Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).@*METHODS@#Six children with R/R-ALL who received blinatumomab treatment from August 2021 to August 2022 were included as subjects, and a retrospective analysis was performed for their clinical data.@*RESULTS@#Among the six children, there were three boys and three girls, with a median age of 10.5 (5.0-13.0) years at the time of inclusion. Of all six children, one had refractory ALL and did not achieve remission after several times of chemotherapy, and 5 relapsed for the first time, with a median time of 30 (9-60) months from diagnosis to relapse. Minimal residual disease (MRD) before treatment was 15.50% (0.08%-78.30%). Three children achieved complete remission after treatment, among whom two had negative conversion of MRD. Five children had cytokine release syndrome (CRS), among whom 3 had grade 1 CRS and 2 had grade 2 CRS. Four children were bridged to allogeneic hematopoietic stem cell transplantation, with a median interval of 50 (40-70) days from blinatumomab treatment to transplantation. The six children were followed up for a median time of 170 days, and the results showed an overall survival rate of 41.7% (95%CI: 5.6%-76.7%) and a median survival time of 126 (95%CI: 53-199) days.@*CONCLUSIONS@#Blinatumomab has good short-term safety and effectiveness in the treatment of childhood R/R-ALL, and its long-term effectiveness needs to be confirmed by studies with a larger sample size.

Anticancer Activity of Diosgenin and Its Molecular Mechanism / 中国结合医学杂志

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.

Effect of different maintenance doses of caffeine citrate on ventilator weaning in very preterm infants with respiratory distress syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the effect of different maintenance doses of caffeine citrate on the success rate of ventilator weaning in very preterm infants (gestational age of ≤32 weeks) with respiratory distress syndrome (RDS).@*METHODS@#A total of 162 preterm infants with RDS who were admitted to the hospital from January 2016 to December 2018 were enrolled in this prospective trial. These infants had a gestational age of ≤32 weeks and required invasive mechanical ventilation. They were randomly divided into a high-dose caffeine group and a low-dose caffeine group, with 81 infants in each group. Within 6 hours after birth, both groups were given caffeine at a dose of 20 mg/kg. After 24 hours, the high- and low-dose caffeine groups were given caffeine at a maintenance dose of 10 mg/kg and 5 mg/kg, respectively. The two groups were compared in terms of re-intubation rate within 48 hours after ventilator weaning, durations of ventilation and oxygen therapy, enteral feeding, weight gain, and the incidence rates of complications and adverse reactions during hospitalization.@*RESULTS@#The high-dose caffeine group had a significantly lower re-intubation rate within 48 hours after ventilator weaning than the low-dose caffeine group (@*CONCLUSIONS@#A high maintenance dose of caffeine can safely and effectively reduce the incidence rate of apnea after ventilator weaning and the failure rate of ventilator weaning in RDS preterm infants with a gestational age of ≤32 weeks, and therefore, it holds promise for clinical application.

Salivary microbial communities associated with severe early childhood caries / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To compare the salivary microbial profiles of healthy subjects and those with severe early childhood caries (S-ECC) by using high-throughput sequencing.</p><p><b>METHODS</b>Salivary samples were obtained from children with S-ECC (group C, n=24) and healthy children (group H, n=24). Total metagenomic DNA was extracted, and DNA amplicons of the V1-V3 hypervariable region of the 16S rRNA gene were generated and subjected to 454 sequencing. The characteristics of oral microbial communities from the two groups were compared based on microbial diversity and taxonomy assignment.</p><p><b>RESULTS</b>First, the microbial richness was significantly higher in group C than group H (P<0.05). Second, the microbial community structure was significantly different for the groups H and C (P<0.01). In addition, caries microbiota was significantly conserved in group C (P<0.001). High expression of suspected cariogenic microorganisms in group C (P<0.1) and health related microorganisms in group H (P<0.1) were identified. Finally, models of caries risk assessment were proposed to distinguish caries from healthy subjects with over 70% accuracy.</p><p><b>CONCLUSIONS</b>Salivary microbiota and certain taxa, such as caries-associated taxa (Prevotella), may be useful to screen/assess the children's risk of developing caries.</p>

