Astrocytes play a key role in maintaining the homeostasis and function of the central nervous system. Abnormal lipid accumulation, ferroptosis, elevated lactic acid, and high DNA methylation mediated by astrocytes in their own or toxic states are particularly closely related to seizures. In recent years, epilepsy treatment from astrocyte energy metabolism perspective has become a research hotspot. Metabolic therapy, such as ketogenic diet, can inhibit seizures via a variety of mechanisms as astrocyte homeostasis maintenance. This paper reviews the relationship between astrocyte energy metabolism and epilepsy pathogenesis and its related metabolic therapy, in order to provide new ideas for clinical treatment of drug-resistant epilepsy.

Vertebrobasilar dolichoectasia (VBD) is a cerebrovascular variant disease. Researches have shown that further development of VBD may lead to severe disability and even death. The pathogenesis of VBD is still unclear, and there is no specific clinical prevention and treatment scheme. Therefore, establishing a stable and reliable animal model helps to further understand the pathophysiological mechanisms and potential therapeutic targets of VBD. This article reviews the establishment methods and research progress of the available VBD animal models.

Diet can be both a trigger and a treatment for migraine. The effects of alcohol, dairy products and pickled foods on migraine have been highly recognized. The effects of plant foods and caffeine on migraine currently have 2 sides. Ketogenic diet (KD), modified Atkins diet (MAD), and high n-3 fatty acid/low n-6 fatty acid diet can improve migraine through protecting nerves, improving mitochondrial function and energy metabolism, reducing calcitonin gene-related peptide (CGRP) levels, and inhibiting neuroinflammation. In this paper, the recent advance in the above content is summarized as follows.

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.
Aged ; Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; Hyperplasia ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell/pathology* ; Male ; Middle Aged ; Neprilysin ; Programmed Cell Death 1 Receptor ; Retrospective Studies

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics* ; Epigenesis, Genetic ; Fanconi Anemia/genetics* ; Germ Cells ; Hematologic Neoplasms/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Retrospective Studies

OBJECTIVE: To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation. RESULTS: CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×10⁶/kg and (4.23±2.33)×10⁶/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×10⁶/kg and (1.87±1.37)×10⁶/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1). CONCLUSION The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;
Antigens, CD34 ; Benzylamines ; Cyclams ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Heterocyclic Compounds ; Humans ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies

Objective: To investigate the application of metagenomic next-generation sequencing (mNGS) in detection of the rare or difficult-to-cultivate pathogens. Methods: One patient with acute lymphoblastic leukemia who went through allogeneic hematopoietic stem cell transplantation (allo-HSCT) developed symptoms of infection after transplantation. Conventional microbial culture, polymerase chain reaction (PCR), and mNGS combined with biological information analysis were performed with plasma and cerebrospinal fluid samples, the anti-infective treatment was adjusted according to the test results, and the efficacy was assessed. Results: No suspected pathogens were detected by microbial culture and PCR in the cerebrospinal fluid and plasma samples since the patient developed infection symptoms. However, Legionella pneumophila was analyzed by mNGS in the cerebrospinal fluid specimen on day 23 after allo-HSCT (reads count: 19 655), and it was considered as the principal pathogen after comprehensively evaluating the patient's clinical manifestations and the test results. Then the antimicrobial treatments were adjusted according to the patient's clinical manifestations and laboratory test results, and the number of gene sequences of Legionella pneumophila was monitored by mNGS method. Azithromycin, tigecycline, and other antibiotics effective for Legionella pneumophila were used after detecting this pathogen. A total of 15 mNGS analysis were performed during the 5-month period, and the highest number of Legionella pneumophila sequences monitored in the cerebrospinal fluid was 2 226, the lowest was 253 and eventually turned negative. The clinical symptoms and treatment outcomes were consistent with the mNGS monitoring results. Conclusions The mNGS technology has significant value in detection of the rare and difficult-to-cultivate pathogens. The mNGS technology provides a valuable supplement to microbial culture and PCR methods.

