Myelodysplastic Syndrome Treated by Integrated Chinese and Western Medicine: A Case Report.

Context: Myelodysplastic syndrome (MDS) is a group of highly heterogeneous, malignant clonal diseases derived from hematopoietic stem cells. PD-1 monoclonal antibodies can have a synergistic effect with hypomethylating agents (HMAs), especially for patients with drug resistance to demethylation drugs. TCM in the treatment of MDS can improve hematological indexes, and for some patients, control the proliferation of primitive cells and delay or even block the transformation to leukemia. Objective: The study intended to examine the therapeutic effects of programmed cell death-1 (PD-1) inhibitors and azacitidine combined with the Yisuifang Thick Decoction in the treatment of MDS with older, high-risk patients. Design: The research team performed five prospective case studies. Setting: The study took place at the East Hospital affiliated with Beijing University of Chinese Medicine in Beijing, China. Participants: Participants were five older, high-risk MDS patients at the hospital who received PD-1 and azacitidine combined with Yisuifang Thick Decoction between April 2020 and June 2021. Outcome Measures: The research team measured: (1) treatment duration, (2) curative effects, (3) myelosuppression, (4) immune-related adverse reactions, (5) ending outcomes, and (6) progression-free survival (PFS). Results: The male to female ratio for the five participants was 3:2, and the median age was 69 years, with a range from 62 to 79 years. Four participants had refractory HR-MDS and one had primary MDS. The median treatment duration was 3 months, with a range from 2 to 4 months, and the median progression-free survival (PFS) was 5 months, with a range from 3 to 14 months. All participants achieved a partial response (PR) or a complete remission with incomplete count recovery (CRi) and showed improvement in serological indexes. Conclusions: Older, high-risk MDS patients generally have poor physical conditions, often accompanied by a poor karyotype prognosis and a poor prognosis for survival. Therefore, the combination of PD-1, azacytidine, and Yisuifang Thick Decoction may be an effective way to treat HR-MDS.

Population Pharmacokinetics and Safety of Dasatinib in Chinese Children with Core-Binding Factor Acute Myeloid Leukemia.

BACKGROUND: Dasatinib, an orally administered Src-family kinase inhibitor, is combined with the standard chemotherapeutic regimen to enhance antineoplastic activity against core-binding factor acute myeloid leukemia (CBF-AML) in adults; however, limited data are available for use in children. In the present study, we studied the pharmacokinetics and safety of dasatinib in children. METHODS: Dasatinib (60 or 80 mg/m2 once daily) was administered to 20 children with CBF-AML. Blood samples were collected and drug concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Population pharmacokinetic analysis and Monte-Carlo simulations were performed using NONMEM software, and safety analyses were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 (NCT03844360). RESULTS: Twenty pediatric patients (3.3-14.4 years of age) were included, and a total of 40 dasatinib concentrations were available for population pharmacokinetic analysis. The mean (standard deviation) of the estimated area under the concentration-time curve extrapolated to steady state (AUCss) of dasatinib 60 and 80 mg/m2 was 366.1 (146.6) ng·h/mL and 425.3 (150.7) ng·h/mL, respectively. The majority of adverse events were grade 1/2 in severity, including thrombocytopenia, rash, and pain in the extremities. The estimated cumulative incidence of complete remission and complete molecular response were 95.0% and 75.5%, respectively. CONCLUSIONS: The population pharmacokinetics of orally administered dasatinib were evaluated in pediatric CBF-AML patients. The AUCss of dasatinib (80 mg/m2) in CBF-AML pediatric patients was similar to those of dasatinib (100 mg) in adult patients. Dasatinib is well-tolerated in pediatric patients with CBF-AML.

A global bibliometric analysis on Kawasaki disease research over the last 5 years (2017-2021).

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that mainly affects children. We aim to conduct a bibliometric analysis to explore the latest research hotspots and trends of KD. Method: By using the keywords "Kawasaki disease," "Kawasaki syndrome", and "Mucocutaneous Lymph Node Syndrome," the Web of Science (WOS) and Scopus databases were searched for publications related to KD from 2017 to 2021. Author, country and journal submissions were classified and evaluated using Biblioshiny software (using R language). VOSviewer (version 1.6.18) was used to visualize the relevant network relationships. Result: According to the search strategy, 5,848 and 6,804 KD studies were published in WOS and Scopus, respectively. The results showed an overall increasing trend in the number of publications and citations during the study period. The three most influential institutions in the WOS were St. Marianna University, Kawasaki Medical School and The University of Tokyo in Japan, while in Scopus, Harvard Medical School, University of California and Tehran University of Medical Sciences were the most influential institutions. The most influential authors of the two databases are Goodman SG, Kazunori Kataoka, and Takeshi Kimura of the WOS and Marx Nikolau and Wang Y, Burns JC, and Newburger JW of the Scopus, respectively. And Scientific Reports and Frontiers in Pediatrics were the most critical journals. The most cited documents were the WOS document by McCrindle et al. and the Scopus document by Benjamin et al. published in 2017, while the keywords in the last few years were focused on "COVID-19," "multisystem inflammatory syndrome," and "pandemic." Conclusion: This bibliometric analysis summarizes for the first time the research progress in KD (2017-2021), providing a qualitative and quantitative assessment of KD research bibliometric information. In the field, researchers mainly from Japan and USA are dominant, followed by China. It is recommended to pay close attention to the latest hot spots, such as "COVID-19" and "multisystem inflammatory syndrome." These results provide a more intuitive and convenient way for researchers to obtain the latest information on KD.

