Objective:To investigate the clinicopathological and molecular genetic characteristics of the neuroepithelial tumor with PATZ1 fusion (NET-PATZ1).Methods:Five cases of NET-PATZ1 diagnosed at the Sanbo Brain Hospital of Capital Medical University, Beijing, China from January 2020 to October 2024 were collected. The clinical, prognostic, imaging, histological and immunohistochemical features and the results of next-generation sequencing (DNA and RNA) of these 5 patients were collected and analyzed. Relevant literature was also reviewed for discussion.Results:Among the 5 cases, there were 4 females and 1 male, with a median age of 9.0 (6.5, 15.5) years. The tumors all occurred in the supratentorial cerebral hemispheres, including the frontal lobe, parietal lobe, lateral ventricle, and thalamus. There were diverse histological features. Two cases exhibited the characteristics of high-grade neuroepithelial tumors, while 3 cases showed those of low-grade neuroepithelial tumors. The tumor cells were mostly arranged in a rosette-like pattern around small blood vessel. The background was rich in vascular components or microvascular hyperplasia. Immunohistochemistry showed that the tumor cells diffusely expressed MAP2 and Vimentin, and had various expression of S-100 protein, GFAP, Olig2, NG2 and CD99, and cytoplasmic and perinuclear expression of Syn. At the genomic level, all cases had PATZ1 gene fusion variants, and the gene breakpoints were all located in exon 1. Four cases had fusion with the EWSR1 gene, and 1 case had fusion with the MN1 gene. The 5 patients all underwent craniotomy for tumor resection. The pathological diagnosis was NET-PATZ1. All cases had no recurrence or metastasis at the end of follow-up except that Case 3 developed spinal cord metastasis 11 months after the surgery.Conclusions:NET-PATZ1 is commonly found in children and adolescents, with diverse histological features. The tumor cells typically arrange in rosette-like patterns, and the background is rich in vascular components or microvascular hyperplasia. Tumor cells express glial cell-related markers to varying degrees, and co-expression of NG2 and CD34 is suggestive of its diagnosis. The establishment of a pathological diagnosis relies on the detection of PATZ1 fusion variations through genetic testing or a DNA methylation profile of NET-PATZ1.

Adamantinomatous craniopharyngioma (ACP) is an epithelial tumor originating from remnants of Rathke's pouch. A highly inflammatory microenvironment and histological presence of the senescence-associated secretory phenotype (SASP) are key pathological features of ACP. Pyroptosis, an inflammatory form of programmed cell death, forms a positive feedback loop with SASP, mutually promoting their effects. This review summarizes the current research progress on regulatory mechanism of SASP and pyroptosis in ACP so as to further understand the pathophysiological mechanisms underlying ACP development.

Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.

Objective:To investigate the clinicopathological and molecular genetic characteristics of the neuroepithelial tumor with PATZ1 fusion (NET-PATZ1).Methods:Five cases of NET-PATZ1 diagnosed at the Sanbo Brain Hospital of Capital Medical University, Beijing, China from January 2020 to October 2024 were collected. The clinical, prognostic, imaging, histological and immunohistochemical features and the results of next-generation sequencing (DNA and RNA) of these 5 patients were collected and analyzed. Relevant literature was also reviewed for discussion.Results:Among the 5 cases, there were 4 females and 1 male, with a median age of 9.0 (6.5, 15.5) years. The tumors all occurred in the supratentorial cerebral hemispheres, including the frontal lobe, parietal lobe, lateral ventricle, and thalamus. There were diverse histological features. Two cases exhibited the characteristics of high-grade neuroepithelial tumors, while 3 cases showed those of low-grade neuroepithelial tumors. The tumor cells were mostly arranged in a rosette-like pattern around small blood vessel. The background was rich in vascular components or microvascular hyperplasia. Immunohistochemistry showed that the tumor cells diffusely expressed MAP2 and Vimentin, and had various expression of S-100 protein, GFAP, Olig2, NG2 and CD99, and cytoplasmic and perinuclear expression of Syn. At the genomic level, all cases had PATZ1 gene fusion variants, and the gene breakpoints were all located in exon 1. Four cases had fusion with the EWSR1 gene, and 1 case had fusion with the MN1 gene. The 5 patients all underwent craniotomy for tumor resection. The pathological diagnosis was NET-PATZ1. All cases had no recurrence or metastasis at the end of follow-up except that Case 3 developed spinal cord metastasis 11 months after the surgery.Conclusions:NET-PATZ1 is commonly found in children and adolescents, with diverse histological features. The tumor cells typically arrange in rosette-like patterns, and the background is rich in vascular components or microvascular hyperplasia. Tumor cells express glial cell-related markers to varying degrees, and co-expression of NG2 and CD34 is suggestive of its diagnosis. The establishment of a pathological diagnosis relies on the detection of PATZ1 fusion variations through genetic testing or a DNA methylation profile of NET-PATZ1.

