Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma.

The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand-receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.

Metabolites of intestinal fora can be used as diagnostic and progressive markers for mild cognitive impairment.

Purpose: The aim of the work was to analyze the metabolites of the intestinal microbiota from the patients with mild cognitive impairment (MCI) and progressive MCI due to Alzheimer's disease (AD). Method: Two cohorts were established. The first one included 87 subjects with 30 healthy controls (NC), 22 patients with MCI due to AD, and 35 patients with AD. The second cohort included 87 patients with MCI due to AD, who were followed up for 2 years and finally were divided into progressive MCI due to AD group (P-G) and unprogressive MCI due to AD group (U-G) according their cognitive levels. Fecal samples were collected to all patients at the baseline time point. Differential metabolites were subjected to pathway analysis by MetaboAnalyst. Results: In the first cohort, we found 21 different metabolites among the three groups (AD, MCI, and NC). In the second cohort, we identified 19 differential metabolites between the P-G and U-G groups. By machine learning analysis, we found that seven characteristic metabolites [Erythrodiol, alpha-Curcumene, Synephrine, o-Hydroxylaminobenzoate, 3-Amino-4-hydroxybenzoic acid, 2-Deoxystreptamine, and 9(S] were of characteristic significance for the diagnosis of MCI due to AD, and six metabolites (Indolelactate, Indole-3-acetaldehyde, L-Proline, Perillyl, Mesaconate, and Sphingosine) were the characteristic metabolites of early warning for the progression of MCI due to AD. D-Glucuronic acid was negatively correlated with Apolipoprotein E4 (APOE4). Perillyl alcohol was negatively correlated with all of the five biomarkers [P-tau181, Neurofilament light chain (NF-light), Aß1-42, Aß1-40, and glial fibrillary acidic protein (GFAP)], but Indoleacetaldehyde was positively correlated with three biomarkers (P-tau181, Aß1-42, and GFAP). Three characteristic metabolites (3-Amino-4-hydroxybenzoate, 2-Deoxystreptamine, and p-Synephrine) were positively correlated with Aß1-42. 2-Deoxystreptamine, 9(S)-HPOT, and Indoleacetaldehyde were positively correlated with GFAP. L-Proline and Indoleacetaldehyde were positively correlated with NF-light. Conclusion: Specific metabolites of intestinal fora can be used as diagnostic and progressive markers for MCI.

Effect of power ultrasound on crystallization characteristics of magnesium ammonium phosphate.

Magnesium ammonium phosphate (MAP) crystallization could be utilized for the recovery of phosphorus from wastewater. However, the effectiveness of the recovery is largely determined by the crystallization process, which is very hard to be directly observed. As a result, a specific ultrasonic device was designed to investigate the crystallization characteristics of MAP under various ultrasonic conditions. The results demonstrated that the metastable zone width (MZW) narrowed along with the rising of the ultrasonic power. Similarly, for the 6mM MAP solution, with the ultrasonic power gradually enhanced from 0W to 400W, the induction time was shortened from 340s to 38s. Meanwhile, the crystallization rate was accelerated till the power reached 350W, and then remained a constant value. It can be observed from the scanning electron microscopy (SEM), the MAP crystal became bigger in size as well as the crystal size distribution (CSD) became broad and uneven, with the increase of ultrasonic power. The results indicate that the crystallization process enhanced by power ultrasound could be used as an effective method to eliminate and recover the phosphorus from wastewater.

Acute paraplegia following embolization of spinal dural arteriovenous fistula.

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.

[Myelin associated inhibitors and regeneration of optic nerve].

The failure of axonal regeneration after optic nerve injury in mammals is closely related to nonpermissive microenvironment in central nervous system as well as to the low regenerative ability of retinal ganglion cells. Myelin associated inhibitors produced by oligodendrocytes are major elements of this nonpermissive microenvironment. Three major inhibitors, Nogo, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein, have been identified, which lead to signal inhibition through the same receptor complex. Blocking the inhibitors and their receptors or changing the intrinsic state of the neuron to overcome the inhibition may promote retinal ganglion cell axonal regeneration after optic nerve injury, which bring a hope to solve the problem of repair of injured optic nerve.

[Establishment of animal model of chronic optic nerve injury and pathological changes thereof: experiment with cats].

OBJECTIVE: To establish an animal model of chronic optic nerve injury which is suitable for experimental research. METHODS: Dil, a tracer, was injected through the bone windows into the brain of 48 cats so as to mark the retinal ganglion cells (RGCs). Two weeks later the 48 cats were randomly divided into 6 equal groups. The normal group did not receive any other treatment. Other 8 cats underwent sham operation. Imitating the clinical pterional approach, a balloon was implanted into the place under the optic nerve and chiasm in the other 32 cats, then the volume of the balloons were increased by injecting contrast agent at different times to cause the optic nerve and chiasm compressed chronically for 1, 2, 4, or 6 weeks. Flash-visual evoked potential (F-VEP) was measured before operation and at the corresponding observation times in different groups. By the end of the experiment the cats were killed with the specimens of retina and optic nerve taken out to undergo light microscopy and electron microscopy to observe the pathological changes. Eight eyes were taken out from each group to calculate the number of RCGs 1, 2, 4, and 8 weeks after operation respectively. RESULTS: Microscopy showed retina showed profound morphological changes 8 weeks after compression; Demyelination of optic nerve began to occur 2 weeks after compression and progressed later. Axonal degeneration was found 4 week after compression and became more significant 8 weeks later. Under electron microscopy, pathological changes of retina was found 4 weeks and more prominent 8 weeks after compression; Slight demyelination and disorganized of cytoskeleton in the optic nerve were shown 2 weeks after compression, and became more profound later; Myelin regeneration was found 8 weeks after compression. The number of RGCs was reduced significantly by 37% (293/465) since 8 weeks after compression. F-VEP recording showed an extension of latency and depression of amplitude 4 weeks after compression, and the changes were more significant 8 weeks later. CONCLUSION: An animal model of chronic optic nerve injury by compression has been established which is stable and well repeatable. The pathological changes of compressed optic nerve are aggravated gradually as the compression lasts and the volume increases. Degeneration of RGCs occurs secondarily and obviously later than the axonal degeneration.

Standard large trauma craniotomy for severe traumatic brain injury.

OBJECTIVE: To study the effect of standard large trauma craniotomy (SLTC) on outcomes of patients with severe traumatic brain injury (TBI) (GCS<=8). METHODS: 230 patients with severe TBI were randomly divided into two groups. 115 patients underwent SLTC (10 cm x 12 cm) as an SLTC group, and other 115 patients underwent temporo-parietal or fronto-temporal craniotomy (6 cm x 8 cm) according to the position of hematomas as a routine craniotomy (RC) group. Other treatments were identical in two groups. According to Glasgow outcome scale (GOS), the prognosis of the patients was evaluated and the complications were compared between two groups. RESULTS: 27 patients got good outcome and moderate disability (23.5%), 40 severe disability and vegetative survival (34.8%), and 48 died (41.7%) in SLTC group. 21 patients got good outcome and moderate disability (18.3%), 28 severe disability and vegetative survival (24.3%), and 66 died (57.4%) in RC group. The incidence of incision hernia was lower in SLTC group than in RC group. However, the incidence of operative encephalocele, traumatic epilepsy and intracranial infection were not different in two groups. CONCLUSIONS: Standard large trauma craniotomy significantly reduces the mortality of patients with severe TBI without serious complications, but does not improve the life quality of the patients.