Nanofiltration (NF) has become an established process for advanced treatment of drinking water, while membrane fouling remains as the main issue slowing the widespread application of the process. In ...this study, the key foulants were identified, and their spatial distribution and potential interactions were investigated based on a two-stage NF engineering project for municipal drinking water treatment. Over half a year of operation showed that the membrane fouling was mostly chemically reversible. Characterizations of the cleaning waste revealed that inorganic fouling dominated at both stages, which was mainly caused by the deposition of Al, Ca, and Si. While the overall fouling was much more severe at Stage 2, the organic fouling was the reverse. Autopsy of one full-size membrane element from each stage indicated that in addition to Al, P and humic acid-like compounds were abundant in the fouling layer for both stages despite the spatial differences. The spatial distribution of foulants was influenced by both concentration effects and presence of feed channel spacers. For the free membrane area, inorganic foulants and humic acid-like compounds had higher contents at Stage 2 than Stage 1. While for the membrane area contacting with spacers, Al and P at Stage 1 were 0.74 and 1.51 times higher than those at Stage 2, respectively. Moreover, statistical analysis, complexation experiments and engineering operation strongly supported that the residual Al and natural organic matter (NOM) were key foulants for the NF process, mainly by forming Al-NOM complexes. Besides the Al-NOM complexes, condensed phosphate, primarily sourced from the dosed phosphate-containing antiscalants, might also co-precipitate with Al or Al-NOM complexes.
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•Membrane fouling was dominated by the reversible inorganic fouling in NF system.•The residual Al and natural organic matter (NOM) were key foulants for the NF process, mainly by forming Al-NOM complexes.•The spatial distribution of inorganic and organic fouling were the reverse.•Feed channel spacers caused local non-uniform distribution of membrane foulants.
Haloacetaldehydes (HAs) are the third prevalent group of disinfection by-products (DBPs) of great health concern. In this study, their formation and speciation during chlorination were investigated ...for raw and process waters collected at three O3-biological activated carbon (BAC) advanced drinking water treatment plants. The results showed that all HA formation potentials (HAFPs) were highly enhanced whenever ozone was applied before or after conventional treatment. Sand filtration and BAC filtration could substantially reduce HAFPs. Trihalomethanes (THMs) were also measured to better understand the role of HAs in DBPs. Very different from HAFPs, THMFPs kept decreasing with the progress of treatment steps, which was mainly attributed to the different precursors for HAs and THMs. Brominated HAs were detected in bromide-containing waters. Chloral hydrate (CH) contributed from 25% to 48% to the total HAs formed in waters containing 100–150 μg L−1 bromide, indicating the wide existence of other HAs after chlorination besides CH production. In addition, bromide incorporation factor (BIF) in HAs and THMs increased with the progress of treatment steps and the BIF values of THMs were generally higher than those of HAs. The BAC filtration following ozonation could significantly reduce HA precursors produced from ozonation but without complete removal. The brominated HAFPs in the outflow of BAC were still higher than their levels in the raw water. As a result, O3-BAC combined treatment was effective at controlling the total HAs, whereas it should be cautious for waters with high bromide levels.
•CH only accounted 25–48% of the total HAs in waters containing 100–150 μg L−1 bromide.•Water treatment with ozone decreased THMFPs, while it significantly enhanced HAFPs.•Brominated HAFPs after BAC filtration were still higher than those in raw waters.•Bromine incorporation by THMs and HAs increased with the progress of treatment steps.
Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves’ disease (GD) and high levels of thyroid hormones (THs) can drive the progression of ...GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.
Background.
Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular ...diastolic dysfunction (LVDD) and its relationship to the dose‐volume of the heart irradiated were evaluated in HER2‐positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT).
Materials and Methods.
Data from 40 breast cancer patients treated with concurrent trastuzumab and left‐sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right‐sided adjuvant RT and 71 patients treated with left‐sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified.
Results.
Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left‐sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15–D40, D60–D70, and V3–V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left‐sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left‐sided RT alone.
