Rethinking the effects of adjuvant beam radiation therapy on overall survival in atypical meningioma patients: age considerations.

Background: This study aimed to investigate the effects of adjuvant beam radiation therapy (ABRT) on overall survival (OS) in patients with primary single intracranial atypical meningioma (AM), with a focus on age-related outcomes. Methods: We conducted a retrospective study using data from SEER database. Our cohort consisted of patients diagnosed with a primary single intracranial AM tumor and had undergone surgery. The primary endpoint was OS. For survival analysis, univariable and multivariable Cox regression analysis were performed. A multivariable additive Cox model was used to assess the functional relationship between age and OS in patients with or without ABRT. Results: Of the 2,759 patients included, 1,650 underwent gross total resection and 833 received ABRT. Multivariable Cox analysis indicated that ABRT did not significantly influence OS across the entire cohort. According to the multivariable generalized additive Cox model, the relative risk of all-cause mortality increased with advancing age in both ABRT-yes and ABRT-no group. ABRT-yes had a lower relative risk than ABRT-no when age ≤ 55 years old while a higher relative risk when age > 55 years old. Subsequent multivariable Cox analysis showed that ABRT was associated with a significant lower risk for all-cause mortality in patients with age ≤ 55 years old while a significant higher risk in patients with age > 55 years old. Conclusion: Our study found that ABRT enhanced OS in younger primary single intracranial AM patients. But we also revealed a negative correlation between OS and ABRT in older patients.

Characterization of a novel galectin in Sarcoptes scabiei and its role in regulating macrophage functions.

Sarcoptes scabiei (S. scabiei) endangers human and other mammalian health. There has been limited research into S. scabiei pathogenic mechanisms and the immunological interaction between S. scabiei and hosts. Galectins have critical roles in biological processes such as cell adhesion, signal transduction, and immune response mediation. Galectins of S. scabiei (SsGalectins) were cloned, expressed, and identified, and their transcriptional levels in S. scabiei were measured at various developmental stages. Fluorescent tissue localization was performed on SsGalectins of S. scabiei and scabies skin. A mouse AD model was constructed to evaluate the effect of rSsGalectins on skin pathogenic changes. Quantitative polymerase chain reaction and enzyme-linked immunoassay were used to identify macrophage polarization-related components and investigate the immunoregulatory effect of rSsGalectins on mouse macrophages. The results demonstrated that the S. scabiei infection causes macrophage infiltration in the scabies skin. The rSsGalectins displayed strong reactogenicity, and distinct genes of the SsGalectins were differently expressed in different developmental stages of S. scabiei. Fluorescence tissue localization revealed that the SsGalectins were mainly in the mouthparts, intestines, and body surface. Additionally, S. scabiei could secrete SsGalectins into the infected skin, proving that SsGalectins were excretion and secretion proteins of S. scabiei. In the mouse atopic dermatitis model, cutaneous macrophage infiltration and inflammation increase after rSsGalectins injection. Simultaneously, when rSsGalectins acted on bone marrow-derived macrophages, M1 macrophage-related polarization factors IL-1ß, IL-6, and inducible nitric oxide synthase all increased, demonstrating that rSsGalectins can induce M1 polarization and produce pro-inflammatory cytokines. In conclusion, the SsGalectins are involved in the pathogenic process of S. scabiei by regulating the polarization of host macrophages to the M1 type when S. scabiei invade the host and promoting the incidence and development of the host's inflammatory response. This study offers fresh light on the pathogenic process of scabies mites, investigates the immunological interaction mechanism between S. scabiei and the host, and offers new insights into S. scabiei prevention and therapy.

Low-coverage and cost-effective whole-genome sequencing assay for glioma risk stratification.

PURPOSE: To investigate chromosomal instability (CIN) as a biomarker for glioma risk stratifications, with cost-effective, low-coverage whole-genome sequencing assay (WGS). METHODS: Thirty-five formalin-fixed paraffin-embedded glioma samples were collected from Huashan Hospital. DNA was sent for WGS by Illumina X10 at low (median) genome coverage of 1.86x (range: 1.03-3.17×), followed by copy number analyses, using a customized bioinformatics workflow-Ultrasensitive Copy number Aberration Detector. RESULTS: Among the 35 glioma patients, 12 were grade IV, 10 grade III, 11 grade II, and 2 Grade I cases, with high chromosomal instability (CIN +) in 24 (68.6%) of the glioma patients. The other 11 (31.4%) had lower chromosomal instability (CIN-). CIN significantly correlates with overall survival (P = 0.00029). Patients with CIN + /7p11.2 + (12 grade IV and 3 grade III) had the worst survival ratio (hazard ratio:16.2, 95% CI:6.3-41.6) with a median overall survival of 24 months. Ten (66.7%) patients died during the first two follow-up years. In the CIN + patients without 7p11.2 + (6 grade III, 3 grade II), 3 (33.3%) patients died during follow-up, and the estimated overall survival was around 65 months. No deaths were reported in the 11 CIN- patients (2 grade I, 8 grade II, 1 grade III) during the 80-month follow-up period. In this study, chromosomal instability served as a prognosis factor for gliomas independent of tumor grades. CONCLUSION: It is feasible to use cost-effective, low-coverage WGS for risk stratification of glioma. Elevated chromosomal instability is associated with poor prognosis.

TRAF3IP3 promotes glioma progression through the ERK signaling pathway.

TRAF3IP3 was reportedly associated with poor prognosis in patients with melanoma; however, its role in glioma is unknown. We aimed to demonstrate the relationship between TRAF3IP3 and glioma and to investigate the potential role of TRAF3IP3 in glioma. Datasets were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We used the Wilcoxon rank-sum test to compared TRAF3IP3 expression in normal and glioma tissues. Kaplan-Meier analysis was performed to evaluate the correlation between TRAF3IP3 and patient survival rate. Gene set enrichment analysis (GSEA) was used to annotate the biological function of TRAF3IP3 in glioma. We also examined the effects of TRAF3IP3 on glioma progression, including characteristics such as cell proliferation, migration, and invasion, using cell proliferation, wound healing, and Transwell assays, respectively, paired with in vitro glioma cell lines and in vivo mouse xenograft models to determine the molecular mechanisms underlying these effects. High TRAF3IP3 expression in glioma tissues was associated with patients with neoplasm cancer tissue source site, and poorer overall survival (OS) (p = 0.03), which was validated using TCGA. GSEA revealed the enrichment of neuroactive ligand-receptor interactions, the olfactory pathway, proteasome pathway, cytokine-cytokine receptor interactions, and calcium signaling pathway in the TRAF3IP3 high-expression phenotype. TRAF3IP3 knockdown markedly suppressed the proliferation, migration, and invasion abilities of U251 glioma cells, whereas TRAF3IP3 overexpression notably promoted the progression of U118 cell tumors. Mechanistic studies revealed that TRAF3IP3 upregulated p-ERK expression in glioma cells. Notably, the ERK signaling pathway inhibitor U0126 drastically attenuated the effects of TRAF3IP3 on p-ERK and markedly blocked its tumor-promoting activity. TRAF3IP3 overexpression also promoted in vivo tumor growth in a nude mouse xenograft model. Collectively, TRAF3IP3 stimulates glioma cell proliferation, migration, and invasion, at least partly by activating the ERK signaling pathway. We hypothesize that TRAF3IP3 may participate in glioma development via the ERK signaling pathway and that elevated TRAF3IP3 expression may serve as a potential biomarker for glioma prognosis.

Corrigendum: The risk of heart disease-related death among anaplastic astrocytoma patients after chemotherapy: A SEER population-based analysis.

[This corrects the article DOI: 10.3389/fonc.2022.870843.].

The Risk of Heart Disease-Related Death Among Anaplastic Astrocytoma Patients After Chemotherapy: A SEER Population-Based Analysis.

