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Objective:To analyze the clinical characteristics and prognostic factors of high-risk neuroblastoma (HR-NB) patients with skeletal metastasis.Methods:The clinical features of 336 newly treated HR-NB patients with skeletal metastases admitted to the Department of Medical Oncology of Beijing Children′s Hospital, Capital Medical University from January 2007 to December 2018 were analyzed retrospectively.Kaplan-Meier method was used for the survival analysis, and Log- Rank test was used for univariate prognosis analysis.The Cox model was used to analyze the multifactorial prognostic analysis. Results:A total of 336 HR-NB patients were recruited, involving 188 males and 148 females with the median age of onset of at 43 (4-148) months.Skeletal metastases affected the viscerocranium (89 cases, 26.5%), neurocranium (193 cases, 57.4%), vertebrae (298 cases, 88.7%), sternum and ribs (183 cases, 54.5%), pelvis (270 cases, 80.4%), upper limbs (182 cases, 54.2%) and lower limbs (240 cases, 71.4%). The 5-year event-free survival (EFS) rate and overall survival (OS) rate were (30.4±2.7)% and (41.3±2.9)%, respectively.Univariate analysis showed a significantly lower 5-year OS rate in skeletal metastatic HR-NB patients with poor prognostic classification, the morphology of neuroblastoma (stroma-poor) and ganglioneuroblastoma (intermixed), high index of mitosis-karyorrhexis index, lactate dehydrogenase≥587 U/L, serum ferritin≥92 μg/L, MYCN amplification and 1p loss of heterozygosity, and metastases in the viscerocranium, neurocranium, vertebrae, sternum and ribs, pelvis, upper limbs and lower limbs (all P<0.05). The 5-year OS rate of HR-NB patients with all 7 regions of skeletal metastases was only (14.2±5.9)%, which was significantly lower than that in patients with a single region metastasis or multi-region metastases[(66.0±10.2)% vs.(43.6±3.4)%, χ2=45.722, P<0.05]. Cox multifactorial analysis showed that MYCN amplification ( HR=4.165, 95% CI: 2.356-7.363) and the viscerocranium metastasis ( HR=2.560, 95% CI: 1.519-4.315) were the independent risk factors affecting the prognosis of HR-NB patients with skeletal metastases (all P<0.05). Conclusions:The prognosis is extremely poor in HR-NB patients with multiple skeletal metastases at the initial diagnosis.The amplification of MYCN and the viscerocranium metastasis are the poor prognostic factors for HR-NB patients with skeletal metastases.
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【Objective】 To carry out serological and molecular biological identification of B (A) subtype, and discuss the rational blood transfusion strategy. 【Methods】 Serological and direct sequencing methods were used to detect serotype and genotype of 7 cases of B (A) subtype, and cross matching was performed by saline medium and anti human globulin card to analyze the red blood cells(RBCs) transfusion strategy. 【Results】 The serology results of blood type of 7 samples were similar, with B(A)04/O01 in 3 cases, B(A)04/O02 in 2 cases and B(A)02/O01 in 2 cases. 7 cases of B (A) subtypes were matched with randomly selected blood donors of type O and B on the major side. 【Conclusion】 B(A) subtypes should be identified by genotyping techniques. Washed RBCs of type B and O can be used for B(A) blood type transfusion.
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Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.
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The 71st Annual Meeting of American College of Cardiology(ACC) was held online and onsite from April 2 to April 4, 2022 in Washington, D. C. As one of the most influential academic annual meeting in the field of cardiovascular diseases, the ACC annual meeting delivers the most advanced research progress and academic hotspots in the field of cardiovascular diseases to the world. As diabetes is a high risk factor for cardiovascular disease and is closely related to heart failure, atherosclerotic cardiovascular disease and so on, this article summarizes the academic advances in the field of diabetes-related cardiovascular disease at the conference, with the aim of providing cutting-edge information for the clinical management of patients.
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Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.