Conclusion.
Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose‐volume of the heart contributes significantly to the risk of LVDD in patients with left‐sided breast cancer treated concurrently with trastuzumab.
Implications for Practice:
Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose‐volume of the heart irradiated in patients with left‐sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose‐volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.
摘要
背景. 左心室射血分数（LVEF）常规用于监测与乳腺癌治疗相关的心脏功能障碍。本研究在接受曲妥珠单抗联合同期辅助放疗（RT）的HER2阳性乳腺癌患者中，对左心室舒张功能障碍（LVDD）的患病率及其与心脏照射剂量‐体积的关系进行了评价。
材料和方法. 我们前瞻性地在2011年9月至2012年10月期间收集了40例接受曲妥珠单抗联合同期左侧辅助放疗的患者数据。另外，我们还回顾性地收集了32例接受曲妥珠单抗联合同期右侧辅助放疗患者数据，以及71例仅接受左侧放疗的患者数据用于对比。在放疗前、放疗后即刻，以及放疗后3个月和6个月行超声心动图检查。确定心脏和左心室（LV）接受的照射剂量。
结果. 在给予曲妥珠单抗联合同期放疗前，基线左心室舒张功能（LVDF）正常的患者中，分别有11/29例（左侧）和8/25例（右侧）在治疗后发生了LVDD。在仅接受左侧放疗的患者中，12/61例基线LVDF正常的患者发生了LVDD。曲妥珠单抗联合同期左侧放疗后发生LVDD的患者左心室Dmean、D15‐D40、D60‐D70和V3‐V10均显著较高。相反，在接受同期治疗和仅左侧放疗的患者中，仅2例患者发生了1级LVEF下降。
结论. 通过比较LVEF检测到的LVDF改变在早期发现心脏毒性方面更为敏感。对于接受同期放疗联合曲妥珠单抗治疗的左侧乳腺癌患者而言，心脏剂量‐体积为LVDD的显著风险因素。The Oncologist 2015;20:605–614
对临床实践的意义： 在接受放疗联合同期曲妥珠单抗治疗的左侧乳腺癌患者中，舒张功能异常在发现急性心脏毒性方面比左心室射血分数改变更为敏感，且与心脏剂量‐体积相关。这项结果强调了在接受曲妥珠单抗联合同期放疗患者中，采用减少心脏照射剂量‐体积作为保护策略的重要性。对于心脏损伤，舒张功能障碍可以作为更为敏感的早期检测工具，并且应该纳入常规心脏毒性功能监测参数之中。
Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose‐volume of the heart irradiated in patients with left‐sided breast cancer receiving radiotherapy with trastuzumab, highlighting the importance of decreasing the dose‐volume as a protective strategy. Therefore, diastolic dysfunction should be incorporated as a routine parameter in the monitoring of cardiotoxicity.
Background:
Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial ...effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice.
Methods:
Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of Ccl2, Itgax, Mrc1, and Adgre1 mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting.
Results:
Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice.
Conclusion:
Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.
Abstract Background Bevacizumab, a recombinant humanized monoclonal antibody that targets the vascular endothelial growth factor, has been approved for use in a variety of malignancies. There have ...been reports of infections associated with the use of bevacizumab. We performed this meta-analysis to determine the overall incidence and risk of infections associated with bevacizumab in cancer patients. Methods Pubmed and oncology conference proceedings were searched for relevant studies from January 2000 to June 2014. Studies were limited to phase II and phase III randomized controlled trials (RCTs) of bevacizumab in cancer patients with adequate safety profiles. Summary incidences, relative risks (RRs), and 95% confidence intervals (95%CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. Results In total 33,526 patients from 41 RCTs were included. The use of bevacizumab significantly increased the risk of developing all-grade (RR 1.45, 95%CI: 1.27–1.66, p < 0.001) and high-grade (RR 1.59, 95%CI: 1.42–1.79, p < 0.001) infections in cancer patients. Sensitivity analysis indicated that the significance estimate of pooled RRs was not significantly influenced by omitting any single study. On subgroup analysis, the risk of developing high-grade infection varied significantly with concomitant drugs ( p = 0.008). When stratified according to specific infectious events, the use of bevacizumab significantly increased the risk of developing severe febrile neutropenia (RR 1.57, 95%CI: 1.34–1.84; p < 0.001) and fistulae/abscesses (RR 2.13, 95%CI: 1.06–4.27; p = 0.033). No evidence of publication bias was observed. Conclusions Bevacizumab treatment significantly increases the risk of infectious events developing in cancer patients. The risk may vary with concomitant drugs. Clinicians should be aware of the risks of infections with the administration of this drug in cancer patients.
