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Background Cancer-related fatigue is one of the most common and persistent issues experienced by cancer patients. Cancer-related fatigue is a distinct form of fatigue that is subjective, long-lasting and unalleviated by rest or sleep. Studies have shown that almost all cancer patients experience severe fatigue that disrupts the quality of life and physical function, but cancer-related fatigue remains under-addressed in clinical care, and only about half of all patients receive treatment. Methods To increase the awareness of cancer-related fatigue and improve current management, the Taiwan Society of Cancer Palliative Medicine and the Taiwan Oncology Nursing Society convened a consensus committee to develop recommendations for the screening, assessment and treatment of cancer-related fatigue. Results Thirteen consensus recommendations were subsequently developed based on the best available evidence and the clinical experience of committee members. Conclusions These recommendations are expected to facilitate the standardization of cancer-related fatigue management across Taiwan and may also serve as a reference for other clinicians.

Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionized the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function, sensitizing PI3K inhibitors, metabolism reprogramming, kinome rewiring, modulation of the proteosome, and many others. The ubiquitin-proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins.We performed transcriptional profiling of the HR(+) breast cancer cell lines MCF7 and T47D treated with Palbociclib. Differential expressed genes were analyzed for novel pathways enriched. The results were further validated with biochemical assays and with real world clinical database cohorts.We uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. Further validation in the HR(+) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. These three E2 enzymes modulate several E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. We further demonstrate the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR(+) breast cancer cells demonstrate dependence on the UBE2C.Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clinical efficacy in cancer.

A lot of evidence has emphasized the function of long noncoding RNAs (lncRNAs) in tumors’ development and progression. Nevertheless, there is still a lack of lncRNA biomarkers that can predict the prognosis of acute myeloid leukemia (AML). Our goal was to develop a lncRNA marker with prognostic value for the survival of AML. AML patients’ RNA sequencing data as well as clinical characteristics were obtained from the public TARGET database. Then, differentially expressed lncRNAs were identified in female and male AML samples. By adopting univariate and multivariate Cox regression analyses, AML patients’ survival was predicted by a seven-lncRNA signature. It was found that 95 abnormal expressed lncRNAs existed in AML. Then, the analysis of multivariate Cox regression showed that, among them, 7 (LINC00461, RP11-309M23.1, AC016735.2, RP11-61I13.3, KIAA0087, RORB-AS1, and AC012354.6) had an obvious prognostic value, and according to their cumulative risk scores, these 7 lncRNA signatures could independently predict the AML patients’ overall survival. Overall, the prognosis of AML patients could be predicted by a reliable tool, that is, seven-lncRNA prognostic signature.

Steam explosion (SE) was a friendly environmentally pretreatment method. In this study, the effect of steam explosion (SE) pretreatment on structure and α-glucosidase inhibitory activity of Ampelopsis grossedentata polysaccharides was evaluated. Two novel polysaccharides (AGP and AGP-SE) were extracted, isolated, purified and analyzed by NMR, FT-IR and methylation. The results indicated that AGP mainly consisted of Rha, Xyl, Glc, and Ara with a molecular weight of 2.74 × 103 kDa and AGP-SE mainly consisted of Man, Ara, and Gal with a molecular weight of 2.14 × 103 kDa. Furthermore, the backbone of AGP and AGP-SE were mainly composed of 5)-Araf-(1→, -Glcp-(1→, 6)-Glcp-(1→, 6)-Galp-(1→, 3,6)-Manp-(1→, and 2,3,6)-Glcp-(1→. Finally, we demonstrated that all polysaccharides exhibited obviously α-glucosidase inhibition activity and mixed type inhibition. AGP-SE had better α-glucosidase inhibition activity and the binding affinity KD on α-glucosidase by using Surface Plasmon Resonance (SPR) than AGP. Overall, SE pretreatment is an effective method for extracting polysaccharide and provides a new idea into the improvement of biological activity.

