGCN in 59 volunteers and abnormal changes in 12 patients caused by neurovascular compression or tumor were observed from multi-planar reconstruction (MPR) images, cryomicrotome section and 3D-CISS MR imaging of cranial cadaver were used to testify the PGCN displayed in 59 volunteers. RESULTS: 3D-CISS MR imaging depicted the proximal cisternal segment of the cranial nerves complex (CN IX, X, XI) at the oblique axial, sagittal planes in 100% (118/118), 99% (117/118) of 118 sides; CNXII in the oblique axial, sagittal planes in 90% (106/118), 91% (107/118) of 118 sides. At the sagittal planes, the CN IX, X, XI were found parallel to each other in the cisternal segment in 45.2% (53/117) of 117 sides, gathering into a bundle of nerves complex before entering the jugular foramen (JF) in 54.7% (64/117) of 117 sides. VAs were blood vessels more often identified, they were found to be in contact with the PGCN in 28.0% (33/118) of 118 sides, and not in contact in 72.0% (85/118) of 118 sides. 3D-CISS MR imaging of volunteers revealed the similar result corresponding to cryomicrotome section and 3D-CISS MR imaging of cranial cadaver. Twelve patients with abnormal changes in the PGCN were all displayed well, among them 8 were pressed by arteries, 1 by arachnoid cyst, and 3 caused by tumors. CONCLUSION: Use of 3D-CISS sequence enables accurate identification of the cisternal segment of the PGCN, neurovascular relationships and abnormal changes caused by neurovascular compression or tumor.

The superiority of 3D-CISS sequence in displaying the cisternal segment of facial, vestibulocochlear nerves and their abnormal changes.

OBJECTIVE: To select the best imaging method for clinical otologic patients through evaluating 3D constructive interference of steady state (CISS) image quality in visualizing the facial, vestibulocochlear nerves (CN:VII-VIII) and their abnormal changes. METHODS: The CN:VII-VIII as well as inner ear structures in 48 volunteers were examined using 3D-CISS and 3D turbo spin echo (TSE) sequences respectively, and displayed to the full at the reformatted and maximum intensity projection (MIP) images. The nerve identification and image quality were graded for the CN:VII-VIII as well as inner ear structures. Statistical analysis was performed using the Wilcoxin test, p<0.05 was considered significant. In addition, 8 patients with abnormality in facial or vestibulocochlear nerves were also examined using 3D-CISS sequence. RESULTS: The identification rates for the cisternal segment of facial, vestibulocochlear nerves and corresponding membranous labyrinth were 100%. Abnormal changes of the facial or vestibulocochlear nerves were clearly shown in 8 patients, among them 1 was caused by bilateral acoustic neurinoma, 1 by cholesteatoma at cerebellopontine angle, 1 by arachnoid cyst, 1 by neurovascular adhesion, 4 by neurovascular compression. CONCLUSION: With 3D-CISS sequence the fine structure of the CN:VII-VIII and corresponding membranous labyrinth can be clearly demonstrated; lesions at the site of cerebellopontine angle can also be found easily.

[Diagnosis of solid-pseudopapillary tumor of the pancreas and the value of post-processing in the surgery by spiral CT].

OBJECTIVE: To study the CT manifestations of the solid-pseudopapillary tumor of the pancreas (SPTP) and to explore the value of post-processing in the surgery. METHODS: Clinical and CT features of 14 patients with SPTP proved pathologically were retrospectively analyzed. RESULTS: (1) 13 tumors were composed of different proportions of solid and cystic parts and 1 tumor was composed of solid part only. The solid portions demonstrated slight enhancement in the arterial phase and marked enhancement in the portal venous phase on post-contrast CT. The cystic portions appeared hypo-attenuation on both pre- and post-contrast CT images. Tumors were encapsulated and the capsule enhanced markedly with well-defined margins on post-contrast images. (2) Dilatation of the common bile duct or pancreatic duct wasn't seen in all of the cases and 1 case with the right adrenal ganglioneuroma. (3) 5 tumors located in the head of the pancreas, 3 of which with the superior mesenteric vein compression and displacement, in 2 cases the vessels were partially encapsulated by tumor. 6 tumors located in the tail of the pancreas, 3 of them with splenic hilum compression and multiple splenic vein tortuosity and dilatation, the veins drained into superior mesenteric vein anteriorly and posteriorly of the tumor. Splenic vein compression and posterior displacement occurred in 2 cases. In one case, there was no clear margin between the tumor and the splenic hilum. CONCLUSION: The SPTP has characteristic CT findings and correct diagnosis could be made by combining clinical features. The relationship of the lesions and surrounding structures could be revealed by the post-processing and was helpful for the operation.