The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study.

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited. Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups. Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS. Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

The influence of light combination on the physicochemical characteristics and enzymatic activity of soil with multi-metal pollution in phytoremediation.

Light irradiation with suitable quality and intensity could influence the success of phytoremediation by improving the biomass yield of plants. However, mechanisms involved in this influence on the contaminant accumulation and translocation ability of plants have rarely been studied. Five light combinations with different red (R) and blue (B) ratios (0, 10, 50, 75 and 100 % blue) at the same intensity (220 µmol m-2 s-1) were used to assist phytoremediation using Noccaea caerulescens, and the change in physicochemical characteristics and enzymatic activities of soils after phytoremediation were evaluated. Compared with the control, the light combinations and monochromic blue light significantly increased the activities of soil ureases, invertases, and phosphatases, whereas monochromic red light strongly inhibited the activities of these enzymes, because different light irradiations altered the formation and excretion of carbohydrates from plants for soil microorganism consumption. Plants under B50R50 treatment accumulated the highest concentrations of metals, but their chlorophyll concentrations and lipid peroxidation were similar to those other species with lower metal concentrations. Hence, light with a proper blue/red ratio can simultaneously improve the physicochemical characteristics and enzymatic activities of soils, increase the metal uptake capacity and oxidation resistance of plants, and reduce the leaching risk during phytoremediation processes.

The phytoremediation efficiency of Eucalyptus globulus treated by static magnetic fields before sowing.

Eucalyptus globulus pre-treated by static magnetic fields of 30, 60, 120, 150 and 400 mT (mT) before sowing were used in a 45-day experiment to remediate soil containing Cd, Hg, Pb, Zn, Cr and Cu. The influence of magnetic fields on its remediation efficiency was evaluated. Magnetic fields with strength of 30, 60, 120 and 150 mT increased the biomass yield of the species by 3.1, 19.4, 48.1 and 60.9%, respectively, while 400 mT decreased the yield by 16.7%. Comparing with the control exposed only to the earth's geomagnetic field, all plants pre-treated by static magnetic field had significantly higher metal concentrations with the highest values achieved in the field of 400 mT. Higher transpiration rate of the plants along with exposure to static magnetic fields induced lower soil moisture content and was beneficial to environmental control because it could reduce the leachate during the phytoremediation process. Among all static magnetic field treatments, 150 mT was the best to improve the phytoremediation and alleviate the environmental risk, which shortened the time to purify Cd, Pb and Cu by 27.8-73.2%, 27.3-74.7% and 2.5-50.6%, respectively and intercepted 31.6-86.1% of the leachate. Therefore, static magnetic field with appropriate intensity is a suitable candidate to improve phytoremediation efficiency through enhancing the biomass production, toxin uptake and leachate interception.

The variation of metal fractions and potential environmental risk in phytoremediating multiple metal polluted soils using Noccaea caerulescens assisted by LED lights.

Different light combinations can improve phytoremediation efficiency by increasing the biomass yield and metal concentrations of plants. However, there has been rare research of using hyperaccumulators to change metal fractions and its possible leaching risk during phytoremediation. It was investigated in this study the impacts of different intensities of blue and red light mixed on the biomass production and metal uptake of Noccaea caerulescens and the changes of water soluble and exchangeable metal fractions in soil. The biomass of N. caerulescens increased with light intensity. The increment was relatively slow at 50 m-2 s-1, dramatically increased at 200 m-2 s-1 and decreased significantly when beyond. Under optimal light condition, N. caerulescens produced less biomass than Thlaspi arvense, but the former is significantly more efficient in phytoremediation than the latter because it can accumulate significantly more metals per unit biomass. Without light irradiation, N. caerulescens can deteriorate the potential leaching risk of Cu and Pb by increasing their water soluble and exchangeable fractions in soil comparing with T. arvense. The proportions of bioavailable fractions did not change under the treatment of light at an intensity of 50 m-2 s-1, but decreased obviously when the intensity exceeded 100 m-2 s-1. Therefore, using hyperaccumulator for multiple metal contaminated soil remediation should be conducted with caution since the species can mobilize all metals in soil but only hyperaccumulate part of them, and proper intensity of light can improve the phytoremediation effect and alleviate the leaching risk through decreasing bioactive metal fractions in soil.

Magnetic field enhance decontamination efficiency of Noccaea caerulescens and reduce leaching of non-hyperaccumulated metals.

