Innovative recovery of matrix layered double hydroxide from simulated acid mine wastewater for the removal of copper and cadmium from wastewater.

This study innovatively added biochar to optimize regulation in the neutralization process of simulated acid mine drainage (AMD) and recovered a new type of matrix layered double hydroxides (MLDH), which can be used to remove copper (Cu(II)) and cadmium (Cd(II)) from wastewater. A series of batch experiments show that MLDH with strong selective removal ability of Cu(II) and Cd(II) can be successfully obtained by adding biochar (BC) at pH = 5 end in the neutralization process. Kinetic and isotherm modeling studies indicated that the removal of Cu(II) and Cd(II) by the MLDH was a chemical multilayer adsorption process. The removal mechanism of Cu(II) and Cd(II) was further analyzed through related characterization analysis with contribution rate calculation: the removal rates of Cu(II) and Cd(II) by ion exchange were 42.7% and 26%, while that by precipitation were 34.5% and 49.9%, respectively. This study can provide a theoretical reference and experimental basis for the recovery and utilization of valuable by-products in AMD and the treatment of heavy metal wastewater.

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM. PATIENTS AND METHODS: Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150-200 mg/m2, orally, every day (QD) d1-5/4 wk) and anlotinib (10 mg, orally, QD, d1-14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27-68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6-99.3]. The disease control rate was 95.2% (95% CI, 76.2-99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9-9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3-84.6). The median overall survival was 16.9 months (95% CI, 7.8-26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study. CONCLUSIONS: Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.

Anlotinib combined with temozolomide for the treatment of patients with diffuse midline glioma: a case report and literature review.

Background: Diffuse midline glioma with a histone H3-K27M mutation is a brand-new tumor entity according to the 2016 edition of World Health Organization (WHO) classification. As diffuse midline gliomas are aggressive and incurable brain tumors, characterized by high levels of intrinsic and acquired resistance to therapy, as well as conventional treatment can hardly work due to an intact blood-brain barrier, leading to very poor outcomes for patients. Anlotinib is a multitarget tyrosine kinase inhibitor and has been used for the treatment of multiple tumor species, with satisfying outcomes. However, anlotinib has not been reported for the treatment of patients with diffuse midline glioma. Case Description: This is a case report about a 51-year-old man suffering from diffuse midline glioma with a histone H3-K27M mutation. After surgery, the patient underwent chemoradiation treatment and then adjuvant temozolomide (TMZ). After 7 months, the tumor had enlarged with severe peritumor edema and hydrocephalus. Bevacizumab was treated for 3 cycles, and then the treatment was changed to anlotinib combined with TMZ. After 8 months, magnetic resonance imaging (MRI) scans showed that the mass was significantly reduced compared with before targeted therapy. Until the present time, the patient has survived for 20 months. Conclusions: Therapy combining anlotinib with TMZ is potential therapeutic option for the patients with diffuse midline glioma.

Learning global dependencies based on hierarchical full connection for brain tumor segmentation.

BACKGROUND AND OBJECTIVE: Because the appearance, shape and location of brain tumors vary greatly among different patients, brain tumor segmentation (BTS) is extremely challenging. Recently, many studies have used attention mechanisms to solve this problem, which can be roughly divided into two categories: the spatial attention based on convolution (with or without channel attention) and self-attention. Due to the limitation of convolution operations, the spatial attention based on convolution cannot learn global dependencies very well, resulting in poor performance in BTS. A simple improvement idea is to directly substitute it with self-attention, which has an excellent ability to learn global dependencies. Since self-attention is not friendly to GPU memory, this simple substitution will make the new attention mechanism unable to be applied to high-resolution low-level feature maps, which contain considerable geometric information and are also important for improving the performance of attention mechanism in BTS. METHOD: In this paper, we propose a hierarchical fully connected module, named H-FC, to learn global dependencies. H-FC learns local dependencies at different feature map scales through fully connected layers hierarchically, and then combines these local dependencies as approximations of the global dependencies. H-FC requires very little GPU memory and can easily replace spatial attention module based on convolution operation, such as Attention Gate and SAM (in CBAM), to improve the performance of attention mechanisms in BTS. RESULTS: Adequate comparative experiments illustrate that H-FC performs better than Attention Gate and SAM (in CBAM), which lack the ability to learn global dependencies, in BTS, with improvements in most metrics and a larger improvement in Hausdorff Distance. By comparing the amount of calculation and parameters of the model before and after adding H-FC, it is prove that H-FC is light-weight. CONCLUSION: In this paper, we propose a novel H-FC to learn global dependencies. We illustrate the effectiveness of H-FC through experiments on BraTS2020 dataset. We mainly explore the influence of the region size and the number of steps on the performance of H-FC. We also confirm that the global dependencies of low-level feature maps are also important to BTS. We show that H-FC is light-weight through a time and space complexity analysis and the experimental results.