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OBJECTIVE To s tudy the impr ovement effects of tilianin on the atherosclerosis （AS）model mice and its potential mechanism. METHODS Eight C 57BL/6J mice were taken as the normal group. Forty ApoE－/－ mice were randomly divided into model group ，tilianin low-dose ，medium-dose and high-dose groups [ 2.1，3.5，7.0 mg/（kg·d）] and simvastatin group [positive control drug ，3.5 mg/（kg·d）]，with 8 mice in each group. Normal group was given normal diet ，and other groups were given high-lipid diet to induce AS model. At the same time ，normal group and model group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，once a day ，for 12 consecutive weeks. The levels of TC ，TG， LDL-C，HDL-C，Ox-LDL，IL-1β，IL-6，MCP-1 and TNF-α in plasma were determined. The pathomorphological changes of the aorta in mice were observed. The positive rate of ICAM- 1，VCAM-1 and PCNA in the aorta were determined. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as protein expressions of TGF-β1，Smad2/3 and p-Smad 2/3 were also determined in aorta of mice. RESULTS Compared with normal group ，the plasma levels of TC ，TG，LDL-C，Ox-LDL，IL-1β， IL-6，MCP-1 and TNF-α in model group were increased significantly（P＜0.01），while HDL-C level was significantly reduced （P＜0.01）. Lipid plaques were formed in the aorta ，and the plaque area was large and caused severe stenosis of the lumen. mRNA expressions of MMP- 2，MMP-9，TGF-β1，Smad2 and Smad 3 as well as positive rate of ICAM- 1，VCAM-1，PCNA and protein expression TGF-β1，Smad2/3，and p-Smad 2/3 in the aorta were significantly increased （P＜0.01）. Compared with model group ， most of above indexes of medication groups were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Tilianin can inhibit the activation of TGF-β1/Smads signaling pathway and then inhibit the proliferation of vascular smooth muscle cells ，reduce ， inflammation and regulate lipid metabolism to inhibit the No.81960766） formation of AS.
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Objective:To evaluate the performance of magnetic beads extraction method (MGE) for the measurement of catecholamine metabolites by liquid chromatography tandem mass spectrometry.Methods:This is a methodological evaluation study. The linearity, limit of quantitation, recovery, precision, and matrix effect of catecholamine metabolites 3-methoxyepinephrine (MN), 3-methoxynorepinephrine (NMN) and 3-methoxytyramine (3-MT) extracted by MGE method were evaluated according to CLSI C62-A. Consensus of method development and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories and other guidelines, 132 clinical residual plasma samples were collected and extracted by automated MGE and traditional solid phase extraction (SPE) method to compare the harmonization of the two extraction methods.Results:The linearity of MN, NMN and 3-MT extracted by automated MGE was>0.99, and the LOQ for MN, NMN and 3-MT were 0.033 5 nmol/L, 0.054 7 nmol/L and 0.011 0 nmol/L, respectively. The repeatability of MN, NMN and 3-MT were 1.3%-5.1%, 2.2%-5.6% and 1.7%-7.1%, respectively. The total imprecision in the laboratory were 1.5%-8.2%, 2.2%-7.7%, 2.1%-11.2%. Although the absolute recovery is low, the average relative recoveries of MN, NMN and 3-MT were 91.5%-108.5%, 92.0%-108.6%, and 89.3%-104.1%, respectively, and the percentage deviation from the expected concentration was within 15%. After isotope internal standard correction, the relative matrix effect is close to 100%, which can compensate for the potential matrix effect. The results of MGE and SPE of MN, NMN and 3-MT showeda good correlation (correlation coefficient r>0.99). The average relative deviations of MN, NMN and 3-MT were 0.2%, -1.4% and 1.0%, respectively. Conclusion:The automatic MGE method hasa good performance in extracting catecholamine metabolites, and is expected to be used in high-throughput analysis of samples in clinical in the future.
