Analysis of the efficacy of autologous peripheral blood stem cell transplantation in high-risk neuroblastoma.

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China. Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared. Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and overall survival (OS) rates for the transplantation group and the nontransplantation group were 65.5% vs. 41.3% (p=0.023) and 77.1% vs. 57.9% (p=0.03), respectively. There was no difference in the distribution of baseline clinical case characteristics between the single transplantation group and the tandem transplantation group (p>0.05), and there was no significant difference in EFS and OS between the two groups (p>0.05). Conclusion: Based on this pretreatment programme, autologous peripheral blood stem cell transplantation is safe and tolerable and significantly improves the prognosis of children in the high-risk group. The value of tandem autologous stem cell transplantation is worthy of further discussion, which should consider various aspects such as the transplantation medication regimen and the patient's state.

Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells.

Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.

MIR-21 regulating distribution of intestinal flora through TNF-α promotes progression of ulcerative colitis.

Background: To study the changes in intestinal flora in patients with ulcerative colitis (UC), and to explore its correlations with micro ribonucleic acid (miR)-21 and serum tumor necrosis factor-a (TNF-α). Methods: A total of 150 patients with UC were selected and divided into remission group and seizure group according to the severity of disease. At the same time, 150 healthy people receiving physical examination in the hospital during the same period were selected as control group. The levels of fecal miR-21 and TNF-α in all subjects were determined via reverse transcription-polymerase chain reaction (RT-PCR). The correlation between miR-21 and TNF-α and their associations with the changes in intestinal bacteria in UC were analyzed using Pearson correlation analysis. The risk factors affecting the occurrence of UC were explored via multivariate logistic regression analysis.

Natural radioactivity level in Yemen: A systematic review of radiological studies.

This paper aimed to conduct a systematic review of 26 published articles from 13 different regions in the Republic of Yemen related to the study of natural radioactivity (NORM) and enhanced artificial radioactivity (TENORM). The study relied on the analysis of various sample types, including air, groundwater, surface water, hot spring water, soil, sand, rocks, building materials, and oil field samples. It also analyzed the study areas, the types of detectors employed, and the study's timeframe. The analytical results raised significant concerns regarding the high levels of radioactivity observed in many of the studied regions. Moreover, some regions indicated the absence of any prior radiological study, despite apparent effects on the population and the environment, which suggest the presence of potential radionuclide concentration. Based on this study, it is strongly recommended that researchers conduct further radiological studies in regions previously studied over extended periods and in areas where no prior radiological studies have been conducted to assess potential radionuclide concentration.