Stereotactic radiosurgery for the treatment of esophageal carcinoma brain metastases.

PURPOSE: The authors evaluated the results of stereotactic radiosurgery (SRS) for the treatment of metastatic brain tumors from esophageal carcinoma. METHODS: We retrospectively analyzed the clinical characteristics and treatment outcomes in 21 patients with metastatic brain tumors from esophageal carcinoma who underwent SRS between July 2011 and February 2019. RESULTS: 21 patients (25 SRS procedures) of a total of 88 tumors underwent Gamma knife SRS. Tumor histology was adenocarcinoma in 6 patients (28.6%) and squamous cell carcinoma in 15 patients (71.4%). The median age was 66 years (range 58-73). Eleven patients (52.4%) presented with multiple metastases (range 2-11), and 10 . (47.6%) with a single metastasis. The median tumor volume was 0.55 cm3 (range 0.004-44.64 cm3). No complications related to radiosurgical treatment were identified. The local tumor control rate in this group was 94.2 %. The median survival time from the diagnosis of esophageal cancer was 22 months and the median survival from SRS was 16 months. Higher Karnofsky Performance Scale (KPS) at the time of procedure was associated with increased survival (p=0.003). After SRS, 4 patients had subsequent SRS (1 for boost therapy, 3 for new metastatic deposits), 1 patient underwent craniotomy due to tumor progression. Of the 19 patients who have died, 17 (89.5%) succumbed to systemic disease progression and 2 (10.5%) had neurologic deaths. CONCLUSION: SRS is an effective and minimally invasive treatment that can prolong survival. Accordingly, SRS could be used as the initial treatment modality, if possible, even in patients with multiple metastases.

Low-Dosage Bevacizumab Treatment: Effect on Radiation Necrosis After Gamma Knife Radiosurgery for Brain Metastases.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKß/NF-κB signaling pathway.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKß/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1ß. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1ß production. Next, we confirmed that LPS-induced MALAT1 activated IKKß/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1ß through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1ß levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

BACKGROUND: Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. PATIENT DESCRIPTION: Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. CONCLUSION: Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis.

OBJECTIVE: This study aimed to explore the mechanism of lncRNA MEG3 on angiogenesis after cerebral infarction (CI). METHODS: The rat brain microvascular endothelial cells (RBMVECs) isolated from rat was used to establish CI model, which were treated with oxygen-glucose deprivation/reoxygenation (OGD/R). The genes mRNA and protein expression levels in RBMVECs were determined by the quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively. The flow cytometry was used to measured cell apoptosis and intracellular reactive oxygen species (ROS) generation. The RBMVECs activities was detected by MTT method. The RNA-immunoprecipitation (RIP) assay was used to detect the interaction between MEG3 and p53, and the relationship between p53 and NOX4 was proved by chromatin co-immunoprecipitation (chip) assay. RESULTS: The results showed that OGD or OGD/R increased MEG3 and NOX4 expression, and there was positive correlation between MEG3 and NOX4 expression in RBMVECs. Next, knockdown of MEG3 indicated that inhibition of MEG3 was conducive to protect RBMVECs against OGD/R-induced apoptosis, with decreased NOX4 and p53 expression, further enhanced pro-angiogenic factors (HIF-1α and VEGF) expression, and reduced intracellular ROS generation. And then the RIP and CHIP assay demonstrated that MEG3 could interacted with p53 and regulated its expression, and p53 exerted significant binding in the promoters for NOX4, suggesting that MEG3 regulated NOX4 expression via p53. At last, knockdown of NOX4 indicated that inhibition of NOX4 protected RBMVECs against OGD/R-induced apoptosis, with increased cell viability and pro-angiogenic factors expression, and reduced ROS generation. CONCLUSION: LncRNA MEG3 was an important regulator in OGD/R induced-RBMVECs apoptosis and the mechanism of MEG3 on angiogenesis after CI was reduced ROS by p53/NOX4 axis.

