Objective:To investigate the clinical characteristics and possible causes of transient spontaneous remission of childhood acute leukemia.Methods:The data of 3 children with acute leukemia who had transient spontaneous remission before standardized chemotherapy in Sun Yat-sen Memorial Hospital of Sun Yat-sen University in July 2018, May 2019 and October 2020 were collected. Moreover, the related influencing factors of spontaneous remission in leukemia were discussed by review of the literature.Results:All 3 children had fever at the onset of the disease, and they achieved transient spontaneous remission after anti-infection therapy. Case 1 obtained partial remission after the initial diagnosis of acute B lymphocytic leukemia (B-ALL), leukemia gene test showed E2A-PBX1 fusion, and relapsed after 12 days. Case 2 obtained spontaneous remission after the initial diagnosis of B-ALL, leukemia gene test showed p16 gene deletion and NRAS and EP300 genes mutation, and relapsed after 20 days. Case 3 obtained spontaneous remission after the initial diagnosis of acute monocytic leukemia, leukemia gene test showed MLL-ENL fusion and NRAS gene mutation, and relapsed after 30 days. A review of the literature showed that the main influencing factors of spontaneous remission in leukemia were Down syndrome, infection and blood transfusion. Other influencing factors included leukemia-related genes, termination of pregnancy and application of drugs.Conclusions:Transient spontaneous remission of childhood acute leukemia is rare in clinical practice, and the possible mechanism is related to infection-induced immune abnormalities. It is recommended that leukemia patients with spontaneous remission should be closely monitored for minimal residual disease.

Objective:To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT).Methods:Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups.Results:Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group ( n=8), the course and total dose of eltrombopag in umbilical cord blood group ( n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients ( n=12) and non-malignant patients ( n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion:Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.

Objective:To explore the clinical characteristics and management of childhood acute lymphoblastic leukemia (ALL) complicated with cerebral venous thrombosis (CVT).Methods:The clinical data of 14 ALL children complicated with CVT who were admitted to Department of Pediatrics of Sun Yat-sen Memorial Hospital and underwent chemotherapy from January 2011 to October 2019 were collected retrospectively. The clinical manifestations, coagulation function, imaging findings, treatment plan and prognosis of patients were analyzed.Results:CVT was diagnosed in 14 (2.8%, 14/505) cases, with a median age of 10 (3-14) years at onset, 11 cases occurred in the stage of induction remission, and the acute onsets were mainly characterized by convulsions (9 cases), consciousness disorders (6 cases) and headache (4 cases). Coagulation function test showed that, before the CVT, antithrombin Ⅲ activity was lower than 60% in 8 cases, D-dimer elevated on the day of onset in 8 cases. Arteriovenous angiography showed filling defects in single (9 cases) or multiple (5 cases) venous sinuses. The most common site of venous sinus enlargement was superior sagittal sinus (10 cases). Secondary cerebral hemorrhage was found in 5 cases. Anticoagulation therapy included combination of low-molecular-weight heparin (LMWH) and warfarin in 9 cases, sequential application of LMWH and warfarin in 2 cases, and LMWH alone in 3 cases. Patients accepted further asparaginase and no CVT recurrence or progression was found.Conclusions:The secondary coagulation dysfunction during induction remission chemotherapy is the major risk factor for CVT in ALL, which needs active monitoring and early prevention. Arteriovenous angiography can diagnose accurately, and the prognosis of anticoagulant therapy with LMWH and warfarin is optimistic.

Platelet is an important component of human blood, which plays a key role in the physiological and pathological processes. Recently, novel drug delivery system based on platelet and platelet membrane bionics attracted much attention. Compared to the traditional drug carriers, platelet and platelet membrane-based biomimetic drug delivery system has great performances in biocompatibility, longer circulation and stronger ability of targeting. This review presented the features, classifications, drug-loading and applications of platelet and platelet membrane-based biomimetic drug delivery systems, promoting their development and application in the future.

