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Background The data in the real-world setting on breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for hormone receptor–positive, human epidermal growth factor receptor-2-negative (HR+, HER2−) breast cancer (BC) is limited. The present study aims to screen for some predictors and investigate the prognostic significance of breast pCR after NAC in HR+, HER2− BC in China. Methods This was a multicenter, retrospective study. In this study, three hundred eighty-four HR+, HER2− BC patients who received NAC were enrolled between 2010 and 2016 from Shanghai Jiaotong University Breast Cancer Database (SJTU-BCDB). These patients were dichotomized according to the presence of breast pCR after NAC. Logistic analysis was used to screen for predictors associated with breast pCR. Kaplan-Meier (K-M) curve and a propensity score matching (PSM) analysis were performed to compare the disease-free survival (DFS) between the two groups. Cox regression was used to analyze the prognostic significance of breast pCR on DFS in HR+, HER2− BC. A nomogram model was established to predict the probability of DFS at 1, 3, and 5 years after NAC. Results Fifty-seven patients (14.8%) achieved breast pCR. Univariate analysis showed that tumor size, estrogen receptor (ER), progesterone receptor (PR), and Ki67 were associated with breast pCR. Further, multivariate analysis showed that tumor size, PR, and Ki67 remained statistically significant. K-M curves showed a statistical difference between the breast pCR and non-pCR groups before PSM (p = 0.047), and a more significant difference was shown after PSM (p = 0.033). Cox regression after PSM suggested that breast pCR, adjuvant ET, clinical T stage, and Ki67 status were the significant predictive factors for DFS in HR+, HER2− BC patients. The adjusted hazards ratio (aHR) for breast pCR was 0.228 (95% CI, 0.070~0.739; p = 0.014), for adjuvant endocrine therapy was 0.217 (95% CI, 0.059~0.801; p = 0.022), for Ki67 was 1.027 (95% CI, 1.003~1.052; p = 0.027), for cT stages 2 and 3 compared with 1, the values were 1.331 (95% CI, 0.170~10.389), and 4.699 (95% CI, 0.537~41.142), respectively (p = 0.043). A nomogram was built based on these significant predictors, providing an integrated probability of DFS at 1, 3, and 5 years. The values of area under the receiver operating characteristic (ROC) curve (AUC) were 0.967, 0.991, and 0.787, at 1 year, 3 years, and 5 years, respectively, demonstrating the ability of the nomogram to predict the DFS. Conclusions This real-world study demonstrates that tumor size, PR, and Ki67 were independent predictive factors for breast pCR in HR+, HER2− BC. Breast pCR after NAC was an independent predictor for DFS in HR+, HER2− patients, regardless of a change in nodes. Furthermore, the nomogram built in our study could predict the probability of individualized DFS in HR+, HER2− BC patients.

Genetic susceptibility plays an important role in the pathogenesis of Parkinson's disease (PD).In all, 54 cases were enrolled in the study, including PD patients carryingTwo classification methods were used; one was based on disease classification, with 26 patients in the PD group (n=12 G/G, n=14 G/A) and 28 in the HC group (n=15 G/G, n=13 G/A), and the other was based on genetic classification, with 27 patients in the G/G group and 27 in the G/A group. In the G/A group, there was a wide range of significant changes in fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) values (P0.05). There was also a significant decrease in FA in the PD-G/A group compared with the PD-G/G and HC-G/A groups (P0.05).There were more extensive brain white matter fiber damage and changes in PD patients; the G/A polymorphism may cause more extensive brain white matter damage.

With the continuous promotion of urbanization, the generation of construction and demolition waste (CDW) is increasing. The environmental problems and safety hazards caused as a result need to be resolved. In this paper, based on the system dynamics (SD) theory, the modeling, the cost, and the environmental benefit of CDW resource management under the life cycle assessment (LCA) are proposed. Specifically, we propose a combined policy derived through three variables, namely, fines, subsidies, and charges. The target is to reduce illegal dumping behavior and landfill volume and to improve the recycling volume and environmental benefits. The model is constructed with the help of the software VENSIM, and the validity and feasibility of the model are demonstrated with data from Nantong City. The results show that a single policy cannot simultaneously improve environmental benefits, illegal dumping, recycling, and landfill behavior. A combined policy combines the advantages of three single policies, fines, subsidies, and charges, which not only can effectively curb illegal dumping and landfill disposal under the premise of prioritizing environmental benefits, but can also promote the recycling of CDW. The reasonable range for the fine is 300–350 CNY/ton; the rational range for subsidies is 30–40 CNY/ton; and the flexible range for treatment charge is 40–80 CNY/ton. The model can be used for the quantitative assessment of urban CDW management costs and environmental benefits and can also provide a theoretical basis for the government.