Breast cancer is one of the leading causes of cancer death in women, and although treatment outcome has substantially improved in the past decades, advanced or metastatic breast cancers still carry a poor prognosis. Gene amplification is one of the frequent genetic alterations in cancer, and oncogene amplification may be associated with cancer aggressiveness and oncogenicity. Targeting amplified genes such as HER2 has vastly improved disease outcome and survival, and anti-HER2 therapeutics have revolutionized the standard of care in HER2 breast cancer. Besides currently known druggable gene amplifications including ERBB2 and FGFR2, other frequently amplified genes are relatively less well known for function and clinical significance. By querying 4 large databases from TCGA and AACR-Genie, from a total of 11,890 patients with invasive ductal breast carcinoma, we discover IKZF3, CCND1, ERBB2 to be consistently amplified across different cohorts. We further identify IKZF3 as a frequently amplified gene in breast cancer with a prevalence of 12–15% amplification rate. Interestingly, IKZF3 amplification is frequently co-amplified with ERBB2/HER2, and is also associated with worse prognosis compared to IKZF3 non-amplified cancers. Analysis of HER2 breast cancer patients treated with trastuzumab revealed decrease in both ERBB2/HER2 and IKZF3 expression. Further investigation using the DepMap for gene dependency by genome wide CRISPR screening revealed dependence on IKZF3 in HER2 breast cancer cell lines. Our study utilized an integrative analysis of large scale patient genomics, transcriptomics and clinical data to reveal IKZF3 as a frequently amplified gene, and suggest a potential role of IKZF3 as a druggable target for HER2 breast cancer.

To investigate the feasibility and prognostic implications of coronary CT angiography (CCTA) derived fractional flow reserve (FFRCT) in patients who have undergone stents implantation. Firstly, the feasibility of FFRCT in stented vessels was validated. The diagnostic performance of FFRCT in identifying hemodynamically in-stent restenosis (ISR) in 33 patients with invasive FFR ≤ 0.88 as reference standard, intra-group correlation coefficient (ICC) between FFRCT and FFR was calculated. Secondly, prognostic value was assessed with 115 patients with serial CCTA scans after PCI. Stent characteristics (location, diameter, length, etc.), CCTA measurements (minimum lumen diameter [MLD], minimum lumen area [MLA], ISR), and FFRCT measurements (FFRCT, ΔFFRCT, ΔFFRCT/stent length) both at baseline and follow-up were recorded. Longitudinal analysis included changes of MLD, MLA, ISR, and FFRCT. The primary endpoint was major adverse cardiovascular events (MACE). Per-patient accuracy of FFRCT was 0.85 in identifying hemodynamically ISR. FFRCT had a good correlation with FFR (ICC = 0.84). 15.7% (18/115) developed MACE during 25 months since follow-up CCTA. Lasso regression identified age and follow-up ΔFFRCT/length as candidate variables. In the Cox proportional hazards model, age (hazard ratio [HR], 1.102 [95% CI, 1.032–1.177]; p = 0.004) and follow-up ΔFFRCT/length (HR, 1.014 [95% CI, 1.006–1.023]; p = 0.001) were independently associated with MACE (c-index = 0.856). Time-dependent ROC analysis showed AUC was 0.787 (95% CI, 0.594–0.980) at 25 months to predict adverse outcome. After bootstrap validation with 1000 resamplings, the bias-corrected c-index was 0.846. Noninvasive ML-based FFRCT is feasible in patients following stents implantation and shows prognostic value in predicting adverse events after stents implantation in low-moderate risk patients. • Machine-learning-based FFRCT is feasible to evaluate the functional significance of in-stent restenosis in patients with stent implantation. • Follow-up △FFRCT along with the stent length might have prognostic implication in patients with stent implantation and low-to-moderate risk after 2 years follow-up. The prognostic role of FFRCT in patients with moderate-to-high or high risk needs to be further studied. • FFR CT might refine the clinical pathway of patients with stent implantation to invasive catheterization.

Anions have been used to regulate the structures and luminescence of heterometallic clusters. Introducing ClO

A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study in vitro showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.

We report the structures, stability and catalysis properties of two Ag

Multigene assays, such as MammaPrint and BluePrint, provide additional information other than conventional immunohistochemistry (IHC) to help making decision of treatment. This study aims to compare the clinical correlation between molecular subtyping (MS) versus surrogate pathological subtyping (PS).A database from patients receiving MS evaluation in Taipei Veterans General Hospital from 2013 to 2018 was reviewed retrospectively. Patients were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal type from MS results and also centrally assessed according to PS (estrogen receptor [ER], progesterone receptor [PgR], HER2, and Ki-67). The clinical correlation between two different subtyping methodologies was analyzed, and the application of chemotherapy was compared.From 2013 to 2018, a total of 130 patients received MS testing in our institute, and 132 tumor samples were sent for analysis. From MammaPrint, 64 (48.5%) and 55 (41.7%) samples were defined as low and high risks, respectively. The other 13 (9.8%) tumor samples were identified as late recurrence low risk. MS restratified 44 tumors as subtype shifting including 20 tumors from A to B in intrinsic subtypes and 24 tumors from B to A after MS evaluation. Chemotherapy was conducted in only one (1.3%) patient with MS-luminal A but in 87.8% (n = 43) of MS-luminal B subtypes.The MS results restratify the subtypes of hormone receptor positive breast cancer and dominate decision-making of adjuvant therapy. The role of surrogate biomarkers as an alternative tool needs further elucidation. The treatment outcome in different subtypes categorized by MS or PS will be the interesting focus of research.

The aim of this study was to test the hypothesis that overexpression of the Multiple Epidermal Growth Factor Like Domains 11 (MEGF11) gene in TNBC cells increases tumor cell survival against anoikis via interaction with platelets.The role of MEGF11 was studied in human TNBC MDA-MB-231 and MDA-MB-468 cells by overexpressing MEGF11 (o/e MEGF11) using non-attached culture. Mouse wild type 4 T1 and Δmegf11-4 T1 cells were implanted into the mammary fat pad of BALB/c mice. Circulating tumor cells were isolated and cultured. Plasma platelets were added to these cell lines to carry out a platelet binding assay by confocal microscopy. Anoikis was observed by Live/Dead staining and a quantitative PBMC-specific cytotoxic assay (with/without platelets) was carried out to measure calcein release. The protein levels of MEGF11, Akt, and caspase 3 were assessed by Western blotting.Reduced number of circulating Δmegf11 4 T1 cells, and 4 T1-platelet clusters and reduced p-Akt expression, accompanied by increased specific calcein release, were observed in the Δmegf11 4T1group compared to the 4 T1 wild type group. There was significant increased cancer-platelet binding using the o/e MEGF11 MDA-MB-231/468 lines. Cell survival, caspase 3 activation and PBMC-specific cytotoxicity in the o/e MEGF11 MDA-MB-468 cells, but not in the MDA-MB-231 cells, could be rescued by platelet binding (+), compared to the platelet (-) group.We conclude that MEGF11 overexpression in TNBC cells rescues tumor cells from anoikis via interaction with platelets in mouse 4 T1 cells and human MDA-MB-468 cells.

A novel polysaccharide from Siraitia grosvenorii residues (SGP, molecular weight 1.93 × 103 KDa) was isolated and purified. SGP was composed of α-L-Arabinose, α-D-Mannose, α- d -Glucose, α-D-Galactose, Glucuronic acid, and Galacturonic acid with the ratio of 1: 1.92: 3.98: 7.63: 1.85: 7.34. The backbone of SGP was consist of galactoses and linked by α-(1,4)-glycosidic bond. The branch chains including α-1,6 linked glucose branch, α-1,6 linked mannose branch, α-1,3 linked galactose branch and arabinose branched (α-L-Ara(1→). The results of bioactivity experiments suggested that SGP had antioxidant in vitro, especially on scavenging DPPH radicals. Besides, SGP resulted in the decrease of ROS and the percentage of apoptotic and necrotic cells in a dose-dependent manner in H2O2 oxide injury PC12 cells. This research could help to develop the potential value and utilization of Siraitia grosvenorii.

GIBP, a homogeneous polysaccharide extracted from Glycyrrhiza inflata Batalin with a molecular weight 1.96 × 103 kDa, had a triple helix structure, smooth and sheet-like structure. Comprehensive analysis showed that the main chain of GIBP was composed of α-D-1,4 linked glucose, branch points were composed of α-D-1,3,6 and α-D-1,2,3,6 linked glucoses, and side chains were composed of α-D-1,3 and β-D-1,6 linked galactose, β-L-1,2 linked arabinose, α-D-1,3 and β-D-1,3 mannose. The scavenging abilities of GIBP (3 mg/mL) against DPPH radical, OH radical, O2− radical and ABTS were 50.75 ± 0.13% and 52.32 ± 0.13, 25.84 ± 0.35% and 44.57 ± 0.15% and it also demonstrated an obvious dose-effect relationship. The inhibitory activity of α-glucosidase showed that the inhibitory effect of GIBP was enhanced with the increase of concentration. When the concentration reached 6 mg/mL, the inhibition rate of α-glucosidase activity reached 64.77%. And the ka, kd and KD were 6.472 × 104 1/Ms., 2.934 × 10−3 1/s and 4.534 × 10−8 M.

AIM To investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP). METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot. RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats. CONCLUSION These findings suggest that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.

To investigate the effect of reader experience, calcification and image quality on the performance of deep learning (DL) powered coronary CT angiography (CCTA) in automatically detecting obstructive coronary artery disease (CAD) with invasive coronary angiography (ICA) as reference standard.A total of 165 patients (680 vessels and 1505 segments) were included in this study. Three sessions were performed in order: (1) The artificial intelligence (AI) software automatically processed CCTA images, stenosis degree and processing time were recorded for each case; (2) Six cardiovascular radiologists with different experiences (low/ intermediate/ high experience) independently performed image post-processing and interpretation of CCTA, (3) AI + human reading was performed. Luminal stenosis ≥50% was defined as obstructive CAD in ICA and CCTA. Diagnostic performances of AI, human reading and AI + human reading were evaluated and compared on a per-patient, per-vessel and per-segment basis with ICA as reference standard. The effects of calcification and image quality on the diagnostic performance were also studied.The average post-processing and interpretation times of AI was 2.3 ± 0.6 min per case, reduced by 76%, 72%, 69% compared with low/ intermediate/ high experience readers (all P 0.001), respectively. On a per-patient, per-vessel and per-segment basis, with ICA as reference method, the AI overall diagnostic sensitivity for detecting obstructive CAD were 90.5%, 81.4%, 72.9%, the specificity was 82.3%, 93.9%, 95.0%, with the corresponding areas under the curve (AUCs) of 0.90, 0.90, 0.87, respectively. Compared to human readers, the diagnostic performance of AI was higher than that of low experience readers (all P 0.001). The diagnostic performance of AI + human reading was higher than human reading alone, and AI + human readers' ability to correctly reclassify obstructive CAD was also improved, especially for low experience readers (Per-patient, the net reclassification improvement (NRI) = 0.085; per-vessel, NRI = 0.070; and per-segment, NRI = 0.068, all P 0.001). The diagnostic performance of AI was not significantly affected by calcification and image quality (all P 0.05).AI can substantially shorten the post-processing time, while AI + human reading model can significantly improve the diagnostic performance compared with human readers, especially for inexperienced readers, regardless of calcification severity and image quality.

Polymeric micelles are considered promising carriers for pulmonary drug delivery. Their interaction with the respiratory epithelium, however, is mostly unknown. In the present study, methoxypoly (ethylene glycol) (mPEG)-poly (lactic-co-glycolic acid) (PLGA) micelles containing curcumin acetate (CA) or a mixture of CA and Nile Red (NR) were prepared using the solvent evaporation method. Calu-3 and NCI-H441 human respiratory epithelial cell monolayers were used as in vitro models of upper and lower respiratory tract epithelium barrier, respectively, to study the cellular uptake and transport of the vesicles. The results show that Calu-3 and NCI-H441 cells internalized micellar particles and that micelles were able to translocate across the cell monolayers. Micelles were more readily internalized into and permeated across Calu-3 cell monolayers when compared to NCI-H441 cells. Furthermore, the presence of inhibitors of endocytic processes, such as methyl-β-cyclodextrin, NaN3 and hypertonic sucrose attenuated the cellular uptake and trafficking of micelles. In conclusion, this study demonstrated that mPEG-PLGA micelles translocate human respiratory epithelium in vitro through clathrin-, energy- and cholesterol-mediated endocytosis.

In this work, the density functional and high-level ab initio theories are adopted to investigate the mechanisms and kinetics of reaction of (CH3)3CC(O)X (X = F, Cl, and Br) with atomic chlorine. Rate coefficients for the reactions of chlorine atom with (CH3)3CC(O)F (k1), (CH3)3CC(O)Cl (k2), and (CH3)3CC(O)Br (k3) are calculated using canonical variational transition state theory coupled with small curvature tunneling method over a wide range of temperatures from 250 to 1000 K. The dynamic calculations are performed by the variational transition state theory with the interpolated single-point energies method at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of theory. Computed rate constant is in good line with the available experimental value. The rate constants for the title reactions are in this order: k1

Cajaninstilbene acid (CSA) exerts wide pharmacological activities, such as anti-inflammation, hypoglycaemic activity, analgesic effect and cognition improvement. However, it underwent severe phase II metabolism mediated by UDP-glucuronosyltransferase (UGT) in the gastrointestinal (GI) tract after oral administration, affecting its oral bioavailability. In the present study, we utilize UGT inhibitory excipient containing self-microemulsion (SME) delivery system to reduce the production of glucuronide metabolites and increase its oral bioavailability. The present results showed that although similar properties in physiochemical, cytotoxicity, cellular uptake, absorption and transport across rat everted gut sacs between SME-1 (inhibitory excipient containing SME) and SME-2 (control SME, without inhibitory excipient), an improved absolute bioavailability of 57.3 % was conferred by SME-1, significantly higher than the value of 35.4 % by SME-2 and 34.0 % by free CSA. Noticeably, the significantly lower AUC value of CSA glucuronide was determined in rats treated with SME-1 than those either treated with SME-2 or free CSA. Thus, the ability of SME-1 to enhance oral bioavailability of CSA is mainly attributed to the inhibition of phase II metabolism in the GI tract.

Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.

Because of the existence of “loads second time effect” in reinforceing damaged internal pressure steel pipeline without prestressed FRP, the fiber cannot fully play it’s advantage of high strength. Prestressed FRP is one of the effective ways to solve this problem. According to the BFRP reinforcement of damaged internal pressure steel pipeline, this paper designed a set of the circumferential prestress stretching and anchoring integral anchorage. And tested the conversion relation between torque and stress of BFRP sheet.

】 The solution of power optical cable online monitoring and cable protection equipment roasted the perfect combination of applications,which can be solved for fiber optic cable line protection, fault location and reduce equipment loss, improve security. Through optical protection equipment improvement, it can increase light protected internal OTDR monitoring channel to achieve the protection of optical communication services and the safeguard of the route line monitoring standby position, and the loss from the original equipment involved 7dB down 3dB, which effectively improve safety and quality of electric power communication optical fiber communication network, and improve management of power optical fiber communication network.

Polymeric micelles represent interesting delivery systems for pulmonary sustained release. However, little is known about their in vivo release and translocation profile after delivery to the lungs. In the present study, curcumin acetate (CA), which is an ester prodrug of curcumin, or the mixture of CA and Nile red was encapsulated into PEG–PLGA micelles by a solvent evaporation method. The micellar formulation increased the stability of CA in water and physiologically relevant fluids and led to a sustained drug release in vitro. Following intratracheal (IT) administration to rats, CA loaded micelles achieved not only prolonged pulmonary retention with AUC values almost 400-fold higher than by IV route, but also local sustained release up to 24 h. In addition, IT delivery of micelles appeared to facilitate the uptake into the pulmonary vascular endothelium and efficiently translocate across the air–blood barrier and penetrate into the brain. Co-localization of CA and Nile red confirmed that micelles in lung and brain tissue were still intact. This study is the first to demonstrate that aerosolized PEG–PLGA micelles are a promising carrier for both pulmonary and non-invasive systemic sustained release of labile drugs.