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Objective:To observe and analyze the clinical characteristics of children who died of intraocular retinoblastoma (RB).Methods:A retrospective clinical study. Fourteen children (23 eyes) with intraocular RB who died after receiving treatment in Beijing Children's Hospital from 2009 to 2017 were included in the study. Among the children, there were 7 males (10 eyes) and 7 females (13 eyes); 5 had unilateral and 9 had bilateral tumor. Age were 17.2±15.5 months. All children underwent RetCam examination. RB was staged according to the international intraocular RB classify. Among the 23 eyes, 1 eye was in stage B, 2 eyes were in stage C, 12 eyes in stage D, and 8 eyes in stage E. Treatment methods included a systemic (vincristine, etoposide and carboplatin) chemotherapy (VEC chemotherapy), enucleation surgery, and vitrectomy. The basic conditions including age, time of diagnosis, pathological diagnosis, treatment and main causes of death were retrospectively analyzed.Results:Among the 14 cases, the first symptom was leukemia in 12 cases, red eye in 1 case, and squintin in 1 case. Systemic VEC chemotherapy was used for 1-6 courses of treatment; 5 cases were enucleated, 3 cases underwent histopathological examination; 3 cases were treated with vitrectomy. Among the 3 cases who underwent histopathological examination, the sclera and optic nerve, optic nerve and optic disc were invasted respectively. Seven patients died of tumor metastasis and/or intracranial lesions (50.0%, 7/14); the median survival time was 19 months. Four patients died of treatment (28.6%, 4/14), including 3 patients died of chemotherapy-related side effects, and 1 died of organ failure after enucleation surgery (7.1%); the median survival time was 3.5 months. Early abandonment of treatment died in 3 cases (21.4%, 3/14); the median survival time was 15 months.Conclusion:Intracranial metastasis is the main cause of death in children with intraocular RB.
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Objective:To summarize the clinical features of neuroblastoma (NB) with bone metastasis in infants and the prognostic factors.Methods:A retrospective analysis was performed on 32 patients aged ≤12 months who were enrolled in Beijing Children′s Hospital, Capital Medical University from January 2010 to December 2019 and had imaging findings suggesting signs of distant bone metastasis.The control group was included NB children, aged ≤12 months, who were admitted to Beijing Children′s Hospital, Capital Medical University during the same period, without signs of distant bone destruction.The clinical manifestations and auxiliary examinations of infants with bone metastasis were summarized, and the efficacy evaluation and survival analysis of infants with regular treatment and follow-up were conducted until December 31, 2020. Kaplan- Meier survival analysis was used for prognostic analysis, and Log Rank test was used for univariate prognostic analysis. Results:There were 32 NB infants with bone metastases, involving 12 males (37.5%) and 20 females (62.5%), accounting for 16.0% (32/200 cases) of infants diagnosed with NB du-ring the same period.The median age of onset was 9 (4.5-12.0) months.The main primary site included the retroperitoneal and adrenal region in 24 cases(75.0%) and mediastinum in 3 cases (9.4%). Among the 32 cases, 14 cases (43.8%) had simple bone metastasis, 19 cases (59.4%) had distant lymph nodes, 18 cases (56.3%) had bone marrow, and 3 cases (9.4%) had intracranial and meningeal metastasis.Bone metastasis mainly occurred in the skull, with 11 cases of single bone metastases and the remaining with 2 or more bone metastases.Compared with 168 NB infants without bone metastasis, the prognosis of those with bone metastasis was significantly worse [3-year overall survival(OS) rate 97.6% vs.82.7%, P=0.001]. Univariate analysis showed that the prognosis of NB children with bone marrow metastasis, meningeal and intracranial metastasis, MYCN gene amplification, and high-risk group was poor (all P<0.05). Two patients returned to the local hospital for treatment after diagnosis.A total of 30 children were recruited for efficacy evaluation and prognostic analysis.Twenty-nine children underwent surgery, of which 6 cases received surgery before chemotherapy and 23 cases received surgery after chemotherapy.One case received chemotherapy only.The mean course of chemotherapy was 6.2 (4-13) times.One case was treated with radiotherapy, 1 case was treated with Metaiodobenzylguanidine (MIBG) therapy, and 1 case was treated with stem cell transplantation.A total of 18 cases (62.1%) event-free survived, and 12 cases (40.0%) had a mean event at 7 (1.5-32.0) months.Among them, 7 cases survived and 5 cases died (16.7%). The expected 3-year event-free survival rate and OS rate were 57.1% and 82.7%, respectively. Conclusions:The most common sites of infant NB metastasis are bone and bone marrow, and the most common sites of bone metastasis are skull.Infants with bone metastasis had a worse prognosis than those without bone metastasis, and infants with bone and bone marrow metastasis had a worse prognosis than infants with single bone metastasis.