[Clinical Characteristics and Prognosis Analysis of Pediatric Severe Aplastic Anemia].

OBJECTIVE: To analyze the clinical characteristics and factors affecting prognosis in children with severe aplastic anemia (SAA). METHODS: Two hundred and five children with SAA treated in our department from January 2008 to April 2018 were selected, and the clinical characteristics and factors affecting prognosis were retrospectively analyzed. RESULTS: Among 205 SAA children, the effective rate (CR+PR) at 3, 6 and 12 months after immunosuppressive therapy (IST) treatment was 50.9%, 59.0% and 73.9%, respectively, and 5-year overall survival rate was 93.1%±2.0%. Univariate analysis showed that 5-year overall survival rate of SAA children of spontaneous delivery was higher than that of cesarean section (P=0.039), while multivariate analysis showed that birth way had no significant influence on 5-year overall survival rate (P>0.05). The response rate at 3 months after IST of children with a recent history of decoration before SAA onset was higher than those without history of decoration (P<0.05). CONCLUSION: Most of the SAA children can achieve high response rate and overall survival rate. Patients with recent history of home/school decoration may be the factor affecting hematological response after 3 months of IST, but have no influence on long-term overall survival.

[Advances in the treatment of juvenile myelomonocytic leukemia].

Juvenile myelomonocytic leukemia (JMML) is a rare chronic myeloid leukemia in children and has the features of both myelodysplastic syndrome and myeloproliferative neoplasm. It is highly malignant and has a poor treatment outcome. Children with JMML have a poor response to conventional chemotherapy. At present, hematopoietic stem cell transplantation is the only possible cure for this disease. In recent years, significant progress has been made in targeted therapy for mutant genes in the Ras signaling pathway and demethylation treatment of aberrant methylation of polygenic CpG islands. This article reviews the treatment and efficacy evaluation of JMML.

[Value of multiparameter flow cytometry in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome].

OBJECTIVE: To investigate the value of multiparameter flow cytometry (MFC) and flow cytometric scoring system (FCSS) in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome (MDS). METHODS: A retrospective analysis was performed for the clinical data of 42 children who were diagnosed with MDS. MFC was performed to investigate the phenotype and proportion of each lineage of bone marrow cells. The correlations of FCSS score with MDS type, International Prognostic Scoring System (IPSS) score, and revised IPSS (IPSS-R) score were analyzed. RESULTS: Of all the 42 children, 20 (48%) had an increase in abnormal marrow blasts, 19 (45%) had a lymphoid/myeloid ratio of >1, 14 (33%) had abnormal cross-lineage expression of lymphoid antigens in myeloid cells, 8 (19%) had abnormal CD13/CD16 differentiation antigens, 5 (12%) had abnormal expression of CD56, 3 (7%) had reduced or increased side scatter of granulocytes, 3 (7%) had reduced expression of CD36 in nucleated red blood cells, 2 (5%) had reduced expression of CD71 in nucleated red blood cells, 1 (2%) had absent expression of CD33 in myeloid cells, 1 (2%) had reduced or absent expression of CD11b in granulocytes, and 1 (2%) had absent expression of CD56 and CD14 in monocytes. There were significant differences in the median overall survival time and event-free survival time among the low-, medium-, and high-risk FCSS groups (P<0.05). Among the low-, medium-, and high-risk FCSS groups, the low-risk FCSS group had the highest 2-year overall survival rate, while there was no significant difference between the medium- and high-risk FCSS groups (P>0.05). The three groups had a 2-year event-free survival rate of 95%, 60%, and 46% respectively (P<0.05). FCSS score was positively correlated with MDS type, IPSS score, and IPSS-R score (P<0.05). CONCLUSIONS: MFC and FCSS help with the diagnosis and prognostic evaluation of childhood MDS.

