Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Bifidobacterium animalis subsp. lactis Probio-M8 alleviates abnormal behavior and regulates gut microbiota in a mouse model suffering from autism.

Probiotics can effectively improve a variety of neurological diseases, but there is little research on autism, and the specific mechanism is unclear. In this study, shotgun metagenomics analysis was used to investigate the preventive and therapeutic effects of Bifidobacterium animalis subsp. lactis Probio-M8 on autism. The results showed that Probio-M8 treatment significantly alleviated valproate (VPA)-induced autism in mice, with autistic symptoms characterized by increased stereotyped behaviors such as grooming, reduced learning ability, and decreased desire to socialize. Further studies have found that Probio-M8 can alleviate autism by optimizing gut microbiota diversity and regulating metabolic levels. Probio-M8 regulates gut microbiota structure by increasing the abundance of beneficial bacteria such as Bifidobacterium globosum and Akkermansia muciniphila. In addition, Probio-M8 regulates metabolic activity by increasing levels of choline, which corrects CAZy disorders. In conclusion, Probio-M8 is therapeutic in the VPA-induced autism mouse model by regulating the gut microbiome and metabolic levels.IMPORTANCEIndividuals with autism often exhibit symptoms of social invariance, obsessive-compulsive tendencies, and repetitive behaviors. However, early intervention and treatment can be effective in improving social skills and mitigating autism symptoms, including behaviors related to irritability. Although taking medication for autism may lead to side effects such as weight gain, probiotics can be an ideal intervention for alleviating these symptoms. In this study, we investigated the effects of Probio-M8 intervention on the behavior of autistic mice using an open-field test, a three-chamber sociability test, and a novel object recognition test. Metagenomic analysis revealed differences in gut microbiota diversity among groups, predicted changes in metabolite levels, and functionally annotated CAZy. Additionally, we analyzed serum neurotransmitter levels and found that probiotics were beneficial in mitigating neurotransmitter imbalances in mice with autism.

Axial Convex-Shaped Hematoma was Associated with Poor Curative Effect of Surgical Treatment for Traumatic Posterior Fossa Epidural Hematoma in Children.

BACKGROUND: Posterior fossa epidural hematoma (PFEDH) is rare which accounts for just 4-12.9% of all EDH cases. Since its frequently subtle and nonspecific clinical presentation, CT scan has great importance for early diagnosis and treatment of PFEDH. However, indications for surgery depending on the findings of CT image are still controversial. METHODS: We retrospectively analyzed 40 pediatric cases of PFEDH. Their baseline characteristic, clinical presentation, imaging findings and outcomes were collected and analyzed. The ellipsoid volume equation X × Y × Z/2 was used to measure the hematoma volume. The Glasgow Outcome Scale (GOS) was used to assess the neurologic functional outcome. RESULTS: A total of 40 pediatric PFEH patients were included with 8 patients having poor outcome and 32 patients having a relatively good prognosis. GCS score showed a significant difference between good and poor outcome groups (p < 0.001). Y value on CT image was significantly bigger in poor outcome group than good outcome group (p < 0.01). Similar results were got in X/Z value (p < 0.05) and Y/Z value (p < 0.01) which reflected the shape of hematoma. A predictive model with Y + X/Z showed the largest area under the ROC curve with a sensitivity of 75.0% and specificity of 93.7%. CONCLUSIONS: GCS score at admission was closely related to the prognosis of the pediatric patients with PFEDH. The morphometry of PFEDH has a crucial role in judging the prognosis. Axial convex-shaped hematoma was associated with poor curative effect of surgical treatment.

Spontaneous Hyperventilation Is Common in Patients with Spontaneous Cerebellar Hemorrhage, and Its Severity Is Associated with Outcome.

