Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling pathways.

BACKGROUND: Angiogenesis strongly reflects poor breast cancer outcome and an important contributor to breast cancer (BC) metastasis; therefore, anti-angiogenic intervention is a potential tool for cancer treatment. However, currently used antibodies against vascular endothelial growth factor A (VEGFA) or inhibitors that target the VEGFA receptor are not effective due to weak penetration and low efficiency. Herein, we assessed the anti-BC angiogenic role of muscone, a natural bioactive musk constituent, and explored possible anti-cancer mechanisms of this compound. METHODS: CCK-8, EdU, scratch and Transwell assessments were employed to detect the muscone-mediated regulation of breast cancer (BC) and human umbilical vein endothelial cells (HUVECs) proliferation and migration. Tube formation, matrigel plug assay and zebrafish assay were employed for assessment of regulation of tumor angiogenesis by muscone. In vivo xenograft mouse model was constructed to compare microvessel density (MVD), vascular leakage, vascular maturation and function in muscone-treated or untreated mice. RNA sequencing was performed for gene screening, and Western blot verified the effect of the VEGFA-VEGFR2 pathway on BC angiogenic inhibition by muscone. RESULTS: Based on our findings, muscone suppressed BC progression via tumor angiogenic inhibition in cellular and animal models. Functionally, muscone inhibited BC cell proliferation and migration as well as tumor cell-conditioned medium-based endothelial cell proliferation and migration. Muscone exhibited a strong suppressive influence on tumor vasculature in cellular and animal models. It abrogated tumor cell growth in a xenograft BC mouse model and minimized tumor microvessel density and hypoxia, and increased vascular wall cell coverage and perfusion. Regarding the mechanism of action, we found that muscone suppressed phosphorylation of members of the VEGF/PI3K/Akt/MAPK axis, and it worked synergistically with a VEGFR2 inhibitor, an Akt inhibitor, and a MAPK inhibitor to further inhibit tube formation. CONCLUSION: Overall, our results demonstrate that muscone may proficiently suppress tumor angiogenesis via modulation of the VEGF/PI3K/Akt/MAPK axis, facilitating its candidacy as a natural small molecule drug for BC treatment.

Enhanced PSO feature selection with Runge-Kutta and Gaussian sampling for precise gastric cancer recurrence prediction.

Gastric cancer (GC), characterized by its inconspicuous initial symptoms and rapid invasiveness, presents a formidable challenge. Overlooking postoperative intervention opportunities may result in the dissemination of tumors to adjacent areas and distant organs, thereby substantially diminishing prospects for patient survival. Consequently, the prompt recognition and management of GC postoperative recurrence emerge as a matter of paramount urgency to mitigate the deleterious implications of the ailment. This study proposes an enhanced feature selection model, bRSPSO-FKNN, integrating boosted particle swarm optimization (RSPSO) with fuzzy k-nearest neighbor (FKNN), for predicting GC. It incorporates the Runge-Kutta search, for improved model accuracy, and Gaussian sampling, enhancing the search performance and helping to avoid locally optimal solutions. It outperforms the sophisticated variants of particle swarm optimization when evaluated in the CEC 2014 test suite. Furthermore, the bRSPSO-FKNN feature selection model was introduced for GC recurrence prediction analysis, achieving up to 82.082 % and 86.185 % accuracy and specificity, respectively. In summation, this model attains a notable level of precision, poised to ameliorate the early warning system for GC recurrence and, in turn, advance therapeutic options for afflicted patients.

Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study.

BACKGROUND: Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses. METHODS: We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS: Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC. CONCLUSION: Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial.

OTUD1 chemosensitizes triple-negative breast cancer to doxorubicin by modulating P16 expression.