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To analyze the clinical characteristics, treatment and prognosis of mediastinal germ cell tumors (GCTs) with concurrent hematologic malignancy (HM). The clinical features, treatment and prognosis of 3 cases of HM associated with mediastinal GCTs treated in the Department of Medical Oncology, Beijing Children′s Hospital from November 2014 to September 2018 were retrospectively analyzed.Meanwhile, relevant cases were searched in the PubMed and Wanfang database from their establishment to December 2019.Three male cases of HM associated with mediastinal GCTs aged from 12 to 16 years.The pathogenesis of mediastinal masses suggested teratoma or yolk sac tumor.All of them were treated with surgery and chemotherapy.Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) was diagnosed respectively at 5 months, 9 months and 31 months after initial GCTs in the 3 cases.Two patients died and 1 child survived at the last follow-up.A total of 135 cases of concurrent GCTs and HM (or leukemia) were reviewed in online databases, involving 127 cases (94.1%) with the mediastinal GCTs associated with HM and 8 cases(5.9%) with GCTs related HM from another original sites.One hundred and twenty-six cases (99.2%) were male and the median age of GCTs diagnosis was 22 (10-48) years.Fifty-three cases (41.7%) were teratoma and 94 cases (74.0%) were GCTs containing teratoma with or without yolk sac tumor.Among the types of HM, 72 cases (56.7%) were AML and 31 cases (24.4%) were AML-M7.The median interval between GCTs and HM was 3 (0-122) months.Forty-six cases (36.2%) presented 2 malignancies simultaneously.HM were diagnosed within 12 months of GCTs in 85 cases (66.9%). The survival data were known in 107 cases, involving 94 (87.9%) deaths and 13 (12.1%) survivors.The median survival time after diagnosis of HM was 2 (0-48) months.The tendency of HM must be highly concerned in adolescent male patients with primary mediastinal GCTs, especially those with yolk sac tumor or teratoma.Their prognoses are very poor.Allogeneic hematopoietic stem cell transplantation is an alternative treatment.
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Objective:To analyze the clinical characteristics and prognosis of infants with rhabdomyosarcoma (RMS), thus enhancing the understanding of this disease.Methods:Clinical data of all RMS patients younger than 12 months treated in the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from May 2006 to June 2019 were retrospectively analyzed, including the age, gender, histological type, tumor primary site, tumor size, and the prognosis.Patients were followed up until December 31, 2019.The 3-year event free survival (EFS) rate of children was performed by plotting the Kaplan-Meier survival curves.Results:A total of 15 RMS children younger than 12 months were enrolled, accounting for 4.9% of all RMS cases in the same period, including 6 males and 9 females.The median age at diagnosis was 7.0 months (3.0-11.5 months). Classified by the primary site, 40.0% (6 cases) located in the head and neck, followed by 26.7% (4 cases) located in the limbs, 26.7% (4 cases) located in other parts, and 6.7% (1 case) located in the urogenital system.Embryonal RMS, alveolar RMS and spindle cell RMS accounted for 46.6% (7 cases), 26.7% (4 cases), and 26.7% (4 cases), respectively.Ten cases (66.7%) were stage Intergroup Rhabdomyosarcoma Study (IRS)-Ⅲ and 1 case (6.7%) was in stage Ⅳ.There were 10 cases (66.6%) in the middle-risk group, 4 cases (26.7%) in the low-risk group, and 1 case (6.7%) in the high-risk group.Two cases had a larger than 5 cm primary tumor; lymph node involvement was confirmed in 3 cases, and pulmonary metastasis occurred in 1 case at the time of diagnosis.All children were treated with chemotherapy, and 13 cases received postoperative chemotherapy and 1 case received preoperative chemotherapy.One case were not operated.Only 3 children underwent radiotherapy, including 1 case underwent particle implantation and 2 cases received external radiotherapy.Among the 15 children with RMS, 5 cases had relapse and disease progression with the 3-year EFS rate of (59.1±14.5)%, and 2 died with the 3-year overall survival rate of (80.8±12.6)%.Conclusions:The median age of diagnosis of RMS in single-center infants is 7 months.Head and neck are the most common primary sites of RMS.Nearly 50% of the children have the primary site of RMS with poor prognosis.More than a quarter of the pathological subtypes are the spindle cell type.Local treatment significantly influences the local progression or recurrence of RMS.