We present the application of redundant modules in the molecular cascade circuit, which can help trace the results of each logic gate. This provides a basis for finding the error position and judging the final circuit result to improve the circuit and the reliability of the system.

Within the Sino-Italian environmental protection cooperation framework established in 2002, a comprehensive air quality monitoring network has been developed in urban Suzhou, a medium-sized Chinese city, in compliance with European standards (Directive 96/62/EC). This paper is among the first attempts to present a systematic and scientific analysis of benzene, toluene, and xylenes (BTX) pollution in China. It presents our analysis of BTX space-related and time-related measurement results. Background BTX concentrations were investigated by passive sampler Analyst(R) in 2003. We depicted the spatial distribution of average BTX concentrations collected from three 15-day campaigns on isoconcentration maps. This is the first time such detailed BTX concentration maps have been developed in China in a city scale. Continuous measurement of BTX by automatic gas chromatography was carried out at two fixed monitoring stations, one in an urban residential zone and one in a heavy traffic zone, from April to December 2005. The results show similar seasonal trends at both sites, the similarities reaching their greatest level in December and their lowest level in August. The average daily profile of BTX shows greater fluctuation in spring and winter with clear morning and evening peaks. Daily average benzene, toluene, and m,p-xylenes concentrations for the study period were 2.64, 11.52, and 3.52 microg m(-3), respectively. The benzene/toluene ratio we found was lower in Suzhou than those published in studies of other worldwide cities, which indicates serious levels of toluene pollution from local stationary sources. The similarities in seasonal trend and spatial distribution in these manual and automatic measurement results were compared with each other, though the concentration values differed.

Previous structure-activity studies indicated that a series of cocaine analogs (3s-aryltropanes with various 2s-diarylmethoxy substitutions) selectively bind the dopamine transporter (DAT) with nM ...

Vertical distribution of traffic-related pollutants inside an open street-canyon were observed in Suzhou, P.R. China, in 2005. The aim was to explore transfer and diffusion characteristics of vehicular exhaust emissions, as well as monitoring constraints associated with street canyons, courtyards and enclosed spaces. Vertical wind speed was found to strongly affect the fluctuation of all the pollutants. Daily average concentrations of NO x , NO 2 and NO, as well as NO 2 /NO x ratio, were found to vary significantly alongside the vertical, proportionate to different average daily trends. Oxidation processes and photochemical activity are discussed to explain these phenomena. Daily CO trends were found to track closely with both NO x and Benzene, while the corresponding ratios were different relative to other published works. Different emission factors and driving conditions, as well as other emission sources types (especially for Benzene) are used to explain this point.

In this study we investigated the effects of sigma receptor ligands and neurosteroids on bradykinin-induced intracellular calcium concentration ([Ca2+]i) changes in SH-SY5Y neuroblastoma cells. [Ca2+]i levels in cells loaded with fura-2 were monitored with dual-wavelength ratiometric fluorescence measurement. Submicromolar concentrations of bradykinin elicited [Ca2+]i responses with a fast rise followed by a slow decline in these cells. Preincubation of low micromolar concentrations of the neurosteroids pregnenolone, dehydroepiandrosterone (DHEA), or the prototypic sigma (sigma) receptor agonist (+)pentazocine potentiated bradykinin-induced [Ca2+]i changes in SH-SY5Y cells. The sigma receptor antagonist haloperidol blocked the enhancing effects on [Ca2+]i by (+)pentazocine or pregnenolone. Progesterone did not significantly affect the basal [Ca2+]i level or bradykinin-induced [Ca2+]i changes in these cells. However, coincubation of progesterone with (+)pentazocine, pregnenolone, or DHEA reversed their potentiating effects. The antagonistic effects of haloperidol and progesterone on the potentiating effects of (+)pentazocine and pregnenolone suggested that these ligands might act through a common mechanism. We further showed that progesterone, pregnenolone, and DHEA competed for [3H]+pentazocine binding in SH-SY5Y cells with Ki values of 0.13 +/- 0.03 microM, 0.98 +/- 0.34 microM, and 5.2 +/- 1.4 microM, respectively. Thus, the modulation of bradykinin-induced [Ca2+]i changes by neurosteroids in these cells is likely due to their actions on sigma receptors.

