Clinical management and survival outcomes of patients withdifferent molecular subtypes of diffuse gliomas in China(2011–2017):a multicenter retrospective study from CGGA

Objective:We aimed to summarize the clinicopathological characteristics and prognostic features of various molecular subtypes of diffuse gliomas(DGs)in the Chinese population.Methods:In total,1,418 patients diagnosed with DG between 2011 and 2017 were classified into 5 molecular subtypes according to the 2016 WHO classification of central nervous system tumors.The IDH mutation status was determined by immunohistochemistry and/or DNA sequencing,and 1p/19q codeletion was detected with fluorescence in situ hybridization.The median clinical follow-up time was 1,076 days.T-tests and chi-square tests were used to compare clinicopathological characteristics.Kaplan‒Meier and Cox regression methods were used to evaluate prognostic factors.Results:Our cohort included 15.5%lower-grade gliomas,IDH-mutant and 1p/19q-codeleted(LGG-IDHm-1p/19q);18.1%lowergrade gliomas,IDH-mutant(LGG-IDHm);13.1%lower-grade gliomas,IDH-wildtype(LGG-IDHwt);36.1%glioblastoma,IDHwildtype(GBM-IDHwt);and 17.2%glioblastoma,IDH-mutant(GBM-IDHm).Approximately 63.3%of the enrolled primary gliomas,and the median overall survival times for LGG-IDHm,LGG-IDHwt,GBM-IDHwt,and GBM-IDHm subtypes were 75.97,34.47,11.57,and 15.17 months,respectively.The 5-year survival rate of LGG-IDHm-1p/19q was 76.54%.We observed a significant association between high resection rate and favorable survival outcomes across all subtypes of primary tumors.We also observed a significant role of chemotherapy in prolonging overall survival for GBM-IDHwt and GBM-IDHm,and in prolonging post-relapse survival for the 2 recurrent GBM subtypes.Conclusions:By controlling for molecular subtypes,we found that resection rate and chemotherapy were 2 prognostic factors associated with survival outcomes in a Chinese cohort with DG.

Updates on management of gliomas in the molecular age

Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.

Current challenges in the treatment of gliomas:The molecular era

Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric glioma.Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis.Molecular characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of treatment.Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma.However,improvements in survival have been modest.Currently,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular biomarkers.Furthermore,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.

Simulation of the Ecosystem Productivity Responses to Aerosol Diffuse Radiation Fertilization Effects over the Pan-Arctic during 2001–19

The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.

Transition from a filamentary mode to a diffuse one with varying distance from needle to stream of an argon plasma jet

Plasma jet has extensive application potentials in various fields, which normally operates in a diffuse mode when helium is used as the working gas. However, when less expensive argon is used, the plasma jet often operates in a filamentary mode. Compared to the filamentary mode, the diffuse mode is more desirable for applications. Hence, many efforts have been exerted to accomplish the diffuse mode of the argon plasma jet. In this paper, a novel single-needle argon plasma jet is developed to obtain the diffuse mode. It is found that the plasma jet operates in the filamentary mode when the distance from the needle tip to the central line of the argon stream(d) is short. It transits to the diffuse mode with increasing d. For the diffuse mode, there is always one discharge pulse per voltage cycle, which initiates at the rising edge of the positive voltage. For comparison, the number of discharge pulse increases with an increase in the peak voltage for the filamentary mode. Fast photography reveals that the plasma plume in the filamentary mode results from a guided positive streamer,which propagates in the argon stream. However, the plume in the diffuse mode originates from a branched streamer, which propagates in the interfacial layer between the argon stream and the surrounding air. By optical emission spectroscopy,plasma parameters are investigated for the two discharge modes, which show a similar trend with increasing d. The diffuse mode has lower electron temperature, electron density, vibrational temperature, and gas temperature compared to the filamentary mode.

