OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To investigate the role of multiple serological methods in the identification of complex antibodies. METHODS: The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. RESULTS: The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jk^a antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies. CONCLUSION It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies exist in the patient's serum by multiple serological methods.
Humans ; Papain ; Blood Group Antigens ; Erythrocytes ; Immunoglobulin G ; Immunoglobulin M

Humans ; Anniversaries and Special Events ; Hypersensitivity

Objective: To analyze the clinical characteristics of patients with Mucopolysaccharidosis ⅣA (MPS ⅣA). Methods: A retrospective study was conducted on 111 patients with MPS ⅣA in Xinhua Hospital of Shanghai Jiao Tong University School of Medcine from December 2008 to August 2020, confirmed by enzyme activity and genetic testing. General situation, clinical manifestations and enzyme activity test results were analyzed. According to the clinical manifestations, it can be divided into severe, intermediate and mild group. The independent sample t test was used to compare the birth body length and weight of children with that of normal boys and girls, and group comparisons of enzyme activities were evaluated by median test. Results: One hundred and eleven unrelated patients, 69 males and 42 females, were classified into 3 subtypes: severe (n=85), intermediate (n=14), and mild (n=12). The age at symptom onset were 1.6 (1.0, 3.0) years, and at diagnosis were 4.3 (2.8, 7.8) years. Skeletal manifestations were observed in all patients and consisted mainly of pectus carinatum (96/111, 86.5%), motor dysfunction (78/111, 70.3%), spinal deformity (71/111, 64.0%), growth retardation (64/111, 57.7%), joint laxity (63/111, 56.8%) and genu valgum (62/111, 55.9%). Eighty-eight patients (88/111, 79.3%) with MPS ⅣA were also along with non-skeletal manifestations, mainly including snoring (38/111, 34.2%), coarse faces (34/111, 30.6%), and visual impairment (26/111, 23.4%). The most common skeletal manifestation was pectus carinatum (79 cases), and non-skeletal manifestation was snoring (30 cases) and coarse faces (30 cases) in severe patients, pectus carinatum (13 cases) and snoring (5 cases) in intermediate type, motor dysfunction (11 cases) and snoring (3 cases) and visual impairment (3 cases) in mild patients. The height and weight of severe patients began to fall below -2 s at 2-<5 years and 5-<7 years, respectively. At the age of 10-<15 years, the standard deviation score of the height of severe patients reached (-6.2±1.6) s in males and (-6.4±1.2) s in females, and the score of weight got (-3.0±1.1) s in males and (-3.5±0.5) s in females. The height of intermediate patients began to fall below -2 s at the age of 7-<10 years, and the standard deviation score of height were -4.6 s and -3.6 s in 2 males, and -4.6 s and -3.8 s in 2 females at the age of 10-<15 years. The weight remained within -2 s in 72.0% (18/25) of intermediate patients compared to age-matched healthy children. In the mild patients with MPS ⅣA, the mean standard deviation score of height and weight was within -2 s. The enzyme activities of mild patients (2.02 (1.05, 8.20) nmol/(17 h·mg)) were both significantly higher than that of intermediate (0.57 (0.47, 0.94) nmol/(17 h·mg)) and severe (0.22 (0, 0.59) nmol/(17 h·mg)) patients (Z=9.91, 13.98, P=0.005, 0.001), and the enzyme activity of intermediate patients was significantly higher than that of severe patients (Z=8.56, P=0.010). Conclusions: The clinical manifestations of MPS ⅣA are charactered by pectus carinatum, motor function impairment, spinal deformity and growth retardation. The clinical characteristics, growth rate and enzyme activity differ among the 3 subtypes of MPS ⅣA.
Male ; Child ; Female ; Humans ; Adolescent ; Mucopolysaccharidosis IV ; Pectus Carinatum ; Retrospective Studies ; Snoring ; China ; Mucopolysaccharidoses ; Growth Disorders ; Vision Disorders

Abstract: Objective　To analyze the serotype distribution, drug resistance rate and drug resistance gene carrying of Streptococcus pneumoniae isolates in hospitalized patients, and evaluate the coverage of the vaccine to the serotype of Streptococcus pneumoniae in this area, so as to provide reference for the rational use of antibiotics in clinic. Methods　A total of 150 strains of non-repetitive Streptococcus pneumoniae isolated from inpatients from January 2015 to December 2019 were collected for serotyping and antimicrobial sensitivity test. The carrying rates of pbp2b, ermB and tetM were detected by PCR. Results　The PCR classification rate of 150 strains of Streptococcus pneumoniae was 93.1%, and the classification rate of capsular swelling test was 100%, and a total of 19 serotypes were divided, mainly 19F and 6B. Children's serotypes were predominantly 19F, 6B, and 15A; adult serotypes were predominantly 19F, 14, and 23F. The coverage rates of the PCV7, PCV10, PCV13 and PPV23 vaccines were 36.8%, 42.1%, 57.9% and 68.4%, respectively. Strains with serotypes of 19F, 6B, 3, and 23F had higher rates of resistance to antimicrobials. The sensitivity of Streptococcus pneumoniae to penicillin was greater than 96.0%. Antimicrobials with significant differences in resistance rates between invasive and non-invasive strains were penicillin, moxifloxacin, and levofloxacin. The percentage of strains carrying both ermB and tetM resistance genes was 96.0%, and the concordance rate between pbp2b, ermB and tetM resistance genes and the resistance phenotype was >98.0%. A total of 10 multi-resistance combinations were detected, with a multi-resistance rate of 62.6%, and the multi-drug resistance pattern of Streptococcus pneumoniae was mainly concentrated in the 19F and 6B serotypes. Conclusion　There are significant age differences in the serotypes of Streptococcus pneumoniae in this area. The vaccine currently used has low coverage in this region and therefore offer limited protection to the population. The drug resistance rates of Streptococcus pneumoniae varied significantly among serotypes. Erythromycin and tetracycline are not recommended for clinical treatment of Streptococcus pneumoniae. Penicillin can still be used as the first choice for clinical treatment of Streptococcus pneumoniae infection.