Chemotherapy remains a critical component of triple-negative breast cancer (TNBC) treatment; however, patients often develop resistance to chemotherapeutic agents. Accumulating evidence indicates that deubiquitylases (DUBs) play pivotal roles in regulating cell proliferation, differentiation, apoptosis, and tumorigenesis. Deubiquitylase OTUD1 is considered a tumor suppressor in various cancers, yet its role in doxorubicin sensitivity in breast cancer patients remains inadequately understood. In this study, we investigated the expression levels and prognostic role of OTUD1 in breast cancer. Our findings demonstrated that OTUD1 was downregulated in TNBC, and lower OTUD1 expression levels were correlated with poor prognosis. We utilized the CCK-8 cell viability assay, flow cytometric analysis, and a TNBC mouse xenograft model to examine the influence of OTUD1 on doxorubicin (DOX) chemotherapy sensitivity in vitro and in vivo. Western blot and immunohistochemistry were employed to explore the correlation between OTUD1 and P16. Our results indicated that upregulation of OTUD1 expression inhibits TNBC cell proliferation and enhances its sensitivity to doxorubicin. Additionally, rescue experiments confirmed that the chemosensitizing effect of OTUD1 overexpression could be reversed by the inhibition of P16. Therefore, our findings reveal that OTUD1 sensitizes TNBC cells to DOX by upregulating P16 expression, suggesting a potential new diagnostic biomarker and therapeutic target for the future treatment of TNBC.

Distinct doorway states lead to triplet excited state generation in epigenetic RNA nucleosides.

N 6-Hydroxymethyladenosine (hm6A) and N6-formyladenosine (f6A) are two important intermediates during the demethylation process of N6-methyladenosine (m6A), which has been proven to show epigenetic function in mRNA. However, there is no knowledge about how the chemical integrity and stability could be altered when these two nucleosides are exposed to ultraviolet (UV) radiation. Herein, we report the first study on excited state dynamics of hm6A and f6A in solutions by using femtosecond time-resolved spectroscopy and quantum chemistry calculations. Surprisingly, triplet excited species are clearly identified in both hm6A and f6A after UV excitation, which is in sharp contrast to the 10-3 level triplet yield of adenosine scaffolds. Moreover, the doorway states leading to triplet states are found to be an intramolecular charge transfer state and a lower-lying dark nπ* state in hm6A and f6A, respectively. These discoveries pave the way to further study their effects on RNA strands and provide insight for understanding RNA photochemistry.

Pan-cancer Analysis Identifies AIMP2 as a Potential Biomarker for Breast Cancer.

Introduction: Aminoacyl tRNA synthetase complex interacting with multifunctional protein 2 (AIMP2) is a significant regulator of cell proliferation and apoptosis. Despite its abnormal expression in various tumor types, the specific functions and effects of AIMP2 on tumor immune cell infiltration, proliferation, and migration remain unclear. Materials and Methods: To assess AIMP2's role in tumor immunity, we conducted a pan-cancer multi-database analysis using the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets, examining expression levels, prognosis, tumor progression, and immune microenvironment. Additionally, we investigated AIMP2's impact on breast cancer (BRCA) proliferation and migration using cell counting kit 8 (CCK-8) assay, transwell assays, and western blot analysis. Results: Our findings revealed that AIMP2 was overexpressed in 24 tumor tissue types compared to normal tissue and was associated with four tumor stages. Survival analysis indicated that AIMP2 expression was strongly correlated with overall survival (OS) in certain cancer patients, with high AIMP2 expression linked to poorer prognosis in five cancer types. Conclusion: Finally, siRNA-mediated AIMP2 knockdown inhibited BRCA cell proliferation and migration in vitro. In conclusion, our pan-cancer analysis suggests that AIMP2 may play a crucial role in tumor immunity and could serve as a potential prognostic marker, particularly in BRCA.

Excited State Dynamics of Methylated Guanosine Derivatives Revealed by Femtosecond Time-resolved Spectroscopy.