Extragastrointestinal stromal tumors with diffuse membranous distribution with bleeding:A case report

BACKGROUND Extragastrointestinal stromal tumors(EGIST)and gastrointestinal stromal tumors are of similar pathological type and form.Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity,the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors.CASE SUMMARY The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days.Upon physical examination,the patient had flat and tough abdomen with mild pressing pain at lower abdomen,no obvious abdominal mass was touchable,and shifting dullness was positive.Positron emission tomography-computed tomography(CT)showed that in his peritoneal cavity,there were multiple nodules of various sizes,seroperitoneum,multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules.Plain CT scanning at epigastrium/hypogastrium/pelvic cavity+enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity,peritoneum and right groin.Tumor marker of carbohydrate antigen 125 was 808 U/mL,diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia,and postoperative pathological examination confirmed EGIST.Imatinib was administered with better therapeutic effect.CONCLUSION Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation,and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.

Influence of bias voltage and oxygen addition on the discharge aspects of a diffuse argon plume in an atmospheric pressure plasma jet

A remote plasma,also referred to as a plasma plume(diffuse or filamentary),is normally formed downstream of an atmospheric pressure plasma jet.In this study,a diffuse plume is formed by increasing the bias voltage(U_(b))applied to the downstream electrode of an argon plasma jet excited by a negatively pulsed voltage.The results indicate that the plume is filamentary when U_(b)is low,which transits to the diffuse plume with increasing U_(b).The discharge initiated at the rising edge of the pulsed voltage is attributed to the diffuse plume,while that at the falling edge contributes to the filament in the plume.For the diffuse plume,the discharge intensity decreases with the increasing oxygen content(C_o).Fast photography reveals that the diffuse plume results from a negative streamer,which has a dark region near the nozzle with C_o=0%.However,the dark region is absent with C_o=0.5%.From the optical emission spectrum,the electron density,electron excitation temperature,gas temperature,and oxygen atom concentration are investigated.

RPRD1B/CREPT facilitates the progression of diffuse large B-cell lymphoma by inhibiting apoptosis through the NF-κB signaling pathway

Objective:To investigate the role of RPRD1B in the progression of diffuse large B-cell lymphoma(DLBCL)and its potential as a therapeutic target.Methods:This study analyzed RPRD1B expression in DLBCL and normal tissues using public databases and assessed its prognostic impact through survival analysis.In vitro and in vivo experiments were conducted to explore the mechanisms by which RPRD1B influences tumor growth and apoptosis.Results:RPRD1B expression was significantly elevated in DLBCL compared to normal tissues and was associated with poor prognosis.In vitro and in vivo experiments demonstrated that RPRD1B promoted lymphoma cell proliferation and inhibited apoptosis through the NF-κB signaling pathway.Conclusions:RPRD1B plays a critical role in the progression of DLBCL by modulating apoptosis and cellular proliferation.Targeting RPRD1B may offer a novel therapeutic strategy for DLBCL,suggesting its potential as a prognostic marker and therapeutic target in hematological malignancies.

Identifying relevant factors influencing cancer-related fatigue in patients with diffuse large B-cell lymphoma during chemotherapy

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a rapidly growing malignant tumor,and chemotherapy is one of the treatments used to combat it.Although advancements of science and technology have resulted in more and more patients being able to receive effective treatment,they still face side effects such as fatigue and weakness.It is important to thoroughly investigate the factors that contribute to cancer-related fatigue(CRF)during chemotherapy.AIM To explore the factors related to CRF,anxiety,depression,and mindfulness levels in patients with DLBCL during chemotherapy.METHODS General information was collected from the electronic medical records of eligible patients.Sleep quality and mindfulness level scores in patients with DLBCL during chemotherapy were evaluated by the Pittsburgh Sleep Quality Index and Five Facet Mindfulness Questionnaire-Short Form.The Piper Fatigue Scale was used to evaluate the CRF status.The Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to evaluate anxiety and depression status.Univariate analysis and multivariate regression analysis were used to investigate the factors related to CRF.RESULTS The overall average CRF level in 62 patients with DLBCL during chemotherapy was 5.74±2.51.In 25 patients,the highest rate of mild fatigue was in the cognitive dimension(40.32%),and in 35 patients the highest moderate fatigue rate in the behavioral dimension(56.45%).In the emotional dimension,severe fatigue had the highest rate of occurrence,34 cases or 29.03%.The CRF score was positively correlated with cancer experience(all P<0.01)and negatively correlated with cancer treatment efficacy(all P<0.01).Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level were related to CRF in patients with DLBCL during chemotherapy.CONCLUSION There was a significant correlation between CRF and perceptual control level in patients.Tumor staging,chemotherapy cycle,self-efficacy level,and anxiety and depression level influenced CRF in patients with DLBCL during chemotherapy.

