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.

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 understand the clinical manifestations, diagnosis, treatment, and prognosis of children with hereditary thrombocytopenia (HT).Methods:The clinical data of 5 patients with HT in the Hematology and Oncology Department of Children′s Hospital of Chongqing Medical University from August 2015 to October 2017 were retrospectively analyzed. The clinical and laboratory characteristics, treatment, and prognosis of HT were discussed by reviewing relevant literatures.Results:Five patients included 3 boys and 2 girls.The median age at onset of 4 years and 2 months old and the median age at diagnose was 4 years and 4 months old.All patients presented with the thrombocytopenia, among which 4 cases were macrothrombocytopenia and 1 case was normothrombocytopenia.The main clinical presentations of 5 patients were skin petechiae and ecchymoses.Four cases were initially misdiagnosed as immune thrombocytopenia (ITP) and received the glucocorticoid and immunoglobulin, while the therapeutic effect was not satisfactory.The gene sequencing confirmed MYH9 gene mutation(c.3493C>T), MYH9 gene mutation(c.5878G>A), NBEAL2 gene compound heterozygous mutation(c.295C>T; c.4169C>T), GP1BA gene mutation(c.1761A>C), and ANKRD26 gene mutation(c.5123A>G), in 5 patients respectively. Conclusions:HT should be suspected among those with recurrent isolated thrombocytopenia and no response to the ITP regimen, and the early gene screening is of great significance to the patients′ treatment and prognosis.

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

OBJECTIVE: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. METHODS: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. RESULTS: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028). CONCLUSIONS SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.
Antineoplastic Agents ; adverse effects ; Child ; Gram-Negative Bacteria ; Humans ; Neutrophils ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Retrospective Studies ; Risk Factors

Objective: To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice. Methods: A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively. Results: (1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05). Conclusions The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.

OBJECTIVE: To evaluate the clinical significance of primary tumor volume(PTV) by preoperative highresolution MRI measurement in subgroup of cT3 low rectal cancer. METHODS: A total of 99 patients with low rectal cancer who confirmed by pathology and assessed at stage-cT3 by MRI,did not undergo neoadjuvant chemoradiotherapy(nCRT) treated in Department of Colorectal Surgery,Fujian Medical University Union Hospital from June 2010 to December 2012 were adopted in the study. The relations between PTV and the depths of tumor infiltration out of mesorectum were analyzed through Spearman correlation analysis. The receiver-operating characteristic(ROC) curve was used to analyze the PTV and 3-year disease-free survival. Cox proportional hazard model was performed for influence factors analysis. RESULTS: The depth of tumor infiltration mesorectum and the PTV were revealed significantly correlated(P<0.001,r=0.457). The average PTV was 2.1-56.5(16.4±10.3)cm~3. ROC showed the best cutoff point of PTV 14.8 cm~3,the area under the curve was 0.829(95%CI 0.745-0.913,P<0.001). Taking the integer 15 cm~3 or 14.8 cm~3,the authors divided the patients into PTV≤ 15 cm~3/> 15 cm~3 or PTV≤14.8 cm~3/>14.8 cm~3. The difference between groups revealed significant in the 3-year disease-free survival rate,the local recurrence rate and the distant metastases rate.COX regression analysis was utilized for 3-year disease-free survival,and the multivariate analysis indicated that PTV was an independent impact factor(HR=0.180,95%CI 0.078-0.415,P<0.05). CONCLUSION: The primary tumor volume (PTV) by preoperative high-resolution MRI measurement might be used as a new prognostic parameter for cT3 low rectal cancer.

De novo variants (DNVs) are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Presently, a plethora of DNVs have been identified using next-generation sequencing, and many efforts have been made to understand their impact at the gene level. However, there has been little exploration of the effects at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues. Therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate a better usage and improve the isoform-level interpretation of variants, we developed NeuroPsychiatric Mutation Knowledge Base (PsyMuKB). It contains a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.

To minimize the predatory harvest of Heterosmilax yunnanensis and maintain the sustainable utilization of its resources, a study on the tending technology of wild H. yunnanensis was carried out. The results showed that the tuber tending model had a higher seed emergence rate, shorter growth period and easier control of male and female ratios than other tending models; by removing shrubs, topping, bending pruning, controlling insects and pests and other effective technical measures, the growth period of H. yunnanensis was shortened; the average annual net income of the tending area was 1 086 yuan/mu (1 mu≈666.67 m²), which was 86.9% higher than before. This study was conducive to increasing the yield and quality of H. yunnanensis in Karst landform area, and instructive for the tending of other wild traditional Chinese medicinal herbs in this area.
Female ; Humans ; Male ; Smilacaceae