Methylated DNA/RNA nucleobases are important epigenetic marks in living species and play an important role for targeted therapies. Moreover, methylation could bring significant changes to the photo-stability of nucleic acid, leading these sites become mutational hotspots for disease such as skin cancer. While a number of studies have demonstrated the relationship between excited state dynamics and the biological function of methylated cytosine in DNA, investigations aimed at unraveling the excited state dynamics of methylated guanosine in RNA have been largely overlooked. In this work, influence of methylation on the excited state dynamics of guanosine is studied by using femtosecond time-resolved spectroscopy. Our results suggest that the effect of methyl substitution on the photophysical properties of guanosine is position sensitive. N1-methylguanosine shows very similar excited state dynamics as that in guanosine, while almost one order of magnitude longer lifetime of the La state is observed in N2, N2-dimethylguanosine. Notably, N7-methylation can lead to a new minimum on the La state and the excited state lifetime is two orders of magnitude longer than that of guanosine. These findings not only help understanding excited state dynamics of methylated guanosines, but also lay the foundation for further studying DNA/RNA strands incorporated with these bases.

Personalized fMRI Delineates Functional Regions Preserved within Brain Tumors.

OBJECTIVE: Accumulating evidence from invasive cortical stimulation mapping and noninvasive neuroimaging studies indicates that brain function may be preserved within brain tumors. However, a noninvasive approach to accurately and comprehensively delineate individual-specific functional networks in the whole brain, especially in brain tissues within and surrounding tumors, is still lacking. The purpose of the study is to develop a clinically useful technique that can map functional regions within tumoral brains. METHODS: We developed an individual-specific functional network parcellation approach using resting state functional magnetic resonance imaging (rsfMRI) that effectively captured functional networks within and nearby tumors in 20 patients. We examined the accuracy of the functional maps using invasive cortical stimulation and task response. RESULTS: We found that approximately 33.2% of the tumoral mass appeared to be functionally active and demonstrated robust functional connectivity with non-tumoral brain regions. Functional networks nearby tumors were validated by invasive cortical stimulation mapping. Intratumoral sensorimotor networks mapped by our technique could be distinguished by their distinct cortico-cerebellar connectivity patterns and were consistent with hand movement evoked fMRI task activations. Furthermore, in some patients, cognitive networks that were detected in the tumor mass showed long-distance and distributed functional connectivity. INTERPRETATION: Our noninvasive approach to mapping individual-specific functional networks using rsfMRI represents a promising new tool for identifying regions with preserved functional connectivity within and surrounding brain tumors, and could be used as a complement to presurgical planning for patients undergoing tumor resection surgery. ANN NEUROL 2022;91:353-366.

Relationship between bronchopulmonary dysplasia, long-term lung function, and vitamin D level at birth in preterm infants.

BACKGROUND: We aimed to investigate the relationship between the level of serum 25 hydroxyvitamin D [25-(OH)D] at birth and the complications of bronchopulmonary dysplasia (BPD), as well as the long-term lung function of preterm infants. METHODS: A total of 286 premature infants who were admitted to the neonatal ward of Haikou Maternal and Child Health Hospital from January 2018 to December 2020 and met the inclusion criteria were selected as the research objects. The level of serum 25(OH)D at birth was detected. The children were divided into a BPD group (79 cases) and a non-BPD group (207 cases). The case information and basic data of the children were recorded. The children were followed up 6 months after correcting the gestational age of 40 weeks, and their long-term lung function development was reported. Logistic regression analysis was used to evaluate the high-risk factors of BPD in preterm infants. RESULTS: The 1- and 5-minute Apgar scores of preterm infants in the BPD group were significantly lower than those in the non-BPD group. Also, the combined neonatal pneumonia, neonatal asphyxia, hospital stay, and total oxygen therapy time in the BPD group were substantially higher than those in the non-BPD group. The mean value of serum 25-(OH)D at birth in the BPD group (33.7±15.1 nmol/L) was significantly lower than that in the non-BPD group (49.5±19.6 nmol/L). Compared with the non-BPD group, the respiratory rate (RR) in the BPD group increased significantly, while the tidal volume (VT), inspiratory to expiratory ratio (TI/TE), ratio of time to peak tidal expiratory flow to total expiratory time (TPEF/TE), and 25% tidal expiratory flow rate (TEF25%) decreased markedly (P<0.05). Total oxygen therapy time, neonatal pneumonia, neonatal asphyxia, and serum 25-(OH)D level at birth were identified as independent risk factors for BPD in preterm infants. CONCLUSIONS: The level of serum 25-(OH)D in preterm infants at birth is closely related to the occurrence of BPD and long-term lung function damage, and is affected by multiple high-risk factors. This study provides a theoretical basis for the individualized treatment of preterm infants and the early prevention of BPD.

Efficacy of intracellular immune checkpoint-silenced DC vaccine.

BACKGROUND: DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency. METHODS: We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy. The adenovirus (Ad-siSSF) delivers two tumor-associated antigens (TAAs), survivin and MUC1; secretory bacterial flagellin for DC maturation; and an RNA interference moiety to suppress SOCS1. A 2-stage phase I trial was performed for patients with relapsed acute leukemia after allogenic hematopoietic stem cell transplantation: in stage 1, we compared the safety and efficacy between gmDC treatment (23 patients) and standard donor lymphocyte infusion (25 patients); in stage 2, we tested the efficacy of the gmDC vaccine for 12 acute myeloid leukemia (AML) patients with early molecular relapse. RESULTS: gmDCs elicited potent TAA-specific CTL responses in vitro, and the immunostimulatory activity of gmDC vaccination was demonstrated in rhesus monkeys. A stage 1 study established that this combinatory gmDC vaccine is safe in acute leukemia patients and yielded improved survival rate. In stage 2, we observed a complete remission rate of 83% in 12 relapsed AML patients. Overall, no grade 3 or grade 4 graft-versus-host disease incidence was detected in any of the 35 patients enrolled. CONCLUSIONS: This study, with combinatory modifications in DCs, demonstrates the safety and efficacy of SOCS1-silenced DCs in treating relapsed acute leukemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01956630. FUNDING: National Institute of Health (R01CA90427); the Key New Drug Development and Manufacturing Program of the "Twelfth Five-Year Plan" of China (2011ZX09102-001-29); and Clinical Application Research of Beijing (Z131107002213148).

Magnesium-deficiency-induced alterations of gas exchange, major metabolites and key enzymes differ among roots, and lower and upper leaves of Citrus sinensis seedlings.

Magnesium (Mg)-deficiency is a widespread problem adversely affecting the quality and yield of crops, including citrus. 'Xuegan' [Citrus sinensis (L.) Osbeck] seedlings were irrigated every other day with nutrient solution at an Mg concentration of 0 mM (Mg-deficiency) or 1 mM (Mg-sufficiency) for 16 weeks. Thereafter, biomass, leaf mass per area, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), pigments in the upper and lower leaves, Mg, gas exchange, organic acids, nonstructural carbohydrates, total soluble proteins, amino acids, phenolics and anthocyanins, and key enzymes related to organic acid, amino acid and phenolic metabolisms in the roots, and upper and lower leaves were assayed in order to test the hypothesis that Mg-deficiency-induced alterations of gas exchange, major metabolites and key enzymes may differ among the roots, and upper and lower leaves. Magnesium-deficiency affected the most measured parameters more in the lower than in the upper leaves except for the nonstructural carbohydrates, but the variation trends were similar between the two. Despite increased accumulation of nonstructural carbohydrates, the lower CO2 assimilation in the Mg-deficient leaves was not caused by the feedback inhibition mechanism via sugar accumulation. Both dark respiration and organic acid metabolism were elevated in the Mg-deficient lower leaves to 'consume' the excess carbohydrates, and inhibited in the Mg-deficient roots with less accumulation of nonstructural carbohydrates to keep the balance of net carbon. More total phenolics and fewer anthocyanins were accumulated in the Mg-deficient lower leaves, whereas the accumulation of both total phenolics and anthocyanins was reduced in the Mg-deficient roots. Interestingly, amino acid biosynthesis was repressed in the Mg-deficient roots and lower leaves, thus lowering the level of total free amino acids in these roots and leaves. To conclude, great differences existed in the Mg-deficiency-induced alterations of gas exchange, major metabolites and key enzymes among the roots, and upper and lower leaves.

Identification of a novel functional JAK1 S646P mutation in acute lymphoblastic leukemia.

The survival rate of childhood acute lymphoblastic leukemia (ALL) is approaching 90%, while the prognosis of adults remains poor due to the limited therapeutic approaches. In order to identify new targets for ALL, we performed whole-exome sequencing on four adults with B-ALL and discovered a somatic JAK1 S646P mutation. Sanger sequencing of JAK1 was conducted on 53 ALL patients, and two cases exhibited A639G and P960S mutations separately. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice. Moreover, a high sensitivity to the JAK1/2 inhibitor ruxolitinib was observed in S646P mutant model. Exploration in a total of 209 ALL cases showed that JAK1 mutations occur at a frequency of 10.5% in T-ALL (2/19) and 1.6% in B-ALL (3/190). Collectively, our results suggested that JAK1 S646P is an activating mutation in vitro and in vivo. JAK-STAT pathway might represent a promising therapeutic target for ALL.

Third-generation CD28/4-1BB chimeric antigen receptor T cells for chemotherapy relapsed or refractory acute lymphoblastic leukaemia: a non-randomised, open-label phase I trial protocol.

INTRODUCTION: There is no curative treatment available for patients with chemotherapy relapsed or refractory CD19+ B cells-derived acute lymphoblastic leukaemia (r/r B-ALL). Although CD19-targeting second-generation (2nd-G) chimeric antigen receptor (CAR)-modified T cells carrying CD28 or 4-1BB domains have demonstrated potency in patients with advanced B-ALL, these 2 signalling domains endow CAR-T cells with different and complementary functional properties. Preclinical results have shown that third-generation (3rd-G) CAR-T cells combining 4-1BB and CD28 signalling domains have superior activation and proliferation capacity compared with 2nd-G CAR-T cells carrying CD28 domain. The aim of the current study is therefore to investigate the safety and efficacy of 3rd-G CAR-T cells in adults with r/r B-ALL. METHODS AND ANALYSIS: This study is a phase I clinical trial for patients with r/r B-ALL to test the safety and preliminary efficacy of 3rd-G CAR-T cells. Before receiving lymphodepleting conditioning regimen, the peripheral blood mononuclear cells from eligible patients will be leukapheresed, and the T cells will be purified, activated, transduced and expanded ex vivo. On day 6 in the protocol, a single dose of 1 million CAR-T cells per kg will be administrated intravenously. The phenotypes of infused CAR-T cells, copy number of CAR transgene and plasma cytokines will be assayed for 2 years after CAR-T infusion using flow cytometry, real-time quantitative PCR and cytometric bead array, respectively. Moreover, several predictive plasma cytokines including interferon-γ, interleukin (IL)-6, IL-8, Soluble Interleukin (sIL)-2R-α, solubleglycoprotein (sgp)130, sIL-6R, Monocyte chemoattractant protein (MCP1), Macrophage inflammatory protein (MIP1)-α, MIP1-ß and Granulocyte-macrophage colony-stimulating factor (GM-CSF), which are highly associated with severe cytokine release syndrome (CRS), will be used to forecast CRS to allow doing earlier intervention, and CRS will be managed based on a revised CRS grading system. In addition, patients with grade 3 or 4 neurotoxicities or persistent B-cell aplasia will be treated with dexamethasone (10 mg intravenously every 6 hours) or IgG, respectively. Descriptive and analytical analyses will be performed. ETHICS AND DISSEMINATION: Ethical approval for the study was granted on 10 July 2014 (YLJS-2014-7-10). Written informed consent will be taken from all participants. The results of the study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report. TRIAL REGISTRATION NUMBER: NCT02186860.

