[Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol]. / CCCG-ALL-2015æ–¹æ¡ˆæ²»ç–—å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: 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.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

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 (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). 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.

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria. / ä¸åŒè¯Šæ–­æ ‡å‡†ä¸‹å„¿ç«¥æ€¥æ€§ä¸æ˜Žè°±ç³»ç™½è¡€ç— çš„ä¸´åºŠç‰¹ç‚¹å’Œé¢„åŽåˆ†æž.

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 (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. 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% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). 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.

[Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia].

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.

Prognostic factors and its predictive value in patients with metastatic spinal cancer.

BACKGROUND: The spine is the most common location of metastatic diseases. Treating a metastatic spinal tumor depends on many factors, including patients' overall health and life expectancy. The present study was conducted to investigate prognostic factors and clinical outcomes in patients with vertebral metastases. AIM: To investigate prognostic factors and their predictive value in patients with metastatic spinal cancer. METHODS: A retrospective analysis of 109 patients with metastatic spinal cancer was conducted between January 2015 and September 2017. The prognoses and survival were analyzed, and the effects of factors such as clinical features, treatment methods, primary lesions and affected spinal segments on the prognosis of patients with metastatic spinal cancer were discussed. The prognostic value of Frankel spinal cord injury functional classification scale, metastatic spinal cord compression (MSCC), spinal instability neoplastic score (SINS) and the revised Tokuhashi score for prediction of prognosis was explored in patients with metastatic spinal tumors. RESULTS: Age, comorbidity of metastasis from elsewhere, treatment methods, the number of spinal tumors, patient's attitude toward tumors and Karnofsky performance scale score have an effect on the prognosis of patients (all P < 0.05). With respect to classification of spinal cord injury, before operation, the proportion of grade B and grade C was higher in the group of patients who died than in the group of patients who survived, and that of grade D and grade E was lower in the group of patients who died than in the group of patients who survived (all P < 0.05). At 1 mo after operation, the proportion of grade A, B and C was higher in the group of patients who died than in the group of patients who survived, and that of grade E was lower in patients in the group of patients who died than in the group of patients who survived (all P < 0.05). MSCC occurred in four (14.3%) patients in the survival group and 17 (21.0%) patients in the death group (P < 0.05). All patients suffered from intractable pain, dysfunction in spinal cord and even paralysis. The proportion of SINS score of 1 to 6 points was lower in the death group than in the survival group, and the proportion of SINS score of 7 to 12 points was higher in the death group than in the survival group (all P < 0.05). The proportion of revised Tokuhashi score of 0 to 8 points and 9 to 11 points were higher in the death group than in the survival group, and the proportion of revised Tokuhashi score of 12 to 15 points was lower in the death group than in the survival group (all P < 0.05). Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were important factors influencing the surgical treatment of patients with metastatic spinal cancer (all P < 0.05). CONCLUSION: Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were helpful in predicting the prognosis of patients with metastatic spinal cancer.

[Second-generation Sequencing Analysis of Ph+ and Ph-like Childhood T-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph+/Ph like T-ALL) using bioinformatics methods, and analyze the core sub-networks for exploration of the development process of Ph+/Ph like T-ALL, so as to find the molecular targets that may be used in clinical diagnosis and treatment. METHODS: The WES/RNA-seq examination results of Ph+/Ph-like T-ALL children had be collected in our hospital, the genetic data that met the requirements had be downloaded from GEO database, then GRO2R online differentially expressed gene screening program was used to screen differentially expressed genes, finally, GO function enrichment analysis and KEGG pathway enrichment analysis were performed to compare differentially expressed genes. At the same time, STRING database and Cytoscape software were used to build protein interaction network and screen hub genes and core sub-networks. RESULTS: For Ph+/Ph like T-ALL, a total of 84 differentially expressed genes had been found, for Ph+ ALL a total of 249 differentially expressed genes, and for T-ALL a total of 175 differentially expressed genes. Based on the results of GO function enrichment, KEGG pathway enrichment analysis and protein interaction network, RPA1, POLD1, POLE and SOCS1 were selected as hub genes. DNA damage repair and JAK/STAT signal transduction pathway were the main functional sub-networks. CONCLUSION: There are obviously abnormal DNA damage repair pathways in children with Ph+/Ph like T-ALL. RPA1, POLD1 and POLE may be important relevant biomarkers for the occurrence and development of Ph+/Ph like T-ALL, which can provide a basis for further research.

