High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study.

BACKGROUND: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI). RESULTS: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination. CONCLUSIONS: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.

Effect of Ibuprofen as an Albumin Binder on Melanoma-Targeting Properties of 177Lu-Labeled Ibuprofen-Conjugated Alpha-Melanocyte-Stimulating Hormone Peptides.

The purpose of this study was to examine how the introduction of ibuprofen (IBU) affected tumor-targeting and biodistribution properties of 177Lu-labeled IBU-conjugated alpha-melanocyte-stimulating hormone peptides. The IBU was used as an albumin binder and conjugated to the DOTA-Lys moiety without or with a linker to yield DOTA-Lys(IBU)-GG-Nle-CycMSHhex {1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Lys(IBU)-Gly-Gly-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex peptides. Their melanocortin-receptor 1 (MC1R) binding affinities were determined on B16/F10 melanoma cells first. Then the biodistribution of 177Lu-labeled peptides was determined on B16/F10 melanoma-bearing C57 mice at 2 h postinjection to choose the lead peptide for further examination. The full biodistribution and melanoma imaging properties of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex were further evaluated using B16/F10 melanoma-bearing C57 mice. DOTA-Lys(IBU)-GG-Nle-CycMSHhex, DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex, DOTA-Lys(Asn-IBU)-GGNle-CycMSHhex, and DOTA-Lys(Dab-IBU)-GGNle-CycMSHhex displayed the IC50 values of 1.41 ± 0.37, 1.52 ± 0.08, 0.03 ± 0.01, and 0.58 ± 0.06 nM on B16/F10 melanoma cells, respectively. 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex exhibited the lowest liver and kidney uptake among all four designed 177Lu peptides. Therefore, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was further evaluated for its full biodistribution and melanoma imaging properties. The B16/F10 melanoma uptake of 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex was 19.5 ± 3.12, 24.12 ± 3.35, 23.85 ± 2.08, and 10.80 ± 2.89% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Moreover, 177Lu-DOTA-Lys(Asp-IBU)-GGNle-CycMSHhex could clearly visualize the B16/F10 melanoma lesions at 2 h postinjection. The conjugation of IBU with or without a linker to GGNle-CycMSHhex affected the MC1R binding affinities of the designed peptides. The charge of the linker played a key role in the liver and kidney uptake of 177Lu-Asp-IBU, 177Lu-Asn-IBU, and 177Lu-Dab-IBU. 177Lu-Asp-IBU exhibited higher tumor/liver and tumor/kidney uptake ratios than those of 177Lu-Asn-IBU and 177Lu-Dab-IBU, underscoring its potential evaluation for melanoma therapy in the future.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention　- A Subanalysis of the PANDA III Trial.

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined. METHODS AND RESULTS: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

Tuning d-orbitals to control spin-orbit coupling in terminated MXenes.

Theory and experiment have revealed that spin-orbit coupling (SOC) strongly depends on the relativistic effect in topological insulators (TIs), while the influence of orbitals is always ignored. Herein, we provide a direct way of controlling effective SOC with the help of orbital effects, reducing the dependence on elements. Taking 5d W2CO2 and 4d Mo2CO2 MXenes as a specific example, we predict that by decreasing the hybridization strength of W atoms with C or O atoms in 2D W2CO2, the nontrivial bandgaps at the Γ-point are directly enhanced. The weak hybridization of W atoms with ligand elements enhances the electron localization of degenerate d-orbitals of three groups under the triangular prism crystal field, inducing stronger on-site Coulomb repulsion that enhances orbital polarization as well as boosts the SOC effect. Meanwhile, similar results have also been observed in 4d Mo2CO2. This implies that the orbital effects are an efficient and straightforward way to control the nontrivial bandgap in 2D MXene TIs. Our work not only provides an alternative perspective on designing large nontrivial bandgaps but also brings a possibility to control the SOC effect for TI devices.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

Effects of Polyethylene Glycol and 8-Aminooctanoic Acid Linkers on Melanoma Uptake of [99mTc]Tc-Tricarbonyl-NOTA-Conjugated Lactam-Cyclized α-MSH Peptides.