Formation of diffuse and spark discharges between two needle electrodes with the scattering of particles

The development of a nanosecond discharge in a pin-to-pin gap filled with air at atmospheric pressure has been studied with high temporal and spatial resolutions from a breakdown start to the spark decay.Positive and negative nanosecond voltage pulses with an amplitude of tens of kilovolts were applied.Time-resolved images of the discharge development were taken with a fourchannel Intensified Charge Coupled Device(ICCD)camera.The minimum delay between the camera channels could be as short as≈0.1 ns.This made it possible to study the gap breakdown process with subnanosecond resolution.It was observed that a wide-diameter streamer develops from the high-voltage pointed electrode.The ionization processes near the grounded pin electrode started when the streamer crossed half of the gap.After bridging the gap by the streamer,a diffuse discharge was formed.The development of spark leaders from bright spots on the surface of the pointed electrodes was observed at the next stage.It was found that the rate of development of the spark leader is an order of magnitude lower than that of the wide-diameter streamer.Long thin luminous tracks were observed against the background of a discharge plasma glow.It has been established that the tracks are adjacent to brightly glowing spots on the electrodes and are associated with the flight of small particles.

New targets for cancer promotion and therapy in gliomas: Scinderin

Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin severing and capping protein that regulates the actin cytoskeleton,is involved in the prolif-eration and migration of certain cancer cells.However,its biological role and molecular mechanism in glioma remain unclear.Lin et al explored the role and mechanism of SCIN in gliomas.The results showed that SCIN mechanically affected cytoskeleton remodeling and inhibited the formation of lamellipodia via RhoA/FAK signaling pathway.This study identifies the cancer-promoting role of SCIN and provides a potential therapeutic target for SCIN in glioma treatment.

A Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Gliomas. The Report on Non-Diffuse Intrinsic Pontine Glioma (Protocol BT-11)

Inoperable brainstem gliomas (BSG) are among the most difficult to treat malignancies. In the intent-to-treat (ITT) population of the BT-11 study for BSG, forty patients (median age 11.2 years old) were enrolled. Antineoplastons A10 and AS2-1 (ANP) were administered intravenously daily. The median daily dose of A10 was 8.70 g/kg/day and AS2-1 was 0.32 g/kg/day. Efficacy analyses were conducted in two subgroups: recurrent pediatric diffuse intrinsic pontine glioma (RPDIPG, N?= 17) and non-diffuse intrinsic pontine glioma (NDIPG, N?= 11). This paper reports the results of the study of the efficacy and safety of ANP in patients with NDIPG. The results in the RPDIPG group were reported before;complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 17.6%. One year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10, and 15 years 6%. In the NDIPG group, there were 36% CR and 27.5% SD. OS at 1, 5, 10, and 15 years was 82%, 73%, 62%, and 50% correspondingly. There was only one serious adverse event (9%) reported in NDIPG represented by hypokalemia, Grade 4. The results suggest that ANP shows efficacy and an acceptable tolerability profile in patients with RPDIPG and NDIPG.

Helicobacter pylori eradication treatment for primary gastric diffuse large B-cell lymphoma:A single-center analysis

BACKGROUND Unlike the already established effect of Helicobacter pylori(H.pylori)eradication on gastric mucosa-associated lymphoid tissue(MALT)lymphoma,its therapeutic effect on primary gastric diffuse large B-cell lymphoma(DLBCL)is still unclear.AIM To clarify the efficacy of H.pylori eradication treatment for primary gastric DLBCL.METHODS We reported on 3 new cases,and added them to 3 previously reported cases.We analyzed the usefulness of H.pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center.RESULTS Of the 6 patients(27-90 years old,3 males and 3 females),all 3 patients with single lesions(one transformed from MALT lymphoma)achieved complete remission(CR)after H.pylori eradication.Regarding the 2 newly reported cases,CR was maintained for more than 6 years with eradication treatment alone.In contrast,none of the 3 patients with 2 lesions achieved CR.In 1 newly reported case,endoscopic CR was achieved in one lesion,while stable disease was obtained in the other lesion.Two patients with progressive disease responded to standard chemo therapy±radiation and remained in CR for more than 6 years.CONCLUSION We believe it is worthwhile to attempt H.pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden.