Purpose This paper presents a novel approach to interpret ground-level O3with the measured atmospheric stability index (ASI). Methods O3 concentrations were monitored by automatic analysers at three types of stations: traffic site, residential site and regional background site in 2005, and the ASI was simultaneously measured by observing radon and its short-lived decay products. Results The observed results showed a clear annual variation of O3 concentrations with a maximum in spring, relatively high at the regional background site over 120 ppb, and lower at the residential and traffic sites at about 70 ppb. ASI gives information about the dilution properties of the lower boundary layer and allows to highlight the relevant role of the dilution factor in determining atmospheric pollution events. We demonstrated the analysis of O3 night peak episodes with vertical wind and ASI. Conclusions With the advantage of ASI and vertical wind profiles, it was possible to isolate particular photochemical pollution phenomena of O3 peaks from the free troposphere reservoir or formed by local reactions. This shows that the index constitutes a powerful and valuable tool for describing O3 night-peak episodes at background station.

In human neuroblastoma SH-SY5Y cell preparations, sigma(1) receptor agonists (+)-pentazocine and 1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737) competed for [3H]haloperidol binding with K(i) values of 67+/-10 and 14+/-10 nM, respectively. (+)-Pentazocine or BD737 up to 10 microM did not affect basal levels of intracellular Ca(2+) concentration ([Ca(2+)](i)) in these cells, but they significantly reduced muscarine-induced [Ca(2+)](i) changes in a dose-related manner. However, the reduction by (+)-pentazocine was not reversed by the sigma(1) receptor antagonist haloperidol. Further studies showed (+)-pentazocine, BD737 and haloperidol could compete for [3H]quinuclidinyl benzilate binding in SH-SY5Y cells with K(i) values of 0.51+/-0.06, 0.32+/-0.07 and 4.4+/-2.3 microM, respectively. Thus, the inhibitory effects on muscarine-induced [Ca(2+)](i) changes by (+)-pentazocine and BD737 in SH-SY5Y cells were likely due to blockade of muscarinic receptors, not due to sigma(1) receptor activation by these ligands.

It has been suggested that neuropeptide Y (NPY) and sigma (sigma) receptor ligands may share a putative NPY/sigma receptor in rat brain. To study whether NPY and sigma receptor ligands have an inverse agonism at this putative NPY/sigma receptor, we measured their effects on G-protein activity in rat brain. Using [35S]GTPgammaS autoradiography, we found that NPY-induced G-protein activation exhibited a discrete distribution pattern in rat brain. G-protein activation in superficial cortical layers and hippocampal CA1-3 region was mainly attributed to Y1 and Y2 receptors, respectively. In the presence of 10 microM sigma-receptor agonist BD737 or 10 microM sigma-receptor antagonist haloperidol, the distribution and density of [35S]GTPgammaS binding stimulated by 10 nM NPY was not significantly altered. In rat cerebellar membranes, NPY stimulated high-affinity GTPase activity in a dose-related manner, with maximal effects of 29% increase over basal level seen at 500 nM. This NPY-elicited GTPase activity was not significantly affected by micromolar concentrations of the sigma-receptor antagonists Dup734 or haloperidol. Since no significant effects by sigma-receptor ligands on NPY-induced G-protein activation were observed, we did not see an inverse agonism of NPY and sigma-receptor ligands at the putative NPY/sigma receptor measured at the level of G-protein activation, suggesting that sigma receptors and NPY receptors do not represent a common population in rat hippocampus and cerebellum. It is also suggested that G-protein activation is not a convergent point for the signal transduction mechanisms of NPY receptors and sigma receptors.

Sigma (sigma) receptors have been implicated in psychosis, cognition, neuroprotection, and locomotion in the central nervous system. The signal transduction mechanisms for sigma receptors have not been fully elucidated. In this study, we examined the possible coupling between sigma(1) receptors and heterotrimeric guanine nucleotide-binding proteins (G proteins) in rodent brain. In sigma(1) receptor-rich cerebellar membrane preparations, the competitive binding curves of two sigma(1) agonists, (+)pentazocine and 1S,2R-(-)-cis-N-[2-(3, 4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737), were unaffected by the addition of 10 microM guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS). Neither (+)pentazocine (1-100 microM) nor BD737 (0.01-10 microM) stimulated GTPase activities significantly above basal levels in agonist-stimulated GTPase activity assays in cerebellar membranes. Furthermore, when using the method of agonist-stimulated [35S]GTPgammaS binding as assessed by autoradiography, we did not observe significant stimulation of [35S]GTPgammaS binding in rat brain sections by either (+)pentazocine or BD737. The above results demonstrate that the sigma(1) receptor is not likely be directly coupled to G proteins.