Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of primary intracranial DICER1-mutant sarcoma in order to better understand this tumor type.Methods:A retrospective analysis was conducted on 7 cases of primary intracranial DICER1-mutant sarcoma diagnosed in the Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China between 2021 and 2023 using next-generation sequencing. At the same time, 10 gliosarcomas, 4 intracranial FET::CREB fusion-positive mesenchymal tumors, 4 malignant meningiomas, 3 malignant solitary fibrous tumors, 3 malignant peripheral nerve sheath tumors, 3 synovial sarcomas and 3 rhabdomyosarcomas (total 30 cases) were selected as control.Results:Among the 7 patients with primary intracranial DICER1-mutant sarcoma, 6 were male and 1 was female, aged 10-32 years (median, 23 years). The tissue morphology was predominantly spindle or pleomorphic sarcoma-like, with 6 cases exhibiting eosinophilic globules, and 3 cases showing rhabdomyoblastic or rhabdomyosarcoma-like cell differentiation. Immunohistochemistry revealed focal desmin expression in 3 cases (3/7), ATRX loss in 3 cases (3/7), and p53 mutant pattern in 4 cases (4/7). Additionally, 4 cases (4/7) showed focal or diffuse SALL4 expression, whereas the control cases (30 cases) did not exhibit SALL4 protein expression, suggesting that SALL4 may possess certain auxiliary diagnostic value. Next-generation sequencing confirmed that all 7 cases of primary intracranial DICER1-mutant sarcoma harbored mutations in the DICER1 gene, with 5 cases having the mutation site at p.E1813D. Until May 2024, all 7 patients were alive.Conclusions:Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.

The nuclear factor I（NFI）family is a group of important transcription factors，consisting of four members：NFIA，NFIB，NFIC，and NFIX. The members of the NFI family are highly conserved in the N-terminal DNA binding and dimerization domain. The NFIX gene is expressed in many parts of the body，including the brain，prostate，muscles，skin，fat，and ovaries.It plays an important role in a variety of biological processes，including nervous system development，tumorigenesis，muscle and bone development，hematopoietic cell proliferation，and spermatogenesis.Currently，there are few studies and clinical reports on the NFIX gene in China，and its specific mechanism remains unclear，requiring further investigation. To draw the attention of clinicians and enhance the understanding of NFIX gene associated diseases，this article summarizes recent literature and reviews the function and clinical progress of the gene.

Infantile spasms(IS)is an age-dependent severe epilepsy syndrome, mainly treated with hormones and anti-seizure medications.However, due to poor efficacy and even serious side effects among some pediatric patients, searching for better alternative treatment options has become a research hotspot.In recent years, as a special diet treatment, ketogenic diet(KD)has been widely studied and gradually applied to the clinical treatment of IS, which has achieved satisfactory results.This article briefly reviews the KD regimen and mechanism of action, and focuses on the research progress in efficacy, safety and short-term prognosis of KD in the treatment of IS, whose purpose is to provide effective reference for clinical application.

Objective: Cerebrovascular disease can be roughly divided into 2 subtypes: Cerebral ischemia (CI) and cerebral hemorrhage (CH). No scale currently exist that can predict the subtypes of cerebrovascular diseases. This study aims to establish a prediction scale for the subtypes of cerebrovascular diseases. Methods:A total of 1200 cerebrovascular disease patients were included in this study, data from 1081 (90％) patients were used to establish the CI-CH risk scale, and data from 119 (10％) patients were used to test it. Risk factors for the CI-CH risk scale were identified by 2 screens, with two-tailed student ' s t-test and two-tailed Fisher ' s exact test preliminarily and with logistic regression analysis further. The scores of each risk factor for CI-CH risk scale were determined according to the odds rate, and the cut-off point was determined by Youden index. Results: Nine risk factors were ultimately selected for score system, including age (≥75 years old was ?1, <75 years old was 0), BMI (<24 kg/m2 was 0, 24?28 kg/m2 was ?1,>28 kg/m2 was?2), hypertension grade (grade 1 was 1, grade 2 was 2, and grade 3 was 3), diabetes status (no was 0, yes was?1), antihypertensive drug use (no was 0, yes was?2), alcohol consumption (<60 g/d was 1, ≥60 g/d was 2), uric acid (less than normal was 0, normal was?1, high than normal was?2), LDL cholesterol (<2 mmol/L was 0, 2?4 mmol/L was?1, and>4 mmol/L was?2), and HDL cholesterol (<1.55 mmol/L was 0,≥1.55 mmol/L was 2). Patients with a score more than 0 were classified as the CH group, Conversely, they were assigned to the CI group;its sensitivity, specificity, and accuracy were 74.5％, 77.9％, and 76.4％, respectively. Conclusion: The CI-CH risk scale can help the clinician predict the subtypes of cerebrovascular diseases.