Non-linear genetic diversity and notable population differentiation caused by low gene flow of bermudagrass [Cynodon dactylon (L.) Pers.] along longitude gradients.

BACKGROUND: Environmental variation related to ecological habitat is the main driver of plant adaptive divergence. Longitude plays an important role in the formation of plant population structure, indicating that environmental differentiation can significantly shape population structure. METHODS: Genetic diversity and population genetic structure were estimated using 105 expressed sequence tag-derived simple sequence repeat (EST-SSR) loci. A total of 249 C. dactylon (L.) Pers. (common bermudagrass) individuals were sampled from 13 geographic sites along the longitude (105°57'34″-119°27'06″E). RESULTS: There was no obvious linear trend of intra-population genetic diversity along longitude and the intra-population genetic diversity was not related to climate in this study. Low gene flow (Nm = 0.7701) meant a rich genetic differentiation among populations of C. dactylon along longitude gradients. Significantly positive Mantel correlation (r = 0.438, P = 0.001) was found between genetic distance and geographical interval while no significant partial Mantel correlation after controlling the effect of mean annual precipitation, which indicated geographic distance correlated with mean annual precipitation affect genetic distance. The genetic diversity of C. dactylon with higher ploidy level was higher than that with lower ploidy level and groups of individuals with higher ploidy level were separated further away by genetic distance from the lower ploidy levels. Understanding the different genetic bases of local adaptation comparatively between latitude and longitude is one of the core findings in the adaptive evolution of plants.

[Clinical observation on the treatment of cervical degenerative diseases with Hybrid surgery].

OBJECTIVE: To investigate the clinical effect of anterior cervical Hybrid surgery in the treatment of cervical degenerative diseases (CDD) and observe the incidence of heterotopic ossification of disc replacement segment at 1 year after surgery. METHODS: From January 2015 to April 2018, 35 patients who received anterior cervical hybrid surgery met the inclusion and exclusion criteria and the complete clinical follow up data were analyzed retrospectively. Complete imaging follow-up data were obtained from 24 patients. There were 15 males and 20 females, aged from 39 to 70(55.57±7.73) years old. The amount of bleeding was for 20 to 100 (40.29±18.39) ml, and the hospitalstay was for 4 to 28(11.03±4.63) days, and the follow-up time was(12.97±1.36) months. Clinical outcomes were assessed by the Tanaka Yasushi cervical spondylitis symptom scale 20 score (YT20), and Japanese Orthopaedic Association (JOA) score. The occurrence of heterotopic ossification after Hybrid surgery was evaluated by X-ray according to McAfee standard one year after operation. Patients with or without heterotopic ossificationwere divided into two groups and their clinical effects were compared. RESULTS: At the final follow up, the mean YT20 score and JOA score were significantly higher than those before operation (P <0.05), and the average improvement rate of JOA was (70.66 ±0.44)%. One year after operation, the heterotopic ossification occurred in 10 of 24 segments, with incidence of 41.70%(10/24), including 29.20% in gradeⅠand 12.50% in gradeⅡ. The results of clinical efficacy comparison between patients with and without heterotopic ossification were as follows:there was no significant difference in JOA score before and after operation (P>0.05);there was no significant difference in YT20 score before operation (P>0.05), and YT20 score in patients with heterotopic ossification was significantly lower than that in patients without heterotopic ossification(P<0.05). CONCLUSION: The short-term clinical effect of Hybrid surgery is satisfactory for cervical degenerative diseases, and the cause of heterotopic ossification still needs tobe further explored.

[Efficacy of Hybrid anterior cervical spine surgery on range of motion and curvature in the treatment of cervical degenerative diseases].

