Rhizoma Dioscoreae Nipponicae Relieves Asthma by Inducing the Ferroptosis of Eosinophils and Inhibiting the p38 MAPK Signaling Pathway.

Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms. A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen I, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR. RDN significantly reduced the numbers of total cells and eosnophils in bronchoalveolar lavage fluid (BALF), inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen I, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression. RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.

Magnetic Resonance Imaging of Fibroblast Activation Protein Using a Targeted Gadolinium-Based Contrast Agent.

The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM-1 s-1 and 5.323 mM-1 s-1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.

Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome.

BACKGROUND: Changes in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS. METHODS: Gene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model. RESULTS: 19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968-1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses. CONCLUSION: A novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects. OBJECTIVE: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI. MATERIALS AND METHODS: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 µg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 µg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation. RESULTS: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 µg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results. DISCUSSION AND CONCLUSION: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

Adaptation strategies of leaf traits and leaf economic spectrum of two urban garden plants in China.

BACKGROUND: Previous studies of the relationships between traits have focused on the natural growth conditions of wild plants. Urban garden plants exhibit some differences in plant traits due to environmental interference. It is unknown whether the relationships between the leaf traits of urban garden plants differ under distinct climates. In this study, we revealed the variation characteristics of the leaf functional traits of trees, shrubs, and vines in two urban locations. Two-way ANOVA was used to reveal the response of plant leaf traits to climate and life forms. Pearson correlation analysis and principal component analysis were used to calculate the correlation coefficient between the leaf functional traits of plants at the two locations. RESULTS: Leaf dry matter content (LDMC) and vein density (VD) of different life forms in Mudanjiang were higher than those in Bozhou (P < 0.05), and the relative water content (RWC) in Bozhou was higher, whereas vein density (VD) of trees and shrubs in the two urban locations was significant (P < 0.05), but the vines were not significant. The photosynthetic pigments of tree and shrub species were larger in Mudanjiang, but the opposite was true for the vines. Both leaf vein density (VD) and stomatal density (SD) showed a very significant positive correlation in the two urban locations (P < 0.01), and both were significantly positively correlated with specific leaf area (SLA) (P < 0.05); and negatively correlated with leaf thickness (LT), and the relationship between pigment content were closer. CONCLUSION: The response to climate showed obvious differences in leaf traits of different life forms species in urban area, but the correlations between the traits showed convergence, which reflects that the adaptation strategies of garden plant leaves to different habitats are both coordinated and relatively independent.

Global and regional estimates of cervical cancer burden associated with human immunodeficiency virus infection from 1990 to 2019.

Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.

Risk factor analysis for diabetic foot ulcer-related amputation including Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio.

Diabetic foot ulcer often leads to amputation, and both nutritional status and immune function have been associated with this process. We aimed to investigate the risk factors of diabetic ulcer-related amputation including the Controlling Nutritional Status score and neutrophil-to-lymphocyte ratio biomarker. We evaluated data from hospital in patients with diabetic foot ulcer, performing univariate and multivariate analyses to screen for high-risk factors and Kaplan-Meier analysis to correlate high-risk factors with amputation-free survival. Overall, 389 patients underwent 247 amputations over the follow-up period. After correction to relevant variables, we identified five independent risk factors for diabetic ulcer-related amputation: ulcer severity, ulcer site, peripheral arterial disease, neutrophil-to-lymphocyte ratio and nutritional status. Amputation-free survival was lower for the moderate-to-severe versus mild cases, for the plantar forefoot versus hindfoot location, for the concomitant peripheral artery disease versus without and in the high versus low neutrophil-to-lymphocyte ratio (all p < 0.01). The results showed that ulcer severity (p < 0.01), ulcer site (p < 0.01), peripheral artery disease (p < 0.01), neutrophil-to-lymphocyte ratio (p < 0.01) and Controlling Nutritional Status score (p < 0.05) were independent risk factors for amputation in diabetic foot ulcer patients and have predictive values for diabetic foot ulcer progression to amputation.

Salidroside attenuates sepsis-associated acute lung injury through PPP1R15A mediated endoplasmic reticulum stress inhibition.

BACKGROUND: This study explored the role and mechanism of salidroside in sepsis-associated acute lung injury (ALI). METHOD: Sepsis-associated ALI in rats was induced by cecal ligation and perforation method, while lipopolysaccharide (LPS) was used to stimulate cell model. After the treatment of salidroside and dexamethasone (DEX), hematoxylin and eosin staining was applied to evaluate the rat lung injury. Next, the number of total cells and neutrophils in rat bronchoalveolar lavage fluid (BALF) was counted, and the lung wet/dry (W/D) ratio and water content were measured. The neutrophil elastase activity and inflammatory factor levels in BALF were detected by Elastase Assay kit and ELISA. The expressions of PPP1R15A and endoplasmic reticulum (ER) stress-related genes were detected by quantitative reverse transcription polymerase chain reaction and western blot. And the effects of silenced PPP1R15A and tauroursodeoxycholic acid (TUDCA) on cell viability, apoptosis and endoplasmic reticulum (ER) stress were determined by cell counting kit-8 assay, flow cytometry and western blot. RESULT: The lung injury, inflammation and edema in sepsis model rats were alleviated by salidroside and DEX, meanwhile salidroside increased the viability and inhibited apoptosis in LPS-treated cells. The expression of PPP1R15A was decreased in sepsis models and increased by salidroside, and salidroside down-regulated the ER stress-related protein expressions in vitro and in vivo. Silenced PPP1R15A reversed the effect of salidroside on cell viability, apoptosis and ER stress, whereas TUDCA could counteract the above effect of silenced PPP1R15A. CONCLUSION: Salidroside targeted PPP1R15A to ameliorate lung injury in sepsis through inhibiting ER stress.

Characterization of inflammatory profiles and endothelial dysfunction in diabetic limb arterial occlusion.

Our study aims to detect the changes of adiponectin (APN), endothelin 1 (ET)-1, nitric oxide (NO), cystatin C (cysC) in diabetic limb arterial occlusion (DLAO) patients and unravel their associations with endothelial function. Total 240 type 2 diabetes mellitus (T2DM) patients were divided into a DM group (n = 80, ankle brachial index (ABI) ≥ 0.9) and a DLAO group (n = 160, ABI < 0.9). ABI, flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), serum APN, ET-1, NO, and cysC were compared. There were significant increases in cysC and ET-1, and significant decreases in APN, NO, FMD and NMD of DLAO patients compared to T2DM patients. Serum APN and NO were positively correlated with ABI, while serum cysC and ET-1 were negatively correlated with ABI. cysC, ET-1 and diastolic blood pressure (DBP) were independent predictors of the severity of DLAO. Serum APN was positively correlated with FMD, NMD and NO, but was negatively correlated with ET-1 and cysC. FMD and NMD were positively correlated with APN and NO, and negatively correlated with ET-1 and cysC. Our study deciphers opposite roles of APN, NO, cysC and ET-1 in the development of DLAO and maintaining endothelial function.

May Measurement Month 2019: an analysis of blood pressure screening results from China.

To report the blood pressure (BP) data obtained in the May Measurement Month (MMM) 2019 in China. Study participants were recruited if ≥18 years of age and had ideally not had their BP measured for ≥1 year. BP was measured three times consecutively with a 1-min interval in the sitting position, using a validated electronic BP monitor. Trained volunteer investigators administered a questionnaire to collect information on lifestyle, medical history, and use of medications. The measurement was performed in 238 387 participants in 250 sites across 31 China provinces. The majority of screening took place in hospitals or clinics (78.7%), with 17.1% in outdoor public areas and 4.2% in other settings. The study participants included 127 853 women (53.6%) and had a mean (±SD) age of 48.9 ± 16.2 years. The mean (of readings two and three) systolic/diastolic BP was 121.8/73.8 mmHg. In all hypertensive patients (n = 66 181, 27.8%), the awareness, treatment, and control rates of hypertension were 51.5%, 48.4%, and 29.1%, respectively. Linear regression models showed differences in systolic and diastolic BP according to sex and age and several other major characteristics, such as previous stroke, myocardial infarction, and diabetes mellitus, antihypertensive medication use and known hypertension, previous hypertension in pregnancy and current pregnancy, alcohol intake and current smoking, and body mass index. The MMM 2019 campaign has been successful in measuring BP in a large member of participants in China.

Fabrication of a Smart Nanofluidic Biosensor through a Reversible Covalent Bond Strategy for High-Efficiency Bisulfite Sensing and Removal.

