[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

Characterization and identification of ferulic acid esterase-producing Lactobacillus species isolated from Elymus nutans silage and their application in ensiled alfalfa.

AIMS: Ferulic acid esterase (FAE)-producing Lactobacillus species isolated from ensiled Elymus nutans growing on the Qinghai-Tibetan plateau were characterized, and effects of their application to the alfalfa ensiling process and the evidence to synergic effect between cellulase and FAE were investigated. METHODS AND RESULTS: The results of 16S rRNA gene sequence and species-specific polymerase chain reaction amplification showed that two screened strains with high FAE activity were Lactobacillus plantarum A1 (LP) and L. brevis A3 (LBr). The optimum temperature and pH for the LP and LBr was 37°C and 6·4 respectively. The FAE exhibited a good stability at temperatures between 25 and 50°C and at pH values of 5·0-7·0. The two strains and a commercial cellulase (CE) were applied as additives to alfalfa silage. After 60 days of ensiling, the lactic acid in the control and CE groups were significantly lower than those of the other treatment groups. The neutral detergent fibre and acid detergent fibre contents in the LP group were significantly lower than those observed in the other groups. At the same time, the combination of CE and FAE-producing lactic acid bacteria synergistically improved the fermentation quality of the silage. CONCLUSIONS: The addition of the FAE-producing strain of L. plantarum A1 to alfalfa silage improved its fermentation quality, and reduced the fibre content of the silage. SIGNIFICANCE AND IMPACT OF THE STUDY: The screened homo-fermentative and FAE-producing strain of L. plantarum A1 could be a candidate strain in improving fermentation quality and fibre digestibility of ensiled forages.

[Effects of mineral trioxide aggregate and ethanolic extracts of Shandong propolis on the biological properties of human dental pulp fibroblasts].

OBJECTIVE: To evaluate the effect of mineral trioxide aggregate (MTA) and propolis from Shangdong province on the cell viability, mineralization and migration and anti-inflammatory ability of dental pulp fibroblasts. METHODS: The human dental pulp fibroblasts were cultured and subjected to 10 mg/L of propolis and 1:8 dilution of MTA extraction. The cell viability was evaluated with cell counting kit-8 (CCK-8) after 1, 5, 7 and 9 days. The cells in the upper inserts and the test culture media on the bottoms of 24-well plates interacted for 15 hours. Then the numbers of cells migrated through the permeable membranes were compared. The cells seeded in the 24-well plates were incubated in osteogenic medium with different materials for 21 days and stained with alizarin red S, then photographed. To evaluate the deposition of calcified matrix, the wells were destained with 100 mmol/L cetylpyridinium chloride. Finally, the cells were exposed to 1 mg/L lipopolysaccharide (LPS) to induce an inflammatory response, in the presence of propolis, MTA extraction. The cells were collected after 3 h, and the expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were determined using real-time polymerase chain reaction (real-time PCR). Statistical analysis was performed by one-way ANOVA and nonparametric tests (P<0.05). RESULTS: The cell viability of propolis group was significantly lower than those of MTA and control groups on days 5, 7 and 9, while MTA significantly increased the numbers of the viable cells on days 7 and 9. The migration cells of propolis group (26.67±2.52) were fewer than control group (61.33±4.93), and the cells of MTA group (80.00±2.65) were statistically more than those of the other two groups. The propolis group significantly induced more calcified matrix deposition than MTA group after 21 days of culture. Propolis significantly suppressed the expressions of IL-1ß and IL-6 after LPS exposure compared with MTA and control groups. CONCLUSION: The propolis from Shandong compared with MTA showed a certain degree of cytotoxicity, and had no significant effect on cell migration. On the other hand, propolis exhibited significant anti-inflammatory and mineralization promotion effect, suggesting that the active ingredients of propolis could be introduced as a supplement of pulp capping materials, or used as an irrigant or intracanal medicament due to its excellent anti-inflammatory effect. Propolis may have potential in vital pulp treatment of young permanent tooth suffering pulp inflammation.

Effect of propolis on preserving human periodontal ligament cells and regulating pro-inflammatory cytokines.