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Objective:To explore the clinical significance of the MYCN gene, PHOX2B gene and plasma cell-free DNA (cfDNA) in risk stratification and predicting the prognosis of high-risk neuroblastoma (NB). Methods:This was a prospective study involving 94 high-risk NB children admitted to Beijing Children′s Hospital, Capital Medical University from August 2017 to December 2018.Relative levels of MYCN and PHOX2B and cfDNA at diagnosis, and 4 and 6 cycles of chemotherapy were detected, and their differences were compared by the Chi- square test.Kaplan-Meier survival analysis was performed to explore their prognostic potential in high-risk NB. Results:Among the 94 high-risk NB children, 14 cases (14.9%) had MYCN amplification, 76 cases (80.8%) had positive expression of PHOX2B and 56 cases (59.6%) had cfDNA level higher than 100 μg/L.The proportion of high lactate dehydrogenase (LDH, ≥1 500 U/L) level in the MYCN gene amplification group (6/14 cases) was higher than that in the normal group (9/80 cases) ( P=0.009). The proportion of multi-site metastasis (54/76 cases) and high neuron specific enolase (NSE) level (NSE≥370 μg/L, 37/76 cases) in PHOX2B positive group were significantly higher than those in the negative group (5/14 cases, 2/14 cases) ( P=0.015, 0.020). The proportion of high LDH and high NSE in high cfDNA concentration (≥229.6 μg/L)group (13/37 cases, 28/37 cases) were significantly higher than those in low cfDNA concentration group (2/48 cases, 10/48 cases) (all P<0.001). With the decreased tumor burden during the treatment, the copy number of PHOX2B gene and cfDNA level were significantly lower than those at the initial diagnosis [0 (0-719.6) copies vs.1 723.5 (0-186 000.0) copies; 19.0 (1.1-225.5) μg/L vs.200.6 (8.0-5 247.4) μg/L, all P<0.001]. The 2-year event-free survival (EFS) rate of the MYCN gene amplification group was significantly lower than that of the normal group[(33.3±13.1)% vs.(58.5±7.1)%, P=0.020]. The 2-year EFS rate of PHOX2B positive group was significantly lower than that of the negative group[(47.9±7.1)% vs.(79.1±11.1)%, P=0.043]. EFS rate in high cfDNA concentration group was significantly lower than that in cfDNA low concentration group[(38.6±9.8)% vs.( 71.7±8.2)%, P=0.001]. After 6 cycles of chemotherapy, EFS rate in the PHOX2B positive group was significantly lower than that in the negative group [(16.7±14.4)% vs.( 60.6±6.6)%, P=0.014]; which was significantly lower in the Metaiodobenzylguanidine (MIBG) positive group than that of the negative group[(35.2±11.7)% vs.(65.8±7.1)%, P=0.037]. The MYCN gene and cfDNA concentration were not correlated with the prognosis of high-risk NB.Survival analysis of the combination of PHOX2B and MYCN gene ( PHOX2B+ /MIBG + , PHOX2B+ or MIBG + , PHOX2B-/MIBG -) showed a significant difference in the survival among three groups[0 vs.(53.6±1.2)% vs.(65.5±7.4)%, P=0.003]. Conclusions:The MYCN and PHOX2B gene and cfDNA concentration are of significance in risk stratification and predicting the prognosis of high-risk NB.Compared with the MYCN gene and cfDNA concentration, the PHOX2B gene is more suitable for monitoring the curative effect of chemotherapy on high-risk NB.A combined analysis of PHOX2B gene and MIBG before treatment can be more accurate in evaluating the treatment effect and residual lesions.
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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.