BACKGROUND: The spontaneous hyperventilation (SHV) accompanying spontaneous cerebellar hemorrhage has yet to attract a sufficient amount of attention. This study aimed to analyze the incidence of SHV in spontaneous cerebellar hemorrhage patients and its risk factors as well as its association with the outcome. METHODS: We retrospectively reviewed the medical records of all spontaneous cerebellar hemorrhage patients who underwent surgical treatment at Tongji Hospital from July 2018 to December 2020. Arterial blood gas (ABG) test results and clinical characteristics, including demographics, comorbidities, imaging features, laboratory tests, and therapy choices, were collected. The Glasgow Outcome Scale was used to assess the outcome at two weeks and six months after admission. RESULTS: A total of 147 patients were included, and of these patients 44.9% had spontaneous hyperventilation. Hypertension (OR, 3.175; CI, 1.332-7.569), usage of sedation drugs (OR, 3.693; CI, 1.0563-8.724), and hypernatremia (OR, 2.803; CI, 1.070-7.340) seemed to positively correlate to SHV occurrence. Hematoma removal had an inverse association with SHV (OR, 0.176; CI, 0.068-0.460). Patients with poor and good outcomes had significant differences in pH, PaCO2, and HCO3- values, and the severity of SHV was associated with the PaCO2 level. CONCLUSIONS: Spontaneous hyperventilation is common in patients with spontaneous cerebellar hemorrhage, and its severity is associated with the outcome.

Extra-Pseudocapsular Transsphenoidal Surgery for Microprolactinoma in Women.

A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II.

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota.

Liver metastasis is the major cause of death in colorectal cancer (CRC) patients. Nevertheless, the underlying mechanisms remain unknown. Gut microbiota intricately affect the initiation and progression of CRC by instigating immune response through the secretion of pro-inflammatory cytokines. In this study, we investigated the contribution of Fusobacterium nucleatum (F.nucleatum) to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When F. nucleatum was orally administered to mice, CRC liver metastasis was evidently exaggerated and accompanied by noticeable deleterious effects on body weight, cecum weight, and overall survival time. Further evaluation of the immune response and cytokine profiles revealed a substantial increase in the levels of pro-inflammatory cytokines such as IL6, IL12, IL9, IL17A, CXCL1, MCP-1, TNF-α, and IFN-γ in the plasma of mice treated with F. nucleatum as compared to that in the untreated control mice. Besides, hepatic immune response was also modulated by recruitment of myeloid-derived suppressor cells, reduction in the infiltration of natural killer (NK) and T helper-17 (Th17) cells, as well as increase in regulatory T cell accumulation in the liver. Additionally, sustained F. nucleatum exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as Enterococcus and Escherichia/Shigella was evidently elevated post F. nucleatum treatment. Thus, our findings suggest that F. nucleatum might be an important factor involved in promoting CRC liver metastasis by triggering of liver immunity through the regulation of gut microbiota structure and composition.

BAY61­3606 attenuates neuroinflammation and neurofunctional damage by inhibiting microglial Mincle/Syk signaling response after traumatic brain injury.

Neuroinflammatory processes mediated by microglial activation and subsequent neuronal damage are the hallmarks of traumatic brain injury (TBI). As an inhibitor of the macrophage­inducible C­type lectin (Mincle)/spleen tyrosine kinase (Syk) signaling pathway, BAY61­3606 (BAY) has previously demonstrated anti­inflammatory effects on some pathological processes, such as acute kidney injury, by suppressing the inflammatory macrophage response. In the present study, the potential effects of BAY on microglial phenotype and neuroinflammation after TBI were investigated. BAY (3 mg/kg) was first administered into mice by intraperitoneal injection after TBI induction in vivo and microglia were also treated with BAY (2 µM) in vitro. The levels of inflammatory factors in microglia were assessed using reverse transcription­quantitative PCR and ELISA. Cortical neuron, myelin sheath, astrocyte and cerebrovascular endothelial cell markers were detected using immunofluorescence. The levels of components of the Mincle/Syk/NF­κB signaling pathway [Mincle, phosphorylated (p)­Syk and NF­κB], in addition to proteins associated with inflammation (ASC, caspase­1, TNF­α, IL­1ß and IL­6), apoptosis (Bax and Bim) and tight junctions (Claudin­5), were measured via western blotting and ELISA. Migration and chemotaxis of microglial cells were evaluated using Transwell and agarose spot assays. Neurological functions of the mice were determined in vivo using the modified neurological severity scoring system and a Morris water maze. The results of the present study revealed that the expression levels of proteins in the Mincle/Syk/NF­κB signaling pathway (including Mincle, p­Syk and p­NF­κB), inflammatory cytokines (TNF­α, IL­1ß and IL­6), proteins involved in inflammation (ASC and caspase­1), apoptotic markers (Bax and Bim) and the tight junction protein Claudin­5 were significantly altered post­TBI. BAY treatment reversed these effects in both the cerebral cortex extract­induced cell model and the controlled cortical impact mouse model. BAY was also revealed to suppress activation of the microglial proinflammatory phenotype and microglial migration. In addition, BAY effectively attenuated TBI­induced neurovascular unit damage and neurological function deficits. Taken together, these findings provided evidence that BAY may inhibit the Mincle/Syk/NF­κB signaling pathway in microglia; this in turn could attenuate microglia­mediated neuroinflammation and improve neurological deficits following TBI.