Objective: To study the diagnostic strategy of β-thalassemia through retrospective analysis of 3 cases of β-thalassemia. Methods: Three patients were admitted to the Department of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2014 to June 2015. The clinical manifestations, hemoglobin electrophoresis and gene detection of these patients and their parents were analyzed, diagnostic ideas and key points were discussed when beta thalassemia gene detection did not explain clinical manifestations or hemoglobin electrophoresis. Results: Case 1, boy, 5 years old, was diagnosed as compound heterozygotes of β41-42 and IVS-Ⅱ-654 with hereditary persistence of fetal hemoglobin(HPFH) according to the clinical manifestations of mild anemia, normal size of liver and spleen, 92.8% fetal hemoglobin (HbF) and gene analysis. Case 2, girl, 3 years old, was confirmed the diagnosis of thalassemia intermedia with β41-42 heterozygote compound and ααα^anti3.7 heterozygote in accordance with the manifestations of severe anemia, hepatosplenomegaly, 8.6% HbF, 4.1% hemoglobin A₂(HbA₂) and gene analysis. Case 3, girl, 3 years old, with severe anemia, hepatosplenomegaly, 51.2% HbF and 3.7% HbA₂, was diagnosed as thalassemia major with compound heterozygotes of PolyA (T→C) and β17 by DNA sequencing. Conclusion The diagnosis of β-thalassemia should be confirmed by clinical manifestations of hemolytic anemia, hemoglobin electrophoresis, gene diagnosis and family survey.

OBJECTIVETo determine the detection rate and distribution characteristics of colorectal adenomas in Ningbo area of China, and to identify the risk factors for colorectal adenoma, in order to provide reference for colorectal cancer screening.

METHODSA cross-sectional study was performed among 8660 subjects undergoing colonoscopy in the Ningbo No.2 Hospital between January and December 2016, using a questionnaire, including demographic data (age, gender, height and weight), history of diseases (diabetes, hypertension, hyperlipidemia, and family history of malignant neoplasm), lifestyle (smoking, alcohol, dietary bias on red meat, dietary bias on fruit and vegetables, dietary frequency of pickled food and physical activities), and intestinal early warning symptoms. All colonoscopically detected polyps were removed for histological examination. Polyps were histologically divided into non-adenomatous (hyperplastic polyps and inflammatory polyps) and adenomatous polyps (tubular, villous, tubulovillous and serrated adenomas). Pathologic features were analyzed according to anatomical site. Multivariate logistic regression analysis was used to identify the risk factors for colorectal adenoma.

RESULTSA total of 7077 subjects who received colonoscopic examination and completed the questionnaire survey were enrolled in this study. There were 3633 males and 3444 females with a median age of 53 (ranged 17 to 83) years. Adenoma detection rate was 15.6% (1103/7077) in all cases, 21.0%(762/3633) for males, and 9.9%(341/3444) for females(P=0.000). Detection rate of 6.2%(29/469) was recorded in individuals aged less than 30 years, 8.0%(87/1086) in those from 30 to 39 years, 12.1%(148/1222) in those from 40 to 49 years, 16.8%(272/1623) in those from 50 to 59 years, 20.4%(326/1601) in those from 60 to 69 years, and 22.4%(241/1076) in those ≥70 years. The detection rate increased according to age(P=0.000). A total of 1521 adenomas were detected in 1103 cases, including 1455 tubular adenomas, 33 tubulovillous adenomas, 9 villous adenomas and 24 serrated adenomas. Among 1521 adenomas, 44.1%(n=671) located in the right hemicolon, 39.0%(n=593) in the left hemicolon, and 16.9%(n=257) in the rectum. Significantly larger number of serrated adenomas and advanced adenomas (advanced adenoma was defined as any adenoma with high-grade intraepithelial neoplasia, diameter ≥10 mm or with villous component) was observed in the right hemicolon compared to left hemicolon and rectum [serrated adenomas: 2.5%(17/671) vs. 0.8% (5/593) and 0.8% (2/257), P=0.029; advanced adenoma: 9.2% (62/671) vs. 5.2% (31/953) and 6.6% (17/257), P=0.021]. Multivariate analysis showed that malely (P=0.003), elderly (P=0.000), obesity (P=0.014), smoking (P=0.001), alcohol (P=0.032), and family history of malignancy (P=0.000) were independent risk factors of colorectal adenoma.