Hyperaccumulators can accumulate high amounts of specific metals and have been widely used to remediate metal polluted soil. However, organic acid secretion and soil acidification (two important mechanisms for hyperaccumulators to mobilize and extract metals) can also activate non-hyperaccumulated metals and then increase the leaching risk. The decontamination efficiency and leaching risk of using Noccaea caerulescens (formerly Thlaspi caerulescens) and Thlaspi arvense were compared in the present study. Although N. caerulescens accumulated significantly more Cd and Zn than T. arvense, it increased the leaching risk of Pb and Cu as well. Under magnetic fields of 30, 60, 120 and 150 mT, the biomass production of N. caerulescens was increased by 18.5, 48.9, 80.4, and 29.3% respectively, but decreased by 21.7% under 400 mT. Comparing with the control, plants raised from seeds pre-treated by magnetic fields accumulated 37.8-250.1% more metals and reduced the leachate volume and leached metals by 1.1-32.9% and 4.6-48.1% respectively. Considering remediation efficiency, environmental risk alleviation and energy consumption, N. caerulescens treated by 120 mT magnetic field is suited to remediate multi-metal polluted soil.

Comparing the risk of metal leaching in phytoremediation using Noccaea caerulescens with or without electric field.

Hyperaccumulators can mobilize all metals in soil through secreting exudates to form soluble compounds but only hyperaccumulate part of them. Metals that cannot be accumulated are defined as non-hyperaccumulated metals and can increase the leaching risk in phytoremediation. Cd and Zn hyperaccumulator Noccaea caerulescens (formerly Thlaspi caerulescens) was utilized to remediate multi-metal polluted soil in the present study, and the leaching risk of non-hyperaccumulated metals including Cu and Pb was investigated during the phytoremediation process. Comparing with Thlaspi arvense, a non-hyperaccumulator, N. caerulescens significantly decreased the concentrations of Cd and Zn in leachate gathered from precipitation simulation experiments without electric field, but meanwhile dramatically increased the concentrations of Cu and Pb in soil solution. Electric field with low (2 V) and moderate (4 V) voltages increased the biomass yield and metal uptake capacity of N. caerulescens simultaneously and therefore further reduced the concentrations of Cd and Zn in the leachate. Although the volume of leachate decreased significantly in pots with electric field, the leaching risk of Pb and Cu was deteriorated. Thus, decontaminating multi-metal polluted soil with electric field and hyperaccumulator should be conducted with caution due to potential secondary environmental risk caused by activated non-hyperaccumulated metals.

Improvement effects of cytokinin on EDTA assisted phytoremediation and the associated environmental risks.

Soil samples containing excess Cd (0.82 mg kg-1), Pb (92.7 mg kg-1) and Cu (72.7 mg kg-1) relative to their corresponding safe thresholds (0.3, 80 and 50 mg kg-1, respectively) from a notorious e-waste disposing and recycling place in southern China were phytoremediated with EDTA addition to evaluate the promotion effects of cytokinin on the remediation efficiency of Eucalyptus globulus. Biomass production of the plant, evapotranspiration amount of the soil, metals accumulation in plant organs and the volume of leachate under various treatments were compared. Relative to the planting control, EDTA application shortened the time required for Cd, Pb and Cu decontamination by 1.7-5.5 times but led to significantly more leachate (996 vs 1256 mL), indicating the negative influence of the chelate treatment on the species and the surrounding environment. The foliar application of cytokinin can expand the advantage and alleviate the adverse impact of individual EDTA application simultaneously as manifested by the increased biomass yield, less time consumption for purification and decreased leachate volume. Cytokinin accelerated the transpiration rate of the plant proved by the least volume of leachate in individual cytokinin treatment. The major factors for effective phytoremediation were the resistance of species to high concentrations of contaminants and less environmental risks generation during the remediation processes. Therefore, synergistic use of such components provides more efficient decontamination of metals and more security for the environment.

The assessment of source attribution of soil pollution in a typical e-waste recycling town and its surrounding regions using the combined organic and inorganic dataset.