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Humans , Anemia, Aplastic/genetics , Epigenesis, Genetic , Fanconi Anemia/genetics , Germ Cells , Hematologic Neoplasms/genetics , Leukemia, Myeloid, Acute/genetics , Retrospective StudiesABSTRACT
【Objective】 To analyze and master the serological and genetic characteristics of the samples with CisAB subtype and their genetic background. 【Methods】 From January 2018 to January 2022, blood samples with discrepant ABO blood typing results, from Zhengzhou voluntary blood donors and hospital patients, were subjected to phenotypic classification using micro column gel card and tube method, as well as amplification of exons 6 and 7 in ABO gene using PCR. The pedigrees of individuals with the same CisAB subtype but different serological typing results in the same family were analyzed. 【Results】 11 The forward typing of 12 samples was AB type, and unexpected antibodies against weaker antigens were found in 11 serum samples, including 9 cases with strong antigen A, 2 cases with strong antigen B, and 1 case with consistent forward and reverse typing results. Gene sequencing confirmed that 11 cases were CisAB01 subtype and 1 case was CisAB05 subtype.Among them, 7 cases had the genotype of CisAB01/O and serological phenotype of A2B3; 2 cases had the genotype of CisAB01/B and phenotype of A2B; 2 cases had the genotype of CisAB01/A and serological phenotype of A1Bx and A1B3; 1 case had the phenotype of AxB. In the CisAB01 family, 1 case of CisAB01/O with A2B3 phenotype and 1 case of CisAB01/B with A2B phenotype were detected. In the CisAB05 family, 2 CisAB05/O01 and 1 CisAB05/O02 were detected. 【Conclusion】 The serological phenotypes of different individuals in the same CisAB01 family can be different when paired with different ABO alleles. It is advisable to accurately identify the CisAB subtype genes with molecular biological methods to ensure blood transfusion safety.
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Objective:To summarize the clinical characteristics of single-center children with low and intermediate-risk neuroblastoma (NB), report the long-term follow-up results of the growth and survival quality, and provide a basis for further clinical research.Methods:Clinical characteristics, including the sex, age, stage, risk of disease, and metastatic site of 370 newly treated children with low and intermediate-risk NB admitted to Hematology Oncology Center, Beijing Children′s Hospital from March 2007 to June 2019 were retrospectively analyzed.Kaplan-Meier method was used for survival analysis.WHO Anthro Plus was used for calculating Z score.Results:A total of 370 eligible children with low and intermediate-risk NB were included, with the mean age at onset of 16.8 months (1-191 months). Among them, 148 cases (40%) were younger than 12 months old.Mediastinal region was the most common primary site of NB (47.8%, 177 cases), followed by retroperitoneum/adrenal gland (41.4%, 153 cases). The median follow-up time of 370 patients was 31 months (0.3-157.0 months), the 5-years event free survival (EFS) and 5-year overall survival (OS) were 86.2% and 96.9%, respectively.Thirty-seven cases had growth and deve-lopment problems, of which 22 cases had stunted growth, 6 cases had low body mass, 9 cases had wasting, and 7.3%(27/370 cases) had scoliosis.5.5% of them had heart damage and 5.0%(18/357 cases) had kidney damage, involving 12 cases related to the primary tumor and 6 cases were surgically related.30.2%(95/315 cases) of them had hair changed after chemotherapy, and curly hair was the most common change.Compared with before treatment, 14.9% of the children had a personality change, with an impatient being the most common.Conclusions:The 5-year overall survival rate of the single-center large sample of low and intermediate-risk NB was high, mediastinal was the most common primary site of tumor, and the long-term quality of life is good, but there were still treatment-related side effects, and further clinical monitoring and long-term follow-up were needed.
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Objective:To summarize the causes of death and severe complication in the early diagnosis of children with neuroblastoma (NB), and to analyze the relative factors of early death of children with NB, so as to raise awareness and reduce early mortality by early detection and early intervention.Methods:Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively, and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients, immediate causes of death, complications, time elapsed between death and diagnosis, whether to receive chemotherapy and other information were collected.Results:A total of 654 cases were included for diagnosis, treatment and follow-up, 31 cases of which died in early stage, accounting for 4.7% of the total.The major complication were pulmonary infection in 18 cases (58.1%) and bone marrow suppression after chemotherapy in 17 cases (54.8%), tumor rupture hemorrhage in 16 cases (51.6%), multiple organ failure in 8 cases (25.8%). Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis: there were statistical differences between early death group and non-early death group in risk grouping ( P=0.006 6), bone marrow invasion ( P=0.020 7), site of primary tumor ( P=0.016 7), age ( P=0.003 3), lactate dehydrogenase (LDH) level ( P<0.000 1), neuron-specific enolase (NSE) level ( P<0.000 1), serum ferritin level ( P=0.016 0), D dimer level ( P<0.000 1), fibrinogen level ( P=0.002 7), diameter of tumor ( P<0.000 1), hemoglobin ( P<0.000 1), platelet level ( P<0.000 1), serum albumin level ( P<0.000 1). Multiple-factor analysis: age younger than 30 months, OR=2.824 (95% CI: 1.084-7.359), LDH level greater than 1 004 IU/L, OR=6.991 (95% CI: 2.135-22.887), albumin level less than 36 g/L, OR= 65.237 (95% CI: 2.024-13.545), hemoglobin level less than 92 g/L, OR=5.358 (95% CI: 2.024-13.545), platelet level less than 192×10 9/L, OR=3.554 (95% CI: 1.267-9.965). Conclusions:Strengthening vital signs detection after admission, identifying severe life-threatening complications such as rupture of tumors as early as possible, implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation, and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.