The purpose of this study was to evaluate the effect of linkers on tumor targeting and biodistribution of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex {[99mTc]Tc(CO)3-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-d-Phe-Arg-Trp-Lys]-CONH2} and [99mTc]Tc(CO)3-NOTA-AocNle-CycMSHhex {[99mTc]Tc(CO)3-NOTA-8-aminooctanoic acid-Nle-CycMSHhex} on B16/F10 melanoma-bearing mice. NOTA-PEG2Nle-CycMSHhex and NOTA-AocNle-CycMSHhex were synthesized and radiolabeled with [99mTc]Tc via the {[99mTc]Tc(CO)3(OH2)3}+ intermediate. The biodistribution of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex and [99mTc]Tc(CO)3-NOTA-AocNle-CycMSHhex was determined on B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex was determined on B16/F10 melanoma-bearing C57 mice. [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex and [99mTc]Tc(CO)3-NOTA-AocNle-CycMSHhex were readily prepared with more than 90% radiochemical yields and exhibited MC1R-specific binding on B16/F10 melanoma cells. [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex exhibited a higher tumor uptake than [99mTc]Tc(CO)3-NOTA-AocNle-CycMSHhex at 2, 4, and 24 h postinjection. The tumor uptake of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex was 13.63 ± 1.13, 31.93 ± 2.57, 20.31 ± 3.23, and 1.33 ± 0.15% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. The tumor uptake of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex was 1.6 and 3.4 times the tumor uptake of [99mTc]Tc(CO)3-NOTA-AocNle-CycMSHhex at 2 and 4 h postinjection, respectively. Meanwhile, the normal organ uptake of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex was lower than 1.8% ID/g at 2 h postinjection. The renal uptake of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex was only 1.73 ± 0.37, 0.73 ± 0.14, and 0.03 ± 0.01% ID/g at 2, 4, and 24 h postinjection, respectively. [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex showed high tumor to normal organ uptake ratios at 2 h postinjection. Single-photon emission computed tomography imaging revealed that the B16/F10 melanoma lesions could be clearly visualized by [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex at 2 h postinjection. Overall, the high tumor uptake and low kidney uptake of [99mTc]Tc(CO)3-NOTA-PEG2Nle-CycMSHhex highlighted its potential for melanoma imaging and warranted the future evaluation of [188Re]Re(CO)3-NOTA-PEG2Nle-CycMSHhex for melanoma therapy.

Simulation and an experimental study on the optical performance of a Wolter-I focusing mirror based on a 3D ray tracing algorithm.

The nested Wolter-I type focusing mirror is widely used in the field of X-ray astronomy. The thin-shell mirrors produced by the electroforming replication method will introduce various shape errors during the fabricating and assembling process. This study introduces a non-analytical 3D geometrical ray tracing algorithm capable of predicting optical performance for large mirror deformations. The algorithm's implementation involves error reconstruction, light source and ray simulation, and optical performance calculation. Experimental and simulation validation underscores the algorithm's precision and effectiveness. The results also indicate that edge deformation can seriously affect imaging contrast which is generally considered to be determined only by surface scattering. Applying the 3D ray tracing algorithm, a range of low-frequency fabrication and assembly errors are simulated, such as absolute radius, taper, roundness, edge effects, mirror posture, and hoisting deformation errors, and their effects on imaging quality are analyzed and discussed.

HbA1c-based rather than fasting plasma glucose-based definitions of prediabetes identifies high-risk patients with angiographic coronary intermediate lesions: a prospective cohort study.

BACKGROUND: Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions. METHODS: A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk. RESULTS: The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143-2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005-2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden's index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients' outcome. CONCLUSIONS: In this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.