Downregulation of miR-199b promotes the acute spinal cord injury through IKKß-NF-κB signaling pathway activating microglial cells.

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

Gamma Knife radiosurgery for the treatment of cavernous sinus hemangiomas.

The present retrospective study aimed to analyze the outcome of patients with cavernous sinus hemangioma (CSH) treated with Gamma Knife radiosurgery (GKS). Between August 2011 and April 2014, 7 patients with CSHs underwent GKS. GKS was performed as the sole treatment option in 5 patients, whilst partial resection had been performed previously in 1 patient and biopsy had been performed in 1 patient. The mean volume of the tumors at the time of GKS was 12.5±10.2 cm3 (range, 5.3-33.2 cm3), and the median prescription of peripheral dose was 14.0 Gy (range, 10.0-15.0 Gy). The mean follow-up period was 20 months (range, 6-40 months). At the last follow-up, the lesion volume had decreased in all patients, and all cranial neuropathies observed prior to GKS had improved. There were no radiation-induced neuropathies or complications during the follow-up period. GKS appears to be an effective and safe treatment modality for the management of CSHs.

Successful treatment of multifoci nocardial brain abscesses: a case report and literature review.

Brain nocardiosis is a serious opportunistic infection with high mortality. It exists more common in the immunocompromised hosts than the immunocompetent patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) has been mostly considered as the choice of the medical treatment. Linezolid is also newly found to be effective to avoid the invasive surgery. The authors reported a case of patient with multifoci nocardial brain abscesses who failed with the combination of linezolid and TMP-SMZ alone but recovered with the surgery intervention and sequential antibiotics for 2 years. The patient lived a high quality life without recurrence and complications during the 30 months follow-up.Through the literature review, we recommend earlier stereotactic aspiration for diagnosis, combination with surgery intervention and prolonged anti-infection therapy would improve the prognosis.

Recurrent cerebral amyloid angiopathy-related hemorrhage.

Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in normotensive elder individuals. Surgical treatment for cerebral hematoma due to amyloid angiopathy remains controversial, and some authors emphasized the difficulty of hemostasis during surgery and the risk of recurrent hemorrhage after surgery. A case study of a 68-year-old man with cerebral amyloid angiopathy and recurrent intracerebral hemorrhages is presented.

[Experience of surgical treatment of huge mediastinal tumors].

OBJECTIVE: The diagnosis and surgical treatment of 36 huge mediastinal tumors were summarized in order to evaluate the effect and safety of the operation. METHODS: Thirty-six huge mediastinal tumor patients treated in our department from June 2006 to June 2013 were retrospective analyzed, of whom clinical manifestations, diagnosis, surgical treatment and prognosis were carefully collected. Twenty-three cases were men and 13 were women. The average age was 39.2 years old. The pathology turned out to be benign in 23 cases and malignant in 13 cases. RESULTS: Complete resection was achieved in 34 cases while palliative resection in 2 cases with no perioperative death. Six cases had developed postoperative complications but all recovered after active treatment. Patients who had been diagnosed with benign tumors were all alive after follow-up periods of 6 months to 7 years. Nine malignat tumor patients developed recurrence or metastasis, including seven deaths. CONCLUSION: Surgery played a vital role in the diagnosis and treatment of huge mediastinal tumors. Preoperative diagnosis, accurate surgical approach and careful operation were the key to successful treatment. Benign huge mediastinal tumors had excellent prognosis with surgery.

Meningeal myofibroblastoma in the frontal lobe: A case report.

Myofibroblastoma is a benign tumor composed of spindle cells in clusters and fascicles. To date, only three cases of intracranial myofibroblastoma have been reported. The present study reports the case of a 47-year-old female with meningeal myofibroblastoma. The patient had a history of ovarian cyst resection and presented with paroxysmal mild headaches that had been apparent for 4 years. Magnetic resonance imaging disclosed a well-circumscribed mass in the left frontal lobe. A resection of the mass was performed. Abundant fascicular clusters of spindle- and oval-shaped cells were found by conventional histopathology. Immunohistochemical staining demonstrated that these cells were strongly positive for smooth muscle actin, weakly positive for epithelial membrane antigen and negative for cluster of differentiation (CD)117, CD34, S-100 or desmin, with a Ki-67 index of >10%. These results supported the diagnosis of myofibroblastoma. No recurrence of the mass was found during the 24-month follow-up period. Overall, the patient exhibited a rare type of meningeal neoplasm. Resection of the tumor proved to be successful and no recurrence were found. Histopathological and immunohistochemical staining is crucial to form a diagnosis. To the best of our knowledge, the present study is the first to show the presence of myofibroblastoma in the left frontal lobe.

Bilateral cranial hemophilic pseudotumor.

Hemophilic pseudotumor is a rare but well-known complication of hemophilia manifesting as recurrent hemorrhage and progressive enlargement of hematoma. A patient with severe hemophilia has 1% to 2% chance to develop pseudotumor. The chronic pressure of osseous hemorrhage usually results in bone destruction or resorption. Cranial hemophilic pseudotumors are extremely rare, with only 7 reported cases associated with mild or moderate factor VIII or IX deficiency. A 42-year-old man with a mild factor VIII deficiency developed a pseudotumor of the bilateral skull. Computed tomography and magnetic resonance imaging revealed an extra-axial lesion with bone destruction, and signal changes are consistent with chronic hemorrhage. With adequate factor-deficient replacement therapy, surgical removal was performed. Histologic examination disclosed old blood coagulum. No recurrence was observed in 3 years of follow-up. Cranial hemophilic pseudotumor is extremely rare, and with adequate factor-deficient replacement therapy, surgical management is a safe and effective way for cranial hemophilic pseudotumor treatment.

Association between XRCC3 T241M polymorphism and glioma risk: a meta-analysis.

X-ray repair cross-complementing group 3 (XRCC3) plays a critical role in homologous recombination repair (HRR) accounting for repair of DNA double-strand breaks (DSB). Attention has been drawn upon the association of XRCC3 T241M polymorphism with glioma risk. The present meta-analysis aimed to examine whether XRCC3 T241M polymorphism was associated with glioma risk. Eligible articles were identified for the period up to March 2013. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately derived from fixed effects or random effects models. Eight case-control studies with a total of 3,455 glioma cases and 4,435 controls were included. Overall, no significant association between XRCC3 T241M polymorphism and glioma was found. In subgroup analysis, this polymorphism seemed to be associated with elevated glioma risk in Asians. No publication bias was detected. This meta-analysis suggested that XRCC3 T241M polymorphism did not confer glioma risk.

Gamma knife surgery for brain metastasis from hepatocellular carcinoma.

OBJECTIVES: The authors evaluated the results of Gamma knife surgery (GKS) for the treatment of metastatic brain tumors from hepatocellular carcinoma (HCC). METHODS AND RESULTS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 14 patients with metastatic brain tumors from HCC who underwent GKS. Twelve (85.7%) patients were male. The mean age of the patients was 53±12 years. There were totally 22 brain metastases in 14 patients and 8 patients (57.1%) presented with a single brain lesion. Intracranial hemorrhages occurred in 13 (59.1%) of the 22 lesions. The mean KPS score was 81±14 (range 50-100). Eleven (78.6%) patients were classified as RTOG RPA Class 2. The mean tumor volume was 8.16±8.15 cm(3) (range 0.59-27.0 cm(3)). The mean marginal dose prescribed was 18.7±3.2 Gy (range 10.0-22.0 Gy). The mean number of shots administered was 10±9 (range 1-27). The median overall survival time after GKS was 5.0±0.93 months (95% CI 3.2-6.8). No complications related to the radiosurgical treatment were identified. Multivariate analysis showed that the total volume of brain metastases, the RTOG RPA class and serum AFP level were significantly correlated with patients' survival time. CONCLUSIONS: Although survival was extremely poor in patients with brain metastasis (BM) from HCC, GKS was shown to lead to prolongation of the survival time. Accordingly, GKS can be considered as a valuable treatment option for proper patients with HCC BM.

Multiple intracranial aneurysms followed left atrial myxoma: case report and literature review.

Cerebral aneurysms follows atrial myxoma is a rare neurological complication. We report a patient with multiple cerebral aneurysms three years after resection of left atrial myxoma and further review the literature. The characteristics of these aneurysms are indefinite and variable. They can occur prior or post the resection of cardiac myxoma. "Metastasize and Infiltrate" theory may be the key mechanism in the formation of these aneurysms. Magnetic resonance imaging (MRI), computed tomography (CT) and angiography are useful in the diagnosis while digital subtraction angiography (DSA) is the best choice. There are no definite guidelines for therapy of these aneurysms. Resection of the cardiac myxomas, chemotherapy, radiotherapy, coil embolization and surgical treatment could be helpful.