Implementing Tobacco Control Assistance in Pediatric Departments of Chinese Hospitals: A Feasibility Study.

BACKGROUND AND OBJECTIVES: Evidence-based tobacco control strategies delivered through pediatric settings could encourage parental smoking cessation and reduce children's exposure to second hand smoke (SHS) in the United States. The extent to which these tobacco control strategies could be routinely implemented in the pediatric setting of a developing country is not known. We tested the feasibility and efficacy of implementing an evidence-based intervention, the Clinical Effort Against Secondhand Smoke Exposure (CEASE), in a Chinese hospital to address the second hand smoke exposure of children in the home and car and to address parental smoking. METHODS: We conducted a quasi-experimental trial of CEASE implementation in the pediatric inpatient departments of 2 Chinese hospitals, 1 assigned as the intervention hospital and another assigned as the control hospital. Data were collected through pre- and postsurveys of parents and clinicians, implementation process surveys, and chart review. RESULTS: In the intervention hospital, pediatricians' rates of delivering different types of tobacco control assistance to smoking parents were all significantly (P < .0001) higher during the post-CEASE implementation period than in the pre-CEASE implementation period. During the post-CEASE implementation period, pediatricians' rates of delivery for all aspects of tobacco control assistance were significantly higher (all P < .0001) in the intervention hospital than in the control hospital, whereas there was no difference during the pre-CEASE period. CONCLUSIONS: The findings of this study suggest that it is feasible to implement a system-level intervention of CEASE in the pediatric inpatient department of a major hospital in southern China. A large-scale trial incorporating measures to increase quit rates and including a long-term follow-up is needed to examine the effectiveness of CEASE implementation in China.

[Clinical characteristics of clonal evolution after immunosuppressive therapy in children with severe/very severe aplastic anemia].

OBJECTIVE: To evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA). METHODS: The clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed. RESULTS: The 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×109/L, CD3+T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3+T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions. CONCLUSIONS: The children with SAA/VSAA who have an increased CD3+T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.

[Prognostic Value of Prednisone Response in CCLG-ALL 2008].

OBJECTIVE: To ovaluate the prognostic value of prednisone response in treatment regimes of children with acute lymphoblastic leukemia. METHODS: A total of 598 newly diagnosed ALL patients were enrolled and received prednisone pre-treatment. Based on the peripheral lymphoblast count on day 8, these patients were divided into 2 groups: prednisone good response (PGR) and prednisone poor response (PPR). PPR patients were classified into high risk group immediately and then received intensed chemotherapy. The all enrolled patients were followed up and the clinical features and treatment outcomes of the two groups were analyzed. RESULTS: Compared with PGR group, PPR group had different characteristics. They were older in age and had higher initial white blood cell count (P<0.05). T-cell ALL (T-ALL) and Philadelphia chromosome positive ALL (Ph+ ALL) were frequent in PPR group (P<0.05). Event-free survival (EFS) rate of PPR group was significantly lower than that of PGR group (P<0.05). 2 year event-free survival(EFS) rate of PGR group was (88.3±1.5)%, while the 2-year EFS rate of PPR group was (58.4±5.3)%. 5 year EFS rates of PGR and PPR were (80.8±2.1)% and (53.4±6.0)%, respectively. The EFS rate of PPR group was falling rapidly within 2 years. PPR group had higher relapse rate, and most relapses occurred within 18 months (P<0.05). PPR group had more high incidence of minimal residual disease (MRD) both on day 33 and on week 12 (P<0.05). No significant difference of EFS and relapse time was found between PPR and high risk PGR patients (P>0.05). In multi-variate regression analysis, the PPR, the presence of BCR-ABL1 and MLL were significantly unfavorable factors (P<0.05). CONCLUSION: Prednisone response has been confirmed to be still great prognostic value and PPR children patients have poor outcomes generally. It is likely that the response to prednisone does not make much sense to high risk ALL patients.

[Defectiveness of bone marrow mesenchymal stem cells in acquired aplastic anemia].

The defectiveness of bone marrow mesenchymal stem cells (BM-MSCs) in acquired aplastic anemia (AA) has been a frequent research topic in recent years. This review summarizes the defectiveness of BM-MSCs which is responsible for the mechanism of acquired AA and the prospective application of BM-MSCs in the treatment of acquired AA. An increasingly number of laboratory statistics has demonstrated that the defectiveness of BM-MSCs is more likely to play an important role in the pathogenesis of AA, namely, the apparently different biological characteristics and gene expression profiles, the decreased ability of supporting hematopoiesis as well as self-renewal and differentiation, and the exhaustion of regulating immune response of hematopoietic environment. Those abnormalities continuously prompt AA to become irreversible bone marrow failure along with the imbalanced immunity. With deepening research on MSCs, infusion of MSCs for the primary purpose of recovering hematopoietic microenvironment may become a new approach for the treatment of AA.

