Multimodal image fusion-assisted endoscopic evacuation of spontaneous intracerebral hemorrhage.

PURPOSE: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. METHODS: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher's exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. RESULTS: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p < 0.001), less blood loss (p < 0.001), better hematoma evacuation (p = 0.003), and a shorter stay in the intensive care unit (p = 0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group (p = 0.014). CONCLUSIONS: Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

Comparison of microwave and hot-air roasting on microstructure of sesame seed, aroma-active, hazardous components, and sensory perception of sesame oil.

The unclear effects of microwaves, as a greener alternative to hot air, on sensory perception, aroma, and hazardous components of sesame oil were investigated. Microwaves (900 W, 6-10 min) created more seed porosity and cell destruction and facilitated more γ-tocopherol release in sesame oil (349.30-408.50 mg/kg) than 200 °C, 20 min hot air (304.90 mg/kg). Microwaves (6-10 min) generated more aromatic heterocyclics (42.40-125.12 mg/kg) and aldehydes (5.15-2.08 mg/kg) in sesame oil than hot air (25.59 mg/kg and 1.34 mg/kg). Microwaves (6 min) produced sesame oil with a stronger roasted sesame flavour, and weaker bitter and burnt flavour than hot air. Microwaves reduced harman (≤775.19 ng/g), norharman (≤1,069.99 ng/g), and benzo(a)pyrene (≤1.59 µg/kg) in sesame oil than hot air (1,319.85 ng/g, 1,168.40 ng/g, and 1.83 µg/kg). Appropriate microwave is a promising alternative to hot air in producing sesame oil with a better sensory profile, more bioactive, and less carcinogenic components.

Coupling Plant Polyphenol Coordination Assembly with Co(OH)2 to Enhance Electrocatalytic Performance towards Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) is kinetically sluggish due to the limitation of the four-electron transfer pathway, so it is imperative to explore advanced catalysts with a superior structure and catalytic output under facile synthetic conditions. In the present work, an easily accessible strategy was proposed to implement the plant-polyphenol-involved coordination assembly on Co(OH)2 nanosheets. A TA-Fe (TA = tannic acid) coordination assembly growing on Co(OH)2 resulted in the heterostructure of Co(OH)2@TA-Fe as an electrocatalyst for OER. It could significantly decrease the overpotential to 297 mV at a current density of 10 mA cm-2. The heterostructure Co(OH)2@TA-Fe also possessed favorable reaction kinetics with a low Tafel slope of 64.8 mV dec-1 and facilitated a charge-transfer ability. The enhanced electrocatalytic performance was further unraveled to be related to the confined growth of the coordination assembly on Co(OH)2 to expose more active sites, the modulated surface properties and their synergistic effect. This study demonstrated a simple and feasible strategy to utilize inexpensive biomass-derived substances as novel modifiers to enhance the performance of energy-conversion electrocatalysis.

Boosting the oxygen evolution electrocatalysis of high-entropy hydroxides by high-valence nickel species regulation.

The addition of an extra metal source induces the transformation from crystalline α-Ni(OH)2 to an amorphous NiCoFeCrMo-based high-entropy hydroxide (HEH) and maximizes the high-valence Ni3+ content in HEH. For OER electrocatalysis, the quinary HEH possesses an overpotential of 292 mV at 10 mA cm-2, a Tafel slope of 54.31 mV dec-1 and the boosted intrinsic activity, surpassing other subsystems.

Genetic alteration and clonal evolution of primary glioblastoma into secondary gliosarcoma.

AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.

Comprehensive Analysis of Differentially Expressed lncRNAs miRNAs and mRNA and Their ceRNA Network of Patients With Rare-Earth Pneumoconiosis.

Rare-earth pneumoconiosis (REP) is the main occupational disease of rare earth exposed workers and there is no specific treatment. In this study, we performed high-throughput sequencing on the plasma of nine REP to describe and analyze the expression profiles of long non-coding RNA (lncRNA), micro RNA (miRNA) and mRNA and investigate their regulatory networks. Our results identified a total of 125 lncRNAs, 5 miRNAs, and 82 mRNAs were differentially expressed in the plasma of patients with REP. Furthermore, Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyze the differentially expressed non-coding RNAs (ncRNA). We found the differential expression of ncRNA are mainly related to the response of cells to stimulation, Hedgehog signaling pathway and so on. We also constructed lncRNA-miRNA-mRNA networks to further explore their underlying mechanism and possible relationships in REP. We found that in the competitive endogenous RNA (ceRNA) networks, lncRNA acts as a sponge of miRNA to regulate the target gene. The expression results were verified by qRT-PCR and the protein interaction networks of differentially expressed genes were constructed via the STRING database. OncoLnc online platform was used to do the lung cancer survival analysis among the top five mRNA analyzed by Protein-protein interaction (PPI) network analysis. We found miR-16-2-3p may used as biomarker for REP, because it is closely related to the occurrence and prognosis of REP through inflammatory reaction and in lung squamous cell carcinoma, its expression levels were positively correlated with the overall survival rate of patients.