Association of sleep quality, its change and sleep duration with the risk of type 2 diabetes mellitus: Findings from the English longitudinal study of ageing.

AIMS: This study aimed to evaluate the association of sleep quality and its long-term change with the risk of type 2 diabetes mellitus (T2DM) and to assess the relationship between sleep duration and the risk of T2DM according to categories of sleep quality. MATERIALS AND METHODS: 5728 participants free of T2DM at wave 4 from the English Longitudinal Study of Ageing were included and received a follow-up with a median time of 8 years. We created a sleep quality score to evaluate sleep quality, which was based on three Jenkins Sleep Problems Scale questions (the frequency of feeling hard to fall asleep, waking up at night, and feeling tired in the morning) and one question for rating overall sleep quality. Participants were allocated into three groups according to their baseline sleep quality scores (groups of good [4-8], intermediate [8-12], and poor quality [12-16]). Sleep duration was assessed by a self-reporting sleep hours from each participant. RESULTS: 411 (7.2%) T2DM cases were documented during the follow-up. Compared with the good quality group, subjects with poor sleep quality showed a significantly higher risk of T2DM (hazard ratio (HR) 1.45, confidence interval (CI) 1.09, 1.92). In participants with good baseline sleep quality, those who experienced worsened sleep quality showed a significantly increased T2DM risk (HR 1.77, 95% CI 1.26, 2.49). Type 2 diabetes mellitus risk was not changed regardless of sleep duration in subjects with good quality. Short sleep duration (≤4h) was associated with an elevated T2DM risk in participants with intermediate sleep quality, and both short (≤4h) and prolonged sleep time (≥9h) were associated with an increased T2DM risk in the poor sleep quality group. CONCLUSIONS: Poor sleep quality is correlated with an increase in T2DM risk, and regulating sleep quality to a good range could potentially be an effective approach for preventing T2DM.

Research Progress on Biological Matrix Reference Materials in Forensic Toxicology.

Biological matrix reference material is a reference material that combines the target material with the biological matrix. The biological matrix reference material has higher consistency with the authentic specimens in forensic toxicology, and its application has a positive effect on improving the accuracy of test results. This paper reviews the research on the matrix reference materials corresponding to three common biological test materials (blood, urine and hair). In order to provide reference for the development and application of biological matrix reference materials in forensic toxicology, this paper mainly introduces the research progress of preparation technology of biological matrix reference materials and some existing products and their parameters evaluation.

Novel Al18F-NOTA-Conjugated Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptides with Enhanced Melanoma Uptake.

The purpose of this study was to evaluate the effect of linker on tumor targeting and biodistribution of Al18F-NOTA-PEG2Nle-CycMSHhex {Al18F-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-poly(ethylene glycol)-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and Al18F-NOTA-AocNle-CycMSHhex {Al18F-NOTA-8-aminooctanoic acid-Nle-CycMSHhex} on melanoma-bearing mice. NOTA-PEG2Nle-CycMSHhex and NOTA-AocNle-CycMSHhex were synthesized using fluorenylmethoxycarbonyl (Fmoc) chemistry. The melanocortin-1 (MC1) receptor binding affinities of the peptides were determined on B16/F10 melanoma cells. The biodistribution of Al18F-NOTA-PEG2Nle-CycMSHhex and Al18F-NOTA-AocNle-CycMSHhex was determined on B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of Al18F-NOTA-PEG2Nle-CycMSHhex was further examined on B16/F10 melanoma-bearing C57 mice because of its higher melanoma uptake and lower renal uptake than that of Al18F-NOTA-AocNle-CycMSHhex. The IC50 values of NOTA-PEG2/AocNle-CycMSHhex were 1.24 ± 0.07 and 2.75 ± 0.48 nM on B10/F10 cells. Al18F-NOTA-PEG2Nle-CycMSHhex and Al18F-NOTA-AocNle-CycMSHhex were readily prepared with more than 55% of radiolabeling yields and displayed melanocortin-1 receptor (MC1R)-specific binding on B16/F10 cells. Al18F-NOTA-PEG2Nle-CycMSHhex exhibited higher tumor uptake and lower kidney and liver uptake than Al18F-NOTA-AocNle-CycMSHhex at 1 and 2 h post injection. The tumor and renal uptakes of Al18F-NOTA-PEG2Nle-CycMSHhex were 17.44 ± 0.76 and 2.07 ± 0.43% ID/g at 1 h post injection, respectively. Al18F-NOTA-PEG2Nle-CycMSHhex showed the high tumor to normal organ uptake ratios after 1 h post injection. The B16/F10 melanoma lesions could be clearly visualized by positron emission tomography (PET) using Al18F-NOTA-PEG2Nle-CycMSHhex as an imaging probe at 1 and 2 h post injection. Overall, high tumor uptake, low kidney and liver uptake, and fast urinary clearance of Al18F-NOTA-PEG2Nle-CycMSHhex highlighted its potential as an MC1R-targeted imaging probe for melanoma detection.