Characteristics of the cellular immune response in HIV/HCV patients with hemophilia during peginterferon/ribavirin therapy in southern China.

OBJECTIVE: The objectives of the study are to characterize the cellular immune response in hepatitis C virus (HCV) genotype 1 and HIV co-infected patients with hemophilia in southern China during treatment with interferon and ribavirin and to study its correlation with the virologic response (VR). Thirty-six HCV genotype 1 and HIV co-infected patients with hemophilia in southern China were enrolled into the study. Using an ELISpot assay, HCV antigen-specific interferon (IFN) γ, interleukin (IL) 2, IL-4, and IL-10 secreting cells were measured in peripheral blood mononuclear cells. Single nucleotide polymorphisms of IL28B were determined, and immunological, virologic, and clinical variables were collected to identify factors associated with HCV-sustained VR (SVR) at week 72 after treatment. At baseline, there were no significant differences in IFN-γ and IL-2 mediated immune responses in subjects with VR versus non-responders. Higher IL-10 specific responses to NS3 were observed in VR patients. Subjects who had significant decreases in IL-10 responses at week 72 compared with baseline for NS3 and NS5 were more likely to be VR. In SVR, IL-2 production decreased moderately, and the levels of IL-4 were low throughout. The main correlation for SVR in genotype-l infected subjects was sustained HCV-specific IFN-γ responses through the whole 72-week period. In subjects with HIV and HCV co-infection combined with hemophilia, IL28B genotype CC, a decrease in HCV specific IL-l0 and IL-2 responses, and the maintenance of IFN-γ responses during treatment were associated with a 12- or 72-week VR.

Impact of decomposing Cinnamomum septentrionale leaf litter on the growth of Eucalyptus grandis saplings.

A pot experiment was performed to study the impact of decomposing Cinnamomum septentrionale leaf litter on the growth of Eucalyptus grandis saplings. The experimental design scheme was 0 (CK), 40 (A1), 80 (A2) and 120 g pot(-1) (A3) of E. grandis leaves, and changes in the volatile oil chemical composition during litter decomposition were assessed in the present study. The results showed that C. septentrionale leaf litter inhibited the growth of E. grandis saplings, as determined by the height, basal diameter and chlorophyll content, after 69 d (T1). Five months after transplantation (T2), the height growth rate of the E. grandis saplings increased and then gradually reduced (A1: 40 g pot(-1) > A2: 80 g pot(-1) > A3: 120 g pot(-1) > CK: 0 g pot(-1)). After eleven months (T3), the variations in the height and basal diameter were the same as observed at T2, and the inhibition on leaf, branch, root and stem biomass increased with increasing leaf litter content. Gas chromatography-mass spectrometry (GC-MS) was used to identify the volatile compound composition. The results indicated that the C. septentrionale original leaf litter (S1) contained thirty-one volatile compounds, but the treated leaf litter S2 (which was mixed with soil for eleven months to simultaneously plant E. grandis saplings) only possessed fourteen volatile compounds, releasing many secondary metabolites in the soil during decomposition. Most of the volatile compounds were alcohols, monoterpenoids, sesquiterpenes, alkanes, alkene, esters and ketones. Most of the allelochemicals of C. septentrionale might be released during the initial decomposing process, inhibiting the growth of other plants, whereas some nutrients might be released later, promoting the height growth of plants. In conclusion, decomposing C. septentrionale leaf litter release of many allelochemicals in the soil that significantly inhibit the growth of E. grandis.

[Three-dimensional construction of the relation between the anterior branches of lumbar nerves 4, 5, lumbosacral trunk and sacroiliac joint].

OBJECTIVE: To construct a three-dimensional model to demonstrate the relation between the anterior branches of lumbosacral 4,5, lumbosacral trunk, and the pelvis. METHODS: An formaldehyde-fixed adult cadaver was dissected to expose the anterior branches of the lumbar nerves 4 and 5, lumbosacral trunk and the sacroiliac. The mixture of titanium powder and adhesive was smeared on the surface of the major branches of L4 and L5 nerves, lumbosacral trunk, femoral nerves and obturator nerves. As soon as the mixture solidified, the specimen was scanned by spiral CT at 3 mm intervals to obtain 159 two-dimensional sectional images for three-dimensional model reconstruction on a personal computer using the software 3-D DOCTOR. RESULTS AND CONCLUSION: The reconstructed model can well demonstrate the spatial relation between the nerves and the pelvis, and allows rotation in every direction, which at the same time can be conveniently applied for purpose of clinical teaching.