Taxus chinensis (Pilg.) Rehder fruit attenuates aging behaviors and neuroinflammation by inhibiting microglia activation via TLR4/NF-κB/NLRP3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the important by-products of Taxus chinensis (Pilg.) Rehder, its fruit (TCF) has a sweet taste, which is commonly used in folklore to make health care wine reputed for enhancing immune function and promoting anti-aging effects, especially popular in the longevity villages of China for a long history. Evidences had showed that Taxus chinensis fruit contained polysaccharides, flavonoids, amino acids and terpenoids, which all were free of toxic compounds, but its medicinal value has not been fully recognized. Our previous studies have found that TCF extract may reverse many biological events, including oxidative stress, inflammatory response, neuronal apoptosis, etc. by in silico methods, suggesting potential avenues for future pharmaceutical exploration in aging and age-related diseases. AIM OF THE STUDY: Yet, the anti-aging properties of TCF have not been specifically studied, this study aims to fill this gap by investigating the effects of TCF extract (TCFE) in an aging mouse model, particularly focusing on its role in inhibiting microglial activation and elucidating its underlying anti-aging mechanisms. MATERIALS AND METHODS: An aging mouse model was induced using D-galactose, with interventions involving high, medium, and low doses of TCFE compared to a positive control (2 mg/kg rapamycin combined with 100 mg/kg metformin). The methodology involved evaluating behavioral changes, serum oxidative and antioxidative markers, hypothalamic ß-galactosidase activity, expression of the aging-related protein P63, serum inflammatory factors, and the TLR4/NF-κB/NLRP3 inflammatory pathway in hypothalamic tissues. Additionally, to strengthen our in vivo findings, we conducted in vitro experiments on LPS-stimulated BV2 microglial cells. Finally, UPLC-MS/MS for precise component analysis using compound standards, coupled with molecular docking analyses, were employed to discern and elucidate the anti-inflammatory mechanisms of TCF. RESULTS: In vivo results revealed TCFE significantly ameliorated behavioral deficits, reduced oxidative stress markers (MDA) and pro-inflammatory cytokines (IL1-ß, IL-6, IFNg, TNFα, IL-17), and increased in antioxidants (SOD, T-AOC) and anti-inflammatory factors (IL-10). TCFE also reduced hypothalamic senescence, improved cellular integrity, lowered p63, and inhibited microglia activation and inflammatory pathways (TLR4, NFKB, NLRP3). The overall effect of TCFE was better than that of the positive drug group (rapamycin combined with metformin). In vitro results further revealed that TCFE markedly decreased IL1-ß, NFKB, and TLR4 levels in BV2 microglial cells, showing comparable efficacy to a TLR4 classic positive inhibitor C34, supporting its anti-inflammatory role. Through UPLC-MS/MS analysis coupled with compound standards, we identified ten bioactive compounds, including gallocatechin, epigallocatechin, catechin, procyanidin B2, kaempferol, quercetin, rutin, naringin, apigenin, ginkgetin. All these compounds showed strong binding affinity to TLR4, notably procyanidin B2 and rutin, potentially through hydrogen bonds, aromatic cation-π interactions, and hydrophobic interactions, suggesting a molecular basis for their anti-inflammatory action. CONCLUSION: TCFE showed strong anti-aging effects by inhibiting microglia activation and lessening oxidative stress and modulating inflammatory pathways. This research supports TCF's use in anti-aging and sets a base for future drug development in the realms of neuroinflammation and aging.

Oral epidemic diseases of exposure personnel in long-term low dose radiation.

Oral epidemic diseases of exposure personnel in long-term low-dose radiation yet have rarely been studied. Referred to WHO oral health survey method and symptom grading standard, data of 341 exposure persons in long-term low-dose radiation including α particle, ß particle, and γ rays, etc., were collected from one camp in China in 2011 with cluster sampling and analyzed? with Foxpro 6.0 and SPSS 16.0 software. The exposure persons worked in low-dose radiation for a long time aged between 23 and 56, whose average age were 27.1 years old.In addition, their lengths of service were from 2 to 34 years (average 7.9 years) and average exposure time was 8 hours a day each year for more than three months. Average annual radiation dose equivalent was from 1.8 to 16.5 mSv (average 7.3 mSv). Total radiation dose equivalent was from 3.8 to 425.0 mSv (average 97.3 mSv).

Synthesis of magnetic nanobiomaterials and its biological effects.

Iron oxides and its hydrate nanoparticles, for example, nanoFe3O4 and nanoFe3O4 with hydroxyl, were synthesized by hydrothermal method, their sizes and features are evaluated by infrared spectra and Scanning Electron Microscope (SEM) etc. The dimensions of these nanoparticles produced are about 50-120 nm. In the investigation of influence of nanoFe3O4 and nanoFe3O4 with hydroxyl on crystalline states of amino acid molecules, their crystalline forms are different to that of pure amino acid molecules. The positions and widths of peaks of these nanoparticles in the infrared spectra of absorption are changed largely relative to that of pure amino acid molecules. From the experiments of microscope observation and infrared spectra of re-crytalline amino acids we see that the nanoFe3O4 and nanoFe3O4 with hydroxyl can change the structure of amino acid molecules. To study the toxicity of synthesized nanoparticles, the MTT (3-(4,5-dimethyl-thiazol 2-yl)-2,5 diphenyltetrazolium bromide) assay was used. The OD value (Optical Density) was used to calculated RGR (Relative Generation Rate) of cells, which determined the grade of cytotoxicity. The RGR of nanoparticles of iron oxide and its hydrate are about 1 to 2, which indicate that they have a lower toxicity.

Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones.

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

A multi-center open-labeled study of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma, or chronic lymphocytic leukemia in Chinese population.

The purpose of this study is to investigate the efficacy and safety of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma (MM), low-grade non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). From December 2005 to November 2006, the patients with MM, low-grade NHL, and CLL were enrolled in this study, male or female, aged > or = 18 years, transfusion-dependant, and receiving anti-neoplasia chemotherapy. Recombinant human erythropoietin-beta was used in this study with the dose initiated at 150 IU/kg, thrice a week, subcutaneously. The total treatment duration was 12 weeks. The primary endpoint of the study is response rate (RR), which is defined as hemoglobin increasing > or = 2 g/dL comparing to baseline level, or returning to normal range, without any transfusion within 6 weeks of evaluation. Fifty out of 82 (64.6%) patients enrolled in this study responded to the treatment and 29 patients had no response. Hypertension (12.2%) is the most common adverse effect; however, all the adverse events were mild, categorized in NCI grade I or II. We conclude that recombinant erythropoietin-beta was effective in the treatment of anemia of the patients with MM, NHL, and CLL, as well as it is well-tolerated.

Prevalence of the Factor V E666D Mutation and Its Correlation With Activated Protein C Resistance in the Chinese Population.

BACKGROUND: Factor V (FV) Leiden mutation-related activated protein C resistance (APCR) is one of the common inherited risk factors for venous thromboembolism (VTE) in caucasian population. Although APCR could be identified in some of the Chinese healthy people and patients with VTE, it was not related to FV Leiden mutation. In 2008, we have identified a novel FV mutation (FV E666D) in exon 13 in a hereditary APCR family. And we presumed that the novel mutation might be a genetic defect of APCR in the Chinese population. The aim of our study was to evaluate the prevalence of FV E666D mutation and its correlation with APCR in the Chinese population in a larger series. METHODS: From June 2009 to January 2011, 163 consecutive patients who underwent thrombophilia tests in our hospital were recruited. The clinical data were retrospectively reviewed. Thrombophilia tests included APCR, anticoagulant proteins, and antiphospholipid antibodies. Factor V E666D mutation was detected. RESULT: Of the 163 patients, 6 (3.7%) were identified as APCR positive, 2.9% for patients without thrombosis and 5.1% for patients with thrombosis or thrombosis history. Factor V E666D mutation was not detectable in all the 163 patients including 6 APCR-positive patients. CONCLUSIONS: The prevalence of APCR either in the nonthrombotic patients or in the patients with thrombosis was lower than that reported in other Chinese studies. Our study couldn't provide illustration whether FV E666D mutation is correlated with APCR in the Chinese population.

Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer agents: syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity.

Four novel thiosemicarbazone metal complexes, [Cu(Am4M)(OAc)]·H2O (1), [Zn(HAm4M)Cl2] (2), [Zn2(Am4M)2Br2] (3) and [Zn2(Am4M)2(OAc)2]·2MeOH (4) [HAm4M=(Z)-2-(amino(pyridin-2-yl)methylene)-N-methylhydrazinecarbothioamide], have been synthesized and characterized by X-ray crystallography, elemental analysis, ESI-MS and IR. X-ray analysis revealed that complexes 1 and 2 are mononuclear, which possess residual coordination sites for Cu(II) ion in 1 and good leaving groups (Cl(-)) for Zn(II) ion in 2. Both 3 and 4 displayed dinuclear units, in which the metal atoms are doubly bridged by S atoms of two Am4M(-) ligands in 3 and by two acetate ions in bi- and mono-dentate forms, respectively, in 4. Their antiproliferative activities on human epithelial cervical cancer cell line (HeLa), human liver hepatocellular carcinoma cell line (HepG-2) and human gastric cancer cell line (SGC-7901) were screened. Inspiringly, IC50 value (11.2±0.9 µM) of complex 1 against HepG-2 cells was nearly 0.5 fold of that against human hepatic cell lines LO2, showing a lower toxicity to human liver cells. Additionally, it displayed a stronger inhibition on the viability of HepG-2 cells than cisplatin (IC50=25±3.1 µM), suggesting complex 1 might be a potential high efficient antitumor agent. Furthermore, fluorescence microscopic observation and flow cytometric analysis revealed that complex 1 could significantly suppress HepG-2 cell viability and induce apoptosis. Several indexes, such as DNA cleavage, reactive oxygen species (ROS) generation, comet assay and cell cycle analysis indicated that the antitumor mechanism of complex 1 on HepG-2 cells might be via ROS-triggered apoptosis pathway.

