Metabolic regulation of innate immunity in cancer immunotherapy

Innate immunity,originally recognized as the primary defense mechanism against pathogenic infections,has also been shown to have an important role in anti-tumor immunity.Host cells recognize cytosolic DNA and RNA,which triggers a cascade of signaling events via nucleic-acid sensing receptors,including endosomal Toll-like receptors(TLRs),cytoplasmic cyclic GMP-AMP synthase(cGAS)for double-stranded DNA sensing,and cytoplasmic retinoic acid-inducible gene I(RIG-I)for double-stranded RNA detection.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury:Stepping Forward

Major advances have been made over the past few decades in identifying and managing disorders of consciousness(DOC)in patients with acquired brain injury(ABI),bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration.Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools,sophisticated neuroimaging,and electrophysiological techniques,a considerably higher diagnostic accuracy rate of DOC may now be reached.During the treatment of patients with DOC,a variety of intervention methods are available,including amantadine and transcranial direct current stimulation,which have both provided class II evidence,zolpidem,which is also of high quality,and non-invasive stimulation,which appears to be more encouraging than pharmacological therapy.However,heterogeneity is profoundly ingrained in study designs,and only rare schemes have been recommended by authoritative institutions.There is still a lack of an effective clinical protocol for managing patients with DOC following ABI.To advance future clinical studies on DOC,we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC.We propose a preliminary clinical decision protocol,which could serve as an ideal reference tool for many medical institutions.

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.

Neuroimage-Based Consciousness Evaluation of Patients with Secondary Doubtful Hydrocephalus Before and After Lumbar Drainage

Hydrocephalus is often treated with a cerebrospinal fluid shunt(CFS) for excessive amounts of cerebrospinal fluid in the brain.However,it is very difficult to distinguish whether the ventricular enlargement is due to hydrocephalus or other causes,such as brain atrophy after brain damage and surgery.The non-trivial evaluation of the consciousness level,along with a continuous drainage test of the lumbar cistern is thus clinically important before the decision for CFS is made.We studied 32 secondary mild hydrocephalus patients with different consciousness levels,who received T1 and diffusion tensor imaging magnetic resonance scans before and after lumbar cerebrospinal fluid drainage.We applied a novel machine-learning method to find the most discriminative features from the multi-modal neuroimages.Then,we built a regression model to regress the JFK Coma Recovery Scale-Revised(CRS-R) scores to quantify the level of consciousness.The experimental results showed that our method not only approximated the CRS-R scores but also tracked the temporal changes in individual patients.The regression model has high potential for the evaluation of consciousness in clinical practice.

Emerging roles of spliceosome in cancer and immunity

Precursor messenger RNA(pre-mRNA)splicing is cat-alyzed by an intricate ribonucleoprotein complex called the spliceosome.Although the spliceosome is consid-ered to be general cell"housekeeping"machinery,mutations in core components of the spliceosome fre-quently correlate with cell-or tissue-specific pheno-types and diseases.In this review,we expound the links between spliceosome mutations,aberrant splicing,and human cancers.Remarkably,spliceosome-targeted therapios(STTs)have become efficient anti-cancer strategies for cancer patients with splicing defects.We also highlight the links between spliceosome and immune signaling.Recent studies have shown that some spliceosome gene mutations can result in immune dysregulation and notable phenotypes due to mis-splicing of immune-related genes.Furthermore,several core spliceosome components harbor splicing-inde-pendent immune functions within the cell,expanding the functional repertoire of these diverse proteins.

Molecular diagnosis and treatment of meningiomas:an expert consensus(2022)

Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations.The fifth edition of the WHO Classification of Tumors of the Central Nervous System(WHO CNS5),published in 2021,introduces major changes that advance the role of molecular diagnostics in meningiomas.To follow the revision of WHO CNS5,this expert consensus statement was formed jointly by the Group of Neuro-Oncology,Society of Neurosurgery,Chinese Medical Association together with neuropathologists and evidence-based experts.The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients.

Ectopic recurrence craniopharyngioma:series report and literature review

Background Craniopharyngioma is a common intracranial tumor located in the sellar-suprasellar region.Due to the involvement of adjacent structures,it can lead to increased intracranial pressure,visual impairment,and endocrine deficiencies.Surgical resection is the primary treatment,but it is a tough challenge to achieve total resection,which will led to the frequency of recurrences and progressions.Among them,distant spread is extremely rare,but important complication,identifying and providing proper therapy,is crucial.Methods We report two cases of ectopic recurrence craniopharyngioma and make a literature review for the published similar case reports.Results Our literature review revealed 63 cases(including our patient).The onset age in children group and adult group ranges from 2-14 years old(6.70±3.33)to 17-73 years old(40.63±15.58),while the interval year between tumor initiation and ectopic recurrence ranges from 0.17-20(7.28±6.76)years to 0.3-34(6.85±7.29).Achieving gross total resection seems not to prevent the ectopic recurrence.The major pathology of ectopic recurrence craniopharyngioma is adamantinomatous type.The most common site of ectopic recurrence is frontal lobe.According to the pathogenesis,35 cases were seeding along the surgical approach,and 28 cases were seeding via the CSF pathway.Conclusion Ectopic recurrence craniopharyngioma is rare,but it can lead to serious symptoms.Delicate surgical procedure can help to reduce the risk of ectopic recurrence,and standardized follow-up can provide valuable information for treatment.

Potential glioblastoma biomarkers identified by mass spectroscopy and iTRAQ labeling

Glioblastoma multiforme(GBM)is the most common primary malignant tumor of the central nervous system.Grade IV GBM is lethal,and has a high rate of relapse despite aggressive therapy.The prognosis is poor because of therapeutic resistance and tumor relapse.1 Very low rates of clinical responses and frequent treatment failures are common.Previous studies have focused on identifying genetic alterations in GBM that have diagnostic and prognostic values and may help to define the subclasses of the GBM patients,2,3 including mutations in isocitrate dehydrogenase 1(IDH1),amplification of epidermal growth factor receptors(EGFR),and mutations and polymorphisms of telomerase reverse transcriptase(TERT)promoter.These markers are useful for identifying the pathogenesis of malignant glioma formation,but they are all associated with tumorigenesis and do not currently influence the treatment of most GBM patients.

Harnessing innate immune pathways for therapeutic advancement in cancer

The innate immune pathway is receiving increasing attention in cancer therapy.This pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal cells.Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical studies.However,to date,the clinical success of drugs targeting the innate immune pathway remains limited.Interestingly,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression.The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation.In this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell types.We propose that within the TME,the innate immune pathway exhibits multidimensional diversity.This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks.The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways.Refining our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

SARS-CoV-2 infection and the antiviral innate immune response

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak be-gan in December 2019,causing the illness known as the novel coronavirus disease 2019(COVID-19).The virus spread rapidly worldwide to become a global public health emergency.As of November 15,2020,more than 53 million confirmed cases and over 1 million deaths worldwide have been reported(World Health Organization,2020).