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

This study was designed to investigate the role of activation of the ferroptosis pathway in the inhibition of esophageal cancer proliferation and metastasis by realgar, using esophageal cancer Eca109 and KYSE150 cells as the target cells. The rate of inhibition and half-inhibitory concentration (IC₅₀) were measured by the CCK-8 method; clone formation ability was measured by clone formation assay; the changes in reactive oxygen species (ROS) were detected by flow cytometry; the ultrastructure of the cells was observed by transmission electron microscopy; the distribution of intracellular iron particles was observed by Prussian blue staining; the expression of glutathione peroxidase 4 (GPX4) was detected by immunofluorescence staining; the scratch assay was used to detect the cell migration ability; the Transwell assay was used to detect the cell invasion ability; and western blotting was used to detect E-cadherin, Slug and N-cadherin protein expression in the cells. The results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells in a time- and concentration-dependent manner, and the IC₅₀ of Eca109 and KYSE150 cells was 64.297 and 51.337 μmol‧L^-1, respectively. Compared with the control group, many mitochondria in the cytoplasm of Eca109 and KYSE150 cells in the realgar 2IC₅₀ group were swollen and blue-stained particles of different sizes and amounts were found, and ROS fluorescence intensity was significantly increased while GPX4 protein expression was significantly reduced (P < 0.01). Compared with the realgar group, the proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly increased, and the cell inhibition rate and E-cadherin protein expression were significantly decreased in Eca109 and KYSE150 cells in the realgar+ZVAD-FMK group (P < 0.05). The proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly decreased, and the cell inhibition rate and E-cadherin protein expression were significantly increased of Eca109 and KYSE150 cells in the realgar +erastin group (P < 0.05). The above results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells and induced partial ferroptosis in the cells, and the proliferation and metastasis effects of realgar on esophageal cancer cells may work through partial ferroptosis pathway activation.

Daturae Flos is a traditional antitussive and antiasthmatic medicine， its flowers and leaves are rich in a variety of compounds， including withanolides， alkaloids， terpenes， flavonoids and amides. Because of its antiasthmatic， antitussive， antispasmodic and analgesia effect， it is traditionally used for the treatment of asthma， cough， cold pain in abdominal cavity， rheumatic arthralgia， infantile chronic eclampsia， and can also be used as raw material for surgical anesthesia. Modern pharmacological studies have shown that in addition to the traditional efficacy， Daturae Flos also has anti-inflammatory， immunosuppression， anti-convulsion and other effects， and is often used in the treatment of psoriasis， Parkinson's disease， epilepsy， rheumatoid arthritis and other diseases. At present， the chemical constituents of Daturae Flos are mainly focused on withanolides and alkaloids. At the same time， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts of this medicine， and little information is available for the pharmacological effects of polysaccharides. Based on this， this paper systematically searched relevant literature of Daturae Flos， and summarized and analyzed its chemical composition， pharmacological effect and clinical application， in order to provide reference for further development and utilization of Daturae Flos.

Objective To explore the effect of cadmium chloride on mitochondrial function of hematopoietic stem cells in mouse bone marrow .Methods After being quarantined for one week , male Kunming mice weighted 20 ±2 g were randomly divided into three groups: control group , low dose cadmium-exposure group and high dose cadmium-exposure group.Mice in low dose and high dose cadmium-exposure groups were exposed to cadmium chloride solution at a dose of 7.5, 15 mg/kg body mass while those in control group were given an equal volume of distilled water through gavage administration every Monday , Wednesday and Friday for six consecutive weeks before cells in mouse bone marrow were collected at the 8th week.Mitochondrial membrane potential and ROS levels of mouse hematopoietic stem cells were detected using a flow cytometry .Results Compared with control group , the gain of body weight was significantly suppressed in cadmium-exposure group (P<0.01).Compared with control group, mitochondrial ROS levels of hematopoietic stem cells significantly increased in cadmium-exposure group and was dose-related(P<0.05,P<0.01). Besides, mitochondrial membrane potential of hematopoietic stem cells decreased in cadmium -exposure group compared with control group and was dose-related(P<0.05,P<0.01).Conclusion Cadmium exposure can lead to dose-related mitochondrial dysfunction of hematopoietic stem cells via oxidative damage in Kunming mice .