Impact of beta-2 microglobulin expression on the survival of glioma patients via modulating the tumor immune microenvironment.

AIMS: High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta-2 microglobulin (B2M) in lower-grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration. METHODS: A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan-Meier survival analysis and meta-analysis were used for survival analysis. GO(Gene-ontology) enrichment analysis, co-expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma. RESULTS: We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta-analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co-expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines. CONCLUSIONS: We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.

Systemic Inflammatory Indicators as Prognosticators in Glioblastoma Patients: A Comprehensive Meta-Analysis.

Background: Inflammation plays an important role in tumorigenesis. Previous studies have reported the prognostic value of several peripheral inflammatory markers in glioma patients, including the neutrophil-to-lymphocyte ratio (NLR). However, it still remains unclear whether inflammatory markers can independently predict the prognosis of glioblastoma (GBM) patients. The present study aims to explore the prognostic value of systemic inflammatory markers, including neutrophils, lymphocytes, platelets, the NLR, and the platelet-to-lymphocyte ratio (PLR), in patients with GBM. Methods: A comprehensive systemic search and review was performed using the PubMed, EMBASE, and Cochrane Library databases to identify all the relevant literature (published before June 30, 2020) that evaluated the association between any of these inflammatory markers and survival in GBM. Results: There were 2 (634 patients), 3 (723 patients), 2 (237 patients), 8 (1,225 patients), and 3 (505 patients) studies examining the correlation of survival with neutrophils, lymphocytes, platelets, the NLR, and the PLR, respectively. An elevated NLR and elevated neutrophil and platelet counts were associated with worse overall survival (OS) in GBM patients (NLR: hazard ratio [HR] = 1.63, 95% confidence interval [CI]: 1.23-2.15, p = 0.0007; neutrophil count: HR = 1.46, 95% CI:1.16-1.83, p = 0.001; platelet count: HR = 1.58, 95% CI: 1.42-1.77, p < 0.00001). However, there was no significant association between the PLR or the absolute lymphocyte count and OS in GBM patients. Conclusion: The NLR and the absolute neutrophil and platelet counts may be valuable and convenient peripheral inflammatory markers to evaluate the prognosis of GBM patients. Further prospective studies are needed to verify its reliability.

Carmustine as a Supplementary Therapeutic Option for Glioblastoma: A Systematic Review and Meta-Analysis.

Background: Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor. Carmustine is used by intravenous injection or local implantation in the resection cavity for gliomas, including GBMs. However, the therapeutic potential of carmustine is not well-recognized. This analysis aimed to evaluate the survival benefits of carmustine in glioma patients, especially those with GBM. Methods: Randomized controlled trials (RCTs) and cohort studies regarding carmustine for glioma treatment were searched in PubMed, the Cochrane Library, and Embase from January 1979 to March 2020. Quality assessment was conducted with Jadad and Newcastle-Ottawa scales (NOS). Statistical analysis was conducted by the Revman 5.3 software. Results: Twenty-two eligible RCTs and cohort studies involving 5,821 glioma patients were included. Overall, glioma patients receiving carmustine as an adjuvant therapy had better progression-free survival [PFS; hazard ratio (HR) = 0.85, 95% CI = 0.77-0.94, P = 0.002] and overall survival (OS; HR = 0.85, 95% CI = 0.79-0.92, P < 0.0001) than those without carmustine treatment. Subgroup analysis showed that the OS benefit was observed in GBM (HR = 0.84, 95% CI = 0.78-0.91, P < 0.00001) but not in anaplastic glioma patients (HR = 1.20, 95% CI = 0.70-2.07, P = 0.50). Additionally, both newly diagnosed and recurrent GBM patients who received carmustine treatment showed better OS (HR = 0.86, 95% CI = 0.79-0.95, P = 0.002; HR = 0.77, 95% CI = 0.67-0.89, P = 0.0002, respectively). Both carmustine implantation in resection cavity and intravenous administration significantly prolonged OS (HR = 0.84, 95% CI = 0.78-0.92, P < 0.0001; HR = 0.86, 95% CI = 0.75-0.99, P = 0.04, respectively). Moreover, GBM patients receiving a combined carmustine and temozolomide (TMZ) therapy had longer OS than those receiving TMZ alone (HR = 0.78, 95% CI = 0.63-0.97, P = 0.03). Conclusion: Carmustine implantation in resection cavity provides survival benefit for GBM patients, and it may be a promising supplement to standard therapeutic protocol by offering a bridge between surgical resection and onset of TMZ therapy.