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Objective:To summarize the clinical characteristics, treatment response and long-term postoperative complications in children with neuroblastoma (NB) in the pelvic and sacral regions as the primary site.Methods:The clinical characteristics of 16 NB children (8 males and 8 females) with primary pelvic and sacral admitted to the Department of Hematology Oncology Center in Beijing Children′s Hospital, Capital Medical University from March 2007 to June 2019 were analyzed retrospectively with respect to the age at first diagnosis, primary tumor site, tumor size, clinical stage, risk grouping, and other clinical characteristics.The clinical characteristics of the patients who were followed up for regular treatment were analyzed, and the postoperative complications of the patients were summarized, and the Kaplan-Meier method was used for survival analysis.Results:The median age at diagnosis of these 16 children was 23.0 months (5.7-102.0 months), of which 6 cases (37.5%) were younger than 12 months old.All these children received chemotherapy, with a median of 6 (1-8) courses of chemotherapy.Fifteen children received surgical resection of the pelvic tumor, with complete resection in 12 cases (80%). The surgical approach was mainly transabdominal (86.7%, 13/16 cases). The median follow-up time of these children was 33.5 (8-136) months.The patella was absent in 3 patients (18.8%) after the operation, and no permanent neurological damage occurred in all patients.Five-year overall survival (OS) rate was 100%.Conclusions:A single-center summary showed a high survival rate for NB patients in the pelvic and sacral regions.Complete tumor resections combined with chemotherapy could be effective measures and rare cases occurred permanent postoperative neurological complications.
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Objective:To investigate the clinical characteristics, treatment effect and prognosis of children with nearly diploid neuroblastoma (NB).Methods:A retrospective analysis of the general clinical characteristics (including age, Gender, risk grouping, location of primary tumor, etc.), laboratory test results, treatment and recent prognosis of NB children with nearly diploidy in bone marrow chromosomes by G-banding technology who admitted to Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2018. Kaplan- Meier method was adopted to calculate survival rate.Univariate analysis was performed using Log- Rank test, and multivariate analysis was conducted with Cox regression model. Results:A total of 43 patients, including 27 males and 16 females, with diagnosis were included, with 14 cases in the hypodiploid group and 29 cases in the hyperdiploid group, and the median age was 35.5 months.The 43 children were all in the high-risk group of International Neuroblastoma Staging System(INSS)-Ⅳ.The primary tumors were mainly located in the retroperitoneal adrenal region (83.7%, 36/43 cases). The largest diameter of the tumors was more than 10 cm (53.5%, 23/43 cases), and often accompanied by 2 or more metastases at the time of consultation.In terms of chromosome karyotype and chromosome karyotype of 14 children in the hypodiploid group was 41-45, the most common karyotype was 45 chromosomes[9 cases(64.3%)]. Among 29 children in the hyperdiploid group of the 47 chromosome karyotypes, 11 cases were common (37.9%). Tumor markers were as follows: neuron enolase (NSE) increased in 41 cases children (95.3%) at first diagnosis, and 25 cases (58.1%)> 370 μg/L; 42 cases (97.7%)had lactate dehydrogenase (LDH). The LDH of children in the hypodiploid group was all> 500 U/L, with 1 case was> 10 000 U/L.Nine cases (20.9%) of MYCN gene were detected by fluorescence in situ hybridization (FISH). Treatment and prognosis: the total course of chemotherapy for 43 patients was 1-12, 19(44.2%) patients received autologous stem cell transplantation, 21 patients (46.5%) received postoperative or autologous radiotherapy or metaiodobenzylguanidine treatment, 28 children developed or relapsed with a median duration of 13.8 months, and 15 cases (34.9%) died.The median follow-up time of the 14 children in the hypodiploid group was 14.9 months (2-38 months), 12 cases progressed or relapsed, and 7 died.The median follow-up of 29 children in the hyperdiploid group was 20.0 months (8.1-51.6 months), with 16 patients progressed or relapsed and 8 cases died. Kaplan- Meier survival analysis illustrated that the 3-year projected event free survival (EFS) rate of 43 children was 18.4%, of which 17.1% were in the hypodiploid group and 29.8% in the hyperdiploid group. Conclusions:Preliminary analysis reveals that children with nearly diploid NB are mostly in the stage Ⅳ high-risk group over the age of 18 months, and 2 or more metastases at the time of consultation.The 3-year estimated EFS of 43 children was 18.4%, and the prognosis was worse in the hypodiploid group.