BACKGROUND/AIM: Propolis has been suggested as a storage medium for avulsed teeth. The aim of this study was to compare the effectiveness of Brazilian propolis with Hank's balanced salt solution and milk in maintaining the viability of human periodontal ligament cells, their osteogenic differentiation potential, and pro-inflammatory cytokine expression. MATERIAL AND METHODS: Cell Counting Kit 8 assays were performed to test human periodontal ligament cell viability in different storage media. The preservative effect on osteogenic differentiation was evaluated using alkaline phosphatase staining and activity assays, Alizarin Red S staining, and western blotting. Quantification of pro-inflammatory cytokines was performed using real-time PCR and enzyme-linked immunosorbent assays. RESULTS: Brazilian propolis at 10 µg/ml was not cytotoxic toward human periodontal ligament cells. The milk group showed the highest cell viability. Brazilian propolis and Hank's balanced salt solution groups showed similar cell viabilities. Alkaline phosphatase staining and activity were similar in all groups. Calcium deposition and mineralization nodule formation were similar in the Brazilian propolis and Hank's balanced salt solution groups, but were higher in the milk group. Osteogenic marker gene and protein levels were similar in all groups. The genes and protein expression levels of IL1ß, IL6, and IL8 decreased significantly after treatment with Brazilian propolis. TNFα mRNA expression showed no significant difference among the experimental groups. Pro-inflammatory cytokine levels in the milk group were higher than in the Brazilian propolis and Hank's balanced salt solution groups. CONCLUSIONS: Brazilian propolis, Hank's balanced salt solution, and milk maintained the viability of human periodontal ligament cells and preserved their osteogenic differentiation ability similarly. However, Brazilian propolis showed a better anti-inflammatory effect. This article is protected by copyright. All rights reserved.

Effects of alendronate on osteoporosis treatment and levels of related cytokines.

Alendronate regulates the activity of osteoclasts and healing of osteoporosis. This study investigated the effect of alendronate on bone healing and changes in the levels of cytokines. Bilateral ovaries of 10 adult female rabbits were removed surgically in aseptic condition to establish the animal model of osteoporosis. Five rabbits in group A were treated with alendronate (1.15 mg·kg-1·week-1) once a week by a stomach tube, whereas the remaining 5 in group B were treated with physiological saline. The success of the animal model establishment and the efficacy of alendronate treatment were evaluated by the sports ability score and the Basso, Beattie, and Bresnahan (BBB) score; the healing degree of osteoporosis was determined by X-ray analysis and measurement of biomechanical properties; the changes in the levels of related cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Treatment improved dyskinesia of the animals in group A than that in group B, with significant improvement occurring in the 4th week of treatment. The BBB score of the group A animals revealed movements similar to normal, but that of the group B animals exhibited significant motor disturbance (P < 0.01). X-ray examination showed that with time, the X-ray ratings increased. Measurement of the biomechanical properties further showed that alendronate had a positive effect on osteoporosis healing. The results of ELISA and immunohistochemistry showed that the levels of ALP, BMP-2, bFGF, and IGF-1 were upregulated in group A. In conclusion, alendronate accelerated osteoporosis healing probably via certain cytokine-related mechanism.

Effect of ensiling whole crop oat with lucerne in different ratios on fermentation quality, aerobic stability and in vitro digestibility on the Tibetan plateau.

The objective of this study was to determine the effect of ensiling different ratios of whole crop oat to lucerne on fermentation quality, aerobic stability and in vitro digestibility of silage on the Tibetan plateau. Four experimental treatments were produced varying in the ratio of forages on a fresh matter (FM) basis: 1) 100% oat (control, dry matter (DM) content: 317 g/kg), 2) 90% oat + 10% lucerne (OL10, DM content: 316 g/kg), 3) 80% oat+ 20% lucerne (OL20, DM content: 317 g/kg) and 4) 70% oat+ 30% lucerne (OL30, DM content: 318 g/kg). All treatments were packed into laboratory-scale silos and ensiled for 60 days and then subjected to an aerobic stability test for 15 days. Further, the four experimental treatments were incubated in vitro with buffered rumen fluid to study the nutrient digestibility. All silages were well preserved with low pH and NH3 -N contents, and high lactic acid contents and V-scores (evaluation of silage quality). Increasing the lucerne proportion increased (p < 0.05) crude protein (CP) content of silage, whereas neutral (NDF) and acid (ADF) detergent fibre contents were not affected. Under aerobic conditions, the control silage showed higher (p < 0.05) yeast counts (>105  cfu/g FM) followed by OL10 silage, and OL10 silage improved aerobic stability for 74 h. OL20 and OL30 silages showed fewer (p < 0.05) yeasts (<105  cfu/g FM) and markedly (p < 0.05) improved the aerobic stability (>360 h). After 48-h incubation, OL30 silage increased (p < 0.05) in vitro dry matter digestibility (IVDMD) and neutral detergent fibre digestibility (IVNDFD) compared with the control silage. These results suggest that replacing oat with lucerne had no unfavourable effects on fermentation quality of silage, but improved CP content, aerobic stability IVDMD and IVNDFD. OL30 silage was the best among the three mixed silages.