[Isolation and identification of Streptococcus mutans strains with different genotype from clinical samples].

OBJECTIVE: To identify Streptococcus mutans (S. mutans) strains from clinical samples. METHODS: Plaque samples from caries-active and caries-free sites on enamel surfaces were obtained and cultivated for S. mutans isolation. Morphology, biochemistry, automatic microorganism analysis system and polymerase chain reaction using primers homologous to surface protein antigen I/II (spaP), glucosyltransferase B (gtfB) and dextranase (dexA) were used to identify S. mutans. Genotype of isolated S. mutans was determined by arbitrarily primed polymerase chain reaction. RESULTS: Forty-six strains of S. mutans were obtained from the 32 subjects and were identified as S. mutans by biochemistry, automatic microorganism analysis system and polymerase chain reaction. Five identical genotypes were found by arbitrarily primed polymerase chain reaction. CONCLUSION: Forty-one strains of S. mutans with different genotype were obtained from clinical samples.

Activities of a novel Schiff base copper(II) complex on growth inhibition and apoptosis induction toward MCF-7 human breast cancer cells via mitochondrial pathway.

In this study, we investigated the newly synthesized Schiff base copper(II) complex, [Cu(II)(5-Cl-pap)(OAc)(H(2)O)]·2H(2)O (1) (5-Cl-pap=N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine), inducing growth inhibition and apoptosis in human breast cancer cell line MCF-7 and its potential antitumor mechanism. The results of cytotoxicity research, fluorescence microscopic observation and flow cytometric analysis revealed that complex 1 could significantly suppress MCF-7 cell viability and induce apoptosis. Comet assay indicated that severe DNA fragmentation in MCF-7 cells was induced after treatment with complex 1. Flow cytometric analysis showed that the antitumor effect of complex 1 on MCF-7 cells was associated with the cell cycle arrest. In addition, atomic absorption analyses displayed that complex 1 caused a rapid increase of intracellular copper uptake in MCF-7 cells in a time-dependent manner. The present work suggested that the antitumor mechanism of complex 1 on MCF-7 cells might be via the mitochondrial pathway, based on the up-regulated expression of Bax and activation of caspase-9 and caspase-3.

Study on potential antitumor mechanism of a novel Schiff base copper(II) complex: synthesis, crystal structure, DNA binding, cytotoxicity and apoptosis induction activity.

A new cytotoxic copper(II) complex with Schiff base ligand [Cu(II)(5-Cl-pap)(OAc)(H(2)O)]·2H(2)O (1) (5-Cl-pap=N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine), was synthesized and structurally characterized by X-ray diffraction. Single-crystal analysis revealed that the copper atom shows a 4+1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the NNO tridentate ligand and the fourth by an acetate oxygen. The interaction of Schiff base copper(II) complex 1 with DNA was investigated by UV-visible spectra, fluorescence spectra and agarose gel electrophoresis. The apparent binding constant (K(app)) value of 6.40×10(5) M(-1) for 1 with DNA suggests moderate intercalative binding mode. This copper(II) complex displayed efficient oxidative cleavage of supercoiled DNA, which might indicate that the underlying mechanism involve hydroxyl radical, singlet oxygen-like species, and hydrogen peroxide as reactive oxygen species. In addition, our present work showed the antitumor effect of 1 on cell cycle and apoptosis. Flow cytometric analysis revealed that HeLa cells were arrested in the S phase after treatment with 1. Fluorescence microscopic observation indicated that complex 1 can induce apoptosis of HeLa cells, whose process was mediated by intrinsic mitochondrial apoptotic pathway owing to the activation of caspase-9 and caspase-3.