Abnormal hubs in global network as potential neuroimaging marker in generalized anxiety disorder at rest.

Background: Mounting studies have reported altered neuroimaging features in generalized anxiety disorder (GAD). However, little is known about changes in degree centrality (DC) as an effective diagnostic method for GAD. Therefore, we aimed to explore the abnormality of DCs and whether these features can be used in the diagnosis of GAD. Methods: Forty-one GAD patients and 45 healthy controls participated in the study. Imaging data were analyzed using DC and receiver operating characteristic (ROC) methods. Results: Compared with the control group, increased DC values in bilateral cerebellum and left middle temporal gyrus (MTG), and decreased DC values in the left medial frontal orbital gyrus (MFOG), fusiform gyrus (FG), and bilateral posterior cingulate cortex (PCC). The ROC results showed that the DC value of the left MTG could serve as a potential neuroimaging marker with high sensitivity and specificity for distinguishing patients from healthy controls. Conclusion: Our findings demonstrate that abnormal DCs in the left MTG can be observed in GAD, highlighting the importance of GAD pathophysiology.

Calcium Sensing Receptor Inhibits Growth of Human Lung Adenocarcinoma Possibly via the GSK3ß/Cyclin D1 Pathway.

The effect of calcium sensing receptor (CaSR) on tumor cell proliferation has been studied in several human cancers, and great discrepancies were found in different tumors. However, the role of CaSR in lung adenocarcinomas (LUADs) is not clear. Therefore, we investigated the function of CaSR on regulating the growth of human LUAD and its possible mechanism. The expression of CaSR protein and its relationship with pathological parameters were examined in paraffin sections from 51 LUAD patients, by immunohistochemistry. The results showed that CasR expression was negatively correlated with the Ki-67 index as well as the grade of malignancy in LUAD. Further, CaSR demonstrated an in vitro inhibitory effect on the proliferation of human LUAD A549 cells by regulating CaSR activity with agonist cinacalcet, antagonist NPS2143, or shRNA-CaSR transfection. Tumor xenograft models also verified the in vivo proliferation-inhibiting role of CaSR by subcutaneous injecting A549 cells into nude mice with or without changes of CaSR activity. Molecularly, Western blotting showed that CaSR positively regulated the activity of glycogen synthase kinase 3ß (GSK3ß), followed by the downregulation of Cyclin D1. We used the dominant negative mutant and the constitutively active mutant plasmid of GSK3ß to alter GSK3ß activity. Our functional experiments showed that the proliferation-inhibition of CaSR was suppressed by the inactivation of GSK3ß and enhanced by the activation of GSK3ß. These results suggested that CaSR played a proliferation-inhibiting role in LUAD, at least partially by regulating the GSK3ß/Cyclin D1 pathway.

Clinical Features and Long-Term Outcome of Primary Intracranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors: 14 Cases From a Single Institution.

OBJECTIVE: Primary intracranial Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare, and only a few studies have reported >4 cases of this disease. The purpose of this study was to explore the clinical features, treatment, and outcome of primary intracranial ES/pPNETs. METHODS: The clinical data of 14 patients who had been surgically treated from February 2003 to November 2017 and in whom immunohistochemical staining results had confirmed the diagnosis of primary intracranial ES/pPNETs were retrospectively analyzed. Kaplan-Meier survival analysis was used to estimate the survival rate and the median survival time (MST). RESULTS: Gross total resection (GTR) was achieved in 7 cases, and subtotal resection was performed in 7 cases. During follow-up, 10 (71.4%) patients had local recurrence and 3 (21.4%) patients had distant metastasis. The overall 1-, 2-, and 5-year survival rates were 78.6%, 47.6%, and 19.0%, respectively. Kaplan-Meier survival analysis showed that postoperative radiotherapy was a significant prognostic factor for longer MST (P = 0.034). GTR and radiotherapy with or without adjuvant chemotherapy yielded the highest 2-year survival rate (100%). Three patients who underwent GTR, radiotherapy, and chemotherapy had the highest 2-year survival rates (100%) and the longest MST (48 months). CONCLUSIONS: Primary intracranial ES/pPNETs have an aggressive clinical course, with a high tendency for local recurrence and distant metastasis. Radiotherapy plays a significant role in improving the survival of patients. GTR combined with radiotherapy and chemotherapy may be the most beneficial treatment modality.