Intra-aortic balloon pump in cardiogenic shock: A propensity score matching analysis.

OBJECTIVE: To assess the impact of intra-aortic balloon pumps (IABP) on patients with cardiogenic shock in an intensive care unit setting. BACKGROUND: IABP counterpulsation is a widely used mechanical circulatory support device, but its performance has been questioned. However, current evidence of IABP use in cardiogenic shock is very limited (mainly from the IABP-SHOCK II trial), which was restricted to cardiogenic shock complicating acute myocardial infarction. METHODS: This was a retrospective, real-world, cohort study based on the Medical Information Mart for Intensive Care III database. Adult patients with a diagnosis of cardiogenic shock were eligible. RESULTS: A total of 1028 patients with cardiogenic shock were assessed, including 384 patients who received IABP and 644 patients who did not. The in-hospital mortality was significantly lower in patients who received IABP (adjusted odds ratio: 0.75, 95% confidence interval: 0.62-0.91, p = 0.009). Analysis of secondary endpoints found that the use of IABP was associated with a significantly lower risk of 1-year mortality. After propensity score matching, the in-hospital mortality remained significantly lower in the IABP group (28.10% vs. 37.59%, p = 0.018). CONCLUSIONS: In the current cohort, IABP treatment was associated with a lower risk of in-hospital mortality in patients with cardiogenic shock. Due to the complexity of pathophysiology in cardiogenic shock and the discrepancies in current evidence, our results should be validated through further studies in the future.

Integrated coronary disease burden and patterns to discriminate vessels benefiting from percutaneous coronary intervention.

OBJECTIVE: To evaluate the prognostic implications of atherosclerosis functional pattern on ischemia-causing vessels received percutaneous coronary intervention (PCI) or conservative treatment. BACKGROUND: Quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) index is recently proposed to characterize atherosclerosis functional pattern, but its prognostic value remains unclear. METHODS: QFR-derived PPG index was retrospectively calculated in patients from the PANDA III trial. Vessels with low or high PPG treated by PCI or not were compared for the risk of 2-year vessel-oriented composite outcome (VOCO), which was a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death. RESULTS: A total of 1444 vessels were included while 94 (6.5%) VOCOs occurred within 2 years. Among physiologically ischemic vessels (QFR ≤ 0.80) treated by PCI, those with low PPG acquired higher VOCO risk than those with high PPG (8.4% vs. 3.8%; adjusted hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.18 to 3.86), and a similar VOCO risk (8.4% vs. 7.8%; adjusted HR 1.11, 95%CI 0.70-1.78) compared to those treated by conservatively. After multiple adjustment, PPG index was an independent predictor for VOCO (HR 1.30, 95% CI 1.05-1.62). The addition of PPG to the model of clinical risk factors substantially improved the predictions of VOCO (C-index 0.67 vs. 0.62, net reclassification index 0.42). CONCLUSIONS: PCI treatment was associated with improved outcomes in vessels with high PPG, but not for those with low PPG, which acquired similar risk of VOCO compared to vessels treated conservatively. QFR-derived PPG might assist the treatment strategy selection in ischemia-causing vessels.

Novel 64Cu-Labeled NOTA-Conjugated Lactam-Cyclized Alpha-Melanocyte-Stimulating Hormone Peptides with Enhanced Tumor to Kidney Uptake Ratios.

The aim of this study was to evaluate the effect of linker on tumor targeting and biodistribution of 64Cu-NOTA-PEG2Nle-CycMSHhex {64Cu-1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid-polyethylene glycol-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2} and 64Cu-NOTA-AocNle-CycMSHhex {64Cu-NOTA-8-aminooctanoic acid-Nle-CycMSHhex} on melanoma-bearing mice. NOTA-PEG2Nle-CycMSHhex and NOTA-AocNle-CycMSHhex were synthesized and purified by HPLC. The melanocortin-1 (MC1) receptor binding affinities of the peptides were examined on B16/F10 melanoma cells. The biodistributions of 64Cu-NOTA-PEG2Nle-CycMSHhex and 64Cu-NOTA-AocNle-CycMSHhex were determined on B16/F10 melanoma-bearing C57 mice. The melanoma imaging property of 64Cu-NOTA-PEG2Nle-CycMSHhex was further examined on B16/F10 melanoma-bearing C57 mice because of its higher melanoma uptake than 64Cu-NOTA-AocNle-CycMSHhex. The IC50 values of NOTA-PEG2Nle-CycMSHhex and NOTA-AocNle-CycMSHhex were 1.24 ± 0.07 and 2.75 ± 0.48 nM on B10/F10 melanoma cells. 64Cu-NOTA-PEG2Nle-CycMSHhex and 64Cu-NOTA-AocNle-CycMSHhex were readily prepared with more than 90% radiolabeling yields and showed MC1R-specific binding on B16/F10 cells. 64Cu-NOTA-PEG2Nle-CycMSHhex exhibited higher tumor uptake than 64Cu-NOTA-AocNle-CycMSHhex at 0.5, 2, 4, and 24 h post-injection. The tumor uptake of 64Cu-NOTA-PEG2Nle-CycMSHhex was 16.23 ± 0.42, 19.59 ± 1.48, 12.83 ± 1.69, and 8.78 ± 2.29% ID/g at 0.5, 2, 4, and 24 h post-injection, respectively. Normal organ uptake of 64Cu-NOTA-PEG2Nle-CycMSHhex was lower than 2% ID/g at 2 h post-injection except for kidney uptake. The renal uptake of 64Cu-NOTA-PEG2Nle-CycMSHhex was 3.66 ± 0.52, 3.27 ± 0.52, and 1.47 ± 0.56 ID/g at 2, 4, and 24 h post-injection, respectively. 64Cu-NOTA-PEG2Nle-CycMSHhex showed high tumor to normal organ uptake ratios after 2 h post-injection. The B16/F10 melanoma lesions could be clearly visualized by positron emission tomography (PET) using 64Cu-NOTA-PEG2Nle-CycMSHhex as an imaging probe at 2 h post-injection. High tumor uptake and low kidney uptake of 64Cu-NOTA-PEG2Nle-CycMSHhex underscored its potential as an MC1R-targeted theranostic peptide for melanoma imaging and therapy.

Influence on imaging performance and evaluation of Wolter-I type mandrel fabrication errors.

The electroforming replication process has been widely used in the fabrication of nested x-ray telescopes. The imaging performance of the mirrors is determined largely by the shape accuracy of the mandrels. To predict the imaging performance of mirrors replicated from mandrels with different parameter and fabrication errors, a special Monte Carlo ray tracing model is established and verified by experiments. Then, based on ray tracing numerical calculation, the influence of each major fabrication error is discussed. Furthermore, according to the results obtained by the simulation of slope error, a method for evaluating the relationship between the mandrel full-band errors and imaging quality is proposed and then verified by experiments. The results show that the power spectral density (PSD) reference given by the method can well reflect the quality of the mandrels, and guide the fabrication process.

Analysis of the Distribution of Total Phosphine and the Characteristics of Phosphine Poisoning in 29 Victims.

OBJECTIVES: To study the distribution of total phosphine in phosphine poisoning victims and summarize the characteristics of phosphine poisoning cases. METHODS: The phosphine and its metabolites in the biological samples of 29 victims in 16 phosphine poisoning cases were qualified and quantified by headspace gas chromatography-mass spectrometry. RESULTS: Five victims among 29 were poisoned by ingestion of aluminium phosphide and 24 by inhalation of phosphine gas. Phosphine metabolites were detected in the biological samples of 23 victims, and the concentrations of total phosphine in blood ranged 0.5-34.0 µg/mL. The total concentration of phosphine in liver tissue was up to 71.0 µg/g. Phosphine was not detected in the blood of the other six survived victims, which may be related to the small amount of phosphine exposure and the delay in blood sampling. CONCLUSIONS: The total concentration of phosphine in blood and tissues caused by aluminum phosphine ingestion is higher than that caused by phosphine gas inhalation. The death cases of phosphine inhalation are characterized by long exposure time, repeated exposures and age susceptibility.

Advanced Materials in Wireless, Implantable Electrical Stimulators That Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration.

Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

Analysis of the misalignment effect and the characterization method for imprinting continuous phase plates.

Continuous phase plates (CPPs) are increasingly being used to realize beam shaping and smoothing in high-power laser systems. With computer controlled optical surfacing (CCOS) technology, CPPs can be imprinted with high accuracy by a series of processing iterations, in which the characterization of the imprinted CPP surface plays a key role. However, the form accuracy evaluation is sensitive to the misalignment caused by the difference between the designed and measured coordinates. In this paper, the matching problem, which is the critical part of characterization, is first summarized as a least squares problem in accordance with the processing principle of CPPs. Then, the misalignment effect on the form error evaluation is analyzed. Necessary attention is paid to the CPP features and the sensibility analysis for different misalignments is conducted. To improve the efficiency and accuracy, an automatic characterization method based on image registration and nonlinear optimization is presented. Considering the smoothness of the CPP surface, the height difference tracing method is proposed to evaluate the matching performance and embedded into the characterization method. Finally, a series of simulations and experiments were undertaken to verify the performance of the proposed characterization method. The results demonstrated the feasibility of the proposed method, indicating that it can provide the reliable form error evaluation with sub-nanometer accuracy for imprinted CPPs.

Freeform surface generation by atmospheric pressure plasma processing using a time-variant influence function.

Based on a controllable chemical reaction, atmospheric pressure plasma processing (APPP) can achieve efficient material removal even when the tool influence function (TIF) size is reduced to several millimeters, resulting in its great application potential for generating freeform surfaces. However, the TIF changes with the local dwell time, introducing nonlinearity into processing, because of the influence of the plasma thermal effect on chemical reactions. In this paper, a freeform generation method using a time-variant TIF is presented and validated. First, the time-variant removal characteristics of APPP and its nonlinear influence on freeform surface generation are analyzed. Then, the freeform surface generation concept is proposed based on controlling the local volumetric removal. Consequently, the dwell time calculation method is developed to suppress the nonlinearity induced by the time-variant TIF. Finally, the developed method is evaluated by the simulation and experimental analysis of the complex structure generation process. Results show that the proposed method can reduce the nonlinear influence of the time-variant TIF by reasonably calculating dwell time, promoting the application of APPP in freeform surface generation.