Objective:To investigate the clinicopathological characteristics and differential diagnosis of DICER1-mutant primary intracranial sarcoma.Methods:Five cases of DICER1-mutant primary intracranial sarcoma at Sanbo Brain Hospital, Capital Medical University, Beijing, China during May 2013 to November 2024 were collected. The clinical and imaging data were retrieved. Histological evaluation, immunohistochemical staining and next generation sequencing were performed. Additionally, a literature review was conducted.Results:All five DICER1-mutant primary intracranial sarcomas were located in the supratentorial region, with one case involving the basal ganglia. There were two males and three females. The median age at diagnosis was 25 (14.0, 30.5) years. Morphologically, they were characterized by high-grade spindle cell sarcoma, with brisk mitotic activity and cytoplasmic eosinophilic globules. Myxoid degeneration, necrosis, and invasion into surrounding brain tissue were observed in some cases. The tumor cells showed diffuse staining of vimentin and variable expression of myogenic marker (desmin), with or without focal MyoD1 and/or Myogenin expression. Four tumors exhibited diffuse, strong expression of TLE1 and p53, while only three tumors showed loss of ATRX (nuclear) expression. Two cases showed mosaic loss of H3K27me3 expression in neoplastic cells. The Ki-67 proliferation index was high (40%-80%). Various neuronal markers, such as synaptophysin, NF, SOX2 and MAP2, were expressed in all tumor samples. Genetically, all tumors samples harbored biallelic abnormalities of DICER1. One was a hotspot missense mutation in the RNase Ⅲb domain within exon 25 on one allele (p.E1813 or p.D1810), while the other allele had mutations including a germline mutation in one case, a somatic mutation in two cases, and a copy number deletion in two cases. In addition, these sarcomas showed alterations in TP53 (4/5), ATRX (3/5), and the genes of the mitogen-activated protein kinase pathway (3/5). Finally, all five cases were diagnosed as DICER1-mutant primary intracranial sarcoma. All patients underwent craniotomy that led to complete tumor resection. Three patients received adjuvant radiotherapy and chemotherapy, with progression-free survival time of 28, 48, and 50 months, respectively. Patient 2 succumbed to the tumor after 3 months post-surgery due to rapid progression and tumor dissemination. Patient 5 was lost to follow-up 3 months after the surgery.Conclusions:DICER1-mutant primary intracranial sarcoma is a newly defined tumor entity in the fifth edition of the World Health Organization Classification of Central Nervous System Tumors, and commonly occurs in children and young adults. High-grade malignant spindle cells are their typical morphological feature. Eosinophilic cytoplasmic globules and myogenic differentiation can help establish the diagnosis. This study suggests that DICER1-mutant primary intracranial sarcomas exhibit immunophenotypic neuronal differentiation. Rendering the diagnosis of DICER1-mutant primary intracranial sarcoma largely relies on detecting DICER1 pathogenic alterations or DNA methylation profiling.

Adamantinomatous craniopharyngioma (ACP) is an epithelial tumor originating from remnants of Rathke's pouch. A highly inflammatory microenvironment and histological presence of the senescence-associated secretory phenotype (SASP) are key pathological features of ACP. Pyroptosis, an inflammatory form of programmed cell death, forms a positive feedback loop with SASP, mutually promoting their effects. This review summarizes the current research progress on regulatory mechanism of SASP and pyroptosis in ACP so as to further understand the pathophysiological mechanisms underlying ACP development.