CONCLUSIONSIn view of a higher detection rate of colorectal adenoma in population aged 40 to 49 years especially in male individuals, the starting age of colonoscopy screening may be advanced to 40 years old. People with family history of malignancy, obesity, and habit of smoking or drinking should be regarded as important subjects for colonoscopy screening. During colonoscopy screening, special emphasis should be given to right hemicolon.

Adenoma ; diagnosis ; epidemiology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Colonic Polyps ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Young Adult

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
APOBEC-1 Deaminase ; genetics ; metabolism ; Base Sequence ; Blastomeres ; cytology ; metabolism ; CRISPR-Cas Systems ; Embryo, Mammalian ; metabolism ; pathology ; Female ; Fibroblasts ; metabolism ; pathology ; Gene Editing ; methods ; Gene Expression ; HEK293 Cells ; Heterozygote ; Homozygote ; Humans ; Point Mutation ; Primary Cell Culture ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; beta-Globins ; genetics ; metabolism ; beta-Thalassemia ; genetics ; metabolism ; pathology ; therapy

Objective To evaluate the effect of self-management education based on nurse-leading on the quality of life in patients with chronic heart failure (CHF).Methods Eighty patients with CHF in a tertiary hospital were enrolled in this study,and were divided into the intervention group and the control group randomly,with 40 cases in each group. Patients in the control group received conventional health education, while patients in the intervention group received the self-management education based on nurse-leading. The score of self-management behavior and the quality of life in two groups were evaluated and compared after six months.Results After six months,the score of self-management in the intervention group was (70.83±12.02), and was significantly higher than that in the control group (55.58±6.46) (t=9.675,P<0.05). The score of total quality of life and self-management in the intervention group was significantly higher than that in the control group (P<0.05).Conclusions Self-management education based on nurse-leading can improve the self-management and the quality of life of patients with CHF.

OBJECTIVETo evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD).

METHODSA retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B.

RESULTSOverall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects.

CONCLUSIONFor IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Child ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Hematologic Diseases ; microbiology ; Humans ; Mycoses ; drug therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Objective To explore the bone marrow stromal cells,anti-late antigen-4 (VLA-4) antibody (aVLA-4),cytarabine (Ara-C) on the proliferation and apoptosis of leukemia HL-60 cells.Methods The experiment was divided into five groups:HL-60 cells were cultured alone (control group),HL-60 cells and stromal cells group (stromal cells group),HL-60 cells + stromal cells + aVLA-4 (antibody group),HL-60 cells + stromal cells + Ara-C group (drug group),HL-60 cells + stromal cells + aVLA-4 + Ara-C group (antibody +drug group).Cell proliferation or inhibition rate was detected by CCK-8 method,the HL-60 cells apoptosis was detected by flow cytometry.The expression of anti-apoptotic gene bcl-2 in HL-60 cells was determined by Western blot.Results After 24 h and 48 h,treatment,the number of the stromal cells group HL-60 cells were higher than that of the control group with significant difference cultured [(7.2±0.3)×1O5/ml vs (5.3±0.4)×105/ml,(8.4±0.2)×105/ml vs (6.8±0.3)×105/m1,P ＜ 0.001],while the HL-60 cell proliferation inhibition rate [(24.3±2.1) ％,(37.0±2.6) ％,(65.6±3.8) ％] and apoptosis rate [(5.7±0.6) ％,(8.0±0.5) ％,(10.4±0.9) ％,(16.5±0.7) ％] of antibody group,drug group,antibody + drug group were higher than the control group with a difference of statistically significant (P ＜ 0.05),and the increase of antibody + drug group was most obvious.With the decreasing of the bcl-2 protein expression,which was most the decrease of antibody + drug group was most obvious.Conclusion Bone marrow stromal cells can stimulate the proliferation of leukemia cells,aVLA-4 interference the interaction between stromal cells and leukemia cells can enhance the chemosensitivity of leukemia cells to Ara-C.