Synthesis and characterization of solution-processable polyelectrolyte complexes and their homogeneous membranes.

Solution-processable polyelectrolyte complexes (PECs) between poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were synthesized in aqueous NaOH and obtained in their solid forms by protection and deprotection of carboxylic acid groups. Elemental analysis, conductance measurement, and FT-IR showed that the composition and ionic complexation degree (ICD) of the PECs can be controlled effectively by tuning the NaOH concentration in both parent polyelectrolyte solutions. Thermal gravity analysis showed that PECs revealed good thermal stability, and differential scanning calorimetry showed that the glass transition temperature (Tg) of PECs increased with increasing ICD and finally became undetectable when ICD was above 0.16. Viscosity properties of the PEC solutions were well correlated to the ICD of PECs, and it was found that solid PECs could be redissolved in dilute NaOH without breaking the ionic complexation between PDDA and PAA. Homogeneous PEC membranes (HPECMs) were made from their concentrated solutions, and their morphologies were examined by field emission scanning electron microscopy. These novel HPECMs were subjected to dehydration of organics for the first time, and a very promising performance was obtained. Furthermore, another two solution-processable PECs between weak anionic polyelectrolyte and cationic polyelectrolyte were also synthesized by the same method and showed a very high separation performance.

The Biological Effect of the NanoTiO2and Its Toxicity.

The proliferation behavior of the person's liver cell under actions of the nanoTiO2has been looked into by 3-(4,5-dimethylthiazol 2-yl)-2,5 diphenyltetrazolium bromide (MTT) colorimetric method of Mosmann. In this case we first give some elementary properties of the nanoTiO2and do further the liver cell cultures, and add the nano TiO2into the cells. In accordance with biological rules we measure the proliferation state of the liver cell in normal condition. The result obtained show that the influence of the nanoTiO2on the proliferation of the person's liver cell is very small, when compared with that of the control group. We found further out the size of the toxicity of the nanoTiO2to the chick embryo fibroblast (CEF) cells by the MTT colorimetric method. Thus we determine the toxicity for the TiO2s of 100nm and of 1000nm by the toxicology which are all first score (or degree).

Biological effects of the carbon nanotubes.

The influences of the carbon nanotubes on proliferation state of chick embryo fibroblast cells and toxicity of the nanotubes to the cells have been investigated by 3-(4,5-dimethylthiazol 2-yl)-2,5 diphenylte-trazolium bromide (MTT) colorimetric method of Mosmann and the toxicology. We found that the toxicity of the carbon nanotubes to the chick embryo fibroblast cells is small, it is about first score (or degree).

Dose-dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension following cardiopulmonary bypass.

BACKGROUND: To investigate the dose dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension (PH) after cardiopulmonary bypass (CPB). METHODS: Thirty-two patients with pulmonary arterial pressure (PAP) above 60 mmHg were recruited. They were assigned randomly to control (Group A, n = 8), and treated groups (Group B with aprotinin = 0.5 x 10(5) KIU/Kg, and Group C with aprotinin = 1.0 x 10(5) KIU/Kg, n = 12 each group). Blood samples were collected at various intervals of time and analyzed, from "0" hour (before CPB as baseline), at the completion of CPB, 4 hours and 24 hours after CPB, to measure the concentrations of interleukin 1beta (IL-1beta), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: All the biomarkers significantly increased after CPB. There was no significant difference in cytokine levels between Group A and group B after CPB. But IL-1beta, IL-8 and TNF-alpha of Group C were not only significantly lower than Group A (p < 0.05), but also lower than Group B at various time points after CPB (p < 0.05). IL-10 of group C was significantly higher than Group A and Group B after CPB (p < 0.05). CONCLUSIONS: High dose aprotinin can suppress the release of pro-inflammatory cytokines IL-1beta, IL-8 and TNF-alpha, and enhance the release of IL-10 in patients with PH after CPB. For patients having PH, there exists a simple and potential way to reduce the inflammatory response by applying high dose aprotinin.