Bioinspired nanochannel based biosensors have been widely applied for sensing ions, small molecules, and biomolecules. However, the low selectivity and difficulty in recycle sensing still heavily hamper their widespread applications. Herein, we designed and fabricated a nanochannel based biosensor for high-efficiency bisulfite (HSO3-) sensing and removal through forming a reversible covalent bond between HSO3- and 4-aminophenyl-phenyl-methanone (APPM). This nanofluidic biosensor displays a promising HSO3- selectivity with high ion rectification/gating ratio (47 and 5) and excellent reversibility and stability. Of note, the L02 cell line containing excess HSO3- could still maintain high vitality in the presence of such an APPM-functionalized biosensor based membrane. These results will not only help to better understand the biological function of HSO3- in living organisms but also inspire us to develop smart artificial nanochannel based biosensors for biological applications.

May Measurement Month 2018: an analysis of blood pressure screening results from China.

To further improve awareness, treatment, and control of hypertension, the May Measurement Month (MMM) campaign continued in 2018 in China. Study subjects were adults aged 18 years or more, ideally those who had not their blood pressure (BP) measured for at least a year. Blood pressure was measured three times consecutively with a 1-min interval in the sitting position, using automated BP monitors in 288 342 participants and transmitted to a central database by a smartphone app. Questionnaire data were collected with the same app. After imputation, the overall proportion of hypertension was 29.8%. Of those with hypertension, the rates of awareness, treatment, and control were 62.3%, 57.3%, and 35.9%, respectively. In analysis based on linear regression models, both systolic and diastolic BP were higher with cigarette smoking, alcohol intake, and overweight and obesity. Our study results suggest that hypertension management is improving in comparison with the data in MMM 2017 and the nationwide survey in 2012-15, and several known lifestyle factors are key to hypertension management.

Effects of the linoleic acid/docosahexaenoic acid ratio and concentration inducing autophagy in Raw264.7 cells against Staphylococcus aureus.

Our study was to understand the autophagy induce by different ratios and concentrations of LA/DHA on Raw264.7 cell, and then to investigate the effect of Raw264.7 autophagy on the clearance of Staphylococcus aureus. Raw264.7 cells was treated by LA/DHA in different concentrations (50/100 µmol/L) and ratios (4:1, 6:1, 8:1, 1:4, 1:6 and 1:8) for 6/12/24 h, cell viability assay was assessed by Cell Counting Kit-8, LC3B, p62, P-mTOR, P-Akt, P-PI3K and BECN 1 were detected by the Western blot. LA/DHA could induce autophagy of Raw264.7 cells through the PI3K-Akt-mTOR signaling pathway, the strong effect on autophagy by the concentration is 100 µmol/L, the ratio is 6:1 of LA/DHA, and the treatment time is 24 h. Compared with the images in the control group obtained by merging red and green fluorescence channels, the treatment of LA, DHA in a ratio of 6:1 at a concentration of 100 µmol/L for 24 h significantly lead to a substantial number of autophagosomes (yellow) as well as autolysosomes (red), enhancing autophagy flux. Autophagy induce by LA/DHA can devour and damage intracellular and extracellular Staphylococcus aureus. These results indicate that LA/DHA cloud induce autophagy and enhance the phagocytosis and killing ability of macrophages to intracellular parasitic bacteria.

Rational Design of a Multifunctional Molecular Dye with Single Dose and Laser for Efficiency NIR-II Fluorescence/Photoacoustic Imaging Guided Photothermal Therapy.

Multifunctional probes integrating accurate multidiagnosis and efficient therapy hold great prospects in biomedical research. However, the sophisticated construction and difficulties in matching the ratios of doses and laser triggers of probes for each modal imaging and therapy still hinder the extensive practice of multifunctional probes in biomedicine. We herein rationally designed an organic dye SY1080 with intrinsic multifunction by introducing both 3,4-ethylenedioxy thiophene (EDOT) and the selenium containing acceptor unit into the backbone to balance the fluorescent brightness and emission wavelength. Under single dose and 808 nm laser irradiation conditions, SY1080 not only carried out NIR-II fluorescence/photoacoustic imaging of real-time and noninvasive tumor delineation with excellent contrast, but also effectively ablated tumors with laser irradiation to perform photothermal therapy under the guidance of dual-modal imaging. These exciting results highlight SY1080 as a multifunctional and universal phototheranostic platform for potential applications.

Separation and simultaneous determination of seven bioactive components in Tripterygium wilfordii Hook. F. and Tripterygium preparations by micellar electrokinetic capillary chromatography.

A simple, comprehensive, and highly selective MEKC method has been developed for simultaneous analysis of seven bioactive components (triptolide, wilfortrine, wilfordine, wilforgine, wilforine, triptophenolide, and triptonide) in the root extracts of Tripterygium wilfordii Hook. F. (TWHF) and Tripterygium preparations (TPs). Optimal BGE consisted of 10 mM sodium tetraborate, 30 mM SDS, and 30% v/v methanol. The separation voltage was 20 kV and the temperature was 25°C. A DAD was used and the detection wavelength was at 218 nm. Under the optimum conditions, the baseline separation of seven components was achieved in less than 26 min. Excellent precision, good stability, and accuracy were obtained. For all analytes, linear calibrations were established within 10-100 µg/mL. The LOD and LOQ were within 1.2-4.2 µg/mL and 4.0-14 µg/mL, respectively. The developed method was suitable for the determination of key components in TWHF and TPs.

[Effect of cigarette smoke extract on RAW264. 7 cell proliferation, autophagy and its mechanism].

OBJECTIVE: To inquiry the effects of cigarette smoke extract(CSE) on RAW264. 7 cell proliferation, autophagy and its mechanism. METHODS: RAW264. 7 cell were used and divided into control, starvation and CSE group(2%, 3%, 4%, 5%CSE). CCK-8 was used to detect the toxic action of CSE on RAW264. 7 cell. Western blot and mRFP-GFP-LC3 cell fluorescence spot count were used to explore the function of CSE on RAW264. 7 cell autophagy and its mechanism. RESULTS: Compared with the control group, the result of CCK-8(0. 671 ± 0. 03、0. 746± 0. 10、0. 584 ± 0. 07、0. 588±0. 05) showed that CSE inhibit the proliferation of RAW 264. 7 cell on 24 hours, the difference was statistically significant(P < 0. 05). The outcomes of Western blot showed that, compared with the control group, LC3 B in the CSE group increased, difference in 6(6. 612 ± 0. 35)/12(4. 383 ± 1. 99)/24(5. 781 ± 0. 78) hours, while P62 decreased in 6(1. 815±0. 08)/12(4. 383±1. 99)/24(0. 414±0. 06) hours also different, P-mTOR(1. 744 ± 0. 15) and P-AKT(0. 376 ± 0. 03) decreased, the difference was statistically significant(P<0. 05), but Beclin1 was not significantly changed. The mRFP-GFP-LC3 cell fluorescence spot count showed that the green fluorescence spot(GFP)decreased and the red fluorescence spot(mRFP) remained stable in CSE group, combined mRFP-GFP is shown as yellow and red spots. CONCLUSION: CSE has toxic effect on cell proliferation and leads to RAW264. 7 cell autophagy enhanced through AKT/m TOR pathways.

Associations between clinical data and computed tomography features in patients with epidermal growth factor receptor mutations in lung adenocarcinoma.

BACKGROUND: To analyse the differences in computed tomography (CT) features between patients with lung adenocarcinoma who have epidermal growth factor receptor (EGFR) mutations and those who have wild-type EGFR. METHODS: Patients with lung adenocarcinoma (n = 156) were enrolled from October 2013 to March 2016, including 56 patients with wild-type EGFR and 100 patients with EGFR mutations. Two independent radiologists evaluated patient characteristics and imaging features. Chi-squared test, Fisher's exact test or ANOVA was applied to discriminate clinical and CT characteristics between the genotypes. A prediction tool for EGFR mutation was devised from principal component analysis. RESULTS: The proportion of females and non-smokers in the exon 19 deletion and exon 21 missense groups was higher than in the wild-type group (P < 0.01). Severe emphysema was higher in the wild-type group than in the exon 19 deletion group (P < 0.01). The maximum diameter in the mediastinal window (MaxDmediastinal) in the wild-type group was longer than in the exon 19 deletion and exon 21 missense groups. The minimum diameter in the mediastinal window (MinDmediastinal) in the wild-type group was also longer than in the exon 21 missense group, with a significant difference (P < 0.05). The tumor shadow disappearance rate (TDR) in the exon 19 deletion group was higher than in the wild-type group. Ground glass opacity (GGO) appeared to be more common in the exon 19 deletion group (P = 0.010). The prediction score for exon 19 deletion mutation was: 0.305 × gender + 0.254 × smoking history + 0.198 × MaxDmediastinal + TDR × 0.254 + 0.280 × GGO + 0.095 × emphysema. The sensitivity and specificity for predicting exon 19 deletion were 59.09 and 76.79%, respectively. The prediction score for the exon 21 missense mutation was: 0.354 × gender + 0.291 × smoking history + 0.410 × MaxDmediastinal + 0.408 × MinDmediastinal. The sensitivity and specificity for predicting exon 21 missense mutation were 72.34 and 78.57%, respectively. CONCLUSION: As well as gender, smoking history and GGO, adenocarcinomas with EGFR mutation were significantly associated with emphysema, TDR, and the diameter in the mediastinal window. As exon 19 deletion and 21 missense mutations might be predicted by those features, the scoring system might be valuable for clinical diagnosis.