Inhibition of element sulfur and calcium oxide on the formation of PCDD/Fs during co-combustion experiment of municipal solid waste.

In order to investigate the effect of element sulfur (S) and calcium oxide (CaO) on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) during municipal solid waste (MSW) combustion process, MSW was incinerated with S or CaO in a laboratory-scale incinerator and heated in the flow of N2-O2 gas mixture at 800°C. It can be concluded that 25% of oxygen concentration is the best condition for the following inhibitors experiments through a series of oxygen variation experiments. With adding S and CaO in MSW incineration, seventeen kinds of 2, 3, 7, 8-substituted PCDD/Fs congeners were analysed with high-resolution chromatography and mass spectrometry method. The results show that S and CaO obviously suppress PCDD/Fs formation. Comparing inhibition effect of S with that of CaO, the inhibitory effect of S on HpCDD/Fs formation was most remarkable, of around 88.1%; while CaO could inhibit the formation of HxCDD/Fs more evidently than sulfur and the inhibition was 85.1%. PCDFs were the main components of dioxins produced from MSW incineration in the experiments, and S and CaO were unable to change the dominating generation route of PCDD/Fs. S and CaO could mainly consume chlorine sources or weaken the chlorination in the PCDD/Fs formation process to restrain the PCDFs formation, but the inhibition mechanisms were different. In addition, some dioxins or precursors might be decomposed by S and CaO.

Cerebral Venous Sinus Thrombosis Following Second Transsphenoidal Surgery: Report of a Rare Complication and Review of Literature.

BACKGROUND: Cushing disease, induced by a pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma, is associated with high risk of stroke. At present, transsphenoidal surgery remains the first line of therapy. Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with variable presentations. There are no previous reports of its occurrence in patients with Cushing disease following transsphenoidal surgery. CASE DESCRIPTION: We report a patient with Cushing disease who sustained CVST several days after a second transsphenoidal surgery. With adequate care and treatment, along with timely diagnosis, the patient made a near-complete recovery with only minor sequelae. CONCLUSIONS: In view of the poor outcome of untreated CVST, symptoms such as severe headache, nausea and vomiting, and cerebrospinal fluid leakage after transsphenoidal surgery could be of valuable assistance in early diagnosis, allowing immediate medical intervention with consequent improved prognosis.

Pretreatment with intravenous amiodarone improves the efficacy of ibutilide treatment on cardioversion rate and maintenance time of sinus rhythm in patients with persistent atrial fibrillation.

The aim of the present study was to assess the efficacy and safety of the pharmacological conversion of persistent atrial fibrillation (AF) using amiodarone or/and ibutilide. Seventy-nine consecutive patients (48 males and 31 females; mean age, 64.6±11.2 years; range, 40-80 years) with non-valvular chronic AF lasting >7 days (range, 7-97 days) that were admitted to hospital for elective pharmacological cardioversion were randomly assigned to receive treatment with intravenous ibutilide (1 mg plus an additional 1 mg if required; n=39) or intravenous amiodarone (300 mg) plus intravenous ibutilide (1 mg; n=40). Success rates of cardioversion were 51.3% (20/39 patients) for ibutilide alone and 71.8% (28/39 patients) for amiodarone + ibutilide (P<0.05). A comparable increase in the QTc interval was observed in the two groups. It was observed that the co-administration of amiodarone and ibutilide was safer than ibutilide alone with regard to the risk of ventricular arrhythmia. Forty-eight patients of successful cardioversion were personally contacted for follow-up. The result indicated that the sinus rhythm maintenance time of the amiodarone + ibutilide group (4.36±2.44 months) was significantly higher than that of the ibutilide group (2.34±1.75 months; P<0.01). In conclusion, pretreatment with intravenous amiodarone + ibutilide for pharmacological cardioversion of persistent AF is considered to be more effective and safer than treatment with ibutilide alone.