Guiyu is a well-known electronic waste dismantling and recycling town in south China. Concentrations and distribution of the 21 mineral elements and 16 polycyclic aromatic hydrocarbons (PAHs) collected there were evaluated. Principal component analyses (PCA) applied to the data matrix of PAHs in the soil extracted three major factors explaining 85.7% of the total variability identified as traffic emission, coal combustion, and an unidentified source. By using metallic or metalloid element concentrations as variables, five principal components (PCs) were identified and accounted for 70.4% of the information included in the initial data matrix, which can be denoted as e-waste dismantling-related contamination, two different geological origins, anthropogenic influenced source, and marine aerosols. Combining the 21 metallic and metalloid element datasets with the 16 PAH concentrations can narrow down the coarse source and decrease the unidentified contribution to soil in the present study and therefore effectively assists the source identification process.

[Inflammatory fibroid polyp of the gastrointestinal tract: a clinicopathologic features of 37 cases].

OBJECTIVE: To study the clinicopathologic features, pathogenesis, and differential diagnosis of inflammatory fibroid polyp (IFP) of the gastrointestinal tract. METHODS: The clinical and pathologic findings of 37 IFPs in the gastrointestinal tract were retrospectively analyzed. Immunohistochemical study and KIT, PDGFRA molecular analysis were carried out and the literatures reviewed. RESULTS: There were 9 males and 28 females. The median age was 57 (range 37 to 78) years. Twenty-two were in the antrum, nine in the ileum, three in the cardia, and one each in the gastric angle, corpora ventriculi and duodenum. The lesion ranged in size from 0.5 to 5.5 cm (mean 3 cm). Grossly, the majority appeared as a solitary non-encapsulated, submucosal, polypoid lesion. There was associated mucosal ulceration in three cases. Microscopically, the gastric lesions showed spindle-shaped cells arranged in an onion skin-like pattern around vessels and mucosal glands in a concentric formation. But the lesions in the ileum represented Vanek's tumor subtype devoid of concentric formations, with spindled to epithelioid cells dispersed in edematous stroma. Most of the lesions were in the mucosa and submucoma, but one small intestinal IFP infiltrated the muscularis propria. The inflammatory component of the lesions consisted predominantly of lymphocytes and eosinophils. Immunohistochemically, all cases displayed diffuse reactivity for vimentin and CD34; and 18 expressed PDGFRA. Analysis of KIT and PDGFRA mutations was performed in 18 cases. No KIT mutations were identified. However, four cases harbored activating mutations in PDGFRA exon 18 (D842V), five showed mutations in exon 12 (p.566-571delSPDGHEinsR). Follow-up in 30 cases showed no recurrence or metastasis. CONCLUSIONS: IFPs not only exhibit two morphologies, but also show mutations in the PDGFRA gene. IFP is a benign mesenchymal tumor rather than a reactive lesion.

An evaluation of EDTA additions for improving the phytoremediation efficiency of different plants under various cultivation systems.

Previous studies have shown that phytoremediation usually requires soil amendments, such as chelates, to mobilize low bioavailability heavy metals for better plant absorption and, consequently, for remediation efficiency. A total dry biomass of 3.39 and 0.0138 kg per plant was produced by a phytoremediator, Eucalyptus globulus, and a nitrogen fixing crop, Cicer arietinum (chickpea), respectively. The accumulation of Pb in E. globulus and chickpea reached 1170.61 and 1.33 mg per plant (700 and 324 mg kg(-1)), respectively, under an ethylene diamine tetraacetic acid (EDTA) treatment, which was a five and sixfold increase over the value in untreated experiments, respectively. EDTA enhanced the phytoremediation efficiency and increased the heavy metal concentration in the soil solution. In pot experiments, approximately 27 % of the initial Pb leached from the spiked soil after EDTA and 25 mm artificial precipitation additions into soil without plants, which was considerably larger than the value under the same conditions without EDTA application (7 %). E. globulus planted in a mixed culture had higher water use efficiency than monocultures of either species in field experiments, and E. globulus intercepted almost all of the artificial precipitation in the pot experiments. This study demonstrates that E. globulus can maximize the potential of EDTA for improving the phytoremediation efficiency and minimizing its negative effects to the environment simultaneously by absorbing the metal-rich leachate, especially in a mixed culture of E. globulus and chickpeas.

Ecological Risk Assessment of EDTA-Assisted Phytoremediation of Cd Under Different Cultivation Systems.