[Eccrine angiomatous hamartoma: a clinicalopathologic analysis of 4 cases].

OBJECTIVE: To investigate the clinical and histopathologic features, diagnosis and differential diagnosis of eccrine angiomatous hamartoma(EAH). METHODS: Four cases of eccrine angiomatous hamartoma were studied by light microscopy and immunohistochemical staining along with review of the literature. RESULTS: There were 3 male and 1 female patients at diagnosis in age of 4 months, 3.5 years, 5.5 years and 14.0 years, respectively. Tumor sites included the left little finger (1 case), right index finger (1 case), lower back (1 case) and knee (1 case). Clinically, most cases presented as a solitary, flesh or reddish papule, plaque or nodule with size of 0.4-6.0 cm in diameter. The skin lesions in 3 cases enlarged commensurate with the growth of the patients, and local hyperhidrosis in one case. Histologically, EAH was characterized by proliferation of well-differentiated eccrine secretory and ductal elements closely associated with thin-walled angiomatous channels in the middle or deep dermis and subcutaneous tissue. By immunohistochemistry, the vascular components were positive for CD31, CD34 and factor Ⅷ related antigen while the eccrine glands were positive for S-100 protein, CEA, EMA, CAM5.2 and GCDFP15. Local surgical resection was performed in 4 cases and follow-up data (0.5 to 4.5 years) showed no recurrence. CONCLUSION: EAH is a rare, benign cutaneous hamartoma. Combination of clinical manifestations, histological changes and immunohistochemical findings is useful for the diagnosis and differential diagnosis.

[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

[Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma].

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.

[Multicenter clinical study on the diagnosis and treatment of childhood renal tumor].

Objective: To summarize the effect of Chinese Children's Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol. Methods: This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis. Results: Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ2=44.329,P<0.01) and failure to achieve CR at the end of the treatment (χ2=49.459,P<0.01) were independent factor for predicting survival. Conclusion: Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

Treatment outcome of rhabdomyosarcoma in Hong Kong Chinese children.

OBJECTIVES: To review the treatment outcome of rhabdomyosarcoma in Hong Kong Chinese children. DESIGN: Retrospective review. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive cases of rhabdomyosarcoma diagnosed and treated by the Department of Paediatrics and Adolescent Medicine of Queen Mary Hospital between 1989 and 2005. Each patient was staged and treated according to the Intergroup Rhabdomyosarcoma Study guidelines. MAIN OUTCOME MEASURES: Overall and event-free survival rates, and toxicity data. RESULTS: Of 19 patients (8 males and 11 females), 14 (74%) were younger than 10 years old. The median age at diagnosis was 6 (range, 0.5-17) years. Primary sites of rhabdomyosarcoma included: the head and neck (n=8; 6 classified as cranial parameningeal), genitourinary (3), extremity (3), pelvis (3), and trunk (2). Thirteen (68%) had embryonal and six (32%) had alveolar histology. Two, 2, 9, and 6 were classified as belonging to Intergroup Rhabdomyosarcoma Study groups 1, 2, 3, and 4, respectively. Respective 5-year overall and event-free survival rates of the entire cohort were 49% (95% confidence interval, 26-73%) and 32% (10-55%), with a median follow-up of 3.4 (range, 0.2-16.7) years. In non-metastatic cases (Intergroup Rhabdomyosarcoma Study groups 1-3), the 5-year overall survival rate was 66% (95% confidence interval, 39-93%) and in metastatic cases (group 4) it was 17% (0-46%). The 5-year overall survival rate for patients aged less than 10 years was 60% (95% confidence interval, 33-87%) compared to 20% (0-55%) in those aged 10 years and over. Significant treatment-related toxicities including myelosuppression, infections, peripheral neuropathy, and second cancers were encountered. CONCLUSIONS: Treatment outcome of rhabdomyosarcoma in this cohort of Chinese children was less favourable than that reported in international studies. Whilst the main reason could have been related to the high proportion of metastatic cases, also non-metastatic cases faired worse. Improved outcomes may be achieved by advances in multidisciplinary (paediatric oncology, pathology, radiotherapy, and surgery) management and supportive care.

[Epidemiological characteristics and environmental risk factors of hemorrhagic fever with renal syndrome in Wei River basin, China, 2005-2015].