Acute diffuse peritonitis secondary to a seminal vesicle abscess:A case report

BACKGROUND Seminal vesicle abscess(SVA)is the manifestation of a relatively rare urinary system infection.In response to urinary system inflammation,an abscess forms in special locations.However,acute diffuse peritonitis(ADP)induced by SVA is unusual.CASE SUMMARY We report a case of a left SVA in a male patient complicated with pelvic abscess,ADP,multiple organ dysfunction syndrome,infectious shock,bacteremia,and acute appendiceal extraserous suppurative inflammation as a result of a long-term indwelling urinary catheter.The patient received a course of morinidazole+cefminol antibiotics but showed no obvious relief,so the perineal SVA underwent puncture drainage and abdominal abscess drainage+appendectomy was performed.The operations were successful.After the operation,anti-infection,anti-shock,and nutritional support treatments were continued and various laboratory indicators were regularly reviewed.The patient was discharged from the hospital after recovery.This disease is a challenge for the clinician because of the unusual spreading path of the abscess.Moreover,appropriate intervention and adequate drainage of abdominal and pelvic lesions are necessary,especially when the primary focus cannot be determined.CONCLUSION The etiology of ADP varies,but acute peritonitis secondary to SVA is very rare.In this patient,the left SVA not only affected the adjacent prostate and bladder but also spread retrogradely through the vas deferens,forming a pelvic abscess in the loose tissues of the extraperitoneal fascia layer.Inflammation involving the peritoneal layer led to ascites and pus accumulation in the abdominal cavity,and appendix involvement led to extraserous suppurative inflammation.In clinical practice,surgeons need to consider the results of various laboratory tests and imaging examinations to make comprehensive judgments involving the diagnosis and treatment plan.

Comparative analysis of conventional ultrasound and shear wave elastography features in primary breast diffuse large B-cell lymphoma

BACKGROUND Primary breast diffuse large B-cell lymphoma(PB-DLBCL)is a rare subtype of non-Hodgkin lymphoma that accounts for<3%of extranodal lymphomas and 1%of breast tumors.Its diagnosis and management are challenging because of its rarity,heterogeneity,and aggressive behavior.Conventional ultrasound(US)is the first-line imaging modality for breast lesions;however,it has limited specificity and accuracy for PB-DLBCL.Shear wave elastography(SWE)is a novel US technique that measures tissue stiffness and may reflect the histological characteristics and biological behavior of breast lesions.AIM To compare the conventional US and SWE features of PB-DLBCL and evaluate their diagnostic performance and prognostic value.METHODS We retrospectively reviewed the clinical data and US images of 32 patients with pathologically confirmed PB-DLBCL who underwent conventional US and SWE before treatment.We analyzed conventional US features(shape,margin,orientation,echo,posterior acoustic features,calcification,and vascularity)and SWE features(mean elasticity value,standard deviation,minimum elasticity value,maximum elasticity value,and lesion-to-fat ratio)of the PB-DLBCL lesions.Using receiver operating characteristic curve analysis,we determined the optimal cutoff values and diagnostic performance of conventional US and SWE features.We also performed a survival analysis to assess the prognostic value of conventional US and SWE features.RESULTS The results showed that the PB-DLBCL lesions were mostly irregular in shape(84.4%),microlobulated or spiculated in margins(75%),parallel in orientation(65.6%),hypoechoic in echo(87.5%),and had posterior acoustic enhancement(65.6%).Calcification was rare(6.3%)and vascularity was variable(31.3%avascular,37.5%hypovascular,and 31.3%hypervascular).The mean elasticity value of PB-DLBCL lesions was significantly higher than that of benign breast lesions(113.4±46.9 kPa vs 27.8±16.4 kPa,P<0.001).The optimal cutoff value of the mean elasticity for distinguishing PB-DLBCL from benign breast lesions was 54.5 kPa,with a sensitivity of 93.8%,specificity of 92.9%,positive predictive value of 93.8%,negative predictive value of 92.9%,and accuracy of 93.3%.The mean elasticity value was also significantly correlated with Ki-67 expression level(r=0.612,P<0.001),which is a marker of tumor proliferation and aggressiveness.Survival analysis showed that patients with higher mean elasticity values(>54.5 kPa)had worse overall survival(OS)and progression-free survival(PFS)than those with lower mean elasticity values(<54.5 kPa)(P=0.038 for OS and P=0.027 for PFS).CONCLUSION Conventional US and SWE provide useful information for diagnosing and forecasting PB-DLBCL.SWE excels in distinguishing PB-DLBCL from benign breast lesions,reflects tumor proliferation and aggressiveness,and improves disease management.