Objective: To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement. Methods: The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT). Results: Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×10(9)/L, 39.4% greater than 50 × 10(9)/L respectively on admission. M(5) (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×10(9)/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%). Conclusion: AML patients with FLT3-ITD and MLL gene rearrangement often presented with M(5), accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3

OBJECTIVETo study the significance of flow cytometric monitoring minimal residual diseases (MRD) in patients with acute leukemia (AL) after allogeneic hemapoietic stem cell transplantation (HSCT).

METHODSFrom January 2007 and January 2008 MRD were detected by flow cytometry (FCM) in 402 bone marrow (BM) in 102 AL patients without leukemic gene and chromosomal changes at first diagnosis after HSCT (1, 2, 3, 6,12 months after HSCT; adding detection frequency in part of high risk patients), The relationship between the MRD results and clinical prognosis were observed. Patients with significantly higher MRD were treated and the effectiveness was monitored by FCM (MRD > 0.01% considered as positive).

RESULTS(1) 71 cases were persistently negative for MRD after HSCT and all them were in hematologic complete remission (CR). Only 3 cases had extramedullary relapse. The disease free survival (DFS) and overall survival (OS) were 66.2% and 90.1%, respectively. (2) Of 27 MRD(+) cases 11 converted to MRD negativity after chemotherapy plus donor lymphocyte infusion (DLI), CIK, NK cells. The DFS and OS were 63.6% and 72.7%, respectively. Other 16 cases had hematologic relapse. The DFS and OS were 11.1% and 25.0%, respectively. The median time from MRD increasing to hematologic relapse was 48 days (7-69 day). (3) Four cases had hematologic relapse after HSCT and died in the end.

CONCLUSIONS(1) The DFS and the OS in MRD(-) cases are significantly higher than those of MRD(+) cases. (2)MRD(+) patients after HSCT coveted to MRD(-) after intervention. Therapy, whose DFS and the OS are still significantly higher than those of MRD(+) cases. (3) Patients with hematologic relapse after HSCT have the worst prognosis and the DFS and OS are significantly low. FCM monitoring of MRD in patients after HSCT is a sensitive, specific, quick and simple method. It can indicate recurrent state in time, facilitates early intervention, reduces the hematologic relapse risk and improves DFS.

Adolescent ; Adult ; Child ; Female ; Flow Cytometry ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; surgery ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; Postoperative Period ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

OBJECTIVETo retrospectively analyze the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on childhood chronic myelogenous leukemia (CML).

METHODOf the 24 consecutive cases, 16 were boys and 8 were girls. The median age of patients was 12 (3 - 16) years old; 16 cases were in chronic phase (CP) of CML, 1 case in accelerated phase (AP) and 5 cases in blastic phase (BP). Allo-HSCT from HLA identical siblings were performed for 5 cases, HLA haplotype was performed for 14 cases and unrelated allo-HSCT for 5 cases. Twenty-four cases underwent allo-HSCT with conditioning regimen of BUCY. Prophylaxis of graft versus host disease (GVHD) included CsA + MTX plus MMF. The average follow-up was 36 months.

RESULTAll of patients were successfully engrafted. The 5-year overall survival (OS) of the 24 cases was 81%. Four patients died after allo-HSCT including 3 cases in BP from haploidentical donors and 1 case in CP from HLA identical sibling. The 5 cases who received unrelated allo-HSCT have been alive. Among the 10 cases who survived over 5 years, 3 had chronic GVHD.

CONCLUSIONChildren with CML could be treated effectively with allo-HSCT. There were no significant differences among different donors. Transplantation to children with CML should be performed as early as possible. Preparative regimen adjustment before transplantation, the transplantation of associated comorbidities and effective prevention and treatment for CML patients after prolonged graft survival of high quality have important significance.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Graft vs Host Disease ; mortality ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; therapy ; Male ; Methotrexate ; administration & dosage ; Retrospective Studies ; Survival Analysis ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome