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Managing cancer pain is a growing challenge. Individualized pharmaceutical care is particularly important for opioid-tolerant outpatients due to variation in terms of their knowledge about pain, treatment adherence, and risk of experiencing inadequate analgesia and severe adverse events. This study aimed to determine the influence of individualized pharmaceutical care on outcomes in opioid-tolerant outpatients with cancer pain.A multicenter, open-label, randomized, controlled study was carried out. Opioid-tolerant outpatients experiencing chronic cancer pain and receiving sustained-release opioids were randomly assigned to the intervention group and the control group with a 1:1 ratio. The intervention group received individualized pharmaceutical care, while the control group received conventional care during 4-week period. The primary endpoint was medication adherence on the intention-to-treat (ITT) population. Secondary outcomes included the patients' knowledge of cancer pain and pain medications, pain score, frequency of breakthrough pain, quality of life (QoL) which were assessed on the ITT population. Adverse events were evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 4.0 on the per-protocol (PP) population.A total of 118 patients were enrolled, and 102 patients (51 in each group) completed the 30-day follow-up from six oncology centers in China. The proportion of patients adhering to opioid medication increased to similar levels in the two groups during the 4 weeks (P=0.149). The intervention group had a significantly lower pain score at 4 weeks compared to the control group (P=0.015), and the proportion of participants without breakthrough pain was significantly higher at 4 weeks than at baseline in the intervention group (P=0.029), but not in the control group (P=0.322). The two groups did not differ significantly in terms of QoL or adverse events.Our results suggest that individualized pharmaceutical care can markedly reduce patient-related problems and significantly improve pain control in opioid-tolerant outpatients. These findings validate the recommendations to include clinical pharmacists in the management of cancer pain.ClinicalTrials.gov identifier: NCT03439904.

Ropivacaine, a common local anesthetic in the clinic, has anti-proliferative and pro-apoptotic effects in numerous cancers, however, the underlying regulatory mechanism of ropivacaine in hepatocellular carcinoma remains unclear. In the current study, human HepG2 cells were stimulated with different ropivacaine concentrations. Cell Counting Kit-8 assay, cell colony formation, and cell cycle were used to monitor cell viability. Cell apoptosis, migration, and invasion were determined by flow cytometry and transwell assays. Tumor xenograft experiments were performed to prove the anti-cancer effect of ropivacaine in vivo. A high dose of ropivacaine inhibited proliferation and promoted apoptosis of HepG2 cells in a dose-dependent manner. Ropivacaine challenge also arrested cells in the G2 phase, followed by a decline in the protein expression of cyclin D1 and cyclin-dependent kinase 2, and an increase in p27 levels in HepG2 cells. Additionally, different ropivacaine doses suppressed cell migration and invasion by upregulating E-cadherin expression and downregulating N-cadherin expression. Mechanically, ropivacaine challenge gradually restrained insulin-like growth factor-1 receptor (IGF-1 R) expression and the activities of phosphorylated-PI3K, AKT, and mTOR in HepG2 cells with increased ropivacaine doses. In the tumor xenograft experiment, ropivacaine was confirmed to inhibit tumor growth, accompanied by inhibition of the IGF-1 R/PI3K/AKT/mTOR signaling axis. In conclusion, ropivacaine suppressed tumor biological characteristics and promoted apoptosis, resulting in the suppression of hepatocellular carcinoma progression by targeting the IGF-1 R/PI3K/AKT/mTOR signaling pathway. It is possible that ropivacaine-mediated local anesthesia may be developed as a novel surgical adjuvant drug for treating hepatocellular carcinoma., Graphical Abstract

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin, cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that kaempferol (KPF) possesses cardioprotective and anti-inflammatory qualities. However, the effect of KPF on cardiac damage caused by conventional cancer chemotherapy remains unclear. In this study, we clarified the protective effect of KPF on cisplatin-induced heart injury, and conducted in-depth research on the molecular mechanism underlying this effect. The results showed that KPF protected against cardiac dysfunction and injury induced by cisplatin in vivo. In H9c2 cells, KPF dramatically reduced cispaltin-induced apoptosis and inflammatory response by modulating STING/NF-κB pathway. In conclusion, these results showed that KPF had great potential in attenuating cisplatin-induced cardiac injury. Besides, greater emphasis should be placed in the future on natural active compounds containing KPF with anti-inflammatory effects for the treatment of these diseases.

The ideal optical system can realize point-to-point imaging, but for an actual observation it is difficult to achieve this ideal phenomenon due to the instrumental effects of imaging system, which is usually described as the instrument profile in the imaging process of a grating spectrometer. The existence of the spectrometer instrument profiles introduces systematic errors in the observed spectral lines, which make the spectrum of the studied objects degenerate and blur. In this paper, we take the spectral data in the $\mbox{H}\upalpha $ band observed by the Multi-Band Spectrometer (MBS) of the New Vacuum Solar Telescope (NVST) as an example; according to the characteristics of its acquired spectral data, we calculate the instrument profiles of the MBS in the spatial and the dispersion direction. The results are, respectively, $0.25''$ and 115 mA, which might reflect the influence of the MBS optical instruments at that time in the $\mbox{H}\upalpha $ band. Then the spectral data is deconvolved separately in the two directions by the corresponding IP to obtain the higher spatial and spectral resolution of the NVST spectral data.

BACKGROUND This study aimed to use three modeling methods, logistic regression analysis, random forest analysis, and fully-connected neural network analysis, to develop a diagnostic gene signature for the diagnosis of ventilator-associated pneumonia (VAP). MATERIAL AND METHODS GSE30385 from the Gene Expression Omnibus (GEO) database identified differentially expressed genes (DEGs) associated with patients with VAP. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment identified the molecular functions of the DEGs. The least absolute shrinkage and selection operator (LASSO) regression analysis algorithm was used to select key genes. Three modeling methods, including logistic regression analysis, random forest analysis, and fully-connected neural network analysis, also known as also known as the feed-forward multi-layer perceptron (MLP), were used to identify the diagnostic gene signature for patients with VAP. RESULTS Sixty-six DEGs were identified for patients who had VAP (VAP+) and who did not have VAP (VAP-). Ten essential or feature genes were identified. Upregulated genes included matrix metallopeptidase 8 (MMP8), arginase 1 (ARG1), haptoglobin (HP), interleukin 18 receptor 1 (IL18R1), and NLR family apoptosis inhibitory protein (NAIP). Down-regulated genes included complement factor D (CFD), pleckstrin homology-like domain family A member 2 (PHLDA2), plasminogen activator, urokinase (PLAU), laminin subunit beta 3 (LAMB3), and dual-specificity phosphatase 2 (DUSP2). Logistic regression, random forest, and MLP analysis showed receiver operating characteristic (ROC) curve area under the curve (AUC) values of 0.85, 0.86, and 0.87, respectively. CONCLUSIONS Logistic regression analysis, random forest analysis, and MLP analysis identified a ten-gene signature for the diagnosis of VAP.

Most smokers are males, and smoking has been indicated as a risk factor for many cancers as well as postoperative complications after cancer surgery. However, little is known about whether smoking is a risk factor for postoperative ileus (POI) after radical rectal cancer resection in males. The aim of this study was to assess whether smoking is a risk factor for POI after radical resection in male rectal cancer patients. Data of 1486 patients who underwent radical resection for rectal cancer were extracted from the clinical medical system in our hospital and were statistically analyzed. POI was defined as nausea, vomiting or pain, failure to have bowel function for more than 4 days postoperatively, and absence of a mechanical bowel obstruction. The rate of POI was 12.79%. Univariate analysis showed that patients in the POI group were more likely to have a history of smoking and drinking and receive intraperitoneal chemotherapy and had a larger intraperitoneal chemotherapy dosage. In the multivariable analysis, smoking remained significantly associated with a higher incidence of POI (OR 2.238, 95% CI [1.545–3.240], P = .000). The results also showed that patients who received postoperative patient-controlled intravenous analgesia had a lower incidence of POI. Male patients with a history of smoking who undergo elective radical resection for rectal cancer have an increased risk for POI complications.

Solar time series analysis is one of the most important topics in statistical astrophysics, which aims at revealing the complex dynamical behavior of long-term solar magnetic activity. In this work, several statistical analysis techniques are combined to study the long-term persistence and phase relationship of monthly filament activity between the low latitudes and the high latitudes during the time period from 1957 April to 2010 June. Based on these advanced analysis approaches, the following remarkable results are found: (1) solar filament activity at the low latitudes lags behind that at the high latitudes with a phase shift of 40 months, and the largest positive coefficient is found to be 0.35; (2) solar filament activity at both the low and the high latitudes exhibits a strong long-term persistence behavior, that is, their nonlinear dynamical behavior could not be regarded as stochastic phenomenon; (3) the relative phase relationships between the low latitudes and the high latitudes are not in phase for the studied periodic scales, but they are coherent in the periods of 10-14 years. To sum up, the analysis results could give more useful information on our understanding the solar and the stellar dynamo theory, and also provide some crucial roles of solar magnetic activity variations.

Solar time series manifests nonlinear and non-stationary behaviors, and perhaps multi-modal dynamical processes operating in solar magnetic indicators. In the present work, the novel ensemble empirical mode decomposition (EEMD) is applied to study the monthly distribution of sunspot areas produced by the extended time series of solar activity indices (ESAI) database in the time interval from 1821 January to 1989 December. It is established that the quasi-periodic variations of monthly sunspot areas consist of at least three well-defined dynamical components: one is the short-term variations which are obviously smaller than one year, the second one is the mid-term variations with periodic scales varying from 1 year to 15 years, and the last component is the periodic variation with periodicities larger than 15 years. The analysis results indicate the EEMD technique is an advanced tool for analyzing the weakly nonlinear and non-stationary dynamical behaviors of solar magnetic activity cycle.

We present a precise and complete procedure for processing spectral data observed by the one-meter New Vacuum Solar Telescope (NVST). The procedure is suitable for both sit-and-stare and raster-scan spectra. In this work, the geometric distortions of the spectra are first corrected for subsequent processes. Then, considering the temporal changes and the remnants of spectral lines in the flat-field, the original flat-field matrix is split into four independent components to ensure a high-precision flat-fielding correction, consisting of the continuum gradient matrix, slit non-uniform matrix, CCD dust matrix, and interference fringe matrix. Subsequently, the spectral line drifts and intensity fluctuations of the science data are further corrected. After precise reduction with this procedure, the measuring accuracies of the Doppler velocities for different spectral lines and of the oscillation curves of the chromosphere and photosphere are measured. The results show that the highest measuring accuracy of the Doppler velocity is within $100~\mbox{m}\,\mbox{s}^{-1}$ , which indicates that the characteristics of the photosphere and chromosphere can be studied cospatially and cotemporally with the reduced spectra of the NVST.

Magnetic field structures on the solar atmosphere are not symmetric distribution in the northern and southern hemispheres, which is an important aspect of quasi-cyclical evolution of magnetic activity indicators that are related to solar dynamo theories. Three standard analysis techniques are applied to analyze the hemispheric coupling (north-south asymmetry and phase asynchrony) of monthly averaged values of solar Hα flare activity over the past 49 years (from 1966 January to 2014 December). The prominent results are as follows: (1) from a global point of view, solar Hα flare activity on both hemispheres are strongly correlated with each other, but the northern hemisphere precedes the southern one with a phase shift of 7 months; (2) the long-range persistence indeed exists in solar Hα flare activity, but the dynamical complexities in the two hemispheres are not identical; (3) the prominent periodicities of Hα flare activity are 17 years full-disk activity cycle and 11 years Schwabe solar cycle, but the short- and mid-term periodicities cannot determined by monthly time series; (4) by comparing the non-parametric rescaling behavior on a point-by-point basis, the hemispheric asynchrony of solar Hα flare activity are estimated to be ranging from several months to tens of months with an average value of 8.7 months. The analysis results could promote our knowledge on the long-range persistence, the quasi-periodic variation, and the hemispheric asynchrony of solar Hα flare activity on both hemispheres, and possibly provide valuable information for the hemispheric interrelation of solar magnetic activity.

In this paper we illustrate the technique used by the New Vacuum Solar Telescope (NVST) to increase the spatial resolution of two-dimensional (2D) solar spectroscopy observations involving two dimensions of space and one of wavelength. Without an image stabilizer at the NVST, large scale wobble motion is present during the spatial scanning, whose instantaneous amplitude can reach 1.3 '' due to the Earth's atmosphere and the precision of the telescope guiding system, and seriously decreases the spatial resolution of 2D spatial maps composed with scanned spectra. We make the following effort to resolve this problem: the imaging system (e.g., the TiO-band) is used to record and detect the displacement vectors of solar image motion during the raster scan, in both the slit and scanning directions. The spectral data (e.g., the H alpha line) which are originally obtained in time sequence are corrected and re-arranged in space according to those displacement vectors. Raster scans are carried out in several active regions with different seeing conditions (two rasters are illustrated in this paper). Given a certain spatial sampling and temporal resolution, the spatial resolution of the composed 2D map could be close to that of the slit-jaw image. The resulting quality after correction is quantitatively evaluated with two methods. A physical quantity, such as the line-of-sight velocities in multiple layers of the solar atmosphere, is also inferred from the re-arranged spectrum, demonstrating the advantage of this technique.

The eruption of the filament with the kink fashion is often regarded as a signature of the kink instability. However, the kink instability threshold for the filament magnetic structure has been not widely understood. Using the H-alpha observation from the New Vacuum Solar Telescope (NVST), we present a partial eruptive filament. In the eruption, a filament thread appeared to split from the middle portion of the filament and to break out in a kinklike fashion. During this period, the left filament material remained below, which erupted without the kinking motion later on. The coronal magnetic field lines associated with the filament are obtained from the nonlinear force-free field (NLFFF) extrapolations using the 12 minutes cadence vector magnetograms of the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamic Observatory (SDO). We studied the extrapolated field lines passing through the magnetic dips that are in good agreement with the observed filament. The field lines are non-uniformly twisted and appear to be made up by two twisted flux ropes winding about each other. One of them has higher twist than the other, and the highly twisted one has its dips aligned with the kinking eruptive thread at the beginning of its eruption. Before the eruption, moreover, the highly twisted flux rope was found to expand with the approximately constant field twist. In addition, the helicity flux maps deduced from the HMI magnetograms show that some helicity is injected into the overlying magnetic arcade, but no significant helicity is injected into the flux ropes. Accordingly, we suggest that the highly twisted flux rope became kink unstable when the instability threshold declined with the expansion of the flux rope., 16 pages, 6 figures, accepted for publication in ApJ