Objective: To understand the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Wei River Basin from 2005 to 2015, and analyze the environmental factors that cause the differences of spatial distribution. Methods: HFRS reported cases in Wei River Basin from 2005 to 2015 were collected form "National Disease Reporting Information System" , and the epidemiological features of HFRS were analyzed. Boosted regression trees (BRT) model was applied to evaluate the environment factors on the geographical distribution of HFRS in Wei River basin at 5 km×5 km gird scale. Results: The number of HFRS cases was 18 629, and the average annual incidence from 2005-2015 in Wei River basin was 7.24/100 000. The highest morbidity was 15.18/100 000 in 2012. The middle and lower reaches of Wei River basin had high incidence of HFRS, such as Xi'an, Weinan city. Patients' age was mainly between 16 to 60, and the largest morbidity occured in people over 60 years old. Boosted regression trees modle identified building land, farmland coverage percentage and altitude had higher contribution to the distribution of HFRS. Conclusions: The epidemiological characteristics of HFRS changed significantly. Patients older than 60 years old were having the highest incidence rates. Environmental factors such as buildup land, farmland and altitude played important roles in the geographical distribution of HFRS in the Wei River basin.

[Analysis on the spatial-temporal characteristics of hand-foot-mouth disease in Shaanxi province, 2009-2013].

Objective: To study the spatial-temporal dynamical features of hand-foot-mouth disease (HFMD) in Shaanxi Province, so as to provide evidence for the development of relative prevention and control programs on HFMD. Methods: Surveillance data of HFMD was collected from the China Information System for Diseases Control and Prevention from 2009 to 2013. Related data on population and gross domestic product (GDP) was obtained from Shaanxi Statistical Yearbook. Statistical tools as R3.4.1, ArcGIS 10.2 and SaTScan 9.2 software were used to describe the spatial-temporal distribution of the disease. Power-law method on spatial-temporal-multicomponent model was used to analyze the spatial-temporal evolution of the HFMD epidemics in Shaanxi Province. Results: A total of 229 904 cases of HFMD were reported in Shaanxi Province from 2009 to 2013, with an average annual incidence as 122.50 per 100 000. Obvious seasonal characteristics were noticed, with 71.71% of the total cases identified between April and July. Counties with high incidence were mainly distributed in the mid-and east parts of Guanzhong area. Through temporal and spatial scan statistics, we identified that ClassⅠ clustering area was fixed to the central and southeast regions of Shaanxi province which were around Xi'an City between 2009 and 2013, with the relative risk (RR) as 2.24, ranging from 2.18 to 3.08. Results from Power-law analysis showed that the continuous follow-up impact from the previous HFMD epidemics appeared strong in Tongguan, Pucheng districts of Weinan City and Weiyang district of Xi'an, with autoregressive components as 1.14, 0.97 and 0.89, respectively. The risk of HFMD seemed high in Huayin city, Changan and Yanta districts and with the endemic components as 5.08, 4.12 and 4.08, respectively. Impact of the epidemics on nearby districts was largely seen in Lianhu district of Xi'an, Wugong district of Xianyang and Gaoling district of Xi'an with epidemic components as 2.12, 2.08 and 1.77, respectively. The etiological constituents of HFMD were mainly Enterovirus 71 between 2009 and 2012, while HFMD was mainly caused by other entero-viruses, in 2013. Conclusion: Significant spatial-temporal heterogeneity of HFMD was seen in Shaanxi province, which called for specific strategies to be developed in the highly endemic areas.

[Characteristics on spatial and temporal distribution as well as the driving effect of meteorological factors on brucellosis in Datong city, Shanxi province, 2005-2015].

Objective: To explore the spatio-temporal epidemic trends and related driving effects of meteorological factors on brucellosis in Datong city, Shanxi province, from 2005 to 2015. Methods: We collected the surveillance data on brucellosis and related meteorological data in Datong city from 2005 to 2015, to describe the epidemic characteristics of the disease. Quasi-Poisson distribution lag non-liner model (DLNM) was built to explore the driving effect of monthly meteorological data on the disease. Results: From 2005 to 2015, Datong city reported a total of 17 311 cases of brucellosis including one death, with the annual average incidence as 47.43 per 100 000 persons. A rising trend was seen during the study period. The monthly incidence of Brucellosis presented an obvious curve with a major peak from March to June, accounted for 48.40% of the total cases. The high incidence areas in the city gradually expanded from the northeast and southeast to the western areas. Results from the DLNM studies suggested that seasonality of brucellosis in Datong was significantly affected by metrological factors such as evaporation, rainfall and temperature. The peak of delayed effect appeared the highest when the monthly cumulative evaporation capacity was 140-260 mm and the monthly cumulative rainfall was 20-60 mm with lag less than 1 month or the monthly temperature was -13 ℃ with lag of 4-5 months. Conclusions: The incidence of human brucellosis in Datong city increased significantly from 2005 to 2015. Meteorological factors such as evaporation, rainfall, temperature all showed significant driving effects on the disease.

