Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China

Since December 2019,COVID-19 has occurred unexpectedly and emerged as a health problem worldw ide.Despite the rapidly increasing number of cases in subsequent weeks,the clinical characteristics of pediatric cases are rarely described.A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province.A total of 25 confirmed pediatric cases of COVID-19 were collected.The demographic data,epidemiological history,underlying discascs,clinical mani festations,laboratory and radiological data,treatments,and outcomes were analyzcd.Of 25 hospitalized patients with COVID-19,the boy to girl ratio was 1.27:1.The median age was 3 years.COVID-19 cases in children aged<3 years,3-6 years,and≥6-years patients were 10(40%),6(24%),and 9(36%),respectively.The most common symptoms at onset of ilness were fever(13[52%]),and dry cough(11[44%]).Chest CT images showed essential normal in 8 cases(33.3%),unilateral involvement of lungs in 5 cases(20.8%),and bilateral involvement in 11 cases(45.8%).Clinical diagnoses included upper respiratory tract infection(n=8),mild pneumonia(n=15),and critical cases(n=2).Two critical cases(8%)were given invasive mechanical ventilation,corticosteroids,and immunoglobulin.The symptoms in 24(96%)of 25 patients were alleviated and one patient had been discharged.It was concluded that children were susceptible to COVID-19 like adults,while the clinical presentations and outcomes were more favorable in children.However,children less than 3 years old accounted for majority cases and critical cases lied in this age group,which demanded extra attentions during home caring and hospitalization treatment.

Chinese research into severe ulcerative colitis has increased in quantity and complexity

AIM To investigate the current state of research output from Chinese studies into severe ulcerative colitis(SUC) using a bibliometric analysis of publications. METHODS The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analyticalstudies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis.CONCLUSION The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.

Dose-individualization Efficiently Maintains Sufficient Exposure to Methotrexate without Additional Toxicity in High-dose Methotrexate Regimens for Pediatric Acute Lymphoblastic Leukemia

Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.

Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in Ph+ Leukemia Cells

Imatinib mesylate(IM)is the first-line treatment for Philadelphia(Ph)chromosomal positive leukemia by inhibiting phosphorylation of substrates via binding to the ABL kinase domain.Because of the drug resistance,side effects and the high cost of IM,it is necessary to find anti-cancer drugs with relatively low toxicity and cost,and enhanced efficacy,such as traditional Chinese medicines(TCMs).As one of TCMs,Huai Qi Huang(HQH)was chosen to treat BV173 and K562 cells.Various concentrations of HQH were added to cells for 24-72 h.Co-treatment of HQH and trametinib,an MEK inhibitor,was used to verify the synergistic effects on cell viability and apoptosis.Knockdown and overexpression of mitogen-activated protein kinase kinase 4(MEK4)were implemented to demonstrate the role of MEK in cell apoptosis.Cell viability and apoptosis were measured by cell counting kit-8 assay(CCK8)and flow cytometry,respectively.Western blotting and real-time quantitative PCR(RT-qPCR)were used to assess protein and mRNA expression levels,respectively.The results showed that HQH inhibited survival and promoted apoptosis of BV173 and K562 cells in a dose-dependent manner,accompanied with down-regulation of PRKCH mRNA as well as CRAF,MEK4,phospho-ERK(pERK)and BCL2 proteins,and up-regulation of cleaved caspase3 protein.Co-treatment of HQH and trametinib had.a synergistic effect on inhibiting survival and promoting apoptosis.MEK4 knockdown increased apoptosis,and had a synergistic effeet with HQH.In contrast,MEK4 overexpression decreased.apoptosis,and had the opposite efect with HQH.Collectively,the results of this study may identify a therapeutic mechanism of HQH on promoting apoptosis,and provide a potential option for treatment of Pht leukemia.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma

Objective This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma(NHL).Methods We compared the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and the ASMR to ASIR ratio(MIR)at national and regional levels and studied the correlation between the MIR and the human development index(HDI)in 2012 and 2018.Results The highest ASIR was in North America in 2012 and in Australia in 2018,and the lowest ASIR was in Central and South Asia in both 2012 and 2018.The highest ASMR was in North Africa in both 2012 and 2018,and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018.The lowest MIR was in Australia in both 2012 and 2018,and the highest MIR was in Western Africa in both 2012 and 2018.HDI was strongly negatively correlated with MIR(r:−0.8810,P<0.0001,2012;r:−0.8895,P<0.0001,2018).Compared to the 2012 data,the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018.Conclusion The MIR is negatively correlated with HDI.Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

An Inexact Affine Scaling Levenberg-Marquardt Method Under Local Error Bound Conditions

We propose an inexact affine scaling Levenberg-Marquardt method for solving bound-constrained semismooth equations under the local error bound assumption which is much weaker than the standard nonsingularity condition. The affine scaling Levenberg-Marquardt equation is based on a minimization of the squared Euclidean norm of linearized model adding a quadratic affine scaling matrix to find a solution which belongs to the bounded constraints on variable. The global convergence and the superlinear convergence rate are proved.Numerical results show that the new algorithm is efficient.

Prognostic significance of cytokine receptor-like factor 2 alterations in acute lymphoblastic leukemia:a meta-analysis

Background:Cytokine receptor-like factor 2(CRLF2)has been shown to play a role in the pathogenesis of acute lymphoblastic leukemia(ALL).Studies have examined the relationship between CRLF2 alterations such as over-expression or deregulation and clinical outcome in childhood ALL,but the results are conflicting.This meta­analysis aimed to explore the association between CRLF2 alterations and survival of pediatric patients with ALL.Methods:Electronic databases updated to March 2014 were searched for relevant studies.A meta-analysis was made of twelve studies including 5945 patients to evaluate the prognostic significance of CRLF2 alterations on survival in childhood ALL.Hazards ratios(HRs)with 95%confidence intervals(CIs)were pooled across the studies using a fixed-effects model.Results:CRLF2 over-expression in childhood ALL was associated with poor prognosis in terms of relapse-free survival(RFS;HR=1.70,95%CI=1.28-2.24,P=0.000),event-free survival(EFS;HR=1.78,95%CI=1.05-3.01,R=0.032),and overall survival(OS;HR=2.28,95%CI=1.42-3.65,R=0.001).The combined data also suggested that CRLF2 deregulation in childhood ALL was correlated with poor EFS(HR=1.95,95%CI=1.46-2.61,R=0.000),RFS(HR=2.20,95%CI=1.53-3.18,P=0.000),and OS(HR=1.89,95%CI=1.24-2.87,P=0.003).Subgroup analysis on multivariate HRs showed that CRLF2 deregulation independently predicted a poor prognosis for childhood ALL.Conclusions:The present meta-analysis reveals that both CRLF2 over-expression and deregulation are associated with poor prognosis in pediatric patients with ALL.

A Filter Line Search Algorithm Based on an Inexact Newton Method for Nonconvex Equality Constrained Optimization

We propose an inexact Newton method with a filter line search algorithm for nonconvex equality constrained optimization. Inexact Newton＇s methods are needed for large-scale applications which the iteration matrix cannot be explicitly formed or factored. We incorporate inexact Newton strategies in filter line search, yielding algorithm that can ensure global convergence. An analysis of the global behavior of the algorithm and numerical results on a collection of test problems are presented.