pH-Responsive doxorubicin-loaded magnetosomes for magnetic resonance-guided focused ultrasound real-time monitoring and ablation of breast cancer.

MR-guided focused ultrasound surgery (MRgFUS) is driving a new direction in non-invasive thermal ablation therapy with spatial specificity and real-time temperature monitoring. Although widely used in clinical practice, it remains challenging to completely ablate the tumor margin due to fear of damaging the surrounding tissues, thus leading to low efficacy and a series of complications. Herein, we have developed novel pH-responsive drug-loading magnetosomes (STPSD nanoplatform) for increasing the T2-contrast and improved the ablation efficiency with a clinical MRgFUS system. Specifically, this STPSD nanoplatform is functionalized by pH-responsive peptides (STP-TPE), encapsulating superparamagnetic iron oxide (SPIO) and doxorubicin (DOX), which can cause drug release and SPIO deposition at the tumor site triggered by acidity and MRgFUS. Under MRgFUS treatment, the increased vascular permeability caused by hyperthermia can improve the uptake of SPIO and DOX by tumor cells, so as to enhance ultrasound energy absorption and further enhance the efficacy of chemotherapy to completely ablate tumor margins. Moreover, we demonstrated that a series of MR sequences including T2-weighted imaging (T2WI), contrast-enhanced T1WI imaging (T1WI C+), maximum intensity projection (MIP), volume rendering (VR) and ADC mapping can be further utilized to monitor the MRgFUS ablation effect in rat models. Overall, this smart nanoplatform has the capacity to be a powerful tool to promote the therapeutic MRgFUS effect and minimize the side effects to surrounding tissues.

Panaxynol ameliorates cardiac ischemia/reperfusion injury by suppressing NLRP3-induced pyroptosis and apoptosis via HMGB1/TLR4/NF-κB axis.

BACKGROUND AND PURPOSE: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI. METHODS: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury. RESULTS: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway. CONCLUSION: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation.

Promoted Sb removal with hydrogen production in microbial electrolysis cell by ZIF-67-derived modified sulfate-reducing bacteria bio-cathode.

Bio-cathode Microbial electrolysis cell (MEC) has been widely discovered for heavy metals removal and hydrogen production. However, low electron transfer efficiency and heavy metal toxicity limit MEC treatment efficiency. In this study, ZIF-67 was introduced to modify Sulfate-reducing bacteria (SRB) bio-cathode to enhance the bioreduction of sulfate and Antimony (Sb) with hydrogen production in the MEC. ZIF-67 modified bio-cathode was developed from a bio-anode microbial fuel cell (MFC) by operating with an applied voltage of 0.8 V to reverse the polarity. Cyclic voltammetry, linear sweep voltammetry and electrochemical impedance were done to confirm the performance of the ZIF-67 modified SRB bio-cathode. The synergy reduction of sulfate and Sb was accomplished by sulfide metal precipitation reaction from SRB itself. Maximum sulfate reduction rate approached 93.37 % and Sb removal efficiency could reach 92 %, which relies on the amount of sulfide concentration generated by sulfate reduction reaction, with 0.923 ± 0.04 m3 H2/m3 of hydrogen before adding Sb and 0.857 m3 H2/m3 of hydrogen after adding Sb. The hydrogen was mainly produced in this system and the result of gas chromatography (GC) indicated that 73.27 % of hydrogen was produced. Meanwhile the precipitates were analyzed by X-ray diffraction and X-ray photoelectron spectroscopy to confirm Sb2S3 was generated from Sb (V).

Silencing GhIAA43, a member of cotton AUX/IAA genes, enhances wilt resistance via activation of salicylic acid-mediated defenses.

Auxin-mediated degradation of Aux/IAA proteins is a crucial step in auxin signaling. Recent researches indicate that Aux/IAA members also play a role in biotic and abiotic stresses. For example, Pseudomonas syringae infection causes Arabidopsis Aux/IAA protein (AXR2, AXR3) turnover. Here, by analyzing RNA-seq data we found that several cotton Aux/IAA genes are responsive to Verticillium dahliae infection, one of these named GhIAA43, was investigated for its role in cotton defense against V. dahliae infection. We demonstrate that the transcript levels of GhIAA43 were responsive to both V. dahliae infection and exogenous IAA application. By producing transgenic Arabidopsis plants overexpressing GhIAA43-GUS fusion, we show that IAA treatment and V. dahliae infection promoted GhIAA43 protein turnover. Silencing GhIAA43 in cotton enhanced wilt resistance, suggesting that GhIAA43 is a negative regulator in cotton defense against V. dahliae attack. By monitoring SA marker gene expression and measurement of SA content in GhIAA43-silenced cotton plants, we found that the enhanced resistance in GhIAA43-silenced cotton plants is due to the activation of SA-related defenses, and the activated defenses specifically occurred in the presence of V. dahliae. Furthermore, exogenous IAA application improve wilt resistance in cotton plants tested. Our results provide novel connection between auxin signaling and SA-related defenses in cotton upon V. dahliae attack.

Highly Stable Lithium/Sodium Metal Batteries with High Utilization Enabled by a Holey Two-Dimensional N-Doped TiNb2O7 Host.

Lithium/sodium metal batteries have attracted enormous attention as promising candidates for high-energy storage devices. However, their practical applications are impeded by the growth of dendrites upon Li/Na plating. Here, we report that holey 2D N-doped TiNb2O7 (N-TNO) nanosheets with high electroactive surface area and large amounts of lithiophilic/sodiophilic sites can effectively regulate Li/Na deposition as an interfacial layer, leading to an excellent cycling stability. The N-TNO interfacial layer enables the Li||Li symmetric cell to sustain stable electrodeposition over 1000 h as well as the Na||Na cell to stably cycle for 2400 h at 1 mA cm-2 and 3 mA h cm-2 with a depth of discharge as high as 50%. The full cells of the Li/Na anodes based on the N-TNO layer paired with the LiFePO4 and NaTi2(PO4)3 cathodes, respectively, show a very stable cycling over 1000 cycles at a negative-to-positive electrode capacity (N/P) ratio up to 3.

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1.

Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped according to their sensitivity to IM as the responder group (N = 66) and the non-responder group (N = 42). Real-time quantitative PCR (RT-qPCR) was performed to evaluate the expression of candidate circular RNAs (circRNAs), microRNA (miRNAs) and messenger RNA (mRNAs). No significant difference was noted regarding demographic and clinicopathological characteristics between the responder group and the non-responder group. The expression of circ_0080145, circ_0051886 and ABL1 mRNA was significantly increased, while the expression of miR-203 and miR-637 was decreased in the non-responder group as compared with the responders. By using in-silicon analysis, it was predicted that circ_0080145 and circ_0051886 targeted miR-203 and miR-637 respectively, and ABL1 was found to be shared direct target gene of miR-203 and miR-637. Ectopic over-expression of circ_0080145 and circ_0051886 respectively reduced the expression of miR-203 and miR-637. The expression of ABL1 mRNA/protein was most upregulated in culture cells co-transfected with circ_0080145 and circ_0051886 as compared with those cells individually transfected. This study established the signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. The deregulation of circ_0080145 and circ_0051886 is, at least partially, responsible for the development of IM chemoresistance in CML by regulating expression of ABL1 via modulating expression of miR-203 and miR-637.

C1q/TNF-related protein 9 decreases cardiomyocyte hypoxia/reoxygenation-induced inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

C1q/TNF-related protein 9 (CTRP9) acts as an adipokine and has been reported to exert numerous biological functions, such as anti-inflammatory and anti-oxidative stress effects, in ischemic heart disease. In the present study, the role of CTRP9 in neonatal rat cardiomyocytes (NRCMs) following hypoxia/reoxygenation (H/R) and the underlying mechanism was investigated. Adenoviral vectors containing CTRP9 or green fluorescent protein were transfected into NRCMs. A H/R model was constructed 2 days after transfection by 2 h incubation under hypoxia followed by 4 h of reoxygenation. Lactate dehydrogenase (LDH), creatine kinase (CK) and CK-myocardial band (CK-MB) levels were detected by a biochemical analyzer using biochemical kits. In addition, cell viability was detected using trypan blue staining to determine the extent of cell injury. Inflammatory cytokines TNF-α, IL-6 and IL-10 were measured by ELISA. Western blotting and reverse transcription-quantitative PCR were used to evaluate the expression levels of CTRP9, toll-like receptor 4 (TLR4), myeloid differentiation primary response (MyD88) and NF-κB. The DNA binding activity of NF-κB was also detected using an electrophoretic mobility shift assay. The results indicated that transfection with adenoviral vectors containing CTRP9 could markedly enhance CTRP9 expression. CTRP9 overexpression increased cell viability and decreased the release of LDH, CK and CK-MB. In addition, CTRP9 overexpression reduced TNF-α and IL-6 levels whilst increasing IL-10 levels, but decreased the expression of TLR4, MyD88 and NF-κB. Furthermore, the DNA binding activity of NF-κB under H/R was also decreased by CTRP9 overexpression. In conclusion, the results of the present study suggested that CTRP9 could protect cardiomyocytes from H/R injury, which was at least partially due to the inhibition of the TLR4/MyD88/NF-κB signaling pathway to reduce the release of inflammatory cytokines.

Study of cuffless blood pressure estimation method based on multiple physiological parameters.

Objective.Noninvasive blood pressure (BP) measurement technologies have been widely studied, but they still have the disadvantages of low accuracy, the requirement for frequent calibration and limited subjects. This work considers the regulation of vascular activity by the sympathetic nervous system and proposes a method for estimating BP using multiple physiological parameters.Approach.The parameters used in the model consist of heart rate variability (HRV), pulse transit time (PTT) and pulse wave morphology features extracted from electrocardiogram (ECG) and photoplethysmogram (PPG) signals. Through four classic machine learning algorithms, a hybrid data set of 3337 subjects from two databases is evaluated to verify the ability of cross-database migration. We also recommend an individual calibration procedure to further improve the accuracy of the method.Main results.The mean absolute error (MAE) and the root mean square error (RMSE) of the proposed algorithm is 10.03 and 14.55 mmHg for systolic BP (SBP), and 5.42 and 8.19 mmHg for diastolic BP (DBP). With individual calibration, the MAE and standard deviation (SD) is -0.16 ± 7.96 (SBP) and -0.13 ± 4.50 (DBP) mmHg, which satisfied the Advancement of Medical Instrumentation (AAMI) standard. In addition, the models are used to test single databases to evaluate their performance on different data sources. The overall performance of the Adaboost algorithm is better on the Multi-parameter Intelligent Monitoring in Intensive Care Unit (MIMIC) database; the MAE between its predicted value and true value reaches 6.6mmHg (SBP) and 3.12mmHg (DBP), respectively.Significance.The proposed method considers the regulation of blood vessels and the heart by the autonomic nervous system, and verifies its effectiveness and robustness across data sources, which is promising for improving the accuracy of continuous and cuffless BP estimation.

Stable Sodium Metal Anode Enabled by an Interface Protection Layer Rich in Organic Sulfide Salt.

Sodium (Na) metal is considered as a promising anode candidate for large-scale energy storage systems because of its high theoretical capacity and low electrochemical redox potential. However, Na anode suffers from a few challenges, such as the dendrite growth and severe parasitic reactions with electrolytes, which greatly hinder its practical applications. In this work, we demonstrate that an organosulfur compound additive (tetramethylthiuram disulfide) provides a facile and promising approach to overcome the above challenges in carbonate-based electrolytes. This unique organosulfur additive can in situ form a stable interfacial protection layer rich in organic sulfide salts on the sodium metal surface during cycling, leading to a stable stripping/plating cycling. Additionally, a cycling Coulombic efficiency of 94.25% is achieved, and the full battery using Prussian Blue as a cathode delivers a reversible capacity of 86.2 mAh g-1 with a capacity retention of 80% after 600 cycles at 4 C.

Effect of ionic liquid assisted hydrothermal carbonization on the properties and gasification reactivity of hydrochar derived from eucalyptus.

This project studies the relationship between the carbonization temperature and ionic liquid (IL) ([Bmim]Cl and [Bmim]OAC) solution and its impact on the structure, properties and gasification reactivity of the hydrochar obtained from eucalyptus via hydrothermal carbonization (HTC). The structure of hydrochar was analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy while its gasification reactivity with air was measured by thermogravimetric analysis at 340 °C. Results showed that the reactivity of hydrochar prepared in the presence of IL was much higher than that prepared using water. SEM analysis revealed some vesicles on the hydrochar surface during HTC at 220 °C, while Raman and XRD results showed more disordered crystal structure of the hydrochar in the presence of ILs. XPS and Raman results revealed that CO contents on the hydrochar surface increased after adding IL which implied that IL can promote opening the loop of aromatic nucleus of biomass. This study provides important information for the preparation of highly active biochar based on IL assisted HTC of eucalyptus for practical applications.

Dendrite-Free Sodium Metal Anodes Enabled by a Sodium Benzenedithiolate-Rich Protection Layer.

Sodium metal is an ideal anode material for metal rechargeable batteries, owing to its high theoretical capacity (1166 mAh g-1 ), low cost, and earth-abundance. However, the dendritic growth upon Na plating, stemming from unstable solid electrolyte interphase (SEI) film, is a major and most notable problem. Here, a sodium benzenedithiolate (PhS2 Na2 )-rich protection layer is synthesized in situ on sodium by a facile method that effectively prevents dendrite growth in the carbonate electrolyte, leading to stabilized sodium metal electrodeposition for 400 cycles (800 h) of repeated plating/stripping at a current density of 1 mA cm-2 . The organic salt, PhS2 Na2 , is found to be a critical component in the protection layer. This finding opens up a new and promising avenue, based on organic sodium slats, to stabilize sodium metals with a protection layer.

Pooled analysis of efficacy and safety of ureteral stent removal using an extraction string.

OBJECTIVE: We conducted a Pooled analysis to investigate the efficacy and safety of ureteral stent removal using an extraction string. METHODS: A systematic review was performed by using the Preferred Reporting Items for Systematic Reviews and Pooled analyses. The sources including EMBASE, MEDLINE, and the Cochrane Controlled Trials Register were retrieved to gather randomized controlled trials of ureteral stent removal using an extraction string. The reference of included literature was also searched. RESULTS: Four randomized controlled trials containing a amount of 471 patients were involved in the analysis. We found that the ureteral stent removal using an extraction string group had a greater decrease of visual analog scale (VAS) (Mean difference (MD) -1.40, 95% confidence interval (CI) -1.99 to -0.81, P < .00001) compared with the no string group. The string group did not show a significant differences in Ureteric Stent Symptom Questionnaire (USSQ) (P = .15), general health (P = .77), stent dwell time (P = .06), and urinary tract infection (UTI) (P = .59) with exception of stent dislodgement (Odds Ratio (OR) 10.36, 95% CI 2.40 to 44.77, P = .002) compared with the no string group. CONCLUSIONS: Ureteral stent removal by string significantly provides less pain than those by cystoscope for patients without increasing stent-related urinary symptoms or UTI. However, this must be balanced against a risk of stent dislodgement and, hence, may not be a good option in all patients.

Identification and Expression Profiling of Protein Phosphatases (PP2C) Gene Family in Gossypium hirsutum L.

The protein phosphatase (PP2C) gene family, known to participate in cellular processes, is one of the momentous and conserved plant-specific gene families that regulate signal transduction in eukaryotic organisms. Recently, PP2Cs were identified in Arabidopsis and various other crop species, but analysis of PP2C in cotton is yet to be reported. In the current research, we found 87 (Gossypium arboreum), 147 (Gossypium barbadense), 181 (Gossypium hirsutum), and 99 (Gossypium raimondii) PP2C-encoding genes in total from the cotton genome. Herein, we provide a comprehensive analysis of the PP2C gene family in cotton, such as gene structure organization, gene duplications, expression profiling, chromosomal mapping, protein motif organization, and phylogenetic relationships of each species. Phylogenetic analysis further categorized PP2C genes into 12 subgroups based on conserved domain composition analysis. Moreover, we observed a strong signature of purifying selection among duplicated pairs (i.e., segmental and dispersed) of Gossypium hirsutum. We also observed the tissue-specific response of GhPP2C genes in organ and fiber development by comparing the RNA-sequence (RNA-seq) data reported on different organs. The qRT-PCR validation of 30 GhPP2C genes suggested their critical role in cotton by exposure to heat, cold, drought, and salt stress treatments. Hence, our findings provide an overview of the PP2C gene family in cotton based on various bioinformatic tools that demonstrated their critical role in organ and fiber development, and abiotic stress tolerance, thereby contributing to the genetic improvement of cotton for the resistant cultivar.

Multimaterial Microfluidic 3D Printing of Textured Composites with Liquid Inclusions.

3D printing with a high degree of spatial and compositional precision could open new avenues to the design and fabrication of functional composites. By combining the direct ink writing and microfluidics, a multimaterial 3D printing system for fabricating textured composites with liquid inclusions of programmable spatial distribution and compositions is reported here. Phase diagrams for the rational selection of desired printing parameters are determined through a combination of simple theoretical analysis and experimental studies. 1D, 2D, and 3D structures programmed with desired inclusion patterns and compositions are fabricated. Moreover, the versatility of this 3D printing framework in fabricating layered composite beams of tunable thermal property and self-healing materials is demonstrated. The proposed multimaterial microfluidic 3D printing framework could be broadly applicable for structural composites and soft robotic devices.

Study of continuous blood pressure estimation based on pulse transit time, heart rate and photoplethysmography-derived hemodynamic covariates.

It is widely recognized that pulse transit time (PTT) can track blood pressure (BP) over short periods of time, and hemodynamic covariates such as heart rate, stiffness index may also contribute to BP monitoring. In this paper, we derived a proportional relationship between BP and PPT-2 and proposed an improved method adopting hemodynamic covariates in addition to PTT for continuous BP estimation. We divided 28 subjects from the Multi-parameter Intelligent Monitoring for Intensive Care database into two groups (with/without cardiovascular diseases) and utilized a machine learning strategy based on regularized linear regression (RLR) to construct BP models with different covariates for corresponding groups. RLR was performed for individuals as the initial calibration, while recursive least square algorithm was employed for the re-calibration. The results showed that errors of BP estimation by our method stayed within the Association of Advancement of Medical Instrumentation limits (- 0.98 ± 6.00 mmHg @ SBP, 0.02 ± 4.98 mmHg @ DBP) when the calibration interval extended to 1200-beat cardiac cycles. In comparison with other two representative studies, Chen's method kept accurate (0.32 ± 6.74 mmHg @ SBP, 0.94 ± 5.37 mmHg @ DBP) using a 400-beat calibration interval, while Poon's failed (- 1.97 ± 10.59 mmHg @ SBP, 0.70 ± 4.10 mmHg @ DBP) when using a 200-beat calibration interval. With additional hemodynamic covariates utilized, our method improved the accuracy of PTT-based BP estimation, decreased the calibration frequency and had the potential for better continuous BP estimation.

Numerical Simulation of Hemodynamic Changes in Central Veins after Tunneled Cuffed Central Venous Catheter Placement in Patients under Hemodialysis.

The tunneled central venous catheter (CVC) plays an important role for hemodialysis patients, but CVC-related thrombosis in the central veins remain problematic. This study is the first try to numerically find out what hemodynamic parameters are predisposed to the initiation and formation of thrombus after CVC insertion. And the potential relationship between hemodynamic parameters and the incidence rates of thrombosis occurrence was explored. The results revealed that the CVC insertion led to a significant increase of hydraulic resistance, wide-ranging abnormally high wall shear stress (WSS), and a great loss of flow rotation in the vein. Moreover, the clinical data showed that thrombosis mainly occurred at sections where most blood flow lost spiral rotation after the CVC insertion, but no corresponding match was observed between the occurrence of thrombosis and the flow velocity or WSS. We speculate that the destruction of the flow rotation in the central vein is a precursor to the thrombus formation around CVC, and an introduction of spiral flow with the CVC insertion may possibly help to protect the central vein from thrombosis. Further animal and clinical experiments should be carried out to test and verify this speculation.

[Effect of different transpulmonary pressures guided mechanical ventilation on respiratory and hemodynamics of patients with ARDS: a prospective randomized controlled trial].

OBJECTIVE: To assess the effect of different transpulmonary pressures (Ptp) guided mechanical ventilation (MV) on respiratory function and hemodynamics parameters of patients with acute respiratory distress syndrome (ARDS), and to find out a more optimized Ptp. METHODS: A prospective randomized controlled trial (RCT) was conducted. The ventilated patients with ARDS admitted to Department of Critical Care Medicine (ICU) of Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University and Department of Emergency and Critical Care Medicine (EICU) of Shenzhen Hospital of South Medical University from February 2013 to August 2016 were enrolled. According to random number table method, all patients were divided into control group and observation group. The patients in observation group was subdivided into three subgroups according to the different setting of Ptp, namely Ptp 10, 15, 20 cmH2O (1 cmH2O = 0.098 kPa) subgroups. The patients in all groups received standard treatment in accordance with the international guidelines for ARDS. The patients in control group were ventilated by guidance of ARDSNet, and the patients in observation group were ventilated by guidance of different Ptp. After setting different Ptp at 1, 24, 48 hours in the process of MV, respiratory function parameters of patients in all groups were determined. The hemodynamic parameters were determined by using pulse indicating continuous cardiac output (PiCCO) technology. The duration of MV, length of ICU stay and 28-day mortality were recorded. RESULTS: A total of 67 patients with ARDS were enrolled, among whom 2 patients died within 48 hours, and 1 case was lost to follow-up. Finally, 64 patients completed the study, 43 patients in observation group, and 21 in control group. There were no significant differences in gender composition, age, oxygenation index (PaO2/FiO2) within 4 hours after hospital admission and acute physiology and chronic health evaluation II (APACHE II) score between the two groups, which showed the baseline was equivalent and comparable. The respiratory function and hemodynamic parameters showed no obvious change in control group at different time points of MV; but with the extension of ventilation, the respiratory function was improved significantly in observation group, and the gradually rising of Ptp had obvious adverse effects on hemodynamics parameters. Compared with control group, at 48 hours of ventilation after setting Ptp, the respiratory function in Ptp 20 cmH2O subgroup was improved significantly, PaO2/FiO2, arterial partial pressure of carbon dioxide (PaCO2), positive end-expiratory pressure (PEEP), airway platform pressure (Pplat), and lung compliance (Cst) were significantly increased [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 220.9±30.8 vs. 178.5±42.9, PaCO2 (mmHg): 55.1±7.6 vs. 38.6±4.8, PEEP (cmH2O): 24.7±4.8 vs. 6.6±2.2, Pplat (cmH2O): 34.4±3.7 vs. 20.7±3.5, Cst (mL/cmH2O): 23.8±3.6 vs. 13.1±4.6; all P < 0.05], and extravascular lung water index (ELWI) was significantly decreased (mL/kg: 6.8±1.7 vs. 10.8±2.6, P < 0.05), but mean artery pressure (MAP), cardiac index (CI), global end-diastolic volume index (GEDVI) such as hemodynamics parameters were also significantly reduced [MAP (mmHg): 58.8±6.7 vs. 69.7±4.7, CI (mL×s-1×m-2): 46.7±23.3 vs. 73.3±30.0, GEDVI (mL/m2): 633.2±45.2 vs. 702.6±55.7; all P < 0.05]; the PaO2/FiO2, PEEP, Pplat, and Cst in Ptp 10 cmH2O subgroup were significantly increased [PaO2/FiO2 (mmHg): 183.4±45.5 vs. 178.5±42.9, PEEP (cmH2O): 14.4±3.6 vs. 6.6±2.2, Pplat (cmH2O): 25.7±5.6 vs. 20.7±3.5, Cst (mL/cmH2O): 16.2±4.3 vs. 13.1±4.6; all P < 0.05], and ELWI was significantly reduced (mL/kg: 8.7±1.8 vs. 10.8±2.6, P < 0.05), but the MAP, CI and GEDVI showed no significant difference [MAP (mmHg): 65.8±4.6 vs. 69.7±4.7, CI (mL×s-1×m-2): 65.0±35.0 vs. 73.3±30.0, GEDVI (mL/m2): 706.7±54.4 vs. 702.6±55.7; all P > 0.05]. The above illustrated that 10 cmH2O Ptp could act as the same as 20 cmH2O did to improve oxygenation and respiratory function, but had no obvious effect on hemodynamics. Compared with control group, the duration of MV and the length of ICU stay showed no significant differences in Ptp 10 cmH2O and 15 cmH2O subgroups, but those in 20 cmH2O subgroup were significantly shortened [duration of MV (days): 95.5±21.5 vs. 130.8±23.6, length of ICU stay (days): 8.1±2.2 vs. 12.8±2.8, both P > 0.05]. There was no significant difference in 28-day mortality among the groups. CONCLUSIONS: MV guided by Ptp of 10 cmH2O could improve oxygenation and respiratory mechanics, while has less hemodynamic influence. It was a safe and effective cardiopulmonary protection ventilation method.

Active targeting theranostic iron oxide nanoparticles for MRI and magnetic resonance-guided focused ultrasound ablation of lung cancer.

Despite its great promise in non-invasive treatment of cancers, magnetic resonance-guided focused ultrasound surgery (MRgFUS) is currently limited by the insensitivity of magnetic resonance imaging (MRI) for visualization of small tumors, low efficiency of in vivo ultrasonic energy deposition, and damage to surrounding tissues. We hereby report the development of an active targeting nano-sized theranostic superparamagnetic iron oxide (SPIO) platform for significantly increasing the imaging sensitivity and energy deposition efficiency using a clinical MRgFUS system. The surfaces of these PEGylated SPIO nanoparticles (NPs) were decorated with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies (mAb) for targeted delivery to lung cancer with EGFR overexpression. The potential of these targeted nano-theranostic agents for MRI and MRgFUS ablation was evaluated in vitro and in vivo in a rat xenograft model of human lung cancer (H460). Compared with nontargeting PEGylated SPIO NPs, the anti-EGFR mAb targeted PEGylated SPIO NPs demonstrated better targeting capability to H460 tumor cells and greatly improved the MRI contrast at the tumor site. Meanwhile, this study showed that the targeting NPs, as synergistic agents, could significantly enhance the efficiency for in vivo ultrasonic energy deposition in MRgFUS. Moreover, we demonstrated that a series of MR methods including T2-weighted image (T2WI), T1-weighted image (T1WI), diffusion-weighted imaging (DWI) and contrast-enhanced T1WI imaging, could be utilized to noninvasively and conveniently monitor the therapeutic efficacy in rat models by MRgFUS.

LC/ESI-MS method for the determination of trimetazidine in human plasma: application to a bioequivalence study on Chinese volunteers.

A rapid liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) method with good sensitivity and specificity has been developed and validated for the identification and quantification of trimetazidine in human plasma. Trimetazidine and lidocaine (internal standard) were isolated from plasma samples by protein precipitation with methanol. The chromatographic separation was accomplished on a Xterra MS C18 Column (150 mm x 4.6 mm, 5 microm particle size) with the mobile phase consisting of methanol and water (40:60, v/v) (pH 2.0, adjusted with trifluoroacetic acid), and the flow rate was set at 0.6 mL/min. Detection was performed on a single quadruple mass spectrometer by selected ion monitoring (SIM) mode (m/z 267.0 for trimetazidine and m/z 235.0 for lidocaine) with the retention time at about 3.47 and 5.05 min, respectively. The calibration curve for trimetazidine was satisfactory with regression coefficient 0.9995 over the range of 2.5-100 ng/mL in the plasma. The LOQ (S/N=10) was accordingly 2.5 ng/mL. The intra-day and inter-day precision expressed as relative standard deviation was 2.83-6.10% and 4.83-5.82%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference product) in 19 healthy male Chinese volunteers. After a single 20 mg dose for the test and reference product, the resulting mean of major pharmacokinetic parameters such as AUC(0-24), AUC(0-infinity), Cmax, Tmax and t(1/2) of trimetazidine were (673.1+/-117.6 ng h mL(-1) versus 652.3+/-121.9 ng h mL(-1)), (717.1+/-120.9 ng h mL(-1) versus 692+/-128.6 ng h mL(-1)), (74.85+/-12.13 ng mL(-1) versus 71.93+/-14.32 ng mL(-1)), (2.312+/-0.663 h versus 2.211+/-0.608 h) and (4.785+/-0.919 h versus 4.740+/-0.823 h), respectively, indicating that these two kinds of tablets were bioequivalent in the Chinese population.