The Ang-(1-7)/MasR axis ameliorates neuroinflammation in hypothermic traumatic brain injury in mice by modulating phenotypic transformation of microglia.

The Ang-(1-7)/MasR axis is critically involved in treating several diseases; For example, Ang-(1-7) improves inflammatory response and neurological function after traumatic brain injury and inhibits post-inflammatory hypothermia. However, its function in traumatic brain injury (TBI) combined with seawater immersion hypothermia remains unclear. Here, we used a mice model of hypothermic TBI and a BV2 cell model of hypothermic inflammation to investigate whether the Ang-(1-7)/MasR axis is involved in ameliorating hypothermic TBI. Quantitative reverse transcription PCR, western blotting assay, and immunofluorescence assay were performed to confirm microglia polarization and cytokine regulation. Hematoxylin-eosin staining, Nissl staining, and immunohistochemical assay were conducted to assess the extent of hypothermic TBI-induced damage and the ameliorative effect of Ang-(1-7) in mice. An open field experiment and neurological function scoring with two approaches were used to assess the degree of recovery and prognosis in mice. After hypothermic TBI establishment in BV2 cells, the Ang-(1-7)/MasR axis induced phenotypic transformation of microglia from M1 to M2, inhibited IL-6 and IL-1ß release, and upregulated IL-4 and IL-10 levels. After hypothermic TBI development in mice, intraperitoneally administered Ang-(1-7) attenuated histological damage and promoted neurological recovery. These findings suggest that hypothermia exacerbates TBI-induced damage and that the Ang-(1-7)/MasR axis can ameliorate hypothermic TBI and directly affect prognosis.

Adenomyosis Accompanied by Multiple Hemorrhagic Cerebral Infarction: A Case Report.

This study aims to present a case of uterine adenomyosis accompanied by multiple hemorrhagic cerebral infarctions (CIs), summarize therapeutic experiences based on the literature review, and improve the clinical diagnosis and treatment of multiple hemorrhagic CIs. This paper describes a 46-year-old female with a four-year history of uterine adenomyosis complicated by multiple hemorrhagic CIs. During treatment, elevated levels of D-dimer, CA-125, and severe anemia were observed. Following internal medicine treatment targeting uterine adenomyosis and hemorrhagic CIs, the cerebral hemorrhage gradually resolved. Women presenting with multiple CIs, particularly hemorrhagic ones, should be evaluated for the presence of gynecological diseases. Treating gynecological conditions may aid in the management of multiple CIs.

TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway.

Purpose: The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1ß, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion: The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.

Identification of cholesterol metabolism-related subtypes in nonfunctioning pituitary neuroendocrine tumors and analysis of immune infiltration.

OBJECTIVE: This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs. METHODS: First, a retrospective analysis of single-center clinical data was performed. Second, the immune cell infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism-related genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed. RESULTS: The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol (P = 0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found three immune cells between invasive and noninvasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. The chi-square test revealed that the two subgroups had statistically significance in the invasive and noninvasive samples (P = 0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand-receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison. CONCLUSION: By clinical data and bioinformatics analysis, cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.

Causes and risk factors of an unplanned second craniotomy in patients with traumatic brain injury.

BACKGROUND: The purpose of this retrospective study was to evaluate the causes and risk factors of an unplanned second craniotomy in patients with traumatic brain injury (TBI). METHODS: A total of 219 patients with TBI who underwent initial unilateral intracranial supratentorial surgery between January 2016 to November 2021 were included. We evaluated the causes of an unplanned second craniotomy in 40 patients, and analyzed the risk factors for a contralateral second craniotomy in 21 patients using a multivariate logistic regression analysis. RESULTS: The most common cause for an unplanned second craniotomy was delayed or enlarged hematoma in the non-operation area (26/40; 65%), followed by recurrent hematoma in the operation area (8/40; 20%), ipsilateral massive cerebral infarction (3/40; 7.5%), diffuse brain swelling (2/40; 5%) and enlarged cerebral contusion (1/40; 2.5%). Multivariate logistic regression analysis showed that a contralateral craniocerebral injury feature (CCIF) (OR = 13.175), defined on preoperative computerized tomography scanning, was independent risk factor for a contralateral second craniotomy. CONCLUSIONS: An unplanned second craniotomy in patients with TBI was mainly related to delayed or enlarged hematoma. An increased risk of a contralateral second craniotomy occurs in patients with CCIF.

Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.

Objective: COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods: A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results: A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P < 0.001), and 0.22 (P < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions: Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.

Complex torcular dural arteriovenous fistula leading to cortical venous reflux-induced severe varix and subsequent bilateral cerebral hemispheric hemorrhage: a case report.

Background and importance: Dural arteriovenous fistulas (dAVFs) with cortical venous reflux (CVR) are associated with a higher incidence of intracranial hemorrhage (ICH). We report a rare case of a complex torcular dAVF with severe cortical veins (CV) varix leading to extensive bilateral cerebral hemorrhages. This discovery suggests a potential new subtype of dAVF. The case underscores the necessity of a comprehensive understanding of hemodynamic changes in dAVFs and the importance of considering venous compensatory capacity in treatment. This case challenges existing classifications and treatment strategies for dAVFs, highlighting the need for further research and discussion within the neurosurgical community. Clinical presentation: A 56-year-old male was admitted to the hospital presenting with dizziness, fatigue, and numbness. Brain CT scans revealed extensive bilateral cerebral hemorrhages. Digital subtraction angiography (DSA) identified a complex torcular dAVF. No cerebral sinus venous thrombosis was detected, but a venous variation in the left transverse sinus was observed. Preoperative DSA demonstrated the patient's well-developed venous compensatory ability. Subsequently, the patient underwent transarterial embolization. The patient made a good recovery. Follow-up DSA and MR angiography at 3 months and 1 year post-treatment showed no recurrence. Conclusion: DAVFs are rare lesions, prone to ICH, particularly when CVR is involved. We report a rare case of CVR with severe varix leading to hemorrhagic lesions in both cerebral hemispheres. Our aim is to alert neurosurgical colleagues worldwide to this potential new subtype and to evaluate treatment options, in order to assist those who may encounter such cases in the future.

A Convolutional Neural Network Model for Detecting Sellar Floor Destruction of Pituitary Adenoma on Magnetic Resonance Imaging Scans.

Objective: Convolutional neural network (CNN) is designed for image classification and recognition with a multi-layer neural network. This study aimed to accurately assess sellar floor invasion (SFI) of pituitary adenoma (PA) using CNN. Methods: A total of 1413 coronal and sagittal magnetic resonance images were collected from 695 patients with PAs. The enrolled images were divided into the invasive group (n = 530) and the non-invasive group (n = 883) according to the surgical observation of SFI. Before model training, 100 images were randomly selected for the external testing set. The remaining 1313 cases were randomly divided into the training and validation sets at a ratio of 80:20 for model training. Finally, the testing set was imported to evaluate the model performance. Results: A CNN model with a 10-layer structure (6-layer convolution and 4-layer fully connected neural network) was constructed. After 1000 epoch of training, the model achieved high accuracy in identifying SFI (97.0 and 94.6% in the training and testing sets, respectively). The testing set presented excellent performance, with a model prediction accuracy of 96%, a sensitivity of 0.964, a specificity of 0.958, and an area under the receptor operator curve (AUC-ROC) value of 0.98. Four images in the testing set were misdiagnosed. Three images were misread with SFI (one with conchal type sphenoid sinus), and one image with a relatively intact sellar floor was not identified with SFI. Conclusion: This study highlights the potential of the CNN model for the efficient assessment of PA invasion.

Expression Profiling of Transcriptome and Its Associated Disease Risk in Yang Deficiency Constitution of Healthy Subjects.

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of "constitution-disease correlation" in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n = 20) and balanced constitution (n = 8) (aged 18-28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of "constitution-disease correlation."