Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective:To analyze the efficacy and influencing factors of cyclosporine(CsA)alone in the treatment of children with acquired aplastic anemia(AA).Methods:The clinical data of children diagnosed with AA and treated with CsA alone from January 1,2016 to December 31,2020 in the Children's Hospital of Chongqing Medical University were collected,and the efficacy and influencing factors of CsA treatment were evaluated.Results:Among the 119 patients,there were 62 male and 57 female,with a median age of 7 years and 1 month.There were 45 cases of very severe AA(VSAA),47 cases of severe AA(SAA),and 27 cases of non-severe AA(NSAA).At 6 months after treatment,the efficacy of VSAA was lower than that of SAA and NSAA,and there was a statistical difference(P＜0.01).6 cases died early,16 cases relapsed,2 cases progressed to AML and ALL.The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA,while high PLT count was a protective factor(P=0.008,P=0.002).The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5 × 109/L,68.5％,respectively.Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST(P=0.020,OR=0.062),and high PLT count was a protective factor(P=0.044,OR=1.038).At 3 months of treatment,CsA response and NSAA were the risk factor for recurrence(P=0.001,0.031).Conclusion:The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone.A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA,and a high proportion of bone marrow lymphocyte was an unfavorable factor.CsA response at 3 months and NSAA were risk factors for recurrence.

Objective : To investigate the effects of gestational diabetes mellitus (GDM) on birth outcome and umbilical artery (UA) blood flow parameters in the third trimester, and to analyze the role of UA blood flow parameters in GDM and birth outcome. Methods : Based on the birth cohort from Wuhu , Anhui , China , 189 pregnant women with GDM were collected as the case group. The non⁃GDM pregnant women were matched 1 ∶ 1 according to age and pre⁃pregnancy body mass index , and 189 normal pregnant women were selected as the control group. Pregnant women with GDM were divided into poorly controlled group and well controlled group according to fasting blood glucose in the third trimester. The UA blood flow parameters and fetal birth outcomes in the third trimester were tracked. Results : Compared with the control group , UA parameters in poorly controlled and well controlled groups significantly increased (F = 6. 63 , P < 0. 05 ; F = 4. 43 , P < 0. 05 ; F = 5. 57 , P < 0. 05) . Poor glycemic control of GDM was associated with increased birth weight and risk of larger than gestational age. The multi⁃factor linear regression model showed that the Z score of the peak systolic velocity/end diastolic velocity (S/D) in the poorly controlled group was negatively correlated with birth weight (β = - 209. 78 , 95% CI: - 301. 48 - 118. 07) . S/D index Z score mediated the relationship between poor blood glucose control and birth weight. The intermediate effect value was - 58. 41 (95% CI: - 106. 40 ~ - 19. 65) , accounting for 25. 98% of the total effect. Conclusion Poor glycemic control in GDM is a risk factor for fetal weight gain , and UA function plays a partial mediating role in influencing neonatal birth weight. GDM pregnant women should strictly control blood glucose level to better protect maternal and infant health.

OBJECTIVE: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876). METHODS: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23). RESULTS: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4⁺CD29⁺ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4⁺CD29⁺ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8⁺CD28^- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8⁺CD28^- T / CD8⁺CD28⁺ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P₃=0.01, P₇=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P₃=0.0351; P₇=0.0142; P₁₄=0.0369). CONCLUSION We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Kinetics ; Myeloid-Derived Suppressor Cells ; Nitriles ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Steroids

Objective : To investigate the correlation between nocturnal sleep duration combined with snoring in the first trimester of pregnancyand small for gestational age(SGA) ，large for gestational age(LGA) ． Methods : Multi- variate Logistic regression model was used to analyze the association between nocturnal sleep duration ，snoring， their combined effects and SGA，LGA. Results : Compared to nocturnal sleep duration 7 to 9 h in the first trimester of pregnancy，sleep duration＜7 h was positively correlated with SGA in male newborn( OR = 4. 22，95% CI : 1. 69 - 10. 52) ; After stratified by snoring，the sleep duration of snoring women＜7 h was positively correlated with SGA ( OR = 5. 68，95% CI : 1. 02－31. 51) ，and the sleep duration of non-snoring women＜7 h was positively correlated with LGA ( OR = 2. 10，95% CI : 1. 16 －3. 81) ． Conclusion Sleep duration＜7 h in the first trimester of preg- nancy is a risk factor for SGA and LGA，and snoring may enhance the association between sleep duration＜7 h in the first trimester of pregnancy and SGA．Pregnant women should keep adequate nocturnal sleep duration to reduce the risk of abnormal neonatal weight.

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group ( RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% ( CONCLUSIONS ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.
Acute Disease ; Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children ( CONCLUSIONS MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.
Child ; Disease Progression ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Neoplasm, Residual ; Prognosis

OBJECTIVE: To investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT). METHODS: Female Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation. RESULTS: In the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P＜0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P＜0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P＜0.05). CONCLUSION MDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.
Animals ; Drugs, Chinese Herbal ; Female ; Hematopoietic Stem Cell Transplantation ; Hematopoietic System ; Mice ; Spleen

OBJECTIVETo examine the association of genetic variants with characteristic symptoms of type 2 diabetes mellitus (T2DM).

METHODSA matched case-control study was performed to investigate the association between common variants in four genes (CDKAL1, GLIS3, GRK5, and TCF7L2) and symptoms of T2DM. Symptoms were examined with questionnaire for 710 subjects. Genomic DNA was extracted from peripheral blood mononuclear cell by salting-out procedure. Genotyping was carried out by direct sequencing of the unpurified polymerase chain reaction products.

RESULTMost of the T2DM patients pressented characteristic symptoms, such as feeling weak in limbs (P =0.0057), hand tremor (P =0.0208), bradymasesis (P =0.0234), and polyuria (P =0.0051). Some of the T2DM patients shared characteristic symptoms, such as desire for cold drinks (P =0.0304), polyphagia (P =0.0051), and furred tongue (P =0.028). The impaired glucose regulation (IGR) cases took only one characteristic symptom of frequent micturition (P =0.0422). GLIS3 rs7034200 and GRK5 rs10886471 were significantly associated with increased T2DM risk (GLIS3 rs7034200 under dominant model: P=0.0307; GRK5 rs10886471 under recessive model: P=0.0092). However, only the rs10886471 polymorphism in GRK5 showed a significant effect on both differentiated symptoms and T2DM risk. The C-allele was involved in both dampness-heat encumbering Pi (Spleen) syndrome (P =0.047) and qi-yin deficiency syndrome (P =0.002) via increased GRK5 expression.

CONCLUSIONSBoth T2DM and IGR exhibited its corresponding characteristic symptoms. The variants of GRK5 were involved with both qi-yin deficiency syndrome and dampness-heat encumbering Pi syndrome.

Muscle-derived stem cells (MDSC) are a population of multipotent stem cells in the muscular tissue. It provide an excellent prospect of hemopathy treatment due to their superiorities, such as rich sources, convenient material resource and a high survival rate after transplantation and so on. However, there are great differences in sampling, separation, purification, and proliferation when MDSC were cultured in vitro. In addition, the proliferation conditions of the MDSC in vitro are yet unclear. The related regulatory mechanisms, which MDSC transformed into haematopoietic cells, need to be investigated. In this article, the experimental researches on the differentiation of MDSC into haematopoietic lineages are reviewed, the concrete problems discussed in this review are culture of MDSC in vitro, identification of MDSC, proleferation of MDSC, differention of MDSC in to hematopoietic lineages and so on.