The improvement of microstructure and mechanical properties of Ti alloys is of great significance for their industrial application. In this study, a developed multi-step hot deformation process was ...employed to regulate the grain boundaries (GBs), hetero-phase boundaries (PBs) and dislocation structure for dual-phase titanium alloy. The effects of accumulative thermal deformation ratios from 33% to 75% (2–8 cycles) on the microstructure and mechanical properties have been investigated. It is found that the sintered sample shows a typical Widmanstätten structure without obvious pores and micro-cracks. However, with the increase of the deformation ratio, for the hexagonal close packed (HCP) Ti, the crystal orientations of {011‾0} and {1‾21‾0} were gradually transformed into {0001}, with the change of high-angle grain boundaries (HAGBs) to low-angle grain boundaries (LAGBs). The density of stored geometrically necessary dislocations (GNDs) density raised dramatically from 1.95 × 1014 m−2 to 6.5 × 1014 m−2, and various types of dislocations have been characterized. For the β phase, in the thermal deformation process, high density α-precipitates with an average thickness below 20 nm had formed with Burgers relationship of {110}BCC//{0001}HCP and <1‾11 >BCC//<21‾1‾0 >HCP. Finally, the yield strength of the dual-phase titanium alloy increased dramatically from 881 MPa to 1178 MPa, and the ductility can still maintain at above 8.5%. The enhanced strength was mainly contributed by the increase of geometrically necessary boundaries (GNBs) and nano-lamellae boundaries (NLBs). Therefore, this strategy of combining hetero-phase boundaries (PBs) and dislocation engineering could open up new avenues to designing strong and ductile titanium matrix materials.
The combination of a surface acoustic wave (SAW) biosensor with graphene oxide (GO) provides a promising perspective for detecting DNA mutation. The GO-modified SAW biosensor was prepared by ...conjugating GO onto the SAW chip surface via electrostatic interaction. Afterward, the probe was immobilized on the GO surface, and detection of DNA mutation was realized by hybridization. The hybridization with a variety of targets would yield different mass and conformational changes on the chip surface, causing the different SAW signals in real time. A total of 137 clinical samples were detected by a single-shot analytical assay based on GO-modified SAW biosensor and direct sequencing in parallel. The diagnostic performance (both sensitivity and specificity) of the assay was evaluated with the direct sequencing as a reference testing method. The phase-shift value of three genotypes in 137 clinical samples was significantly different (p < 0.001). Furthermore, testing of diagnostic performance yielded diagnostic sensitivity and specificity of 100% and 88.6% for identifying CT and CC genotype, 98.0% and 96.2% for identifying CT and TT genotype, respectively. The single-shot analytical assay based on the GO-modified SAW biosensor could be exploited as a potential useful tool to identify CYP2D6*10 polymorphisms in clinical practice of personalized medicine.
Phyllodes tumors of the breast are rare tumor types that consist of 0.3-1.0% in all breast tumors. The naming and classification of breast phyllodes tumor have been debated for years. Based on the ...classification criteria modified by WHO in 2003, this review mainly introduced the clinicopathologic characteristics, pre-operational diagnosis and the treatment of breast phyllodes tumors, and also summarized the prognostic factors related to tumor recurrence.
Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of ...patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination S-C therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.
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