OBJECTIVE: To observe the change of cervical curvature and range of motion (ROM) on imaging at 6 months after Hybrid surgery. METHODS: A total of 29 patients with cervical degenerative disease who underwent Hybrid surgery from January 2017 to July 2018 were retrospectively analyzed. Also, they all met the inclusion criteria and had complete preoperative and 6 months postoperative imaging data. There were 11 males and 18 females, aged from 34 to 76 (55.86±10.69) years, and the operation time was from 2 to 4(3.03±0.51) hours. The Cobb angle method was used to measure the changes of cervical curvature and ROM of C2-C7, replacement segments, fusion segments, and upper adjacent segments on cervical lateral X-rays before and 6 months after surgery. RESULTS: There was no statistically significant difference in C2-C7 curvature and ROM between 6 months after operation and before operation (P>0.05). The degree of curvature and ROM of the replacement segment increased compared with that before operation (P<0.05). The curvatureof the fusion segment was increased than that before operation (P<0.05). There was no statistically significant difference in ROM of the fusion segment compared with that before operation (P>0.05). There was no statistically significant difference in the curvature and ROM of the upper adjacent segments compared with those before operation (P>0.05). There was no significant difference in the curvature between the replacement and fusion segments before and 6 months after operation (P>0.05);the ROM of the replacement segment was higher than that of the fusion segment at 6 months after operation (P<0.05). CONCLUSION: Hybrid surgery reconstructs the lordotic curvature of the entire cervical spine and the responsible segment, retains the ROM of the cervical replacement segment, and restores the biomechanical function of cervical spine.

[Growth and differentiation effect on HL60 cells by adenovirus-mediated exogenous wnt5a gene modification on human bone marrow mesenchymal stem cells].

OBJECTIVE: To study the effect of human bone marrow mesenchymal stem cell (bMSCs) modified by the adenovirus-mediated exogenous wnt5a gene on the hematopoietic function of bone marrow and the inhibition of the growth of HL60 leukemia cells. METHODS: BMSCs were identified through flow cytometry and modified by Ad5-wnt5a, The transfection rate of wnt5a gene in bMSCs was detected by RT-PCR. The cell growth curves were detected in different groups (bMSCs group, Ad5-GFP group, Ad5-wnt5a group). Ad5-wnt5a-bMSCs and HL60 cells were co-cultured, the surface differentiation antigen (CD13, CD14, CD68) and cell cycles were detected by immunocytochemical and flow cytometry in different groups (HL60 cell group, HL60+bMSCs group, HL60+ Ad5-GFP group, HL60+ Ad5-wnt5a group), respectively. RESULTS: Adenovirus-mediated exogenous wnt5a gene was transfected into bMSCs. The expression of differentiation antigens of CD14, CD68 in HL60+Ad5-wnt5a group were higher than those in control group (P < 0.05), the expression of differentiation antigen CD13 were not significant difference in different groups (P > 0.05). Compared with control group, the cell cycle in HL60+ Ad5-wnt5a group was blocked at G2 phase in the fourth day. CONCLUSION: Exogenous wnt5a gene can promote the growth of bMSCs, and induce HL60 cells to differentiation and maturation.

Diversity Patterns of Bermuda Grass along Latitudinal Gradients at Different Temperatures in Southeastern China.

Cynodon dactylon (L.) Pers. (common Bermuda grass) has a limited capacity to grow at low temperatures, which limits its geographical range. Exploring its evolutionary relationship across different environmental gradients is necessary to understand the effects of temperature change on the genetics of common Bermuda grass. In this study, high-throughput transcriptome sequencing was performed on 137 samples of C. dactylon from 16 latitudinal gradients to explore the differential molecular markers and analyze genetic diversity and structure along latitudinal gradients at different temperatures. We primarily sampled more high-quality single nucleotide polymorphisms (SNPs) from populations at lower and middle latitudes. Greater intraspecific genetic variation at each level of temperature treatment could be due to factors such as wind pollination and asexual breeding. Populations of C. dactylon at high latitudes differed from populations at middle and low latitudes, which was supported by a principal component analysis (PCA) and genetic structure analysis, performed at different temperatures. We observed more genetic variation for low-latitude populations at 5 °C, according to an analysis of three phylogenetic trees at different temperature levels, suggesting that low temperatures affected samples with low cold resistance. Based on the results of phylogenetic analysis, we found that samples from high latitudes evolved earlier than most samples at low latitudes. The results provide a comprehensive understanding of the evolutionary phenomenon of landscape genetics, laying the groundwork for future structural and comparative genomic studies of C. dactylon.