The distribution of neutron flux is simulated by MCNP code from reactor start-up to criticality when the control rods are drawn different length from reactor core on ex-core detector area of the WWER reactor of TianWan. Because physical model built is very large, in order to save calculation time, the moving process of control rod is simplified. The results of calculation show that The neutron mainly distributed in the range of 0-400cm outside the pressure vessel. The value of the relative neutron flux ex-core is maximum in the range of 110cm to 180cm, so detection effect is better when the detector is set in this region.

Crotoxin (CrTX) is the primary toxin in South American rattlesnake (Crotalus durissus terrificus) venom, and exhibits antitumor and other pharmacological actions in vivo and in vitro. Here, we investigated the molecular mechanisms of the antitumor action of CrTX in human lung carcinoma cells in vitro.Human lung squamous carcinoma SK-MES-1 cells were tested. The cytotoxicity of CrTX was evaluated in both MTT and colony formation assays. Cell cycle was investigated with flow cytometry. Cell apoptosis was studied with Hoechst 33258 and Annexin V-FITC staining. The levels of relevant proteins were analyzed using Western blot assays.CrTX (25, 50, 100 μmol/L) inhibited the growth and colony formation of SK-MES-1 cells in dose- and time-dependent manners. CrTX increased the proportion of S phase cells and dose-dependently induced cell apoptosis, accompanied by down-regulating the expression of proliferating cell nuclear antigen (PCNA), and increasing the level of cleaved caspase-3. Furthermore, CrTX dose-dependently increased the expression of autophagy-related proteins LC3-II and beclin 1, and decreased the level of p62 in the cells. Moreover, CrTX (50 μmol/L) significantly increased p38MAPK phosphorylation in the cells. Pretreatment of the cells with SB203580, a specific inhibitor of p38MAPK, blocked the inhibition of CrTX on cell proliferation, as well as CrTX-induced apoptosis and cleaved caspase-3 expression.The p38MAPK signaling pathway mediates CrTX-induced apoptosis and autophagy of human lung carcinoma SK-MES-1 cells in vitro.

High-speed multi-frame camera has been widely used for time-resolved measurement of electron beam parameters (especially for high energy and high current beam) for its fast response and high resolution. According to the requirements of a electron beam observation experiment, a three-channel framing camera optical system is designed. The system has 300mm focal length, 2.5 F#, 200lp/mm resolution. To validate the design results, visual microscope and magnify methods are used to test the consistency of image quality of three image planes. Test results show that the system fully meet the design requirements. (2013) Trans Tech Publications, Switzerland.

In this paper, aiming at the Fuyu high angle holes cementing technical issues, in-depth study the quick-setting, high early strength and micro-expansion anti-channeling slurry system. Use this system in Fuyu region high angle holes cementing engineering, the completion of 10 high angle holes were all qualified, 8 of which were quality well, the pass rate of 100% and quality rate of 80%.Solve the difficult problem of the cementation quality and packer formation of the cement sheath, ensure the cementing Quality of Fuyu city high angle wells, which has an important guide and reference on Jilin Oilfield in the future development of the deep horizontal and cementing technology.

Six esterase inhibitors, namely EDTA·2Na(+), NaF, phenylmethanesulfonyl fluoride, dichlorvos, bis-nitrophenyl phosphate (BNPP) and thenoyltrifluoroacetone, and the mixture of NaF and BNPP, were evaluated for the stabilization of labile benzoate containing zeylenone in rat plasma. The mixture appeared to exhibit the most effectively stabilizing effect with the degraded content of zeylenone decreasing from >60% (in the absence of inhibitors) to

This study aimed to evaluate the radioprotective effect of flavonoids extracted from the seeds of Astragalus complanatus R.Br. (FAC) and their protective mechanism against radiation damage. FAC increased the survival rate of mice and made the damaged organ injured by (60)Co γ-irradiation recovered to normal appearance with the mechanism of enhancing immune function and blood-producing function in vivo. The molecule mechanism of FAC against radiation is involved in the reduction of DNA injury and mutation in vitro. Eleven monomers of the FAC were analyzed by HPLC. These results seem to support the use of FAC in relieving radiation damage.

The objectives of this study were to investigate the effects of mucoadhesive excipients on systemic bioavailability of an inhaled drug and to evaluate the feasibility of using the pulmonary route for non-invasive systemic delivery of scutellarin, a poorly orally absorbed flavonoid glucuronide. Following intratracheal spray of the scutellarin solution, the bioavailability was found to be approximately 77% in rats, which was >30-fold higher than that via the peroral route. In addition, the pulmonary absorption of scutellarin appeared to avoid the intestinal first-pass metabolism accompanied by peroral administration. Spray-dried scutellarin particles with the presence of mucoadhesive excipients were found to affect the corresponding mucociliary transport rate (MTR) as evaluated by a frog palate model. The pharmacokinetic results indicated that the magnitude of AUC0–480 of intrapulmonary delivered drug particles was not correlated to the fine particle fraction (FPF) but inversely related to the MTR. Incorporating mucoadhesive polymeric mixtures into the scutellarin particles, the MTR decreased by sixfold, and the absolute bioavailability of the drug was found to increase from 70.1% to 97.9% despite a decrease in the FPF. Moreover, in vitro results evaluated using Calu-3 and A549 cell lines showed that scutellarin and spray-dried particles with or without the presence of mucoadhesives exhibited no local cell cytotoxic effects in the tested concentration range. In conclusion, the conducting airway is well permeable to scutellarin, and scutellarin may be effectively delivered systemically through inhalation of respirable droplets or particles.

The immunological assays for detection of antibodies against SARS-CoV were developed in-house and some of them are available commercially. However, the antigens used in these assays differed. In order to validate the reliability of these assays, the standard panel should be established. In this study, we have expressed and purified severe acute respiratory syndrome (SARS) structural proteins and their fragments and developed indirect enzyme-linked immunosorbent assays (ELISAs) that detect antibodies against the SARS N, N1, N2, S1, SC, S2, and M proteins as well as the human coronavirus OC43 and 229E N proteins. These assays were used to screen 58 samples from SARS convalescent patients, 40 serial serum specimens from patients at different phases of SARS infection, and 88 plasma specimens from normal blood donors. The samples from normal blood donors were also tested for antibodies against other respiratory virus. The representative samples were chosen to comprise a reference panel of SARS antibodies that may be used for the detection of SARS. The panel is composed of 25 positive samples, 25 negative samples, 7 diluted samples for anti-N antibody, 6 diluted samples for anti-S antibody, and one sample for validating precision. Comparison of detection results with different SARS antibody assays indicated that our panel should differentiate the specificity and sensitivity of different assays.

Background/Purpose Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. Methods The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. Results The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count ( r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score ( r = 0.409, p = 0.018; r = −0.399, p = 0.021; and r = −0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. Conclusion High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma.