Impact of systolic blood pressure on visit-to-visit blood pressure variability in middle-aged and elderly people / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the impact of systolic blood pressure (SBP) on visit-to-visit blood pressure variability (BPV) in middle-aged and elderly people.</p><p><b>METHODS</b>Visit-to-visit BPV was determined in 5440 workers in the Kailuan study cohort from 2006 to 2007. The subjects were ≥ 40 years-old and had no history of stroke, transient ischemic attack or myocardial infarction. Participants were divided into five groups according to different levels of SBP. Linear regression was used to analyze the related factors which might affect BPV.</p><p><b>RESULTS</b>Mean systolic BPV of all subjects was 10.35 mm Hg [coefficient of variation (CV 7.96%)]. The mean systolic BPV of males was 10.54 mm Hg (CV 7.90%) while the mean SBPV of females was 10.06 mm Hg (CV 7.90%). The BPV of males was significant higher than that of females (P < 0.001). CV of SBP was similar between males and females. Furthermore, higher SBP was associated with higher BPV. There were significant differences in BPV between different groups with different levels of SBP (P < 0.001). Linear regression analysis demonstrated that SBP, age, gender, high-sensitivity C-reactive protein (hsCRP) were affecting factors of BPV. Twenty mm Hg SBP increase was linked with 2.02 mm Hg BPV increase and 0.388%CV increase. Age increase of 1 year was associated with 0.044 mm Hg BPV increase and 0.029% CV increase.</p><p><b>CONCLUSION</b>SBP, age, gender and hsCRP are important factors affecting BPV in middle-aged and elderly people. Higher SBP is closely related to greater BPV in this cohort.</p>

Overexpression of hSav1 promotes Mst1-induced apoptosis in HeLa cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To elucidate the effect of hSav1 expression on Mst1-mediated apoptosis in HeLa cells.</p><p><b>METHODS</b>Plasmids pCMV-HA-hSav1 and pcDNA/4TO-Flag-Mst1 were constructed and cotransfected into HeLa cells. Triple immunofluorescent labeling of hSav1, Mst1 and nucleus was performed to determine their subcellular localization. Plasmids pCMV-HA-hSav1 and/or pcDNA/4TO-Flag-Mst1 were transfected into HeLa cells, and 36 hours later cisplatin (50 micromol/L) as a pro-apoptotic agent was added for 14 hours. Cell apoptosis was analyzed by annexin V/PI assay.</p><p><b>RESULTS</b>Plasmids pCMV-HA-hSav1 and pcDNA/4TO-Flag-Mst1 were constructed and the authenticity of constructs was verified by sequencing. The binding in vitro showed that hSav1 could be detect from the anti-Mst1 immunoprecipitation complex. The immunofluorescent labeling showed that hSav1 and Mst1 had the same localization in cells. Overexpressed protein hSav1 did not induce a significant cell apoptosis. However, co-expression of hSav1 with Mst1 resulted in a significant increase of apoptosis above the level seen with Mst1 alone (24.5% +/- 2.4% vs. 39.3% +/- 4.0%, P < 0.05).</p><p><b>CONCLUSION</b>Our findings indicate that hSav1 is a newly identified protein that interacts with Mst1 and augments Mst1-mediated apoptosis.</p>

Preparation of suspension of gastric mucous membrane single cell and expression of cyclins in cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore a method which can remove the gastric mucus in order to prepare mucous membrane single cell suspension for the research of cytomics.</p><p><b>METHODS</b>Enzymology was used to remove the mucus gel and to separate mucous layer from the normal fresh gastric tissue. The mucous layer was broken to prepare single cell suspension with machine method. Expression of major cyclins in mucous layer cells was examined by cytoimmunochemistry, flow cytometry(FCM) and confocal microscopy.</p><p><b>RESULTS</b>The 0.1% pepsin could dissolve the mucus gel and 1.2-2.4 U/L dispase could separate the mucous layer completely. The single mucous cell suspension was prepared successfully. FCM results from mucous single cell suspension revealed that expression of cyclin D(3), B(1) was obvious, that of cyclin D(2) was weak and that of cyclin D(1), A, E was the least. Similar results were found with confocal microscopy.</p><p><b>CONCLUSIONS</b>Single cell suspension from mucous layer can be easily prepared by pepsin and dispase. Cyclins schedule expression in vivo is different from cyclins schedule expression in vitro.</p>