(-)- and (+)-Securidanes A and B, Natural Triarylmethane Enantiomers: Structure and Bioinspired Total Synthesis.

Two pairs of enantiomers, (-) and (+)-securidanes A (1 and 2) and B (3 and 4) featuring unprecedented triarylmethane (TAM) skeletons, were isolated from Securidaca inappendiculata. Their structures were established by spectroscopic data, X-ray crystallography, and CD analysis. A plausible biosynthetic pathway for 1-4 based on the co-isolated precursors was proposed. Bioinspired total synthesis of 1-4 was completed in high yield, which in turn corroborated the biosynthetic hypothesis. Compounds 1-4 showed good inhibition against protein tyrosine phosphatase 1B (PTP1B). The molecular docking demonstrated that the strongest inhibitor 3 (IC50 = 7.52 µM) reaches deeper into the binding pocket and has an additional H-bond.

[Long-term results of multicenter study based on childhood acute lymphoblastic leukemia 2005 protocol].

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions: In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells.

Activity of voltage-gated K+ channels (KV) in pulmonary arterial smooth muscle cells (PASMC) is pivotal in controlling membrane potential, cytoplasmic free Ca2+ concentration ([Ca2+]cyt, and pulmonary vasomotor tone. Acute hypoxia selectively inhibits KV channels, depolarizes PASMC, raises [Ca2+]cyt, and causes pulmonary vasoconstriction and vascular remodeling. Prolonged hypoxia (24-60 h) decreased significantly the mRNA levels of KV channel alpha subunits, KV1.2 and KV1.5. Consistently, the protein levels of KV1.2 and KV1.5 were also decreased significantly by hypoxia (48-72 h). Nevertheless, hypoxia affected negligibly the mRNA levels of KV channel beta subunits (KVbeta1, KVbeta2, and KVbeta3). The native K+ channels are composed of pore-forming alpha and auxiliary beta subunits. Assembly of KV beta subunits with alpha subunits confers rapid inactivation on the slowly or non-inactivating delayed rectifier KV channels. KV beta subunits also function as an open-channel blocker of KV channels. Thus, the diminished transcription and expression of KV alpha subunits may reduce the number of KV channels and decrease KC currents. Unchanged transcription of KV beta subunits may increase the fraction of the KV channel alpha subunits that are associated with beta subunits and further reduce the total KV currents. These data demonstrate a novel mechanism by which chronic hypoxia may cause pulmonary vasoconstriction and hypertension.

Pulmonary vasoconstrictor effects of prostacyclin in rats: potential role of thromboxane receptors.

Endogenous prostacyclin (PGI2; epoprostenol) is a potent endothelium-derived pulmonary vasodilator. However, the effects of exogenous PGI2 on isolated arteries could be either relaxant or contractile, depending on the species and organ studied. The present study investigated the distal pathways involved in the PGI2-induced contraction in rat intrapulmonary artery (PA) and relaxation in lamb PA. When vessels were precontracted with 30 mM K+, PGI2 (1 microM) induced relaxation in lamb PA but caused contraction in rat PA. Use of 30 mM K+, phenylephrine, serotonin, angiotensin II, or hypoxia to precontract the vessels did not alter the contractile effect of PGI2 in rat PA. Nevertheless, PGI2 produced a mild relaxation in rat PA precontracted by U-46619, a thromboxane A2 (TxA2)-receptor agonist, whereas the TxA2-receptor blocker SQ-29548 (0.1-0.5 microM) abolished the contractile response in rat PA. These data suggest that PGI2-induced contraction is mediated by activation of TxA2 receptors. The PGI2-induced modest relaxation in rat PA, which was only observed when TxA2 receptors were blocked by SQ-29548, suggests that the PGI2-mediated vasorelaxant pathway is diminished in these vessels. Simultaneous application of forskolin, an adenylate cyclase activator, and rolipram, a phosphodiesterase inhibitor, caused similar relaxation in both rat and lamb PA. This suggests that the adenosine 3',5'-cyclic monophosphate-dependent relaxing pathway is intact in rat PA and is comparable to that in lamb PA. On the basis of these data, we conclude that the pathways responsible for the paradoxical effects of PGI2 on rat and lamb PA are located upstream of the adenosine 3',5'-cyclic monophosphate-dependent relaxing pathway and that a paucity of PGI2 receptors in rat PA may be responsible.