Objective: To investigate the recessive infection rate of healthy children and guardians in different epidemic periods of hand, foot and mouth disease (HFMD) in Qingdao, analyze the risk factors affecting recessive infection, so as to provide the basis for HFMD prevention and control. Methods: In the nonepidemic period of 2022, the random cluster sampling method was used to selected 546 children and guardians from 4 childcare institutions in Laoshan District and Pingdu City. In the epidemic period of 2023, 690 children and guardians were selected from 6 childcare institutions in Shibei District, Laoshan District and Pingdu District. A questionnair survey was conducted in the epidemic period. Logistic regression analysis was used to analyze the factors affecting the recessive infection. Dominance analysis was used to explore the relative importance of the risk factors affecting recessive infection. Results: The results showed that the recessive infection rates of healthy children and guardians in the epidemic period were 18.84% and 13.62%, respectively; the recessive infection rates were 9.09% and 4.44% in the nonepidemic period, respectively. The results of multivariate Logistic analysis showed that rural areas (OR=4.71, 95%CI=2.57-8.61) and recessive infection of guardians (OR=18.62, 95%CI=7.45-46.56) were positively correlated with recessive infection of HFMD in healthy children (P<0.05). Washing hands (OR=0.09, 95%CI=0.04-0.20), using towels alone (OR=0.17, 95%CI=0.07-0.40), and EV71 vaccination (OR=0.42, 95%CI=0.20-0.87) were negatively correlated with recessive infection of HFMD in healthy children (P<0.05). Public toilets (OR=3.02, 95%CI=1.50-6.09) and drying bedding once per quarter (OR=3.89, 95%CI=1.75-8.68) were positively correlated with recessive infection of HFMD in healthy guardians. Housing with good lighting (OR=0.31, 95%CI=0.12-0.79), and tableware disinfection (OR=0.31, 95%CI=0.15-0.65) were negatively correlated with recessive infection of HFMD in healthy guardians (P<0.05). The results showed that recessive infection of guardians was relatively the most important for healthy children (41.51%), and tableware disinfection was relatively the most important for recessive infection of guardians (28.87%). Conclusions The recessive infections of HFMD are common among healthy populations in Qingdao, and the recessive infection rate among children during the epidemic period is relatively higher. Guardians play an important role in the recessive infection of healthy children. Therefore, healthy education should be strengthened for key populations, especially to enhance parents awareness of prevention and control to reduce the occurrence of recessive infections of hand, foot and mouth disease in children and guardians.

ObjectiveBy observing the effect of Qianyang Yuyin granules on the phenotype of renal tubule epithelial cells， the intervention of Qianyang Yuyin granule on renal interstitial fibrosis was investigated. MethodThe renal tubular epithelial cells （HK-2） were treated with different concentrations of transforming growth factor （TGF）-β₁ （5， 10， 15， 20， 25 μg·L^-1） for 24 hours， and cell morphology and growth state were observed with an inverted phase contrast microscope. The 20 μg·L^-1 was selected as the most appropriate concentration of TGF-β₁ according to Western blot results for subsequent experiments. HK-2 cells were divided into six groups： blank group， TGF-β₁ group （concentration of 20 μg·L^-1）， low， medium， and high dose Qianyang Yuyin granule groups （concentration of 0.5， 1， 2 g·L^-1）， and valsartan group （1 × 10^-5 mol·L^-1）. The cell activity was measured by cell proliferation and cell counting kit-8 （CCK-8）. The cell migration ability was detected by scratch test. The Transwell method was used to detect the invasiveness of cells. Western blot was used to detect levels of fibronectin （FN）， E-cadherin， α-smooth muscle activator （α-SMA）， Vimentin， collagen type Ⅰ（Col Ⅰ）， collagen type Ⅳ（Col Ⅳ）， and other related proteins. ResultTGF-β₁ stimulating epithelial-mesenchymal transition （EMT） in renal tubular epithelial cells was time- and concentration-dependent. Compared with the blank group， higher concentration in the TGF-β₁ group indicates longer intervention time and more obvious long spindle change of cells， and the migration and invasion ability of the cells was significantly enhanced. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ increased significantly （P<0.05， P<0.01）， while the expression level of E-cadherin protein decreased （P<0.05）. Compared with the TGF-β₁ group， Qianyang Yuyin granule groups could maintain normal cell morphology， and the migration and invasion ability of the cells was inhibited. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ decreased （P<0.05， P<0.01）， and the expression of E-cadherin protein was significantly restored （P<0.05）. ConclusionQianyang Yuyin granule can reverse TGF-β₁-induced interstitial transformation of renal tubular epithelial cells by reducing the phenotypic expression of mesenchymal cells and increasing the phenotypic expression of epithelial cells.

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment