[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

A prospective multicenter study investigating rituximab combined with intensive chemotherapy in newly diagnosed pediatric patients with aggressive mature B cell non-Hodgkin lymphoma (CCCG-BNHL-2015): a report from the Chinese Children's Cancer Group.

The evidence for the safety and efficacy of adding rituximab to intensive chemotherapy in pediatric patients with aggressive mature B cell non-Hodgkin lymphoma/leukemia (B-NHL/B-AL) is not yet robust. In this prospective multi-institutional trial, 419 evaluable patients ≤ 16 years of age with newly diagnosed B-NHL/B-AL were enrolled. Patients were stratified into 4 risk groups according to stage, resection status, and serum lactate dehydrogenase. Patients in group R1 received 3 therapy courses in the treatment order A-B-A. Patients in group R2 received 5 courses A-B-A-B-A. Patients in group R3 received 6 courses A-BB-AA-BB-AA-BB. For patients in group R4, rituximab was added to the chemotherapy backbone for patients in R3 (A-RBB-RAA-RBB-RAA-BB). At a median follow-up of 54 months, the 4-year event-free survival (EFS) for the entire group was 88.3 ± 1.6% (76.0 ± 4.3% in the historical study). The EFS rates according to the intention-to-treat principle were 100%, 98.6 ± 1.2%, 94.2 ± 1.8%, and 73.5 ± 3.7% for patients in treatment groups R1, R2, R3, and R4, respectively (P < 0.001). There were 9 (2.1%) toxic deaths due to infection during treatment. Regarding the toxicities of rituximab, grade 3/4 thrombocytopenia, mucositis, and infection occurred in 44.0%, 33.3%, and 64.0% after courses R-BB and grade 3/4 neutropenia, thrombocytopenia, and infection occurred in 96.3%, 77.8%, and 54.1% after courses RAA. The addition of rituximab to intensive chemotherapy is feasible even in a developing country. EFS was significantly improved when compared with the historical data. clinicals.gov identifier: NCT02405676.

[Diagnosis of drowning by detecting gyrB and 16S rRNA genes of Aeromonas hydrophila using PCR-capillary electrophoresis].

OBJECTIVE: To establish a method for diagnosis of freshwater drowning by amplifying gyrB and 16S rRNA genes of Aeromonas hydrophila using PCR coupled with capillary electrophoresis (CE). METHODS: DNA samples were extracted from human, 18 planktons (including Candida albicans, Aeromonas hydrophila, and 16 species of algae), and 30 cases of tissue samples (including the lung, liver, and kidney, all examined with microwave digestion-vacuum filtration-automated scanning electron microscopy) from human cadavers, including 28 freshwater drowning victims and 2 with natural death. The DNA samples were amplified with the primer AH (for gyrB gene) and primer Ah (for 16S rRNA gene), and the products were analyzed with CE. RESULTS: PCR amplification followed by CE yielded negative results for DNA of human, Candida albicans and 16 species of algae, whereas a positive result was found for Aeromonas hydrophila DNA with PCR products of 195 bp (with primer AH) and 350 bp (with primer Ah). In the 28 drowning cases, the detection rates of Aeromonas hydrophila using primer AH were 96.4% in the lung tissue, 71.4% in the liver tissue, and 60.7% in the kidney, as compared with the rates of 75.0%, 42.9%, and 32.1% using primer Ah, respectively. The positive rates for Aeromonas hydrophila in the organs of the drowning victims were 82.1% and 53.6% with primer AH and primer Ah, respectively. The detection showed negative results in the 2 cases of natural deaths. The two primers produced significantly different detection rates of Aeromonas hydrophila (P<0.05). CONCLUSION: PCR coupled with CE for detecting gyrB gene of Aeromonas hydrophila has a high sensitivity in assisting a diagnosis of freshwater drowning. Detection of both the gyrB gene and 16S rRNA gene of Aeromonas hydrophila can yield more convincing evidence of the diagnosis of freshwater drowning.

Antioxidant activities of crude phlorotannins from Sargassum hemiphyllum.

Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl4), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds.

[Effect of Eupolyphaga fibrinolytic protein on microvessel density and the expression of vascular endothelial growth factor in mice tumor].

OBJECTIVE: To study the effect of Eupolyphaga fibrinolyric protein (EFP) on microvessel density (MVD) and the expression of vascular endthelial growth factor in transplantation S180 and H22 mice. METHODS: The MVD in tumor was measured with immunohistochemical SP method and the VEGF level in serum was measured with ELISA method. RESULTS: Compared with the control group, EFP could significantly reduce the microvessel density and decrease the expression of vascular endothelial growth factor. CONCLUSION: EFP has the effect of anti-angiogenesis.

[The effect of transgenic cell strains expressing recombinant adenovirus vector of hOSM gene on the proliferation and homing ability of umbilical cord blood CD34(+) hematopoietic stem/progenitor cells].

AIM: To establish the transgenic cell strains expressing recombinant adenovirus vector of human Oncostain M(hOSM)gene which is supposed to be used as feeder layer cells for the proliferation of umbilical cord blood CD34(+) hematopoietic stem/progenitor cell (HSPC) and compare its migration capacity before and after amplification in vitro. METHODS: Establish the transgenic cell strains expressing recombinant adenovirus vector of hOSM gene, and the objective gene was detected by RT-PCR and ELISA. The purity of umbilical cord blood CD34(+) HSPC separated by magnetic-activated cell sorting (MACS) was detected by the FCM. After culturing with feeder layer cells, detect the rate of proliferation by flow cytometry (FCM). To compare the homing ability of HSPC after amplification in vitro, detect the spontaneous migration rate and migration rate induced by SDF-1 using transmembrane migration assay (Transwell experiment). RESULTS: The green fluorescence was observed by fluorescence microscope in the transgenic cell strains, and the objective gene was confirmed by RT-PCR and ELISA.The purity of umbilical cord blood CD34(+) HSPC separated by MACS could reach(96.8 ± 2.28)%. After culturing with feeder layer cells for 7 days, the CD34(+) cells were 15.73 times in group containing hOSM more than in group without hOSM. The expression rate of adhension molecules on the surface of CD34(+) cells were also higher in the group containing hOSM than without hOSM. After using Transwell assys to detect the homing ability of culturing cells, the induction migration rate of stem cells clturing on transgenic cell strains was (40.68 ± 1.35)%, significantly higher than the control, which reveals a better homing ability. CONCLUSION: Recombinant adenovirus vector of hOSM gene as feeder layer cells can effectively proliferate umbilical cord blood CD34(+) HSPC in vitro and delay it differentiate, what's more, the stem cells retain a high homing ability after culturing on transgenic cell strains in vitro.

[The research of thrombolytic and hemolysis effect from Eupolyphage fibrinolyric protein and its inhibitory effect on S180 ascites tumor of mice].

OBJECTIVE: Eupolyphage fibrinolyric protein (EFP) was isolated and purified from Eupolyphage sineses, and its thrombolytic effect, hemolysis effect and inhibitory effect on S180 ascites tumor were investigated. METHODS: EFP was isolated and purified by ammonium precipitation and DEAE ion exchange chromatography. It's thrombolytic and hemolysis effect were determined. MTT method and Colony-forming method were used to determine the inhibitory effect on S180 ascites tumor. RESULTS: the EFP was proved to have the effect of Thrombolytic and Hemolysis, and both increased dose-dependently, however at a lower concentration, the EFP had no hemocytolysis. The EFP was also proved the effect of inhibitory on cell proliferation and Colony-forming on S180 ascites tumor of Mice. CONCLUSION: EFP has a strong thrombolytic activity and weak hemolytic, and has inhibitory effect on S180 ascites tumor of mice.

A novel and selective assay for the quantitative analysis of molybdenum(VI) at nanogram level by resonance light scattering quenching technique.

A novel method is designed for the direct determination of trace amounts of molybdenum(VI) in tap water, human hair, and Chinese herbal medicine by means of decreasing resonance light scattering (RLS) technique. The characteristics of RLS spectra, the effective factors, and optimum conditions of the reaction were studied. In the medium of hydrochloric acid (pH 2.38), Mo(VI), dibromohydroxyphenylfluorone (DBHPF), and Triton X-100 react to form a complex, resulting in significant decreasing RLS signals of DBHPF-Triton X-100. The decreasing RLS intensity at 583.0 nm is proportional to the concentration of Mo(VI) up to 8.0 ng mL(-1). The detection limit is 0.013 ng mL(-1). The method is simple, reproducible, with reaction rapidity and stability of complexes formed. Moreover, the high selectivity and sensitivity of this method permits its direct determination of molybdenum(VI) in tap water, human hair, and Chinese herbal medicine and the results are in agreement with those obtained by the inductively coupled plasma atomic emission spectrometry (ICP-AES) method.

[Separation, purification and spectrum analysis of total flavonoids from Cercis chinensis].

OBJECTIVE: To separate, purify total flavonoids from Cercis chinensis Bge and analyze their flavonoid aglycones and content by spectrum method. METHODS: The total flavonoids from Cercis chinensis Bge were extracted by 15 volume of 55% ethyl alcohol and hot water refluence at 100 degrees C and separated, purified by polyamide resin chromatography. Based on reference substances of rutin, quercetin, kaempferol, it was analyzed and detected by UV-Vis spectroscope at 200-600 nm and by KBr infrared spectroscope at 400-4000 cm(-1). RESULTS: Average extraction rate of crude total flavonoids was 7.32% , and extraction rate of purified total flavonoids was 2.20%. The results of UV-Vis and IR scanning spectrum showed that purified total flavonoids from Cercis chinensis Bge contained of 3 kinds of flavonoid aglycones of rutin, quercetin, kaempferol, and their content was 0.8271, 0.2169, 0.3007 mg/ml respectively. CONCLUSION: Content of total flavonoid aglycones in purified flavonoids of Cercis chinensis Bge was 24.30%, and content of total flavonoid was 0.5346%.

[Purification and activity calculated of fibrinolyric factors from Eupolyphaga sinensis].

Three kinds ( EFF-1, EFF-2 and EFF-3) of fibrinolytic factor were separated by ammonium sulphate precipitation, DEAE-cellulose and preparative PAGE electrophoresis from female Eupolyphaga sinensis Walker. Their molecular weights were proved to be 41kd, 32.9 kd and 30.6 kd respectively with SDS-PAGE electophoresis. Their Activities as plasminogen activator were 171.3 U/mg, 234.0 U/mg and 148.5 U/mg. In addition, EFF-2 and EFF-3 were not only fibrinolytic activities but also have plasminogen activator on fibrinous plate lacked of plasminogen . There had been no such components of plasminogen activator and fiberinolytic enzyme from Eupolyphaga sinensis reported yet.

[Purification and biochemical character of a fibrinolytic protein from Eupolyphaga sinensis].

A novel of fibrinolytic protein has been separated and purified by ammonium sulfate fractionation, DEAE-cellulose and SephadexG-75 Column chromatography from the tissue of the female Eupolyphaga sinensis in the paper. The protein showed an apparent molecular weight of 41.3 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. In addition, it includes 10.5% sugar. Its specific activity to hydrolyze fibrin was 547.86 u/mg. The enzyme activity was inhibited by Mg2+, Ca2+, protein inhibitors, such as 8mol/L urea and 1% beta-mercaptoethanol, and serine protease inhibitor such as phenylmethanesulfonyl fluoride (PMSF), but wasn't inhibited by Na+, K+ and ethylenediaminotetraacetic acid (EDTA). The protein was stable under 40 degrees C and it's optimal temperature was also 40 degrees C. It's optimal pH was 8.0. It showed a different way between the activity and UK when they degrade the plasminogen. Based on all the messages the protein can be suggested to be a novel fibrinolytic protein. There have been no such component of fiberinolytic enzyme from Eupolyphaga sinensis walker reported yet.

[Spectral analysis and study of the microsome cytochrome P450 aromatase of Thais clavigera].

The microsomes were prepared from the viscera masses of Thais clavigeras. It is well known that there are some main components in microsome cytochrome P450 aroamtase, including cytochrome P450, cytochrome b5 and NADPH-cytochrome P450 reductase. So the contents of cytochrome P450 and cytochrome b5, and the activity of NADPH-cytochrome P450 reductase were determined by Shimadzu UV Visible spectrophotometer. And the microsomal proteins were analysed by SDS-PAGE. All the results indicated that there exists P450 arom in the T. clavigeras.

[Determination of several substrate-decomposition enzyme activities of Agrocybe cylindracea at different stages of development with spectrophotometer].

In the present paper the authors studied the activities of amylase, peroxidase, laccase, protease and cellulase at different developmental stages of agrocybe cylindracea and its mutation with the spectrophotometer. The result showed that the activity of amylase and peroxidase in hyphal stage is the highest for the two basidiomycetes. It can be concluded that these two enzymes are important in vegetative growth stage, but they may have little effect after the appearance of fruit body. The change of their protease is similar: in the hyphal growth stage it is higher than that of mature mushroom. But the activities of laccase and cellulase are very different between the two basidiomycetes. It is obvious that they are some different in physiology and biochemistry.

Contamination of soil, leaves and vegetables by polychlorinated biphenyls in Xiamen region, China.