[Clinical significance of HA117 expression in children with acute leukemia].

OBJECTIVE: To explore the role of the expression of HA117 gene in bone marrow mononuclear cells (BMMNC) with acute leukemia and multidrug resistance. METHODS: HA117 gene expressions in 36 children with acute leukemia and 10 children with Idiopathic thrombocytopenic purpura (ITP) were tested using semi quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique. RESULTS: The HA117 gene was expressed in 75% of children with acute leukemia. There was no significant difference in HA117 gene expression between children with acute lymphoblastic leukemia (ALL, 69.57%) and children with acute myeloid leukemia (AML, 91.67%). But the semi-quantitative expression of HA117/beta-actin in AML childern was significantly higher than in ALL children (q=4.5852, P<0.01). The expressions of HA117 gene and HA117/beta-actin in both ALL and AML children were significantly higher than in ITP children chi2=5.05, 8.81; q=4.4612, 6.9695; P<0.05). The remission patients had lower expression of HA117/beta-actin and similar expression of HA117 compared with initially diagnosed patients. The remission patients had higher expression of HA117 gene and similar expression of HA117/beta-actin compared with patients with ITP. The non-remission patients had higher expression of HA117/beta-actin than remission patients and ITP patients (q=3.1705, 4.4102, P<0.05), but no significant difference from initially diagnosed patients (q=0.5470, P>0.05). CONCLUSION: The expression of HA117 gene is high in the BMMNC of initially diagnosed and non-remission patients with AL. But the remission patients have similar semi-quantitative expression of HA117 as patients with ITP, which indicates that a quantitative testing is more important. The expression of HA117 gene decreases with the improvement of the illness. HA117 is one of the factors that may affect the clinical remission of AML. The new gene HA117 may also be associated with multidrug resistance of leukemia.

Adverse drug events in Chinese pediatric inpatients and associated risk factors: a retrospective review using the Global Trigger Tool.

Understanding the epidemiology and risk factors of adverse drug events (ADEs) in pediatric inpatient is essential if we are to prevent, reduce or ameliorate the harm experienced. The Global Trigger Tool (GTT) is a method of retrospective medical record review that measures harm in hospitalized children. We employed a three-stage retrospective chart review of random samples of 1800 pediatric inpatients discharged from January 2013 to December 2015. 31 kinds of pediatric-specific triggers were made based on the previous trigger tool studies developed for use in adult or pediatric. Positive predictive value (PPV) of individual triggers, as well as ADEs detection rates were calculated. Stepwise logistic regression was performed to investigate risk factors associated with ADEs. Of 1746 patients, detected in 221 patients (12.7%) with 247 ADEs. The PPV of the trigger tool was 13.3%. Of the 247 ADEs, 82.6% were identified as category E, 11.7% category F and 5.7% category H. The pediatric-focused trigger tool is a feasible and useful tool for detecting pediatric ADEs. Especially for patients who have had more drugs, more doses or more admissions which needs to be closely monitored as triggers to improve the safety.

[Acute leukemia associated with Down syndrome: clinical analysis of 21 cases].

OBJECTIVE: To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL). METHODS: The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed. RESULTS: Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5%). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months. CONCLUSION: Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.

[The burden caused by injury in countryside residents in Dongying, Shandong Province].

