Heisenberg-limited spin squeezing in a hybrid system with silicon-vacancy centers.

In this paper, we investigate the spin squeezing in a hybrid quantum system consisting of a Silicon-Vacancy (SiV) center ensemble coupled to a diamond acoustic waveguide via the strain interaction. Two sets of non-overlapping driving fields, each contains two time-dependent microwave fields, are applied to this hybrid system. By modulating these fields, the one-axis twist (OAT) interaction and two-axis two-spin (TATS) interaction can be independently realized. In the latter case the squeezing parameter scales to spin number as ξ R2∼1.61N -0.64 with the consideration of dissipation, which is very close to the Heisenberg limit. Furthermore, this hybrid system allows for the study of spin squeezing generated by the simultaneous presence of OAT and TATS interactions, which reveals sensitivity to the parity of the number of spins Ntot, whether it is even or odd. Our scheme enriches the approach for generating Heisenberg-limited spin squeezing in spin-phonon hybrid systems and offers the possibility for future applications in quantum information processing.

Prognostic value and cost benefit of HPV testing for oropharyngeal cancer patients.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) can cause oropharyngeal squamous cell carcinoma (OpSCC). The revised 8th edition of the AJCC Staging Manual now stages OpSCC by incorporating p16 immunohistochemistry (IHC), the surrogate marker for HPV status. This study assessed the prognostic values of p16 and HPV markers. METHODS: We identified 244 OpSCC patients diagnosed between 2000 and 2008 from the British Columbia Cancer Registry with enough tissue to conduct experiments. Formalin-fixed, paraffin-embedded tissue sections were stained for p16 IHC, RNA in situ hybridization (ISH) HPV 16 and 18, and DNA ISH HR-HPV. Electronic charts were reviewed to collect clinical and outcome data. Combined positive RNA and/or DNA ISH was used to denote HPV status. RESULTS: Human papillomavirus was positive among 77.9% of samples. Using HPV as the benchmark, p16 IHC had high sensitivity (90.5%), but low specificity (68.5%). Distinct subgroups of patients were identified by sequential separation of p16 then HPV status. Among both p16-positive and p16-negative groups, HPV-positive patients were younger, more males, and had better clinical outcomes, especially 5-year overall survival. We further evaluated the technical costs associated with HPV testing. CONCLUSION: Human papillomavirus is more prognostic than p16 for OpSCC. Clinical laboratories can adopt HPV RNA ISH for routine analysis.

Lithium Storage Performance Boosted via Delocalizing Charge in Znx Co1- x PS3 /CoS2 of 2D/3D Heterostructure.

A promising anode material consisting of bimetallic thiophosphate Znx Co1- x PS3 and CoS2 with 2D/3D heterostructure is designed and prepared by an effective chemical transformation. Density functional theory calculations illustrate that the Zn2+ can effectively modulate the electrical ordering of Znx Co1- x PS3 on the nanoscale: the reduced charge distribution emerging around the Zn ions can enhance the local built-in electric field, which will accelerate the ions migration rate by Coulomb forces and provide tempting opportunities for manipulating Li+ storage behavior. Moreover, the merits of the large planar size enable Znx Co1- x PS3 to provide abundant anchoring sites for metallic CoS2 nanocubes, generating a 2D/3D heterostructure with a strong electric field. The resultant Znx Co1- x PS3 /CoS2 can offer the combined advantages of bimetallic alloying and heterostructure in lithium storage applications, leading to outstanding performance as an anode material for lithium-ion batteries. Consequently, a high capacity of 794 mA h g-1 can be retained after 100 cycles at 0.2 A g-1 . Even at 3.0 A g-1 , a satisfactory capacity of 465 mA h g-1 can be delivered. The appealing alloying-heterostructure and electrochemical performance of this bimetallic thiophosphate demonstrate its great promise for applications in practical rechargeable batteries.

Synchronous Extraction, Antioxidant Activity Evaluation, and Composition Analysis of Carbohydrates and Polyphenols Present in Artichoke Bud.

This study investigated the optimization of ultrasonic-assisted aqueous two-phase synchronous extraction of carbohydrates and polyphenols present in artichoke bud, evaluated their antioxidant activities in vitro, and analyzed the composition of carbohydrates and polyphenols by high-performance liquid chromatography (HPLC). The powder mass, ultrasonic time, ammonium sulfate concentration, and alcohol-water ratio were considered the influencing factors based on the single-factor experiment results, and a dual-response surface model was designed to optimize the synchronous extraction process to extract carbohydrates and polyphenols. The antioxidant activity was evaluated by measuring the scavenging capacity of ABTS+· and DPPH· and the reducing capacity of Fe3+. The optimal process conditions in this study were as follows: the powder mass of 1.4 g, ammonium sulfate concentration of 0.34 g/mL, alcohol-water ratio of 0.4, and ultrasonic time of 43 min. The polyphenol content in artichoke bud was 5.32 ± 0.13 mg/g, and the polysaccharide content was 74.78 ± 0.11 mg/g. An experiment on in vitro antioxidant activity showed that both carbohydrates and polyphenols had strong antioxidant activities, and the antioxidant activity of polyphenols was stronger than that of carbohydrates. The HPLC analysis revealed that the carbohydrates in artichoke bud were mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, and the molar ratio was 10.77:25.22:2.37:15.74:125.39:48.62:34.70. The polyphenols comprised chlorogenic acid, 4-dicaffeoylquinic acid, caffeic acid, 1,3-dicaffeoylqunic acid, isochlorogenic acid B, isochlorogenic acid A, cynarin, and isochlorogenic acid C, and the contents were 0.503, 0.029, 0.022, 0.017, 0.008, 0.162, 1.621, 0.030 mg/g, respectively. This study also showed that the carbohydrates and polyphenols in artichoke bud could be important natural antioxidants, and the composition analysis of HPLC provided directions for their future research. Carbohydrates and polyphenols in artichoke buds can be separated and enriched using the optimized process technology, and it is an effective means of extracting ingredients from plants.

Se4P4nanoparticles confined within porous carbon as a lithium-ion battery anode with superior electrochemical performance.

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se4P4) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g-1at 0.1 A g-1), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices.

Total chemical synthesis of the phosphorylated p62 UBA domain reveals that Ser407Pi but not Ser403Pi enhances ubiquitin binding.

As an autophagic adaptor, p62 specifically targets ubiquitinated proteins to an autophagosome for lysosomal degradation through a critical ubiquitin-associated (UBA) domain. Recent research studies reported that the Ser403 and Ser407 sites on the UBA domain were modified by phosphorylation, increasing the binding affinity between p62 and ubiquitin (Ub). However, the exact role of each phosphorylation site in the regulation of the UBA domain and Ub binding remains unclear. In this text, we applied total chemical synthesis to prepare four types of phosphorylated UBAs, among which the bisphosphorylated UBA was successfully synthesized via the pseudo-dipeptide unit and auxiliary-mediated hydrazide-based native chemical ligation (NCL). Isothermal titration calorimetry (ITC) assays showed that the phosphorylation at S407 enhanced the binding affinity between UBA and Ub, while that at S403 did not. It was suggested that phosphorylation at S407 might be important for promoting the interplay between the UBA domain and Ub, whereas phosphorylation at S403 was not directly involved in this interaction.

[Effects of silencing the SEMG1 protein on the cycle and apoptosis of GC-1 spg cells].

OBJECTIVE: To investigate the effects of silencing the semenogelin 1 (SEMG1) protein on the cycle and apoptosis of the spermatogonia germ cell line (GC-1 spg). METHODS: SEMG1-specific siRNA was transfected into GC-1 spg cells by lipofectamine 2000 (the siRNA-SEMG1 group), the relative expression levels of the SEMG1 protein in the GC-1 spg cells of the siRNA-SEMG1, blank control and negative control groups were detected by Western blot, and the apoptosis and cycle of the cells in different groups were determined by flow cytometry. RESULTS: The expression of the SEMG1 protein in the GC-1 spg cells was dramatically decreased in the siRNA-SEMG1 group compared with those in the blank and negative control groups (1.80±0.05 vs 2.51±0.13 and 2.50±0.12， P < 0.01), but the apoptosis rate was remarkably higher in the former than in the latter two groups (ï¼»6.77 ± 0.15ï¼½% vs ï¼»0.70 ± 0.06ï¼½% and ï¼»0.8 ± 0.06ï¼½%, P < 0.01). No statistically significant difference was observed in the cell cycles among the three groups (P > 0.05). In addition, Western blot showed that the expression of the caspase-3 protein was significantly higher and that of the BCL2 protein markedly lower in the siRNA-SEMG1 than in the blank and negative control groups (P < 0.05). CONCLUSIONS: SEMG1-specific siRNA can effectively silence the expression of the SEMG1 protein in GC-1 spg cells and promote their apoptosis.

CD8+ T cells mediate the antitumor activity of frankincense and myrrh in hepatocellular carcinoma.

BACKGROUND: Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an extremely poor prognosis. Frankincense and myrrh are anti-inflammation agents commonly used in clinic. The purpose of this study is to investigate whether extract of frankincense and myrrh (FM) downregulates inflammatory microenvironment of HCC and thereby restores antitumor immune responses. METHODS: The water-decocting FM was obtained and quantified. HCC cell lines HCCLM3 and Hepa1-6 were used to evaluate the efficacy of FM targeting NF-κB and STAT3 signaling with western blot and qRT-PCR analysis. CD8+NKG2D+ cells were derived from human peripheral blood and were used for evaluation of immune cells-mediated inflammation and oncolysis on HCCLM3 cells. The antitumor efficacy of FM was investigated both in immune compromised and immune competent mice bearing subcutaneous HCC. Mice received daily oral gavage of FM at 60 mg/kg. Immune activity within tumor microenvironment (TME) was assessed by ELISpot assay and flow cytometry, respectively. Depletion of CD8+ T cells or NK cells was achieved by intraperitoneal injection of respective neutralizing antibody. RESULTS: FM significantly inhibited the activation of NF-κB and STAT3 signaling in HCC cells induced by cytokines (TNF-α or IL-6) and in co-culture system with CD8+NKG2D+ cells. Furthermore, FM sensitized HCC cells to CD8+NKG2D+ cells-mediated oncolysis. In HCC-bearing mice, FM at a non-toxic dose failed to reduce tumor growth in immune compromised mice, whereas it significantly inhibited tumor growth and prolonged life span in immune competent mice. While the number of IFN-γ-producing cells within TME was increased in mice treated with FM, the infiltration of CD8+ T cells and NK cells was not increased. Finally, we identified that depletion of CD8+ T cells rather than NK cells abrogated the antitumor activity of FM. CONCLUSIONS: Our results show for the first time that CD8+ T cells mediate the antitumor activity of FM at a non-toxic dose. This may provide new insights to this ancient mysterious prescription in cancer therapy, which offers a novel and practical therapeutic strategy and the possibilities of combined immunotherapy for HCC as well as other inflammation-related cancers in clinic.

Inferring spatial patterns and drivers of population divergence of Neolitsea sericea (Lauraceae), based on molecular phylogeography and landscape genomics.

The relative roles of geography, climate and ecology in driving population divergence and (incipient) speciation has so far been largely neglected in studies addressing the evolution of East Asia's island flora. Here, we employed chloroplast and ribosomal DNA sequences and restriction site-associated DNA sequencing (RADseq) loci to investigate the phylogeography and drivers of population divergence of Neolitsea sericea. These data sets support the subdivision of N. sericea populations into the Southern and Northern lineages across the 'Tokara gap'. Two distinct sublineages were further identified for the Northern lineage of N. sericea from the RADseq data. RADseq was also used along with approximate Bayesian computation to show that the current distribution and differentiation of N. sericea populations resulted from a combination of relatively ancient migration and successive vicariant events that likely occurred during the mid to late Pleistocene. Landscape genomic analyses showed that, apart from geographic barriers, barrier, potentially local adaptation to different climatic conditions appears to be one of the major drivers for lineage diversification of N. sericea.

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities.

A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 - 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D- and 2D-NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 - 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase-3 levels in A549 cells were also determined by Western-blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC50 value of 1.51 µm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5-fold and increased 10-folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11-fold increase in the level of caspase-3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.

Degradation of diclofenac by UV-activated persulfate process: Kinetic studies, degradation pathways and toxicity assessments.

Diclofenac (DCF) is the frequently detected non-steroidal pharmaceuticals in the aquatic environment. In this study, the degradation of DCF was evaluated by UV-254nm activated persulfate (UV/PS). The degradation of DCF followed the pseudo first-order kinetics pattern. The degradation rate constant (kobs) was accelerated by UV/PS compared to UV alone and PS alone. Increasing the initial PS dosage or solution pH significantly enhanced the degradation efficiency. Presence of various natural water constituents had different effects on DCF degradation, with an enhancement or inhibition in the presence of inorganic anions (HCO3- or Cl-) and a significant inhibition in the presence of NOM. In addition, preliminary degradation mechanisms and major products were elucidated using LC-MS/MS. Hydroxylation, decarbonylation, ring-opening and cyclation reaction involving the attack of SO4•- or other substances, were the main degradation mechanism. TOC analyzer and Microtox bioassay were employed to evaluate the mineralization and cytotoxicity of solutions treated by UV/PS at different times, respectively. Limited elimination of TOC (32%) was observed during the mineralization of DCF. More toxic degradation products and their related intermediate species were formed, and the UV/PS process was suitable for removing the toxicity. Of note, longer degradation time may be considered for the final toxicity removal.

Perioperative risk factors and cumulative duration of "triple-low" state associated with worse 30-day mortality of cardiac valvular surgery.

ABSRACT: Hospital stay and mortality in high-risk patients after noncardiac surgery has been associated with a triple low anesthesia. However, the association between anesthesia-related factors and perioperative outcome after cardiac surgery remains unclear.We tested the effect of a novel triple low state: low mean arterial pressure (MAP) <65 mmHg and low bispectral index (BIS) <45 during a low target effect-site concentration (Ce) <1.5 µg ml-1 of propofol anesthesia on postoperative duration of hospitalization and 30-day mortality in cardiac valvular patients. In this prospective observational study, univariable and multivariable logistic regression analyses were used to determine whether perioperative factors, in particular, cumulative duration of triple low state were independently associated with duration of hospitalization and 30-day mortality among patients who underwent elective valvular replacement. 489 patients were included in the final analysis. After adjusting for related covariates, cumulative duration of the triple-low state was not associated with prolonged hospitalization (multivariable odds ratio: 1.007; 95 % confidence interval 0.997-1.017; P = 0.564), but was a significant predictor of 30-day mortality (multivariable odds ratio: 1.016; 95 % confidence interval 1.002-1.031; P = 0.030). Compared to a triple-low duration of <15 min, a duration >60 min increased the 30-day mortality rate by 8 times. After adjusting for patient- and procedure-related characteristics, the cumulative duration of a triple-low state (intraoperative low MAP, low BIS, and low Ce) was associated with poorer 30-day mortality, but not with prolonged duration of hospital stay.The mortality risk was even greater when a cumulative time >60 min.

Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons.

The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L-1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L-1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L-1 (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L-1 and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca2+ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.

Chemical Analysis of Dietary Constituents in Rosa roxburghii and Rosa sterilis Fruits.

Both Rosa roxburghii and R. sterilis, belonging to the Rosaceae, are endemic species in Guizhou Province, China. The fruits of these two species are mixed-used as functional food in the region. Aiming to elucidate the phytochemical characteristics of R. roxburghii and R. sterilis fruits, the essential oils and constituents in a methanol extract have been analyzed and compared by GC-MS and UFLC/Q-TOF-MS, respectively. As a result, a total of 135 volatile compounds were identified by GC-MS and 91 components were different between R. roxburghii and R. sterilis fruits; a total of 59 compounds in methanol extracts were identified by UFLC/Q-TOF-MS, including 13 organic acids, 12 flavonoids, 11 triterpenes, nine amino acids, five phenylpropanoid derivatives, four condensed tannins, two stilbenes, two benzaldehyde derivatives and one benzoic acid derivative; and nine characteristic compounds were found between R. roxburghii and R. sterilis fruits. This systematic study plays an important role for R. roxburghii and R. sterilis fruits in the product development.

Discovery and pharmacophore studies of novel pyrazole-based anti-melanoma agents.

Due to the rising incidence and lack of effective treatments, malignant melanoma is the most dangerous form of skin cancer, so that new treatment strategies are urgently needed. Several recent developments indicate that the V600E mutant BRAF (BRAF(V600E) ) is a validated target for antimelanoma-drug development. Based on in silico screening results, a series of novel pyrazole derivatives has been designed, synthesized, and evaluated in vitro for their inhibitory activities against BRAF(V600E) melanoma cells. Compound 3d exhibited the most potent inhibitory activity with an IC50 value of 0.63 µM for BRAF(V600E) and a GI50 value of 0.61 µM for mutant BRAF-dependent cells. Furthermore, the QSAR modeling and the docking simulation of inhibitor analogs provide important pharmacophore clues for further structural optimization.

Residues and potential health risks of DDTs and HCHs in commercial seafoods from two coastal cities near Yangtze River Estuary.

Five species of commercial seafoods collected from the local markets in two coastal cities near Yangtze River Estuary (Ningbo and Zhoushan) in 2010 were analyzed to study the residues, potential sources, and health risks of dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) in these areas. The total levels of DDTs and HCHs in the samples ranged from 1.13-20.2 ng g(-1) and 1.23-3.05 ng g(-1) wet weight, respectively, and were at a middle level compared with those from other marine systems. Results from one-way analysis of variance (ANOVA) indicated species-specific distributions of DDTs and HCHs in the seafoods of the studied area, which may be related to their different lipid contents and ecological characteristics. Compositional analysis suggested that historical usage dominates in this area, and fresh inputs of lindane and dicofol may also have part contributions. With respect to DDTs, it can be metabolized into both DDD and DDE simultaneously in seafoods tested. Assessment based on maximum residue levels, acceptable or tolerable daily intakes, and hazard ratios for non-carcinogens suggested no obvious adverse health effects, while the lifetime cancer risks may be increased from dietary exposure to DDTs and HCHs.

[Evaluation for Merchandise Character and Quality of Bupleurum chinense Root from Different Habitats].

OBJECTIVE: To evaluate the merchandise character and quality of Bupleurum chinense root from different habitats. METHODS: The spectrophotometer method was used to determine the content of total saponins and total flavonoids in Bupleurum chinense root. The content of alcohol-soluble extract and total ash were determined according to the method in the Chinese Pharmacopoeia. RESULTS: The quality of Bupleuri Radix from different habitats varied greatly. There were also differences (P < 0.05) between the merchandise packaged with selection and the merchandise packaged without selection of Bupleurum chinense root from the same habitats. The merchandise packaged without selection had the better quality, whose root length, root diameter, weight, total length proportional share of residual stems, total saponins, total flavonoids, total alcohol-soluble extract and total ash was 14.50 cm/plant, 0.59 cm/plant, 5.14 g/plant, 36.85%, 0.721%, 0.615%, 12.993% and 4.890%, respectively. CONCLUSION: Bupleurum chinense root from Tong'an, Jiangsu has the best quality in the test samples from different habitats.

Drug-induced reduction in estimated glomerular filtration rate in patients with ALK-positive non-small cell lung cancer treated with the ALK inhibitor crizotinib.

BACKGROUND: To the best of the authors' knowledge, the renal side effects of crizotinib have not been investigated previously. METHODS: The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based prediction equation during the first 12 weeks of crizotinib therapy and after crizotinib but before the introduction of any further systemic therapy. RESULTS: A total of 38 patients with stage IV anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer who were treated with crizotinib were identified. The mean eGFR decreased by 23.9% compared with baseline (P < .0001; 95% confidence interval, 21.3%-26.6%), with the majority of the decrease occurring within the first 2 weeks of therapy. Clinical history and blood urea nitrogen/creatinine ratios did not suggest prerenal causes. The objective response rate among evaluable patients (n = 27) was 41%. Tumor shrinkage was not correlated with changes in eGFR (correlation coefficient, -0.052; P = .798). Among the 16 patients for whom data after treatment with crizotinib were available, recovery to within 84% of the baseline eGFR occurred in all patients. After adjusting for the number of scans with intravenous contrast and the use of known nephrotoxic drugs, the issue of whether a patient was on or off crizotinib treatment was found to be significantly associated with changes in eGFR (P < .0001). CONCLUSIONS: As assessed by the Chronic Kidney Disease Epidemiology Collaboration prediction equation, eGFR is reduced by treatment with crizotinib, but the majority of patients will recover their eGFR after the cessation of therapy. The early onset, size of the change, minimal cumulative effect, and rapid reversibility raise the possibility that this may be a pharmacological and/or tubular creatinine secretion effect rather than a direct nephrotoxic effect. Increased vigilance with regard to the concomitant use of renally cleared medications or nephrotoxic agents should be considered for patients receiving crizotinib and, when eGFR is reduced, additional renal investigations should be undertaken.

Sarcomas of the aorta: a systematic review and pooled analysis of published reports.

BACKGROUND: Aortic sarcomas are rare and aggressive tumors with a propensity for arterial embolization, disseminated metastases, and rapid clinical deterioration. Overall, little is known about the evaluation and management of this disease. METHODS: A systematic review and pooled analysis were performed from a comprehensive search of the MEDLINE database for reports of primary aortic sarcomas published in the English language. RESULTS: One hundred sixty-five cases were analyzed. The median age was 60 years, and the male:female ratio was 1.5:1. High tumor grade (87.3%), arterial embolization (46.7%), and metastatic disease at diagnosis (44.8%) were common. Typical histologies were undifferentiated (39.4%), angiosarcomatous (37%), leiomyosarcomatous (13.3%), and fibroblastic (7.3%). Management was diverse and included combinations of surgical resection (46.7%), palliative vascular surgeries (37.7%), chemotherapy (28.7%), and radiotherapy (14.7%). The median survival was 11 months, and the 1-, 3-, and 5-year survival rates were 46.7%, 17.1%, and 8.8%, respectively. On univariate analyses, metastatic disease at diagnoses, surgical resection, and chemotherapy were associated with survival. On multivariate analysis, only metastatic disease remained significant (P < 0.001). CONCLUSIONS: Aortic tumors are devastating malignancies with distinct clinical features from sarcomas at other sites. Although prognosis is poor overall, long-term survivors have been reported, and aggressive management with surgical resection and adjuvant therapy should be considered in medically suitable patients. High embolic rates suggest a potential role for prophylactic anticoagulation.