The paper aimed to identify the primary of polychlorinated biphenyls(PCBs) in the Jiulong River Estuary, investigate the spatial distribution of PCBs contamination in the environment, localize the atmospheric source and evaluate ongoing PCBs emissions by analyzing soil samples collected along the Jiulong River region. In addition, the accumulation of PCBs in the human food chain was quantified by analyzing leaf of orange trees and vegetable samples collected along a gradient of soil/atmospheric contamination moving away from the source. Consequently, the impact on the human health and the ecosystem was quantified, different management options were proposed to reduce this impact and to carry out research on organic contaminants along the Jiulong River and Xiamen region.

[Differential expression of STRBP8, a new candidate oncogene, in cancerization of human immortalized esophageal epithelial cells].

BACKGROUND & OBJECTIVE: Recently, changes in composition, structure, and function of nuclear matrix proteins (NMPs) in generation and development of tumors evoked more and more attention. Separation and identification of tumor-related NMPs is a new way to search for tumor specific biomarkers, and to study tumor pathogenesis. This study was to analyze differential expression of STRBP8, one of esophageal carcinoma specific NMPs, in cancerization of immortalized human esophageal epithelial cells. METHODS: NMPs were extracted from immortalized human esophageal epithelial cell line SHEE and malignantly transformed esophageal carcinoma cell line SHEEC. Differential expression of STRBP8 was detected by two-dimensional electrophoresis (2-DE), matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS), and reverse transcription-polymerase chain reaction (RT-PCR). STRBP8 cDNA obtained by RT-PCR was linked to pGEM-T easy vector, and introduced into TOP10F' E.coli competent cells. Positive clones were sequenced and analyzed with BLAST. RESULTS: STRBP8 was only detected in SHEEC cells by 2-DE, MALDI-TOF-MS, and RT-PCR. The sequence of positive clones contained STRBP8 cDNA was identical to that in GenBank database. CONCLUSION: STRBP8, as a candidate oncogene, might relate to cancerization of esophageal epithelial cells, which might be a specific biomarker of esophageal carcinoma, and probe into the pathogenesis of esophageal carcinoma.

[Study on BS-12 as a new probe for the determination of DNA by resonance light scattering].

A new method has been developed for the determination of DNA by resonance light scattering with dodecyl dimethyl betaine (BS-12) in aqueous solution as a new probe. At pH 9.3, the interactions of BS-12 and DNA gave strong RLS signals at 388.0 nm. Linear relationships were found between the enhanced intensity of RLS and the concentration of DNAs in the range 0.25-12.0 microg x mL(-1) for fsDNA and 0.25-11.0 microg x mL(-1) for ctDNA. The limits of detection were 0.15 ng x mL(-1) and 0.16 ng x mL(-1) for fsDNA and ctDNA, respectively. The method was applied to the determination of synthetic samples with satisfactory results.

Separation and identification of differentially expressed nuclear matrix proteins between human esophageal immortalized and carcinomatous cell lines.

AIM: To separate and identify differentially expressed nuclear matrix proteins (NMPs) between the immortalized human esophageal epithelial cell line (SHEE) and the malignantly transformed esophageal carcinoma cell line (SHEEC), and to provide new ways for finding specific markers and the pathogenesis of esophageal carcinoma. METHODS: SHEE and SHEEC cell lines were used to extract NMPs. The quality of NMPs was monitored by Western blot analysis including DNA topoisomerase IIalpha, proliferation cell nuclear antigen (PCNA) and histone. NMPs of SHEE and SHEEC were analyzed by two-dimensional electrophoresis (2-DE), silver staining and PDQuest6.2 image analysis software. Three spots in which the differentially expressed NMPs were more obvious, were selected and analyzed with matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI- TOF-MS) and database search. RESULTS: Western blot analysis revealed that DNA topoisomerase IIalpha and PCNA were detected, and the majority of histones were deleted in NMPs of SHEE and SHEEC. After 2-DE image analysis by PDQuest6.2 software, the 2-DE maps were detected with an average of 106+/-7.1 spots in SHEE and 132+/-5.0 spots in SHEEC. Most of them were matched one another (r=0.72), only 16 protein spots were found differing in intensity. Three NMPs including cytoskeletal tropomyosin, FK506-binding protein 6, similar to retinoblastoma binding protein 8 were preliminarily identified by MALDI- TOF-MS. CONCLUSION: These differentially expressed NMPs may play an important role during malignant transformation from SHEE to SHEEC. Their separation and identification will contribute to searching for specific markers and probing into the pathogenesis of esophageal carcinoma.