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Embryonal tumors of central nervous system (CNS) are highly invasive malignant tumors that mainly affect infants.Even if the current active treatment strategies are given, the prognosis is still very poor.The 2016 World Health Organization(WHO) classification integrates the genetic information of diseases with histopathology, so as to make the classification and diagnosis of these tumors more accurate.In the new classification, embryonal tumors of CNS include the most common medulloblastoma, and the rare embryonal tumor with multilayered rosettes, C19MC-altered, embryonal tumor with multilayered rosettes, not otherwise specified (NOS), medulloepithelioma, CNS neuroblastoma, CNS ganglioneuroblastoma, CNS embryonal tumor, NOS, atypical teratoid rhabdoid tumor, and CNS embryonal tumor with rhabdoid features.Further study and exploration on the biological nature of these rare brain tumors will provide scientific basis for new treatment methods.
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OBJECTIVE：To s tudy the effects of Dracocephalum moldavica total flavonoids （TFDM）on AMPK/SIRT 1/PGC-1α signaling pathway ，and to explore the mechanism of its protective effect on myocardial ischemia reperfusion injury （MIRI）rats. METHODS：Totally 50 healthy male SD rats were randomly divided into sham operation group ，model group ，TFDM group [ 60 mg/（kg·d），by extract] ，Compound C+TFDM group [ig administration of 60 mg/（kg·d）TFDM+intravenous injection of 250 μg/kg Compound C（AMPK inhibitor ）via tail vein 15 min before reperfusion] ，EX-527+TFDM group [ig administration of 60 mg/ （kg·d）TFDM+ip injection of 5 mg/kg EX- 527（SIRT1 inhibitor）20 min before reperfusion] ，with 10 rats in each group. They were given relevant medicine intragastrically ，once a day ，for consecutive 7 days. After last ig administration ，sham operation group underwent sham operation ，other 4 groups were established MIRI model by ligating left anterior descending coronary artery ， ischemia for 30 min and reperfusion for 2 h. After reperfusion ，the myocardial histopathological changes were observed by HE staining；RP-HPLC method was used to determine the contents of ATP ，ADP，AMP and NAD + in cardiac tissue. mRNA expressions of AMPK ，SIRT1 and PGC- 1α were detected by quantitative real-time PCR assay. Western blotting assay was the expressions of SIRT 1 and PGC- 1α protein in myocardium. RESULTS： Compared with sham operation group ， model group showed myocardial fib ers arranged disorder and horizontal stripes disappearance ，cell swelling burst and necrosis ，and nuclei deformation displacement ；the contents of ATP and NAD+，mRNA expression of AMPK ，SIRT1 and PGC- 1α，protein expression of SIRT 1 and PGC- 1α in cardiac tissue were decreased significantly （P＜0.05 or P＜0.01）；the contents of ADP and AMP ，the phosphorylation level of AMPK protein were increased significantly （P＜0.01）. Compared with model group ，myocardial pathological morphology were improved significantly in TFDM group ；the contents of ATP and NAD + in cardiac tissue ，mRNA expression of AMPK ，SIRT1 and PGC- 1α，the phosphorylation level of AMPK protein ，the protein expression of SIRT 1 and PGC- 1α were increased significantly（P＜0.05 or P＜ 0.01），while the contents of ADP and AMP were decreased significantly （P＜0.01）. Compared with TFDM group ，improvement effects of Compound C + TFDM group and EX- 527 + TFDM group on above indexes were reversed （P＜0.05 or P＜0.01）. CONCLUSIONS：TFDM may play a protective role on myocardium by activating AMPK/SIRT 1/PGC-1α signaling pathway and regulating energy metabolism.