Dual T1 and T2 weighted magnetic resonance imaging based on Gd3+ loaded bioinspired melanin dots.

In this report, a novel T1/T2 dual modal nanoprobe based on highly efficient and bioinspired melanin dots (M-dots) with directly loading gadolinium (Gd-M-dots) for magnetic resonance imaging (MRI) is described. In vitro and in vivo investigations have revealed that Gd-M-dots showed nontoxicity and good biocompatibilitity. Gd-M-dots relaxivity values on 3 T were determined to be r1 = 23.4 and r2 = 123.3 mM-1 s-1, which were much higher than both Gd-DTPA (r1 = 5.1, r2 = 6.2 mM-1 s-1) and Fe-M-dots (r1 = 1.2, r2 = 2.1 mM-1 s-1). For in vivo MRI, after injection of Gd-M-dots, simultaneous T1 and T2 contrast enhancement have been observed in the MRI of mice abdomen and mice bearing U87MG tumors. Furthermore, all the veins showed high signal intensity on T1-weighted MRI and remained for 2 h. Overall, in vitro and in vivo studies indicate that Gd-M-dot with high r1 relaxivity and r2 relaxivity has high potential to be a promising nanoprobe for MR venography and molecular imaging.

Simultaneous separation and analysis of camptothecin alkaloids in real samples by large-volume sample stacking in capillary electrophoresis.

Large-volume sample stacking (LVSS) is commonly used as an effective online preconcentration method in capillary zone electrophoresis (CZE). In this paper, the method LVSS combined with CZE has been proposed to analyze camptothecin alkaloids. Optimum separation can be achieved in the following conditions: pH 9.0; 25mm borate buffer containing 20 mm sulfobutylether-ß-cyclodextrin and 20 mm ionic liquid 1-ethyl-3-methyllimidazole l-lactate; applied voltage 20 kV; and capillary temperature 25 °C. The LVSS was optimized as hydrodynamic injection 4 s at 5.0 psi and the polarity switching time was 0.17 min. Under the above conditions, the analytes could be separated completely in <20 min and the detector response was increased compared with conventional hydrodynamic injection. The limits of detection were between 0.20 and 0.78 µg/L. A good linearity was obtained with correlation coefficients from 0.9991 to 0.9997. The recoveries ranged from 97.72 to 103.2% and the results demonstrated excellent accuracy. In terms of the migration time and peak area, the experiment was reproducible. The experimental results indicated that baseline separation can be obtained and this method is suitable for the quantitative determination of camptothecin alkaloids in real samples.

Simultaneous separation and determination of praeruptorin A, B and C by micellar electrokinetic chromatography using sodium dodecyl sulphate and sodium cholate as mixed micelles.

INTRODUCTION: Praeruptorin A, B and C are major bioactive constituents in Peucedani Radix. They display anti-inflammatory effect, anti-hypertension effect, antiplatelet aggregation, potential anti-cancer activities and so on. They are worthy of investigation as potentially novel and versatile drugs. OBJECTIVE: To develop a method using micellar electrokinetic chromatography (MEKC) for the application in simultaneously separation and determination of praeruptorin A, B and C from Peucedani Radix and its medicinal preparations. METHODS: Method optimisation was carried out by investigating influences of significant factors on the separation. The method was subjected to validation. The determination of praeruptorin A, B and C in Peucedani Radix and its drug formulations was accomplished by the developed method. RESULTS: The optimal separation condition was 20 mM borate buffer containing 40 mM sodium cholate (SC), 22 mM sodium dodecyl sulphate (SDS) and 25% (v/v) acetonitrile (pH 10.00); 15 kV of voltage; 25°C of temperature; detection at 224 nm. Under this condition, three analytes were baseline separated within 16 min. A good linearity was obtained with correlation coefficients from 0.9988 to 0.9995. The limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.50 to 0.80 µg/mL and from 1.50 to 2.50 µg/mL, respectively. The recoveries ranged between 95.3% and 103.4%. CONCLUSION: The proposed method has been successfully applied to the simultaneous determination of praeruptorin A, B and C in Peucedani Radix and its pharmaceutical preparations. Additionally, it could be a potential alternative to the quality control of Peucedani Radix.