A long-term field experiment was designed to assess remediation efficiency and ecological risk of phytoremediation of Cd under different cultivation systems with or without ethylene diamine tetraacetic acid (EDTA). EDTA can significantly improve the phytoremediation effectiveness of a historically polluted e-waste dismantling site through enhancing Cd uptake by plants in all cultivation systems along with higher ecological risks to different receptors especially in the presence of Cicer arietinum (chickpea). Moisture content at each layer of soil profile under Eucalyptus globules L. cultivated sites was consistently lower than under chickpea monoculture as a result of E. globules' high water use efficiency. Besides low soil moisture, E. globules can intercept more Cd-rich leachate than chickpea regardless of the presence of EDTA. E. globules could be used for Cd phytoremediation as they can take full advantage of EDTA and decrease ecological risk caused by the chelator.

Multidrug resistance-associated biomarkers PGP, GST-pi, Topo-II and LRP as prognostic factors in primary ovarian carcinoma.

This study aims to investigate the expression of P-glycoprotein (PGP), glutathione S-transferase pi (GST-pi), DNA topoisomerase II (Topo-II) and lung resistance-related protein (LRP) in ovarian carcinoma, thus providing better chemotherapy choice and post-operative prognosis for ovarian carcinoma patients. A total of 80 primary ovarian carcinoma, 16 benign ovarian epithelial neoplasm, and 12 normal ovarian tissue samples were collected. Immunohistochemistry was used to detect the expression of PGP, GST-pi, Topo-II and LRP, and the results were analysed by correlation with clinicopathological parameters. Positive expression rates of PGP, GST-pi, Topo-II and LRP in patients with ovarian carcinoma (57.5%, 58.8%, 76.3% and 73.8%, respectively) were all higher than those found in normal and benign tissue (P<0.05). In clinical stages I/II vs. III/IV, the expression rates of PGP, GST-pi, Topo-II and LRP were 40.7% vs. 66% (P<0.05), 40.7% vs. 67.9% (P<0.05), 66.7% vs. 81.1% (P>0.05) and 55.6% vs. 83.0% (P<0.05), respectively. Carcinoma differentiation ranged from well to poor, and expression levels of each marker were as follows: PGP, 57.9%, 62.1% and 53.1% (P>0.05); GST-pi, 36.8%, 55.2% and 75.0% (P<0.05); Topo-II, 52.6%, 79.3% and 87.5% (P<0.05); and LRP, 84.2%, 69.0% and 71.9% (P>0.05). Ovarian carcinoma patients with PGP-, GST-pi-, Topo-II- and LRP-positive expression had a shorter median survival time than those who were negative for these markers (PGP: 36 months vs. 48 months [P=0.0017]; GST-pi: 36 months vs. 41 months [P=0.0103]; Topo-II: 37 months vs. 39 months [P=0.3811]; LRP: 37 months vs. 55 months [P=0.002]). COX regression analysis demonstrated that the clinical stage of the tumour, and the expression of PGP, GST-pi or LRP, may influence patient survival time after surgery. The relative death risk for patients with clinical stage III/IV tumours increased 9.46-fold compared to those with stage I/II tumours. The relative death risk in the PGP-, GST-pi- and LRP-positive groups increased by 2.049-, 2.452- or 2.609-fold, respectively, compared with the corresponding negative groups. PGP, GST-pi, Topo-II and LRP are all expressed in primary ovarian carcinoma, indicating the presence of multidrug resistance in this disease. Combined evaluation of PGP, GST-pi, Topo-II and LRP expression may enable better chemotherapeutic choice and provide an accurate prognosis for ovarian carcinoma patients.

Increased levels of soluble vascular endothelial cadherin are associated with poor outcome in severe sepsis.

Endothelial cells are thought to play a key role in sepsis pathogenesis: vascular endothelial damage occurs in severe sepsis and multiple organ dysfunction. Soluble vascular endothelial cadherin (VE-cadherin) levels were investigated in a prospective study involving 28 consecutive critically ill patients with or without severe sepsis who were admitted to surgical intensive care; 13 healthy age-matched volunteers were included as controls. Soluble VE-cadherin levels increased significantly in patients with severe sepsis compared with ill patients without severe sepsis and healthy controls. There was a significant linear correlation between soluble VE-cadherin levels and illness severity scores. Soluble VE-cadherin levels were significantly higher in patients who died compared with survivors. In vitro cell culture showed that serum from patients with severe sepsis greatly decreased VE-cadherin staining at intercellular junctions and total VE-cadherin expression in human umbilical cord vein endothelial cells. These findings suggest that endothelial cells play an important role in the poor outcome of patients with severe sepsis.