Construction and Verification of an RNA-Binding Protein-Associated Prognostic Model for Gliomas

Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.

Drug clinical trials on high-grade gliomas: challenges and hopes

Gliomas are the most common group of malignant central nervous system tumors across all ages and have high heterogeneity.According to histopathologic criteria and molecular pathology,gliomas are classified as grades 1–4.High-grade gliomas(HGG),including the most aggressive subtype,glioblastoma(GBM),belong to grade 3 or 4.Although a standard therapy comprising surgical resection,chemotherapy,and radiation is available,almost all patients with HGG experience recurrence within several months and a dismal prognosis1.

Exploratory therapy for brainstem gliomas

Brainstem gliomas comprise both slow-growing and highly aggressive tumors,the latter carrying a dismal prognosis of approximately 10 months in children.Given their common locations along the brainstem,they are often not amenable to surgical resection.There are currently a host of exploratory therapies under investigation ranging from immunotherapy,small molecular inhibitors,epigenetic-modifying agents,and radiation protocols to combat these difficult-to-treat tumors.Recent discoveries highlighting the role of H3 histone mutations in diffuse midline glioma oncogenesis have yielded a variety of new targetable antigens and aberrant signaling pathways.Although many of these studies have shown promise in terms of inhibiting tumor growth and disease progression,results to date have been modest in their ability to translate into meaningful clinical benefit.This review will serve as an updated report on the current state of literature concerning pre-clinical and clinical therapies being investigated for brainstem glioma.In addition,this review will serve as a guide for clinicians as we review the evolving nomenclature of brainstem gliomas,commonly presenting symptoms,diagnostic tools,and standard therapies.

The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities

Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation.Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation.Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor microenvironment.Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy.Here,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on tumors.Finally,we describe potential therapeutic approaches and targets beyond standard treatments.

Does Diffuse Circumnuclear Gas around Sgr A^(*) Achieve Collisional Ionization Equilibrium or Remain Non-equilibrium Ionization?

The feeding and feedback processes at the vicinity of a supermassive black hole(BH)are essential for our understanding of the connection between supermassive BH and its host galaxy.In this work,we provide a detailed investigation,both observational and theoretical,on the diffuse(~2"-20",~0.08-0.8 pc)X-ray emission around Sgr A*.Over two-decade Chandra observations are gathered to obtain highest signal-to-noise to date.We find that,the line center of iron lines of the outer 8"-18"region,ε_(c)=6.65+0.02-0.03 keV,is comparable to that(ε_(c)=6.60+0.05-0.03 keV)of the inner 2"-5"region.This is somewhat unexpected,since the gas temperature decreases further away from the central BH.Based on a dynamical inflow-outflow model that considers the gas feeding by stellar winds from Wolf-Rayet stars,we calculate the X-ray spectrum based on both the conventional collisional ionization equilibrium(CIE)assumption,and the newly developed non-equilibrium ionization(NEI)assumption.We find that,theoretically gases within~8"-10"remain in a CIE state,outside of this radius they will be in the NEI state.A comparison of the properties of~6.6 keV iron lines between CIE and NEI is addressed.Interestingly,the NEI interpretation of outer region is supported by the Chandra line center ε_(c) measurements of this region.