Outcome of myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation for refractory/relapsed AML patients in NR status.

To further find effective method to improve the long term survival of refractory or relapsed acute myeloid leukemia (AML) patients, we retrospectively analyzed the outcomes of myeloablative hematopoietic stem cell transplantation (HSCT) for 133 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) therapy related AML(t-AML) in not remission status. The overall 3-year OS and DFS were 40.9% and 35.6% respectively. The variables associated with improved long term DFS were a bone marrow blast cell count less than 20% and an intensified conditioning regimen. In addition, the t-AML group had higher rates of relapse and III-IV acute GVHD than the primary AML group. The unrelated donor group had similar OS and DFS with sibling groups. Our study suggested that decreasing bone marrow blast cell counts before HSCT and strengthening the conditioning regimen may improve long-term DFS for refractory/relapsed AML patients, and unrelated donor group can get similar effect when compared to the sibling group.

[Effects of body mass index and serum inflammatory cytokines on asthma control in children with asthma].

OBJECTIVE: To explore the effects of body mass index (BMI) and the levels of serum inflammatory cytokines on asthma control in children with asthma. METHODS: One hundred and sixteen children with asthma were divided into three groups: normal (n=59), thin (n=31), and obesity (n=26) based on their BMI. The levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined using ELISA, and the level of high-sensitivity C-reactive protein (hs-CRP) was measured by immunoturbidimetric assays. Asthma control status in each group was evaluated by the Childhood Asthma Control Test (C-ACT) after 4 weeks of treatment. RESULTS: The serum levels of IL-6, hs-CRP, and TNF-α were highest in the obesity group, followed by the thin group and the normal group (P<0.05), while the C-ACT score was highest in the normal group, followed by the thin group and obesity group (P<0.05). The normal group had significantly higher complete controlled and partially controlled rates than the thin and obesity groups (P<0.05); however, there were no significant differences between the thin and obesity groups (P>0.05). The levels of IL-6, hs-CRP, and TNF-α were negatively correlated with the C-ACT score (P<0.05). There were no significant correlations of BMI with the C-ACT score and levels of IL-6, hs-CRP, and TNF-α (P>0.05). CONCLUSIONS: When BMI is too high or too low, the levels of serum inflammatory cytokines are all increased, which is harmful to asthma control. Maintaining a healthy weight in children with asthma may reduce the levels of serum inflammatory cytokines and improve the asthma control rate.

[Determination of flumorph and dimethomorph residues in vegetables by improved QuEChERS-gas chromatography-mass spectromery].

To determine the residues of flumorph and dimethomorph in vegetables, a method was established with improved QuEChERS-gas chromatography coupled to mass spectrometry (GC-MS). With acetonitrile as the extraction solvent, the samples were pretreated with the improved QuEChERS method including extraction, salting-out and purification processes. Then all the sample extracts were analyzed with GC-MS in selected-ion monitoring (SIM) mode, and quantified by matrix-matched standard solution in external standard method. Under electron ionization conditions, the analysis was carried out with a capillary column (DB-5 MS, 30 mx 0. 25 mm x 0. 25 µm) at a flow rate of 1. 1 mL/min. The quantitation was performed to detect ions of m/z 285, 371, 165 for flumorph and m/z 301, 387, 165 for dimethomorph. Good linearity was obtained in the range of 10-1 000 µg/kg for both pesticides with correlation coefficients greater than 0. 999. The recovery experiments were carried out by spiking blank samples of ginger, tomato, carrot, spinach, cabbage and tremella at the three levels of 10, 20 and 100 µg/kg. For both pesticides in different matrices, the limits of detection (S/N=3) were in the range of 0. 67-2. 42 µg/kg. The average recoveries of flumorph and dimethomorph ranged from 71% to 116% with the relative standard deviations (RSDs) in the range of 1. 8%- 14. 7%. Meanwhile, the pyrolysis mechanism and matrix effect for the determination of flumorph and dimethomorph in vegetables were investigated in this study. The method is simple, rapid and accurate, and can be used for the routine analysis of flumorph and dimethomorph in vegetables.

Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer.

BACKGROUND: Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC. METHODS: 28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared. RESULTS: This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P > 0.05). There is no significant relationship between ORR and cycles of treatment (P > 0.05), but DCR was significantly related with cycles of treatment (P < 0.05). No clinically significant side effects were observed. There were no significant changes of T cell subsets including CD3+, CD4+, CD8+, CD4+ CD25+ Treg cells except Th1 in peripheral blood between day 30 after immunotherapy and 1 day before immunotherapy in 11 patients. CONCLUSION: DC-CIK is feasible and effective in treating advanced renal cancer and thus provides a new approach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01924156. Registration date: August 14, 2013.

[Determination of indicator polychlorinated biphenyls in vegetable oils by double clean-up-gas chromatography].

To investigate the residues of seven indicator polychlorinated biphenyls (PCBs) in vegetable oils, a method was established for the determination of trace PCBs in vegetable oils by double clean-up coupled with gas chromatography (GC). After extracted with acetonitrile, the sample extract was concentrated to dryness followed by re-dissolving with hexane. And the solution was pretreated by adding concentrated sulfuric acid followed cleaned-up with silica gel in dispersive solid-phase extraction protocol, then analyzed by GC with external standard meth- od. Under the optimized chromatographic conditions, the analysis was carried out with a capillary column (HP-5, 30 m x 0.32 mm x 0.25 µm) at a flow rate of 0.8 mL/min, and the sample volume was 1.00 µL. Monitoring with an electron-capture detector, all the target analytes were separated by temperature-programming of the column. Good linearities were obtained in the range of 10-500 µg/L for the seven indicator PCBs with the correlation coefficients greater than 0. 999. For different matrices, the limits of detection (S/N = 3) and limits of quantitation (S/N = 10) were in the range of 1.8-8.9 pg/kg and 5.9-29.8 µg/kg, respectively. At three spiked levels of 10, 20 and 100 µg/kg of the seven indicator PCBs in olive oil, palm oil and peanut oil blank samples, the average recoveries ranged from 71.0% to 105.5% with the RSDs of 4.0%-11.3%. The method is simple, rapid and accurate, and can be used for the routine analysis of the indicator PCBs in vegetable oils.

Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis.

PURPOSE: Metastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue. METHODS: A search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study were assessed according to the selection criteria and were divided into two groups: ACI versus no ACI. Outcomes were toxicity, objective response, 1-, 3- and 5-year survival. Risk ratio (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by value of I(2) or P. RESULTS: 4 studies (469 patients) were included. Most of ACI-related adverse reactions were grade 1 or 2 and reversible. ACI provided significant benefit in terms of objective response (RR = 1.65; 95% CI, 1.15 to 2.38; P = 0.007, I(2) = 49%), 1-year survival (RR = 1.30; 95% CI, 1.12 to 1.52; P = 0.0008, I(2) = 0%), 3-year survival (RR = 2.76; 95% CI, 1.85 to 4.14; P<0.00001, I(2) = 46%) and 5-year survival (RR = 2.42; 95% CI, 1.21 to 4.83; P = 0.01, I(2) = 28%). CONCLUSIONS: ACI may be a safe and effective treatment for improving objective response, 1-, 3- and 5-year survival in patients with mRCC. Besides, five obstacles for ACI, including high degree of personalization, unsuitable WHO/RECIST response criteria, inadequate identification of tumor-associated antigens (TAAs), lack of effective combination treatments and less attention paid to the quality of ACI products, should be overcome during the successful development of more potent ACI for cancer in the future.