The development of dry powder inhalation (DPI) products of traditional Chinese medicine (TCM) remains to be a challenge due to chemical complexity and batch-to-batch variations in constituent composition. This study was to investigate the feasibility of using spray-dried corrugated particles to improve the aerodynamic performance of a TCM, Shuang-Huang-Lian (SHL), in carrier-based DPI. Particles with different surface roughness were spray-dried by the addition of leucine and concomitant manipulation of spray-drying parameters. The surface roughness was determined by atomic force microscopy, whilst the aerodynamic performance of drug particle-mannitol/lactose blends was evaluated using a next-generation pharmaceutical impactor through a Cyclohaler. Although the emission efficiency for corrugated particle-based DPI was ~10% lower than that for smooth SHL, the fine particle fractions (FPF(4.4 μm)) of 32.4-36.8% for the former were significantly higher than those of 14.7-16.2% for the latter. In particular, the FPF and fraction of drug detached from the carrier appeared not to be significantly affected by the variation in constituent composition of SHL. This study demonstrates that the use of corrugated particles in carrier-based DPI improved aerosol performance by facilitating drug detachment from the carrier, independent of variation in constituent composition, and such particles were potentially applicable to the development of SHL DPI products.

The patient was a 67-year-old woman, who was evaluated by her primary care physician for progressively worsening right knee pain, described as constant in nature and as having been present for the past week. The patient's symptoms were insidious in onset, not associated with a traumatic event, and interfered with activities of daily living and sleeping. J Orthop Sports Phys Ther 2012;42(7):659. doi:10.2519/jospt.2012.0413

AIM: To observe the anti-liver fibrosis effect of Astragalus complanatus flavonoids (ACF) in rats. METHODS: The liver fibrosis model in rats was established by injecting interperitoneally 0.2 mL/100 g 0.5% dimethylnitrosamine, thrice a week. Meanwhile, the rats were administered ACF (30, 60, 120 mg/kg) or colchicine (0.1 mg/kg) once a day for 1 mo. Serum N-propeptide of type I procollagen (PINP) and type III procollagen (PIIINP) was measured using ELISA. Malondialdehyde (MDA) and superoxide dismutase (SOD) in hepatic tissue were evaluated. Matrix metal protease-1 (MMP-1) mRNA expression was assayed by RT-PCR and the protein expression of tissue inhibitor of metal protease-1 (TIMP-1) was analyzed by immunohistochemistry. RESULTS: In the ACF groups, SOD activity increased and MDA content decreased in comparison to the liver fibrosis model group. The serum PINP and PIIINP contents in ACF-2 and -3 group decreased compared to those in model group. In ACF-2 and -3 group, the expression of MMP-1 mRNA increased significantly and the protein expression of TIMP-1 decreased compared to that in model group. CONCLUSION: The antifibrotic mechanisms of ACF are associated with its influence on lipid peroxidation and collagen synthesis and degradation.

Background Daylily flowers, the flower and bud parts of Hemerocallis citrina or H. fulva, are well known as Wang-You-Cao in Chinese, meaning forget-one’s sadness plant. However, the major types of active constituents responsible for the neurological effects remain unclear. This study was to examine the protective effects of hydroalcoholic extract and fractions and to identify the active fractions. Methods The extract of daylily flowers was separated with AB-8 resin into different fractions containing non-phenolic compounds, phenolic acid derivatives and flavonoids as determined using UPLC-DAD chromatograms. The neuroprotective activity was measured by evaluating the cell viability and lactate dehydrogenase release using PC12 cell damage models induced by corticosterone and glutamate. The neurological mechanisms were explored by determining their effect on the levels of dopamine (DA), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), noradrenaline (NE) and acetylcholine (ACh) in the cell culture medium measured using an LC-MS/MS method. Results Pretreatment of PC12 cells with the extract and phenolic fractions of daylily flowers at concentrations ranging from 0.63 to 5 mg raw material/mL significantly reversed corticosterone- and glutamate-induced neurotoxicity in a dose-dependent manner. The fractions containing phenolic acid derivatives (0.59% w/w in the flowers) and/or flavonoids (0.60% w/w) exerted similar dose-dependent neuroprotective effect whereas the fractions with non-phenolic compounds exhibited no activity. The presence of phenolic acid derivatives in the corticosterone- and glutamate-treated PC12 cells elevated the DA level in the cell culture medium whereas flavonoids resulted in increased ACH and 5-HT levels. Conclusion Phenolic acid derivatives and flavonoids were likely the active constituents of daylily flowers and they conferred a similar extent of neuroprotection, but affected the release of neurotransmitters in a different manner.