Febrile infection-related epilepsy syndrome is a rare and one of the most serious epileptic encepha-lopathy.It commonly affects school-aged children who are healthy previously and have a normal developmental history.The patients suffer from a progressively worse seizure after several days of a nonspecific prior febrile and abruptly develop status epilepticus.It remains unclear about its etiology and pathogenesis.Although there is a lack of specific biological markers, poor treatment outcomes would usually be achieved, early identification and reasonable treatment may improve the prognosis.

Myelin oligodendrocyte glycoprotein(MOG)is expressed in oligodendrocytes of the mammalian central nervous system, which is located on the surface and an important component of the myelin sheath.MOG antibody related inflammatory demyelinating disease is a hot topic in the field of neurology in recent years, and its clinical phenotype spectrum varies.Currently, cell-based assay(CBA)is recommended to detect MOG antibodies in peripheral blood.Due to the complexity and diversity of the clinical manifestations, and different manifestations in different age groups, it is difficult to make the clinical diagnosis.The exact pathogenesis is still unclear, and the therapeutic options and long-term prognosis remain controversial.In this article, the pathogenesis, clinical manifestations, treatment options and clinical prognosis of MOG antibody related inflammatory demyelinating diseases will be reviewed.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective:To investigate the clinical and imaging characteristics of liver density changes in patients with initial-treated drug-sensitive secondary tuberculosis during standardized treatment and after withdrawal when cured.Methods:A retrospective analysis was conducted of 34 patients with initial-treated drug sensitive pulmonary tuberculosis in Beijing Chest Hospital of Capital Medical University and the First Affiliated Hospital of Xinxiang Medical University from January 2014 to April 2019. The chest computed tomography (CT) examination and sputum culture were performed before treatment. The patients received the standardized treatment and they were divided into three groups according to the course of treatment (three, nine and 12 months). Liver density and liver function were followed up during treatment (three, six, nine and 12 months) and after drug withdrawal (3, 6 and 12 months). The measurement data were analyzed by t-test. Results:The average liver density of these three groups gradually decreased during the treatment period, and gradually increased after drug withdrawal. There were five and nine cases of fatty liver occurred at three and six months of treatment in the six-month treatment group, respectively; and six, two and zero cases of fatty liver occurred at three, six, and 12 months after drug withdrawal, respectively. There were four, eight and 11 cases of fatty liver occurred at three, six, and nine months of treatment in the nine-month treatment group, respectively; and seven, two and zero cases occurred at three, six, and 12 months after drug withdrawal, respectively.There were five, 10, 14 and 14 cases of fatty liver occurred at three, six, nine and 12 months of treatment in the 12-month treatment group, respectively; and 12, 10 and five cases occurred at three, six, and 12 months after drug withdrawal, respectively. During the course of treatment, the density of livers of some cases decreased unevenly, and the density of right lobe of the liver was lower than the left lobe. The density of left lobe of the liver was (49.8±4.0) HU, (45.0±3.9) HU, (37.0±9.9) HU, (45.3±8.1) HU, (48.4±6.6) HU at the treatment of six, nine and 12 months and drug withdrawal of three and six months, and the density of right lobe of the liver was (44.0±6.1) HU, (37.2±7.7) HU, (25.5±15.8) HU, (38.5±11.7) HU, (43.8±9.9) HU, the differences were statistically significant ( t=4.611, 4.512, 2.307, 2.803 and 2.291, respectively, all P<0.05), while those were not statistically significant among three months of treatment and 12 months after drug withdrawal ( t=1.573 and 1.199, respectively, both P>0.05). There were two cases showed alanine aminotransferase (ALT) and aspartate amiotransferase (AST) accompanied elevated (ALT>2×upper limits of normal (ULN), AST<2×ULN) at three and six months of treatment, with no abnormalities detected of alkaline phosphatase (ALP) and total bilirubin (TBil). Conclusions:The liver density gradually decreases and uneven fatty liver could appear during anti-tuberculosis treatment, but it gradually returns to normal or relieves after drug withdrawal. The degree of fatty liver is not synchronized with the changes of liver function indexes (ALT, AST, ALP and TBil), which belongs to chronic reversible injury.