Background: Despite improved overall survival outcomes, chemotherapy has brought concerns for heart disease-related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear. Methods: We obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan-Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias. Results: AA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736-0.83, P<0.001). For competing risk regression analysis, the cumulative incidence of HDRD in non-chemotherapy exceeded HDRD in the chemotherapy group (P<0.001) and multivariable analysis showed a lower HDRD risk in AA patients with chemotherapy (adjusted SHR=0.574, 95%CI=0.331-0.991, P=0.046). In the PSM-after cohort, there were no significant association between chemotherapy and the increased HDRD risk (adjusted SHR=0.595, 95%CI=0.316-1.122, P=0.11). Landmark analysis showed that AA patients who received chemotherapy had better heart disease-specific survival than those in the non-chemotherapy group (P=0.007) at the follow-up time points of 216 months. No difference was found when the follow-up time was more than 216 months. Conclusion: AA patients with chemotherapy are associated with a lower risk of HDRD compared with those without chemotherapy. Our findings may help clinicians make a decision about the management of AA patients and provide new and important evidence for applying chemotherapy in AA patients as the first-line treatment. However, more research is needed to confirm these findings and investigate the correlation of the risk of HDRD with different chemotherapy drugs and doses.

Treatment Strategies for Different Types of Intraneural Offending Vessels in Microvascular Decompression Surgery for Trigeminal Neuralgia: An Analytic Report of 58 Cases.

BACKGROUND: Microvascular decompression (MVD) surgery is the treatment of choice for trigeminal neuralgia (TGN). However, decompression becomes difficult when the offending vessel penetrates the trigeminal nerve root. OBJECTIVE: To estimate the rates and patterns of different types of intraneural offending vessels in patients with TGN for MVD and to discuss respective management strategies. METHODS: All patients with TGN undergoing MVD in our center from January 1, 2015, to December 31, 2019, were analyzed retrospectively. The intraneural offending vessels included veins and arteries. The postoperative pain relief rate, complications, and recurrences were evaluated. RESULTS: Of the 302 TGN cases, the intraneural offending vessels were identified in 58 of the cases (19.2%). The 9 cases (15.5%) of intraneural offending arteries were decompressed using shredded Teflon wrapping interposition. Of the 49 cases (84.5%) of intraneural offending veins (INOVs), 29 were not considered true offending vessels, and the treatment only addressed the offending artery in these patients. Of the remaining 20 INOVs, 15 were electrocoagulated and divided, and 5 were decompressed with shredded Teflon. Complete pain relief was achieved in all 58 patients. However, the pain recurred in 5 patients (8.6%), and transient hemifacial numbness occurred in 4 patients (6.9%). CONCLUSION: Intraneural offending vessels requiring treatment are uncommon and are seen in less than 1 in 10 patients undergoing MVD for TGN. For intraneural offending artery, decompression by shredded Teflon wrapping interposition is recommended. Management of the INOV depends on the individual situations, and the management includes sacrifice, wrapping decompression, or leaving them untreated.

Microvascular decompression for hemifacial spasm involving the vertebral artery: A modified effective technique using a gelatin sponge with a FuAiLe medical adhesive.

Microvascular Decompression for Hemifacial Spasm Involving the Vertebral Artery (VA): A Modified Effective Technique Using a Gelatin Sponge with a FuAiLe Medical Adhesive. (a)The VA pushes the anterior inferior cerebellar artery (AICA) which compressed the root exit zone (REZ) of the facial nerve. (b) The VA was adhered to the petrous dura, and the AICA was decompressed from the REZ by a Teflon pad.

Knockdown of ribosomal protein S15A induces human glioblastoma cell apoptosis.

BACKGROUND: RPS15A is a ribosome protein that is highly conserved in many organisms from yeast to human. A number of studies implied its role in promoting cancer cell growth. METHODS: Here, we firstly conducted RPS15A gene expression analysis in brain cancer using Oncomine database and found RPS15A was remarkably overexpressed in glioblastoma (GBM) compared with that in normal tissues. Then, the expression of RPS15A was specifically silenced in GBM cell line U251 using lentiviral-mediated RNA interference technique. We further investigated the effect of RPS15A knockdown in U251 cells using MTT assay, colony formation test, and flow cytometry analysis. We detected the protein level of Bcl-2 and poly (ADP-ribose) polymerase (PARP) as well as activation of caspase-3. RESULTS: Our results showed that the knockdown of RPS15A could inhibit cancer cell growth and colony formation in vitro, as well as induced cell cycle arrest at G0/G1 phase and cell apoptosis. In addition, Western blot analysis indicated that the knockdown of RPS15A could significantly inhibit bcl-2 and activate caspase-3 and PARP. CONCLUSIONS: Our findings suggest RPS15A may play an important role in the progression of GBM and lentiviral-mediated silencing of RPS15A could be an effective tool in GBM treatment.

[Efficacy analysis of endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas].

OBJECTIVE: To analyze the safety and efficacy of surgical removal of recurrent or regrowing pituitary adenomas by endoscopic endonasal transsphenoidal approach. METHODS: The clinical data were retrospectively reviewed for 28 patients undergoing endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas between April 2010 and December 2013. There were 9 males and 19 females with a mean age of 44. 2 (11 - 73) years. The maximal tumor diameter ranged from 2. 1 to 6.9 cm. The Knosp grades were 1 -2 (n = 11), 3 (n =8) and 4 (n =9). Fifteen tumors were endocrinically functional and the remainder endocrinically nonfunctional. All operations were performed with an assistance of intraoperative neuronavigation. Neuro-ophthalmological, neuroimaging and endocrinological results were followed up postoperatively. And surgical outcomes and risk factors were analyzed for incomplete tumor resection in previous operations. RESULTS: The mean follow-up period was 19. 1 (3 - 45) months. Gross total resection(n = 18, 64. 3%), subtotal resection(n = 6, 21. 4%) and partial resection(n = 4, 14. 3%) were achieved. Postoperatively, visual acuity improved in 11 patients (73. 3%) and 6 patients (40. 0%) showed endocrine remission. Qne patient had short-term postoperative leakage of cerebrospinal fluid (CSF). CONCLUSION: Endoscopic endonasal transsphenoidal surgery is both safe and effective for recurrent or regrowing pituitary adenomas.

Effect of Fluoride on Arsenic Uptake from Arsenic-Contaminated Groundwater using Pteris vittata L.

High-arsenic groundwater in inland basins usually contains high concentrations of fluoride. In the present study, the effects of fluoride on arsenic uptake by Pteris vittata and on arsenic transformation in growth media were investigated under greenhouse conditions. After P. vittata was hydroponically exposed to 66.8 µM As (V) in the presence of 1.05 mM F- in the form of NaF, KF, or NaF+KF for 10 d, no visible toxicity symptoms were observed, and there were not significant differences in the dry biomass among the four treatments. The results showed that P. vittata tolerated F- concentrations as high as 1.05 mM but did not accumulate fluoride in their own tissues. Arsenic uptake was inhibited in the presence of 1.05 mM F-. However, in hydroponic batches with 60 µM As (III) or 65 µM As (V), it was found that 210.6 and 316.0 µM F(-) promoted arsenic uptake. As(III) was oxidized to As(V) in the growth media in the presence and absence of plants, and F- had no effect on the rate of As(III) transformation. These experiments demonstrated that P. vittata was a good candidate to remediate arsenic-contaminated groundwater in the presence of fluoride. Our results can be used to develop strategies to remediate As-F-contaminated water using P. vittata.

Reversal of doxorubicin resistance by guggulsterone of Commiphora mukul in vivo.

Our previous study has shown co-administration of guggulsterone resulted in significant increase in chemosensitivity of multidrug-resistant human breast cancer MCF-7/DOX cells to doxorubicin (DOX) in vitro. The present study was designed to investigate whether guggulsterone had the similar modulatory activities in vivo. MCF-7/DOX and MCF-7 xenograft mice models were established. At the end of the experiment (day 28), doxorubicin treatment alone did not significantly inhibit tumor growth in MCF-7/DOX xenograft, indicating that it retained doxorubicin resistance. Whereas, doxorubicin treatment alone significantly inhibited tumor growth in MCF-7 xenograft, suggesting that it maintained doxorubicin sensitivity. When doxorubicin and guggulsterone were co-administrated, their antitumor activities were augmented in MCF-7/DOX xenograft. However, combination therapy did not enhance the antitumor effects of doxorubicin in MCF-7 xenograft. The expression of proliferative cell nuclear antigens PCNA and Ki67 after doxorubicin treatment alone was not significantly different from that of vehicle group in MCF-7/DOX xenograft. On the contrary, doxorubicin treatment alone significantly reduced PCNA and Ki67 expression in MCF-7 xenograft. Combination therapy also significantly reduced PCNA and Ki67 expression in MCF-7/DOX xenograft, compared to doxorubicin treatment alone. However, combination therapy did not enhance the inhibitory effects of doxorubicin on PCNA and Ki67 expression in MCF-7 xenograft. Examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effects of guggulsterone on Bcl-2 and P-glycoprotein expression were the possible reason to increase chemosensitivity of MCF-7/DOX cells to doxorubicin in vivo. Examining body weight, hematological parameters, hepatic, cardiac and gastrointestinal tracts histopathology revealed that no significant signs of toxicity were related to guggulsterone. Guggulsterone might reverse doxorubicin resistance in vivo, with no severe side effects.

Bioinformatics analysis reveals potential candidate drugs for different subtypes of glioma.

Gliomas are the most common primary brain tumors of the central nervous system. However, current approaches for treating glioma have limited success, with a low 5-year survival rate. Besides, gliomas can be classified based on various criteria and the exact method of grading changes over time, it is hard for the surgeons to choose the suitable treatment strategies for glioma patients. In present study, we sought to explore the commonalities between different subtypes of glioma, and then identify biologically active small molecules capable of targeting all subtypes of glioma using a computational bioinformatics analysis of gene expression. Results showed that there were common differentially expressed genes between different subtypes of glioma. Pathways related to tumorigenesis and signaling transduction were dysfunctional in the progression of glioma. Further, we identified a group of small molecules. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for glioma. However, further evaluation for their potential use in the treatment of glioma is still needed.

Groundwater geochemistry and its implications for arsenic mobilization in shallow aquifers of the Hetao Basin, Inner Mongolia.

Arsenic concentrations in shallow groundwaters from the Hetao Basin of Inner Mongolia range between 0.6 and 572 microg/L. High As groundwaters generally occur in the shallow alluvial-lacustrine aquifers, which are mainly composed of black (or dark grey) fine sands in a reducing environment. They are characterized by high concentrations of dissolved Fe, Mn, HCO(3)(-), P and S(2-), and low concentrations of NO(3)(-) and SO(4)(2-). Low SO(4)(2-) coupled with high S(2-) suggests that SO(4)(2-) reduction has been an active process. In the reducing groundwaters, inorganic As(III) accounts for around 75% of total dissolved As. Total As contents in the sediments from three representative boreholes are observed to be 7.3-73.3 mg/kg (average of 18.9 mg/kg). The total As is mildly-strongly correlated with total Fe and total Mn, while a quite weak correlation exists between total As and total S, suggesting that the As is associated with Fe-Mn oxides, rather than sulfides in the sediments. It is found in the sequential extraction that chemically active As is mainly bound to Fe-Mn oxides, up to 3500 microg/kg. The mobilization of As under reducing conditions is believed to include reductive dissolution of Fe-Mn oxides and reduction of adsorbed As. Although exchangeable As is labile and very vulnerable to hydrogeochemical condition, the contribution is relatively limited due to the low concentrations. The competition between As and other anions (such as HPO(4)(2-)) for binding sites on Fe-Mn oxides may also give rise to the release of As into groundwater. Slow groundwater movement helps accumulation of the released As in the groundwaters.