A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation.

Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients. Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I 2 = 0%; PPS: HR = 0.70, 95% CI 0.57-0.88, p < 0.01, I 2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47-3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82-1.10, p = 0.51, I 2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies. Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation.

Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials.

PURPOSE: The aim of this study was to assess the neuroprotective effect of progesterone administration on severe traumatic brain injury (TBI) for different follow-up periods and administration route by completing a meta-analysis of randomized clinical trials (RCTs). METHODS: A systematic literature search of PubMed, Embase, and Cochrane databases and the Web of Science (from establishment of each to September 1, 2018) was performed to identify original RCTs that evaluated the associations between progesterone treatment and the prognosis of patients with severe TBI. RESULTS: Eight RCTs enrolling 2,251 patients with severe TBI were included. Within 3 months post-injury, patients with progesterone administration had a lower mortality (risk ratio [RR] =0.59; 95% CI [0.42-0.81], P=0.001) and better neurologic outcomes (RR =1.51; 95% CI [1.12-2.02], P=0.007) than those who received placebo. However, these differences did not persist at 6 months post-injury for mortality (RR =0.96; 95% CI [0.65-1.41], P=0.83) or neurologic outcomes (RR =1.09; 95% CI [0.93-1.27], P=0.31). The analysis stratified by administration route showed that beneficial effects were only observed in patients who received progesterone intramuscularly (RR =1.61, 95% CI [1.19-2.18], P=0.002); no benefit was observed with intravenous administration (RR =0.99, 95% CI [0.91-1.07], P=0.75). CONCLUSION: Progesterone administration improved the clinical outcomes of severe TBI patients within 3 months but may not have significant long-term benefits 6 months post-injury.

The Clinical Significance of O6-Methylguanine-DNA Methyltransferase Promoter Methylation Status in Adult Patients With Glioblastoma: A Meta-analysis.

BACKGROUND AND OBJECTIVE: Promoter status of O6-methylguanine-DNA methyltransferase (MGMT) has been widely established as a clinically relevant factor in glioblastoma (GBM) patients. However, in addition to varied therapy schedule, the prognosis of GBM patients is also affected by variations of age, race, primary or recurrent tumor. This study comprehensively investigated the association between MGMT promoter status and prognosis in overall GBM patients and in different GBM subtype including new diagnosed patients, recurrent patients and elderly patients. METHODS: A comprehensive search was performed using PubMed, EMBASE, Cochrane databases to identify literatures (published from January 1, 2005 to April 1, 2017) that evaluated the associations between MGMT promoter methylation and prognosis of GBM patients. RESULTS: Totally, 66 studies including 7,886 patients met the inclusion criteria. Overall GBM patients with a methylated status of MGMT receiving temozolomide (TMZ)-containing treatment had better overall survival (OS) and progression-free survival (PFS) [OS: hazard ratio (HR) = 0.46, 95% confidence interval (CI): 0.41-0.52, p < 0.001, Bon = 0.017; PFS: HR = 0.48, 95% CI 0.40-0.57, p < 0.001, Bon = 0.014], but no significant advantage on OS or PFS in GBM patients with TMZ-free treatment was observed (OS: HR = 0.97, 95% CI 0.91-1.03, p = 0.08, Bon = 1; PFS: HR = 0.76, 95% CI 0.57-1.02, p = 0.068, Bon = 0.748). These different impacts of MGMT status on OS were similar in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM. Among patients receiving TMZ-free treatment, survival benefit in Asian patients was not observed anymore after Bonferroni correction (Asian OS: HR = 0.78, 95% CI 0.64-0.95, p = 0.02, Bon = 0.24, I2 = 0%; PFS: HR = 0.69, 95% CI 0.50-0.94, p = 0.02, Bon = 0.24). No benefit was observed in Caucasian receiving TMZ-free therapy regardless of Bonferroni adjustment. CONCLUSION: The meta-analysis highlights the universal predictive value of MGMT methylation in newly diagnosed GBM patients, elderly GBM patients and recurrent GBM patients. For elderly methylated GBM patients, TMZ alone therapy might be a more suitable option than radiotherapy alone therapy. Future clinical trials should be designed in order to optimize therapeutics in different GBM subpopulation.