OBJECTIVE: To make clear the burden of injury in residents living in countryside of Dongying, Shandong Province. METHODS: A retrospective questionnaire survey was conducted among 15,276 residents in 20 villages of Dongying Municipality of Shandong Province with a multiphase cluster randomly sampling on cases of injury from March 1, 2002 to February 28, 2003. The injury was decided with three principles which had been carried out through the nation. The standardized incidence and mortality rates were calculated on base of the population data of Shandong Province in 2000. The burden of injury was evaluated by incidence rate, mortality rate, years of potential life lost (YPLL) system, disability adjusted life year (DALY), direct and indirect economic costs, et al. RESULTS: Totally 902 were injured cases in which the crude incidence rate was 5.90%, and the standardized incidence rate was 5.93%. It was shown higher in men (7.79%) than in women (4.03%). The crude death rate was 12.438 per million. And the standardized death rate was 11.257 per million. 27 cases were crippled. The years, the working years and the valued years of the potential life lost were 24, 19.6 and 8.7 years respectively for each death case. Disability adjusted life years was 566.61 years. Direct economic cost for medical expenses of all cases was 816.3 thousand RMB Yuan and 200.1 thousand RMB Yuan for else costs. Indirect economic cost was 5,492.9 thousand RMB Yuan according to DALY. CONCLUSION: Injury was common incidence in rural residents in Dongying which caused a heavy burden on them. Prevention and control of injuries would be enhanced.

Bone marrow mesenchymal stem cell-derived Wnt5a inhibits leukemia cell progression in vitro via activation of the non-canonical Wnt signaling pathway.

Leukemia is one of the most common malignancies in humans worldwide; however, the molecular mechanism of the effect of bone marrow mesenchymal stem cells (bMSCs) on leukemia cell growth remains unclear. The present study demonstrated that Wnt5a protein expression was significantly induced in bMSCs via an adenovirus vector (P<0.01). The results showed that the proliferation of HL60 cells, a leukemia cell line, was significantly inhibited when the cells were stimulated with the culture supernatant of adeno-Wnt5a bMSCs compared with the culture supernatants of bMSCs and adeno-vector bMSCs for 24 or 48 h (P<0.01). The promoted maturation levels of HL60 cells were also observed following stimulation with the culture supernatant of adeno-Wnt5a bMSCs (P<0.01). However, no significant difference was identified in the proliferation and maturation of HL60 cells among the three groups stimulated with the culture supernatants containing a neutralization antibody against Wnt5a. Furthermore, the bMSC-derived Wnt5a was found to influence the maturation and proliferation of the HL60 cells by enhancing the non-canonical Wnt signaling pathway, while inhibiting the canonical Wnt signaling pathway by upregulating the expression of receptor tyrosine kinase-like orphan receptor 2 and calcium/calmodulin-dependent protein kinase II, and suppressing the expression of ß-catenin and cyclin D1. In conclusion, bMSC-derived Wnt5a modifies the proliferation and maturation of HL60 cells via activation of the non-canonical Wnt signaling pathway.

A B3LYP and MP2(full) theoretical investigation on the cooperativity effect between hydrogen-bonding and cation-molecule interactions and thermodynamic property in the 1: 2 (Na⁺: N-(Hydroxymethyl)acetamide) ternary complex.

The cooperativity effects between the O/N-H∙∙∙O hydrogen-bonding and Na⁺∙∙∙O cation-molecule interactions in the 1: 2 (Na⁺: N-(Hydroxymethyl)acetamide) systems were investigated at the B3LYP/6-311++G**, MP2(full)/6-311++G** and MP2(full)/aug-cc-pvtz levels. The thermodynamic cooperativity calculations were also carried out for two pathways of the ternary-complex formation. The result shows that, in most ternary complexes, the O/N-H∙∙∙O and Na⁺∙∙∙O interactions are weakened in comparison with those in binary systems, leading to the anti-cooperativity effects, in particular in the complexes in which only the Na⁺∙∙∙O interactions exist. Shifts of electron density confirm the existence of anti-cooperativity. The increase of favorable enthalpic contribution leads to the positive cooperativity effect with negative ΔG(coop.) on forming the ternary complex by initial N-(Hydroxymethyl)acetamide dimer followed by addition of Na⁺. In forming the ternary complex by Na⁺∙∙∙N-(Hydroxymethyl)acetamide with the second N-(Hydroxymethyl)acetamide unit, the large unfavorable entropy change leads to the negative cooperativity effect with positive ΔG(coop.). The ternary complex is more easily formed by the pathway in which Na⁺ binds to N-(Hydroxymethyl)acetamide dimer.